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Hybrid Computational Phantoms of the Developing Fetus and Pregnant Female

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Title:
Hybrid Computational Phantoms of the Developing Fetus and Pregnant Female Construction and Application to Select Internal Radiation Dosimetry Studies
Physical Description:
1 online resource (181 p.)
Language:
english
Creator:
Maynard, Matthew R
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Biomedical Engineering
Committee Chair:
Bolch, Wesley Emmett
Committee Members:
Hintenlang, David Eric
Aris, John Phillip
Tillman, Mark D
Shifrin, Roger Yale
Moawad, Nashat Sayed

Subjects

Subjects / Keywords:
female -- fetus -- phantom -- pregnant -- radiation -- solo -- urals
Biomedical Engineering -- Dissertations, Academic -- UF
Genre:
Biomedical Engineering thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
The developing human fetus is sensitive to ionizing radiation and can experience a number of deleterious health effects following radiation exposure. Although not as immediately severe as many possible health effects, radiation-induced cancer nevertheless represents an important risk, particularly for studies such as to the European Union's Epidemiological Studies of Exposed Southern Urals Populations (SOLO) project, which investigates long-term health effects from protracted radiation exposures. For such studies, dose estimates for individual organs are required in order to mathematically quantify organ-specific health risks. One method to estimate fetal radiation doses associated with in utero exposures is by computationally simulating irradiation events using virtual replicas of the pregnant female and her fetus. First, several series of anatomically-detailed computational phantoms were constructed to represent the pregnant mother and fetus of the Western and Russian Urals populations. Second,through computational simulations performed on these phantoms, a comprehensive set of fetal radiation dose coefficients (S-values), which correlate internal radiation activity in source organs with absorbed doses in target organs, was calculated for radionuclides of interest to SOLO. Among all fetal ages, S-values ranged in magnitude from ~10-14 to ~10-10 Gy-Bq-1-s-1 for fetal source organs and from ~10-18 to ~10-14 Gy-Bq-1-s-1 for maternal source organs, depending on particle type, particle energy and fetal age. For a given radionuclide and fetal age, S-values for fetal source organs were approximately two orders of magnitude larger than for maternal source organs. Little variation in S-value was observed among fetal source organs, while variations of over 100% with respect to the mean were observed for maternal source organs near the fetus. S-value variations from maternal source organs were highly dependent on the position of the fetus and separation distance from the source organ. The computational phantoms developed in this work provide novel pathways for assessing fetal radiation dosimetry at the level of individual organs. This anatomical resolution is critical for dose tracking and cancer risk estimates associated with various radiation exposures,including non-medical sources such as those involving the SOLO cohorts and Japanese atomic bomb survivors as well as medically-administered radiation from procedures such as computed tomography (CT).
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Matthew R Maynard.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: Bolch, Wesley Emmett.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2015-08-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0045953:00001

MISSING IMAGE

Material Information

Title:
Hybrid Computational Phantoms of the Developing Fetus and Pregnant Female Construction and Application to Select Internal Radiation Dosimetry Studies
Physical Description:
1 online resource (181 p.)
Language:
english
Creator:
Maynard, Matthew R
Publisher:
University of Florida
Place of Publication:
Gainesville, Fla.
Publication Date:

Thesis/Dissertation Information

Degree:
Doctorate ( Ph.D.)
Degree Grantor:
University of Florida
Degree Disciplines:
Biomedical Engineering
Committee Chair:
Bolch, Wesley Emmett
Committee Members:
Hintenlang, David Eric
Aris, John Phillip
Tillman, Mark D
Shifrin, Roger Yale
Moawad, Nashat Sayed

Subjects

Subjects / Keywords:
female -- fetus -- phantom -- pregnant -- radiation -- solo -- urals
Biomedical Engineering -- Dissertations, Academic -- UF
Genre:
Biomedical Engineering thesis, Ph.D.
bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract:
The developing human fetus is sensitive to ionizing radiation and can experience a number of deleterious health effects following radiation exposure. Although not as immediately severe as many possible health effects, radiation-induced cancer nevertheless represents an important risk, particularly for studies such as to the European Union's Epidemiological Studies of Exposed Southern Urals Populations (SOLO) project, which investigates long-term health effects from protracted radiation exposures. For such studies, dose estimates for individual organs are required in order to mathematically quantify organ-specific health risks. One method to estimate fetal radiation doses associated with in utero exposures is by computationally simulating irradiation events using virtual replicas of the pregnant female and her fetus. First, several series of anatomically-detailed computational phantoms were constructed to represent the pregnant mother and fetus of the Western and Russian Urals populations. Second,through computational simulations performed on these phantoms, a comprehensive set of fetal radiation dose coefficients (S-values), which correlate internal radiation activity in source organs with absorbed doses in target organs, was calculated for radionuclides of interest to SOLO. Among all fetal ages, S-values ranged in magnitude from ~10-14 to ~10-10 Gy-Bq-1-s-1 for fetal source organs and from ~10-18 to ~10-14 Gy-Bq-1-s-1 for maternal source organs, depending on particle type, particle energy and fetal age. For a given radionuclide and fetal age, S-values for fetal source organs were approximately two orders of magnitude larger than for maternal source organs. Little variation in S-value was observed among fetal source organs, while variations of over 100% with respect to the mean were observed for maternal source organs near the fetus. S-value variations from maternal source organs were highly dependent on the position of the fetus and separation distance from the source organ. The computational phantoms developed in this work provide novel pathways for assessing fetal radiation dosimetry at the level of individual organs. This anatomical resolution is critical for dose tracking and cancer risk estimates associated with various radiation exposures,including non-medical sources such as those involving the SOLO cohorts and Japanese atomic bomb survivors as well as medically-administered radiation from procedures such as computed tomography (CT).
General Note:
In the series University of Florida Digital Collections.
General Note:
Includes vita.
Bibliography:
Includes bibliographical references.
Source of Description:
Description based on online resource; title from PDF title page.
Source of Description:
This bibliographic record is available under the Creative Commons CC0 public domain dedication. The University of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Statement of Responsibility:
by Matthew R Maynard.
Thesis:
Thesis (Ph.D.)--University of Florida, 2013.
Local:
Adviser: Bolch, Wesley Emmett.
Electronic Access:
RESTRICTED TO UF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE UNTIL 2015-08-31

Record Information

Source Institution:
UFRGP
Rights Management:
Applicable rights reserved.
Classification:
lcc - LD1780 2013
System ID:
UFE0045953:00001


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1 HYBRID COMPUTATIONAL PHANTOMS OF THE DEVELOPING FETUS AND PREGNANT FEMALE: CONSTRUCTION AND APPLICATION TO SELECT INTERNAL RADIATION DOSIMETRY STUDIES By MATTHEW R. MAYNARD A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2013

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2 2013 Matthew R. Maynard

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3 To Mom and Dad

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4 ACKNOWLEDGMENTS I ow e a tremendous debt of gratitude to my dissertation chair, Dr. Wesley Bolch, for recognizing my potential providing me the opportunity to pursue my dreams an d mentoring me throughout my graduate studies. I would also like to deeply thank the other member s o f my PhD superv isory committee : Drs. John Aris, David Hintenlang, Nash Moawad, Roger Shifrin and Mark Til lman. Their expertise has been in valuable. Dr. Brandi O r merod deserves special recognition for serving as a substitute committee member during my fi nal defense. Drs. Tim Fell and Natalia Shagina also deserve many thanks and recognition for their support and collaboration throughout the SOLO project. Countless past and current student colleagues deserve recognition for their contributions to my persona l and professional endea v ors. While a comprehensive list is impossible to include here, some noteworthy individuals are Drs. Justin Hanlon, Choonsik Lee, Daniel Long, Laura Padilla, Deanna Pafundi and Michael Wayson Mr. John Geyer and Mmes. Nelia Long and Reilly. Individuals not listed here by name should know they are also truly valued and appreciated. I can scarcely describe the appreciation I have for my entire family and the endless support and encouragement they have provided throughout my l ife, particularly my parents, Pamela Dougherty and Terry Maynard Thank you all from the bottom of my heart. Far too many supportive loved ones were not able to see this journey to completion: Patricia Maynard, Vicki Walters and Alexander Walters. Their sm iling faces and comforting words are deeply missed. Lastly, I would be remiss if I did not thank the universe for my dachshund, Oscar, and his limitless, joyful companionship which h as spanned nearly my entire academic career.

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5 TABLE OF CONTENTS P age ACKNOWLEDGMENTS ................................ ................................ ................................ .. 4 LIST OF TABLES ................................ ................................ ................................ ............ 8 LIST OF FIGURES ................................ ................................ ................................ ........ 10 LIST OF ABBREVIATIONS ................................ ................................ ........................... 13 ABSTRACT ................................ ................................ ................................ ................... 17 CHAPTER 1 RESEARCH AIMS ................................ ................................ ................................ .. 19 2 INTRODUCTION ................................ ................................ ................................ .... 22 Background and Significance ................................ ................................ ................. 22 Sources of Fetal Radiation Exposure ................................ ............................... 22 In Utero Health Effects ................................ ................................ ..................... 23 Epidemiological Studies of Exposed Southern Urals Populations (SOLO) ....... 24 Previous Studies and Limitations ................................ ................................ ............ 25 Mathematically Stylized and Voxel Phantoms ................................ .................. 25 Hybrid (BREP) Computational Phantoms ................................ ......................... 26 3 URALS BASED HYBRID COMP UTATIONAL FETAL PHANTOMS ....................... 31 Overview ................................ ................................ ................................ ................. 31 Phantom Construction Methods ................................ ................................ .............. 31 Summary of Methods and Design Criteria ................................ ........................ 31 Target Fetal Ages ................................ ................................ ............................. 32 Feasibility of Methods ................................ ................................ ....................... 33 Implementation in All Target Ages ................................ ................................ .... 34 Base phantom assignments ................................ ................................ ....... 34 Scaling factors ................................ ................................ ........................... 35 Biometry scaling ................................ ................................ ......................... 35 Matching individual bone masses ................................ .............................. 36 Matching whole body masses ................................ ................................ .... 39 Conversion to Voxel Format ................................ ................................ ............. 40 Results and Discussion ................................ ................................ ........................... 41 4 HYBRID COM PUTATIONAL PREGNANT FEMALE PHANTOMS ......................... 60 Overview ................................ ................................ ................................ ................. 60

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6 Phantom Construction Methods ................................ ................................ .............. 60 Summary of Methods and Design Criteria ................................ ........................ 60 Image Acquisition and Segmentation ................................ ............................... 61 NURBS and Polygon Mesh Modeling ................................ ............................... 63 UF phantom series 38 weeks ................................ ................................ .. 63 UF phantom series remaining ages ................................ ........................ 66 SOLO phantom series ................................ ................................ ............... 66 Conversion to Voxel Format ................................ ................................ ............. 67 Results and Discussion ................................ ................................ ........................... 69 Completed Phantom Series ................................ ................................ .............. 69 Phantom Series Limitations ................................ ................................ .............. 70 5 RADIATION S VALUES FOR THE SOLO RADIONUCLIDES .............................. 104 Overview ................................ ................................ ................................ ............... 104 Radiation Transport Methods and S Value Calculations ................................ ....... 105 S ummary of Methods ................................ ................................ ..................... 105 Radiation Transport ................................ ................................ ........................ 106 Phantom geometry ................................ ................................ ................... 106 Target tissues ................................ ................................ .......................... 107 Source definitions ................................ ................................ .................... 108 Verification of transport physics ................................ ............................... 109 Variance reduction ................................ ................................ ................... 111 Source particle histories ................................ ................................ ........... 113 Transport simulation runs ................................ ................................ ........ 113 Data Processing and S value Calculation ................................ ...................... 114 Results and Discussion ................................ ................................ ......................... 115 Intra fetal Irradiation ................................ ................................ ....................... 116 Fetal whole body source skeletal average ................................ ............ 11 6 Fetal whole body source individual bone sites ................................ ...... 116 Maternal Crossfire Irradiation ................................ ................................ ......... 117 Maternal whole body source ................................ ................................ .... 117 Maternal urinary bladder contents source ................................ ................ 118 Maternal stomach contents source ................................ .......................... 119 Comparisons with previous studies ................................ ................................ 119 6 CONCLUSIONS AND FUTURE WORK ................................ ............................... 141 Urals Based Hybrid Computational Fetal Phantoms ................................ ............. 141 Hybrid Computational Preg nant Female Phantoms ................................ .............. 142 Radiation S values for the SOLO Radionuclides ................................ .................. 142 Future Work ................................ ................................ ................................ .......... 144 APPENDI X A ADDITIONAL PHANTOM DATA ................................ ................................ ........... 146

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7 B ADDITIONAL RADIATION TRANSPORT DATA ................................ .................. 169 LIST OF REFERENCES ................................ ................................ ............................. 177 BIOGRAPHICAL SKETCH ................................ ................................ .......................... 181

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8 LIST OF TABLES Table P age 1 1 List of completed and anticipated publications from this work ............................ 21 3 1 Target SOLO fetal ages and assigned UF base phantoms. ............................... 44 3 2 Target biometry measurements for S OLO fetal phantom series. ........................ 45 3 3 Voxel resolutions and matrix sizes of voxelized SOLO fetal phantoms .............. 46 3 4 SOLO fetal phantom vox el masses ................................ ................................ .... 47 3 5 T arget bone and fetus masses and percent error of modeled values for the SOLO fetal phantom series. ................................ ................................ ............... 52 3 6 Ratio of ossified bone mass to whole bone mass for several bone sites in the SOLO fetal phantom series. ................................ ................................ ............... 53 3 7 Comparison of whole bone masses for common ages of SOLO and UF fetal phantom series. ................................ ................................ ................................ .. 54 3 8 Soft tissue mass comparisons between SOLO and UF fetal phantom series. .... 55 4 1 Voxel dimensions and matrix sizes of voxelized U F pregnant female phantoms ................................ ................................ ................................ ............ 72 4 2 Voxel dimensions and matrix sizes of voxelized SOLO pregnant female phantoms ................................ ................................ ................................ ............ 73 4 3 UF pregnant female phantom tissue masses ................................ ..................... 74 4 4 Percent differences of relevant tissue masses to target masses in UF pregnant female phantom series ................................ ................................ ........ 80 4 5 SOLO pregnant female phantom tissue masses ................................ ................ 81 5 1 Percent difference in S values of mass weighted UF fetal phantoms compared to Urals fetal phantoms. Source: whole ossified bone so urce irradiating ossified bone ................................ ................................ .................... 123 A 1 Mass densities of SOLO fetal phantom tissues. ................................ ............... 147 A 2 Mass densities of the UF 50 th percent ile fetal phantom tissues. ....................... 151 A 3 Mass densities of UF and SOLO pregnant female phantom m aternal tissues 155 A 4 UF 50 th percent ile fetal phantom voxel masses ................................ ................ 157

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9 A 5 Voxel resolutions and matrix sizes of voxelized UF 50 th percentile fetal phantoms ................................ ................................ ................................ .......... 162 A 6 E lemental compositions of the UF and SOLO fetal soft tissues ........................ 163 A 7 Elemental compositions of the SOLO fetal spongiosa ................................ ...... 164 A 8 Ele mental compositions of the UF fetal spongiosa ................................ ........... 165 A 9 Elemental compositions of the UF and SOLO pregnant female phantoms ....... 166 B 1 F etal target tissues of interest to the SOLO project ................................ .......... 170 B 2 Fetal source tissues of interest to the SOLO project ................................ ........ 171 B 3 Maternal source tissues of interest to the SOLO project ................................ .. 172 B 4 UF adult female blood source volume sampling distrib utions ........................... 173 B 5 UF adult female skeletal source volume sampling distributions ....................... 175 B 6 I 131 and Ba 137m radiation transport directional biasing half angles for the SOLO pregnant female series ................................ ................................ .......... 176

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10 LIST OF FIGURES Figure P age 2 1 6 month stylized pregnant female phantom. Adapted from Stabin et al. ............ 27 2 2 26 week stylized pregnant female phantom from Chen.. ................................ .... 28 2 3 Tomographic voxel fetal phantom from Shi and Xu. ................................ ........... 29 2 4 3 month, 6 month and 9 month BREP pregnant female phantoms from Xu et al. ................................ ................................ ................................ ....................... 29 2 5 UF reference fetal hybrid computation phantom series from Maynard et al. ..... 30 3 1 Comparison of 50% volume reduction of 38 week fetal mandible achieved through various scaling methods ................................ ................................ ........ 56 3 2 Mesh face intersections produced by inward offset mesh of simp le cone. ......... 57 3 3 To scale sagittal size comparison of Urals based computational fetal phantoms ................................ ................................ ................................ ............ 58 4 1 Representative segmented CT i mage slice of 36 week pregnant female. .......... 87 4 2 Incorporation of segmented 36 week maternal abdominal organs into UF adult non pregnant female ................................ ................................ .................. 88 4 3 Conversion of 36 week poly gon mesh uterus to NURBS format ....................... 89 4 4 Central tracks of small intestine and large intestine in the 38 week UF pregnant female phantom. ................................ ................................ .................. 90 4 5 Approxim ate left occiput anterior fetal orientation in 38 week UF pregnant female phantom. ................................ ................................ ................................ 91 4 6 Completed 8 week UF pregnant female p hantom. ................................ ............. 92 4 7 Completed 10 week UF pregnant female phantom. ................................ ........... 93 4 8 Completed 15 week UF pregnant female phantom. ................................ ........... 94 4 9 Completed 20 week UF pregnant female phantom. ................................ ........... 95 4 10 Completed 25 week UF pregnant female phantom. ................................ ........... 96 4 11 Completed 30 week UF pregnant female phantom. ................................ ........... 97 4 12 Completed 35 week UF pregnant female phantom. ................................ ........... 98

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11 4 13 Completed 38 week UF pregnant female phantom. ................................ ........... 99 4 14 To scale left side comparison of completed Urals based pregnant female phantom series. ................................ ................................ ................................ 100 4 15 Voxel representation of 38 week Urals based pregnant female phantom. ....... 101 4 16 Center of gravity discrepancy in the UF an d SOLO pregnant female phantoms ................................ ................................ ................................ ......... 102 4 17 Qualitative comparison of spinal curvatures of two UF fetal phantoms. ........... 103 5 1 Dual lattice representation of the 38 week SOLO preg nant female phantom in MCNPX. ................................ ................................ ................................ ........ 124 5 2 Directional biasing half angle for the SOPF38WK thyroid photon source ......... 125 5 3 Example of imp ortance weighting variance reduction.. ................................ ..... 126 5 4 Irradiation of whole fetal body by whole fetal body for all radionuclides for all SOLO fetal phantoms. ................................ ................................ ...................... 127 5 5 Skeletal average S values for all radionuclides including fetal and maternal contributions ................................ ................................ ................................ ..... 128 5 6 12 week individual bone site S value variations for Ba 137, Sr 90 and Pu 239 fetal whole body source ................................ ................................ .................... 129 5 7 26 week individual bone site S value variations for Ba 137, Sr 90 and Pu 239 fetal whole body source ................................ ................................ .................... 130 5 8 38 week individual bone site S value variations for Ba 137, Sr 90 and Pu 239 fetal whole body source ................................ ................................ .................... 131 5 9 12 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source ................................ .......................... 132 5 10 26 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source ................................ .......................... 133 5 11 38 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source ................................ .......................... 134 5 12 12 week in dividual bone site S value variations for Ba 137, I 131, and Y 90 maternal stomach content source ................................ ................................ ..... 135 5 13 26 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal s tomach content source ................................ ................................ ..... 136

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12 5 14 38 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal stomach content source ................................ ................................ ..... 137 5 15 Comparisons of Y 90 fetal whole body irradiating fetal whole body S values for several phantoms ................................ ................................ ........................ 138 5 16 Comparisons of Ba 137m maternal urinary bladder content irradiating fe tal whole body S values for several phantoms ................................ ...................... 139

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13 LIST OF ABBREVIATIONS 1D one dimensional 2D two dimensional 3D three dimensional AF absorbed fraction ALRADS Advanced Laboratory for Radiation Dosimetry Studies AST all soft tissues B A 137 M barium 137 metastable BBREM bremsstrahlung physics card (MCNPX) BPD biparietal diameter B Q Becquerel SI unit for radiation activity B Q S Becquerel second SI equivalent to one nuclear transformation BREP boundary representation CB corti cal bone CBS cortical bone surface CBV cortical bone volume C S 137 cesium 137 CT computed tomography EPA Environmental Protection Agency ESTEP electron sub steps (MCNPX) E V electron Volt F 18 fluorine 18 FDG fluorodeoxyglucose FL femur length G Y Gray SI unit for radiation absorbed dose

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14 HBVF homogeneous bone volume fraction I 131 iodine 131 ICRP International Commission on Radiological Protection ICRU International Commission on Radiation Units and Measurements IMP importance weighting IRB Institutional Re view Board ITS integrated TIGER series J Joule KG kilogram LET linear energy transfer LI large intestine LM lunar month LMP last menstrual period LOA left occiput anterior MC medullary cavity MCNP Monte Carlo N Particle MCNPX Monte Carlo N Particle Extende d M E V mega electron Volt MIRD Medical Internal Radiation Dose Committee MR magnetic resonance MRI magnetic resonance imaging NPS number of particle histories NURBS non uniform rational B spline ORNL Oak Ridge National Laboratory PACS Picture Archiving and Communication System

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15 PC post conception PET positron emission tomography PM polygon mesh PMB Physics in Medicine and Biology P U 239 plutonium 239 RAM random access memory REB Radiation and Environmental Biophysics RERF Radiation Effects Research Foundation ROA right occiput anterior RS rectosigmoid SAF specific absorbed fraction SI International System of Units SI small intestine SOLO Epidemiological Studies of Exposed Southern Urals Populations SOLO##WK Urals based hybrid fetal phantom, fetal of age ## wee ks, e.g. UFHF38WK SOPF##WK Urals based pregnant female phantom, fetal of age ## weeks, e.g. SOPF38WK SP spongiosa S R 89 strontium 89 S R 90 strontium 90 TB trabecular bone TBS trabecular bone surface TBV trabecular bone volume UF University of Florida UF HP C UF High Performance Computing

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16 UFHF##WK UF hybrid fetal phantom, fetal of age ## weeks, e.g. UFHF38WK UFPF##WK UF pregnant female phantom, fetal of age ## weeks, e.g. UFPF38WK Y 90 yttrium 90

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17 Abstract of Dissertation Presented to the Graduate School of t he University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy HYBRID COMPUTATIONAL PHANTOMS OF THE DEVELOPING FETUS AND PREGNANT FEMALE: CONSTRUCTION AND APPLICATION TO SELECT INTERNAL RADIATION DOSIMETRY STUDIES By Matthew R. Maynard August 2013 Chair: Wesley Bolch Major: Biomedical Engineering The developing human fetus is sensitive to ionizing radiation and can experience a number of deleterious health effects following radiation exposure Although not as immediately severe as many possible health effects, radiation induced cancer nevertheless represents an important risk particularly for studies such as to the European Union's Epidemiological Studies of Exposed Southern Urals Populations (SOLO) project which investigates long term health effects from protracted radiation e xposures For such studies dose estimates for individual organs are required in order to mathematically quantif y organ specific health risks. One method to estimate fetal radiation doses associated with in utero exposures is by computational ly simulating irradiation events using virtual replicas of the pregnant female and her fetus First, several series of anatomically detailed computational phantoms were constructed to represent the pregnant mother and fetus of the Western and Russian Urals populations. Second, through computational simulations performed on these phantoms, a co mprehensive set of fetal radiation dose coefficients ( S values ) which corre late internal radiation activity in source organs with absorbed doses in target

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18 organs, was calculated for radionuclides of interest to SOLO A mong all fetal ages, S values ranged in magnitude from ~10 14 to ~10 10 Gy Bq 1 s 1 for fetal source organs and from ~10 1 8 to ~10 14 Gy Bq 1 s 1 for maternal source organs depending on particle type, particle energy and fetal age For a given radionuclide and fetal age, S values for fetal source organs were approximately two order s of magnitude larger than for maternal source organs. L ittle variation in S value was observed among fetal source organs while variations of over 100% with respect to the mean were observed for maternal source orga ns near the fetus. S value variations from maternal source organs were highly dependent on the position of the fetus and separation distance from the source organ. The computational phantoms developed in this work provide novel pathways for assessing fetal radiation dosimetry at the l e vel of indiv idual organs This anatomical resolution is critical for dose tracking an d cancer risk estimates associated with various radiation exposures including non medical sources such as those involving the SOLO cohorts and J apanese atomic bomb survivors as well as medical ly administered radiation from procedures such as computed tomography (CT)

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19 C HAPTER 1 RESEARCH AIMS The principle objective s of this doct oral dissertation are to advance the fields of fetal and pregnant female computational dosimetry by 1) developing anatomical models of th e developing fetus and pregnant female which are capable of organ level radiation dose assessments and 2) estimating a comprehensive set of organ specific radiation dose coefficients (S values) within those populations by computationally simulating selec t internal radiation exposure scenarios. The major components of this work are divided into seven research aims and summa rized below. A summary of completed and anticipated submissions for publication in the literature is provided in Table 1 1. 1. Design and construct a series of reference hybrid computational phantoms, including 10 th 50 th and 90 th weight percentiles, which re present the developing human fetus and are capable of providing individual organ level and bone site level radiation dosimetry. 2. Unify Aim 1 phantom series by incorporating those additional tissues present in the 35 and 38 week phantoms into the six younge r fetal ages: 8, 10, 15, 20, 25 and 30 weeks. 3. Design and construct a series of hybrid computational fetal p hantoms representing the Urals, Russia population at ages 12, 18, 22, 26, 30, 34 and 38 weeks by systematically altering subset of phantoms from Aim 1. 4. Utilize Aim 3 phantoms to computationally simulate intra fetal radiation exposures following uptake of several radionuclides and report corresponding fetal organ absorbed dose coefficients. 5. Design and c onstruct a comprehensive series of pregnant female computation al phantoms by systematically altering the UF adult female phantom and combining with the Aim 1 50 th percentile fetal phantoms. 6. Design and c onstruct a series of pregnant female computational phantoms representing the Urals, Russia population by systematically altering pregnant female phantoms from Aim 5 and virtually combining them with the Urals based fetal phantoms from Aim 3.

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20 7. Utilize Aim 6 phantoms to computationally simulate fetal radiation exposures from maternal organs following the uptake of several radionuclides and report corresponding fetal organ absorbed dose coefficients.

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21 Table 1 1. List of completed and anticipated publications from this work Journal name Associated aim(s) Status Physics in Medicine and Biology (PMB) 1 published Physics in Medicine and Biology (PMB) 2,5 in preparation Radiation and Environmental Biophysics (REB) 3,6 in preparation Radiation and Environmental Biophysics (REB) 4,7 in preparation

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22 CHAPTER 2 INTRODUCTION Background and Significance Sources of Fet al Radiation Exposure The developing fetus can be exposed to ionizing radiation through a number of different sources, both med i cal and non medical In addition, depending on the type of source, ionizing radiation can originate external to the pregnant mo ther or from within her own tissues following biokinetic accumulation of radiopharmaceuticals or radionuclides Computed tomography ( CT ) examinations are typically performed on pregnant females suspected of suffering from pulmonary embolism, ac ute appendicitis or trauma and have increased at an annual rate of 25% from 1997 2006 1 F luoroscopically guided interventions are rarely performed when pregnancy is known or suspected except for life saving procedures including (1) percutaneous n ephrostomy for renal obstruction, (2) embolization of organs and blood vessels in the abdomen and pelvis for bleeding due to trauma, (3) embolization of visce ral renal or splenic aneurysms and (4) percutaneous drainage of an abdominal or pelvic abscess 2 Nuclear medicine pharmaceuticals are o ccasionally administered to pregnant females either purposefully, in the case of ventilation perfusion, thyroid, bone and renal scans 3 r adioactive iodine 4 o r two patients receiving 18 F FDG as part of a P ET/CT study lymphoma 5 6 Radiation exposures to the human fetus are not limited to planned medical procedures. The fetus can also be exposed to non medical sources of ionizing radiation

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23 as in the case of the Japanese atomic bomb survivors 7 or the Techa River Offspring Cohorts studied in the Epidemiological Studies of Exposed Southern Urals Populations (SOLO) project 8 In Utero Health Effects Health effects of ionizing radiation are generally divided into two categories: deterministic and stochastic. The severity of deterministic effects is dependent upon radiation dose and is bound by a lower threshold below which no effe ct is observed. The severity of stochastic effects is independent of radiation dose however the probability of their occurrence is dependent on radiation dose. Stochastic effects are assumed to have no lower threshold for occurrence. The sensitivity of the human fetus to ionizing radiation is a well documented issue 9 A number of deleterious deterministic effects, including death, congenital malformations, mental retardation all demonstrate measurable correlations with both fetal absorbed dose and age During embryonic organogenesis (weeks 2 to 8 post conception), the risk of fetal death is substantially reduced, whereas the risk of congenital malformation coincides with peak developmental periods for many major organ systems 10 During the period of fetal growth ( week 9 to bi rth), and at dose s below 50 mGy, no significant impact on fetal growth and development has been demonstrated 11 Fetal doses from medical procedures are typically low (~10 mGy) thus sparing the fetus from deterministic health risks. However, the stochastic nat ure of radiation induced cancer indicates its risk of occurrence is not limited to any threshold dose. 12 14 A number of radiation epidemiological studies of pr egnant females exposed to atomic bomb irradiation at Hiroshima and Nagasaki have suggested an increased risk of

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24 childhood cancer mortality 15 and cancer incidence. 7 However small, the risk of fetal induced cancer due to radiation exposures received in utero is finite and worthy of further consideration. The University of Florida is actively involved in such efforts thr ough many avenues, the SOLO project being of primary interest to this work Epidemiological Studies of Exposed Southern Urals Populations (SOLO) The Epidemiological Studies of Exposed Southern Urals Populations or SOLO is a European Union sponsored project that began in S pring of 2010 as a four year multi disciplinary, multi nation project whose aim is the examine the excess health risks associated with low and protracted radiation exposures. The primary exposures of interest are those related to the worker s within and villages located near the Mayak nuclear weapons facility in the late 1940s to early 1960s in the Southern Urals mountains Significant levels of radioactive waste were released into the nearby Techa River, where it was incorporated into the wa ter and food supplies and surrounding natural environment. The SOLO project is comprised of four subprojects, of which the University of Florida is involved in Subproject 4 Cancer following in utero irradiation. The subproject focuses around a cohort of 11,532 persons who were exposed to radiation in utero to radiation stemming from waste release at Mayak. The overall objective of sub project 4 is to facilitate the possibility to derive long term cancer risk estimates for subjects exposed in utero to prot racted low to medium dose rate ioniz ing radiation However, until recently, available dosimetry model studies did not provide sufficient anatomical resolution for organ specific cancer risk estimates to be feasible.

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25 Previous Studies and Limitations In case s where cancer and other diseases are induced by exposure to ionizing radiation, dose estimates to individual affected organs are necessary to mathematically quantify organ specific health risks. One method for obtaining dose estimates is to computationall y simulate radiation exposures and their effects on virtual human However, the majority of existing computational phantoms of the human fetus are limited in their definition of the majority of soft tissue organs and, th erefore, incapable of providing organ level radiation doses from simulated exposures a critical need to the SOLO project Mathematically Stylized and Voxel Phantoms Mathematically stylized models of a 36 week human fetus have been developed by Stabin et al. 16 with o rgan refinements by Chen 17 where the fetal anatomy is represented by simple shapes a cylindrical shell of homogeneous bone with hemispherical caps surrounding a homogenous region of soft tissue (see Figures 2 1 and 2 2 ) Shi and Xu 18 developed a v oxel model of a 30 week human fetus from segmented CT images obtained from an emerge ncy scan of a pregnant woman (Figure 2 3). Although the anatomical detail of this voxel model is improved over the stylized models, the comparatively large image slick thic kness (7 mm) limits the resolution of the fetal skeleton. In addition, the scan did not cover the entirety of the fetal cranium and had to be manually corrected. Also, cartilage and fibrous soft tissues were not modeled. Similarly, a set of voxel models of pregnant female abdominal anatomy were constructed by Angel et al 19 in a 24 patient retrospective CT dose study. Image slice thicknesses ranged from 1.25 mm to 1 0 mm. Only homogeneous fetal bone and

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26 homogeneous fetal soft tissue were defined in each phantom, with no consideration of cartilage and fibrous soft tissues. Hybrid (BREP) Computational Phantoms Another type of computational phantoms are hybrid or bounda ry representation (BREP) phantoms in which anatomical boundaries and contours are defined by combinations of polygon mesh objects and deformable non uniform rational B spline (NURBS) surfaces (see Bolch et al 20 ). Xu et al 21 published the first set of BREP pregnant female computational phantoms at 3, 6 and 9 months of pregnancy, wherein the fetal anatomy is represented by a rescaled outer skin contour of an at term n ewborn with internal anatomy that only includes the stylized brain of Chen 17 and the s keleton of Shi and Xu 18 Maynard et al. 22 developed a comprehensive series of hybrid computational phantoms representing the human fetus at different stages of gestation and weight percentiles. The unique feature of this phantom series is the resolution of the fetal anatomy, which was obtained from MRI images of preserved fetal specimens. All major soft organs were modeled at each fetal age. Individual bone sites are modeled as two regions: homogeneous spo ngiosa and un ossified fibrous tissues. In addition, extensive efforts were undertake to model the age dependent relative levels of ossification in each bone site. The anatomical resolution of this phantom series made it the ideal candidate from which to d erive the Urals based SOLO fetal hybrid computational phantom series for the SOLO project.

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27 Figure 2 1. 6 month stylized pregnant female phantom. Adapted from Stabin et al. 23

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28 Figure 2 2. 26 week stylized pregnant female phantom from Chen. 17 Reproduced with permission. 1 1 J. Chen, "Mathematical models of the embryo and fetus for use in radiological protection," Health Phys Vol. 86 285 295 (2004).

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29 Figure 2 3. Tomographi c voxel fetal phantom from Shi and Xu. 18 Reproduced with permission 2 Figure 2 4. 3 month, 6 month and 9 month BREP pregnant female phantoms from Xu et al. 21 Reproduced with permission 3 Institute of Physics and Engineering in Medicine. Published on behalf of IPEM by IOP Publishing Ltd. All rights reserved. 2 C. Shi, X.G. Xu, "Development of a 30 week pregnant female tomographic model from computed tomography (CT) images for Monte Car lo organ dose calculations," Med Phys Vol. 31 2491 2497 (2004). 3 X.G. Xu, V. Taranenko, J. Zhang, C. Shi, "A boundary representation method for designing whole body radiation dosimetry models: pregnant females at the ends of three gestational periods -RPI P3, P6 and P9," Phys Med Biol Vol. 52, 7023 7044 (2007).

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30 Figure 2 5. UF reference fetal hyb rid computation phantom series from Maynard et a l. 22 Reproduced with permission 4 Inst itute of Physics and Engineering in Medicine. Published on behalf of IPEM by IOP Publishing Ltd. All rights reserved. 4 M.R. Maynard, J.W. Geyer, J.P. Aris, R.Y. Shifrin, W. Bolch, "The UF family of hybrid phantoms of the developing human fetus for computational radiation dosimetry," Phys Med Biol Vol. 56 4839 4 879 (2011).

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31 CHAPTER 3 URALS BASED HYBRID COMPUTATIONAL FETAL PHANTOMS Overview The development of a comprehensive series of computational phantoms s pecifically representing the fetal population of the Urals region of Russia was an important goal for SOLO studies particularly as a Urals based phantom series would provide strong continuity between the radionuclide biokinetic models and the radiation do se coefficients ( based on UF supplied radionuclide S values) that would eventuall y be calculated using the phantom series. This chapter details the efforts undertaken to achieve t his goal through the construction of a series of computational phantoms repre senting the Urals fetal population across several gestational ages. Phantom Construction Methods Summary of Methods and Des ign Criteria The series of Urals based ( SOLO ) computational fetal phantoms were constructed using a set of methods derived from those adopted for the construction of the UF reference computational fetal phantoms presented by Maynard et al. 22 All phantom modeling was performed in the software Rhi noceros TM a NURBS based computer animation and modeling program. The principle components of the construction method s included 1) identifying appropriate base phantoms from among the set of UF reference 50 th percentile computational fetal phantoms, 2) 3 D volumetric scaling of base phantoms to match biometry data representing the fetal population of the modern Urals region Russia 24 and 3) adjusting the NURBS surface contours and polygon mesh boundaries of specific tissues to match mid twentieth century Russian fetal mass data presented by Borisov 25

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32 The goal of the Borisov study was to investigate weight ratios of different fetal bones and the accumulation of stable calcium and strontium in the fetal skeleton Borisov reported masses of individual bone sites, whole skeleton and whole body as well as mass ratios of several newborn bone sites. Each completed phantom of the Urals based fetal phantom series (or SOLO phantom series, in reference to the funding grant) was assigned a unique, eight digit mnemonic with the following format: SOLO##WK, where ## refers to the age of the fetus in weeks post conception (PC). For example, the completed the 30 week Urals fetal phantom was assigned the mnemonic SOLO30WK. In all, a total of eight fetal phantoms comprised the completed series. The validity of t he construction method was confirmed for one target fetal age (30 weeks) before being implemented in the remaining target ages. Once complete d each phantom needed to be converted from its native NURBS/polygon mesh format to a voxel format in order to be i nterpretable by radiation transport software. The details of these efforts are detailed presently. Target Fetal Ages Eight fetal ages in total were targeted in the Urals fetal series. Six target ages were derived from Borisov 25 who reported various data as a function of six fetal age bins in units of lunar months (LM). The four center bins w ere each one LM in width and collectively ranged from 5 LM to 9 LM. The data corresponding to each age bin was assigned to a targ et fetal age equal to the midpoint of each bin. Each target fetal was age was converted from lunar months (LM) to weeks post conception (PC). The oldest term fetal age of 3

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33 were assigned to 18 weeks PC. Lastly, two additional fetal ages were targeted: 12 weeks to represent the end of the first trimester and 8 weeks to represent the beginning of the fetal dev elopment period. As no Urals representative anatomical data were available for the latter target age, the UF 8 week 50 th percentile fetal phantom was adopted as is into the Urals series. Feasibility of Methods A feasibility study was first performed to con firm the validity of the Urals phantom construction method. T he 30 week 50 th percentile computational fetal phantom presented by Maynard et al 22 was adopted as a base phantom for constructing the 30 week Urals based phantom First, the entire base phantom was scaled in 3 D t o match the 50 th perc entile femur length (FL) and biparietal diameter (BPD) measured in the modern 30 week Urals fetal population. Second, three candidate bone sites with vastly different physical morphologies specifically the skull, ribs, and femur were selected as test subje cts for various scaling and resizing methods for matching their respective whole bone mass data presented by Borisov. 25 T he 30 week skeletal mass densities derived by Maynard et al. 22 were adopted to convert modeled volumes to masses and vice versa. A combi nation of the Rhinoceros TM commands 3 D scale, 2 D scale 1D scale, and offset mesh were employed to resize the three test bone sites to match their target whole bone masses while simultaneously maintaining the ir overall physical morphologies The success of the procedure for these three representative bone sites lent credence to its applicability for the rest of the fetal skeleton and was therefore adopted for the construction of the remainder of the Urals based phantom series.

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34 Implementation in All Target A ges Base phantom assignments As in the feasibility study, t he target Urals fetal ages of 12 weeks, 18 weeks, 22 weeks, 26 weeks, 30 weeks, 34 weeks and 38 weeks were each assigned a base phantom from the UF series of hybrid computational fetal phantoms 22 The principle criterion for base phantom assignment was proximity of the target fetal age and the age of the base phantom An exception to this was the decision to assign the UF 20 week 50 th percentile phantom, rather than the UF 21 week specimen specific phantom, as the base for the target Ura ls age of 22 weeks. Maynard et al. 22 es timated age dependent relative levels of ossification of each fetal bone by deriving homogenous bone volume fractions (HBVF), defined as the ratio of ossified homogenous bone volume to whole bone volume. The rationale for the exception in base phantom assi gnment was thus two fold: 1) the relative levels of ossification as quantified by the derived HBVFs do not vary greatly between 20 weeks and 2 1 weeks (max: 4%) and 2) the preference to maintain the implicit level of overall anatomical continuity of the set of UF 50 th percentile phantoms However, the same rationale was not applied in the case of the 12 week target age. The HBVFs of the U 10 week 50 th percentile phantom and the UF 11.5 week specimen specific phantom showed greater variation (max: 8%), prompt ing the decision to adopt the 11.5 week specimen specific phantom as the base phantom for the target Urals age of 12 weeks. Table 3 1 summarizes all the bas e phantom assignments Due to the proximity of the fetal ages of the UF base phantoms and their Urals targets, the relative level s of ossification in each bone site ( HBVF ) w ere left unaltered during the construction of the Urals based series.

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35 Scaling factors The native Rhinoceros TM scaling commands p ermit the user to volumetrically scale an object to precisely match desired physical dimensions, e.g. volume or length. The main user 3D, 2D, and 1D s caling factors (f) relate to the physical di mensions of an object through simple analytic expressions as demonstrated in Equations 3 1, 3 2, and 3 3 (3 1) (3 2) (3 3) T hese scaling factors expressions allow, for exampl e, a user to scale a cranium to exactly match a desired biparietal diameter ( L F ) if the current biparietal diameter ( L 0 ) is known. Similar calculations can be performed when target volumes are desired Figu re 3 1A D visually illustrates the reduction of the volume of a 38 week mandible by 50% using 3D, 2D and 1D scaling commands. Biometry scaling B iometry data were targeted to the fetal population of the Urals region of modern Russia. 24 These data are summarized in Table 3 2. First, e ach base phantom was scaled in 3 D to match the r e spective target femur length. Second, the head of each phantom was scaled in 3 D to match the respective target bi parietal diameter. Biometry measurements in Rhinoceros TM roughly mimicked

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36 those methods used in modern ultrasonography 26 27 e.g. excluding any epiphyseal islands of ossification when assessing femur length Matching individual bone masses Genera l procedure. The masses of i ndividual whole bone s of the SOLO fetal phantom series were targeted (when available) to Russian based data provided by Borisov. 25 Because the computational phantoms are volume based, mass d ensities were required to calculate corresponding masses. Mass densities for cartilage and homogeneous bone/spongiosa were adopted from Maynard et al 22 e ither directly or through linear interpolation of t hose data and are summarized in Table A 1 Each bone site was adjusted in its entirety using a combination of 3D, 2D and 1D volumetric scaling commands (discussed above) and the offset mesh command, which mesh object by a user specified thickness. Difficulties did arise when using the offset mesh command to alter bone sites. Those issues and their solutions are detailed in a later section. Long bones were adjusted by 2D scaling in order to maintain the length attained during biometry scaling. The cranium, vertebrae and sacrum were adju sted exclusively by offset mesh due to geometrical constraints associated with soft organs (e.g. cranium) or interfaces with neighboring bone sites (e.g. vertebrae and sacrum). Remaining bone sites were adjusted using various combinations of the different scaling commands. For all bone sites, scaling adjustments were performed such that the overall morphology of the bone was preserved while matching target mass data. Borisov 25 reported additional skeletal mass data fo r the oldest age bin (38 weeks) which were also incorporated into that phantom. The additional skeletal data were ratios of mean cartilage mass to bone tissue mass for several bone sites. Those

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37 data were manipulated and incorporated into the phantom as rat ios of mean bone tissue mass to total bone mass. These data were not reported for younger fetal ages; however, efforts were taken to ensure these ratios were monotonically increasing for each bone site as a function of fetal age Exceptions. Exceptions to this procedure were necessary for 18 weeks and 12 weeks. For the 18 week phantom no data on the individual whole bone masses (only whole skeleton mass) w ere reported by Borisov. 25 T he contributions of the mass of each bone site to the overall skeletal mass were thus approximated by averaging the corresponding contributions observed in the older ages. Approximating the 18 week bone mass contributions in this manner was deemed acceptable as the contributions varied only slightly with fetal age. These estimated mass contributions were then used as a guide to scale the individual 18 week bone sites to match the target whole skeleton mass For the 12 week phantom, no skeletal mass data (individual bones or whole skeleton) w ere reported by Borisov 25 Consequently, no adjustments were made to the individual bone sites or whole skeleton of this phantom once biometry scaling was completed. Limitations of the offset mesh command Polygon mesh objects in Rhinoceros TM are defined by a collection of vertices which form the corners of the planar mesh faces that define the virtual dimensions of the object. Each mesh vertex has associated with it a normal vector defining a reference direction The o ffset mesh boundaries of a polygon mesh object by a desired physical thickness. To modify mesh boundaries Rhinoceros TM translates each vertex along its unique re ference vector,

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38 rebuilding the polygon mesh faces in the process and thus generating a new polygon mesh object. C omplications arise however, when the translation distance of the mesh vertices causes the rebuilt mesh faces to erroneously overlap. In a perfect polygon me sh object the mesh faces interface with each other only at the edges, never elsewhere. Overlapping mesh faces cause Rhinoceros TM to incorrectl y calculate the volume of the object, leading to inaccurately matched target volumes and discrepancies with volume s of voxelized phantoms ( voxelization discussed later). Figure 3 2 illustrates this effect using a simple polygon mesh cone. The mesh vertices comprising the top portion of the cone are closer in distance than the mesh vertices comprising the bottom porti on. An inward offset mesh of 5 millimeters causes a large number of mesh faces to intersect one another essentially inverting portion s of the cone The intersecting mesh faces can be readily identified via their associated reference vectors (shown in whit e). Reference vectors that were previously facing outward from the original cone are clearly facing inwards in the inverted portion of the offset cone (Figure 3 2B). Rhinoceros TM interprets the volumes of m esh objects (or portions of mesh objects) with inw ard facing reference vectors as negative, a non physical artifact. Rhinoceros TM reports the volume of the mesh object in Figure 3 2B as negative. While there is currently no method of avoiding this effect in susceptible mesh objects, the Rhinoceros TM smoot h command can provide significant (although not complete) correction to the object. The smooth command applies a vertex position averaging algorithm to the mesh object and rebuilds the corresponding mesh faces and

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39 reference vectors. The degree of smoothing can be controlled by the user. By averaging the vertex positions and rebuilding the reference vectors, the smooth command reduces the number of intersecting mesh faces and incorrectly oriented reference vectors, which minimizes regions of negative volume. Figure 3 2C shows a smoothed version of the offset cone. Reference vectors in the upper portion of the object are oriented correctly and the number of intersecting mesh faces is reduced, particularly in the lower portion. Rhinoceros TM reports a positive v olume for this object. A consequence of using the smooth command to correct intersecting mesh faces and incorrectly oriented reference vectors is the loss of some topographical detail due to vertex position averaging. The degree of detail loss is dependen t of the degree of smoothing specified by the user. The cases of undesirable offset mesh side effects encountered in this work were far more subtle than the cone example. Many consecutive low degree smooth commands were applied to affected bone sites which in all cases, preserved appropriate topographical detail while sufficiently correcting undesirable side effects. Figure 3 1E illustrates a successful 50% volume reduction of a 38 week mandible by offset mesh and smoothing. Notice the loss of some minor t opographical detail. Matching whole body masses Once available skeletal mass data were matched in each phantom, the outer skin contour was realistically adjusted to match the total fetal mass reported by Borisov 25 Met hods of c ontour adjustment mimicked those presented by Maynard et al. 22 most notably assigning the majority of volume changes to the chest, abdomen and limbs while minimizing contour adjustm ents around the skull and spine. As in Maynard et al 22

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40 a fetal residual soft tissue mass density of 1.03 g cm 3 was adopted for volume to mass conversions. Conversion to Voxel Format Despite recent advancement s 28 most radiation transport codes are unable to directly interpret the complicated NURBS and po lygon mesh file formats To circumvent this limitation, phantoms are conver ted to a voxel format represented by a simple binary file with an ordered array of bytes containing the unique identifier (tag) of each tissue as assigned in Rhinoceros TM This typ e of file conversion is well established within ALRADS 29 which employs an in house MATLAB TM script (.m file) that converts a NURBS/polygon mesh (PM) model into a 3D array of cubical voxels (b o xes). The voxel dimensions or resolutions are specified by the user. For the SOLO phantom series vox el resolutions were determined iteratively based on two criteria: 1) the percent difference between original mass and voxelized mass should be low (ideally <1%) for each tissue and 2) the total matrix size of the voxelized phantom should be near fifty five million voxels. Methods for achieving the first criterion are well known. 29 The second criterion serves to minimize computer memory burden when radiation transport simulations are being performed. Table 3 3 summari z es the voxel resolutions that satisfied the specified criteria in the SOLO fet al phantom series The 50 th percentile fetal phantoms presented by Maynard et al. 22 were previously converted to voxel format by the same procedure presented here. The tissue densities, tissue masses, and voxel resolutions are highly relevant to later chapters of this work and are thus provided in Appendix A in Tables A 2 A 4 and A 5 respectively.

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41 Results and Discussion The completed series is presented visually to scale in Figure 3 3. Table 3 4 summarizes the fetal tissue masses of the voxelized phantoms. Figure 3 4 shows a mid line sagittal slice of the SOLO38WK voxelized phantom, illustrating the successful representation of the fetal anatomy in voxel form for the purposes of future radiation transport simulations. Table 3 5 summarizes the targeted individual bone, whole skeleton and whole f etus masses as well the percent errors of the actual masses in the voxelized phantoms. Table 3 6 summarizes the age dependent ratios of ossified bone mass to whole bone mass, including the percent error of the SOLO38WK phantom compared to the target Boriso v 25 data (these data were not reported for other ages). A ll targeted data were matched within 1% of their expected value with the exception of the 18 week whole fetus mass, which was matched with 2% of its expected v alue ( on the underweight side ). The skeletal frame of the 18 week phantom appeared incapable of reasonably accommodating the whole fetus mass reported by Borisov. 25 This exception was likely due to disharmony between the biometry data of the modern Chelyabinsk fetal population which guides the overall dimensions of the fetus, and the assumption regarding the youngest age bin of Borisov 25 which was assumed to represent 18 weeks po st conception. It would be equally valid to assume, for example, the youngest age bin of Borisov 25 represented 19 weeks post conception. By targeting the femur length and biparietal diameter of a slightly older fetal age, the overall size of the phantom would be larger compared to 18 weeks bringing the whole fetus mass closer to the value reported by Borisov. 25 In addition, limitations in the biometry scaling methodology could hav e contributed to the discrepancy. For example, variations in

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42 crown rump length were not explored but could have a similar impact on overall fetal mass as femur length and biparietal diameter. The SOLO and UF fetal phantom series share two common ages: 30 w eeks and 38 weeks. Comparisons of bone and soft tissue organs masses were made between each series for these common ages and are summarized in Tables 3 7 and 3 8. Large differences were observed among the cranium and ribs for both ages. Because these bone sites have large surface areas, slight variations in the surfaces th a t define these objects can yield significant fluctuations in volume and mass. The hands and feet of the UF 30 week phantom were undersized compared to their SOLO counterparts, likely due to variations in the original segmentation performed by Maynard et al 22 For similar reasons the mandibles of both the UF 30 week and 38 week phantoms were oversized compared to their SOLO counterparts. Remaining bones of the skeleton exhibited good agreement between phantom series. Discrepancie s in bone mass can also be dependent on many other factors, at least two of which are immediately recogniz ed and undoubtedly significant: 1) the necessarily simplistic treatment of fetal bone densities due to lack of quality data and 2) unlike the SOLO ser ies, individual bone sites in the UF series were not matched to specific masses due to lack of Western population data S tronger knowledge of fetal bone masses and densities is needed to better guide the morphological data provided medical images of preser ved fetal specimens for the construction of fetal phantom skeletal anatomy. Similar mass comparisons were made for several major soft tissue organs of the SOLO and UF fetal series. The brain showed good agreement for both 30 weeks and 38 weeks, however dis crepancies were observed among the liver and lungs for both

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43 ages with the SOLO values being much smaller than their UF counterparts These differences are nearly entirely due to limitations in available abdominal and thoracic volumes as defined by the ext ents of the ribcage. D ue to its large surface area and unique morphology, the ribcage represented a significant design challenge, requiring a complex combination of offset mesh and 3D, 2D and 1D volumetric scaling in order to match the target mass. Likely further complicating the design, as before, was the simplistic treatment of fetal bone densities. These factors ultimately led to decreased abdominal and thoracic cavity volumes compared to the UF series, an unavoidable outcome once modeling the rib cage a s accurately as possible was declared the priority Because future radiation transport simulations performed under SOLO would specifically emphasize the fetal skeleton over fetal soft tissue organs, the decision was made to accept these organ mass discrepa ncies as limitations of the phantoms. As previously discussed, improved knowledge of individual bone densities and masses would allow a more accurate declaration of the physical extents of the ribcage, possibly minimizing the organ mass differences observe d here.

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44 Table 3 1 Target SOLO fetal ages and assigned UF base phantoms. Target SOLO fetal age (weeks) Assigned UF 50 th percentile base phantom (weeks) 8 a 8 a 12 11.5 b 18 20 22 20 26 25 30 30 34 35 38 38 a The UF 50 th percentile 8 week phantom wa s adopted as is. b UF 11.5 week specimen specific phantom

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45 Table 3 2 Target biometry measurement s for SOLO fetal phantom series. Fetal age (weeks) Femur length (mm) Biparietal diameter (mm) 12 13.0 25.6 18 31.7 46.7 22 42.8 59.1 26 52.6 71.6 30 61.3 80.9 34 69.5 88.6 38 75.8 93.5 Note: No 8 week data were reported

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46 Table 3 3 Voxel resolutions and matrix sizes of voxelized SOLO fetal phantoms Voxel Resolution (cm) Number of Voxels Phantom X Y Z X Y Z Total (x10 6 ) SOLO08WK 0.0065 0.0065 0.006 5 332 453 367 55.20 SOLO12WK 0.01338 0.01338 0.01338 285 502 384 54.94 SOLO18WK 0.0289 0.0289 0.0289 364 381 395 54.78 SOLO22WK 0.0371 0.0371 0.0371 368 382 391 54.97 SOLO26WK 0.0457 0.0457 0.0457 385 383 373 55.00 SOLO30WK 0.04895 0.04895 0.04895 339 371 436 54.84 SOLO34WK 0.059 0.059 0.059 288 442 432 54.99 SOLO38WK 0.0654 0.0654 0.0654 258 435 450 50.50

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47 Table 3 4 SOLO fetal phantom voxel masses Fetal Tissue Fetal tissue mass (g) SOLO08WK SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34W K SOLO38WK Residual soft tissue 1.77E+00 2.68E+01 2.68E+02 4.11E+02 7.23E+02 9.06E+02 1.18E+03 2.28E+03 Adrenal (L) 9.41E 03 6.04E 02 2.97E 01 7.38E 01 9.01E 01 1.17E+00 2.29E+00 1.95E+00 Adrenal (R) 1.04E 0 2 8.04E 02 3.08E 01 7.58E 01 9.07E 01 1.40E+00 2.27E+00 3.30E+00 Brain 6.98E 01 6.72E+00 3.42E+01 8.34E+01 1.27E+02 1.98E+02 3.04E+02 3.13E+02 Breast (L) n/a n/a n/a n/a n/a n/a 3.05E 02 4.21E 02 Bronchi 3.79E 04 2.45E 03 2.45E 02 6.02E 02 9.11E 02 1.21E 01 3.03E 01 4.02E 01 Whole colon wall a 3.59E 03 2.95E 02 2.24E 01 5.47E 01 8.65E 01 1.08E+00 n/a n/a Whole colon cont. a 2.76E 03 2.27E 02 1.73E 01 4.26E 01 6.56E 01 8.52E 01 n/a n/a R ight colon wall a n/a n/a n/a n/a n/a n/a 3.26E+00 3.58E+00 Right colon cont. a n/a n/a n/a n/a n/a n/a 7.11E+00 7.79E+00 Esophagus 2.62E 03 2.07E 02 1.54E 01 3.80E 01 5.85E 01 8.10E 01 1.38E+00 1.84E+00 Eye balls 1.56E 02 1.34E 01 5.25E 01 1.28E+00 2.00E+00 2.91E+00 4.74E+00 4.97E+00 Gall bladder wall 1.31E 03 1.07E 02 6.73E 02 1.65E 01 2.56E 01 2.99E 01 2.64E 01 3.41E 01 Gall bladder cont. n/a n/a n/a n/a n/a n/a 1.54E+00 1.92E+00 Whole h eart 6.85E 02 2.44E 01 1.20E+00 2.96E+00 4.41E+00 6.07E+00 1.24E+01 1.39E+01 Whole kidney (L) a 5.78E 03 5.68E 02 7.48E 01 1.84E+00 2.98E+00 4.42E+00 n/a n/a Whole kidney (R) a 7.78E 03 5.93E 02 7.55E 01 1.86E+00 4.41E+00 5.40E+00 n/a n/a Kidney cortex (L) a n/a n/a n/a n/a n/a n/a 5.60E+00 6.20E+00 Kidney cortex (R) a n/a n/a n/a n/a n/a n/a 5.55E+00 6.16E+00 Kidney medulla (L) a n/a n/a n/a n/a n/a n/a 1.98E+00 2.20E+00 Kidney medulla (R) a n/a n/a n/a n/a n/a n/a 1. 97E+00 2.18E+00 Kidney pelvis (L) a n/a n/a n/a n/a n/a n/a 4.00E 01 4.47E 01 Kidney pelvis (R) a n/a n/a n/a n/a n/a n/a 3.98E 01 4.47E 01 Larynx n/a n/a n/a n/a n/a n/a 9.19E 01 1.23E+00 Lens n/a n/a n/a n/a n/a n/a 1.05E 01 1.11E 01 Liver 3.96E 01 1.75E+00 8.04E+00 1.98E+01 2.66E+01 3.44E+01 7.35E+01 8.94E+01 Lung (L) 2.75E 02 3.64E 01 2.08E+00 5.13E+00 7.06E+00 8.47E+00 1.54E+01 1.62E+01 Lung (R) 3.67E 02 4.97E 01 2.16E+00 5.31E+00 7.33E+00 8.97E+00 1.78E+01 1.86E+01 Nasal layer (ant.) n/a n/a n/a n/a n/a n/a 1.04E 01 1.05E 01

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48 Table 3 4 Continued Fetal Tissue Fetal tissue mass (g) SOLO08WK SOLO 12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Nasal layer (post.) n/a n/a n/a n/a n/a n/a 9.21E 01 1.00E+00 Oral cavity layer n/a n/a n/a n/a n/a n/a 4.00E 01 4.69E 01 Ovary (L) 6.56E 04 5.46E 03 3.54E 02 8.76E 02 8.71E 02 9.32E 02 1.04E 01 1.41E 01 Pancreas 4.03E 04 4.61E 03 2.13E 01 5.25E 01 7.09E 01 9.93E 01 2.01E+00 2.51E+00 Penis n/a n/a n/a n/a n/a n/a 4.22E 01 6.11E 01 Pharynx n/a n/a n/ a n/a n/a n/a 2.52E 01 3.14E 01 Pituitary gland n/a n/a n/a n/a n/a n/a 8.06E 02 8.50E 02 Prostate n/a n/a n/a 3.88E 03 5.92E 03 7.67E 03 5.69E 01 7.57E 01 Rectosigmoid wall a n/a n/a n/a n/a n/a n/a 1.79E+ 00 1.97E+00 Rectosigmoid cont. a n/a n/a n/a n/a n/a n/a 5.53E+00 6.05E+00 Salivary glands (parot.) c 1.80E 03 8.61E 03 7.53E 02 1.83E 01 2.80E 01 3.63E 01 1.91E+00 2.27E+00 Scrotum n/a n/a n/a n/a n/a n/a 8.57E 01 1.21 E+00 SI wall and cont. b 1.86E 02 3.70E 01 1.46E+00 3.60E+00 6.43E+00 8.73E+00 n/a n/a SI wall b n/a n/a n/a n/a n/a n/a 1.44E+01 1.57E+01 SI cont. b n/a n/a n/a n/a n/a n/a 1.51E+01 1.64E+01 Skin 8.69E 02 9.56E 01 8.75E+00 1.62E +01 2.68E+01 4.40E+01 7.57E+01 1.18E+02 Spinal cord 3.32E 03 2.74E 02 2.97E 01 7.95E 01 1.26E+00 1.59E+00 3.96E+00 6.24E+00 Spleen 8.51E 04 8.32E 03 2.35E 01 5.79E 01 1.25E+00 2.46E+00 5.73E+00 7.02E+00 Stomach wall 5.73E 03 5.96 E 02 1.03E 01 2.55E 01 3.96E 01 4.57E 01 3.92E+00 4.82E+00 Stomach cont. 7.62E 03 5.16E 02 1.28E 01 3.17E 01 4.92E 01 5.74E 01 1.38E+01 1.69E+01 Testes 1.43E 03 1.19E 02 2.06E 02 5.05E 02 7.77E 02 1.00E 01 6.04E 01 8.07E 01 Thy mus 5.42E 04 1.72E 02 3.10E 01 7.60E 01 1.63E+00 2.75E+00 6.16E+00 6.77E+00 Thyroid 3.32E 03 7.74E 03 9.57E 02 2.37E 01 3.73E 01 6.17E 01 8.97E 01 1.21E+00 Tongue n/a n/a n/a n/a n/a n/a 1.91E+00 2.27E+00 Tonsil n/a n/a n/a n/a n/a n/a 5.31E 02 6.63E 02 Trachea 1.00E 03 6.69E 03 6.49E 02 1.62E 01 2.43E 01 3.37E 01 3.51E 01 4.79E 01 Urinary bladder wall 9.68E 04 8.00E 03 8.98E 0 2 2.21E 01 3.38E 01 4.38E 01 2.84E+00 3.80E+00 Urinary bladder cont. 5.27E 04 4.35E 03 1.10E 01 2.71E 01 4.12E 01 5.28E 01 6.77E+00 9.05E+00 Uterus 1.06E 03 8.74E 03 7.34E 02 1.80E 01 2.75E 01 3.54E 01 2.84E+00 3.80E+00

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49 Table 3 4 Continued Fetal Tissue Fetal tissue mass (g) SOLO08WK SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Fluid (in body) 8.56E 04 5.75E 03 4.85E 02 1.18E 01 1.81E 01 2.49E 01 1.48E+00 1.72E+00 Left colon wall a n/a n/a n/a n/a n/a n/a 3.34E+00 3.66E+00 Left colon cont. a n/a n/a n/a n/a n/a n/a 8.86E+00 9.70E+00 Salivary glands (mand.) c 9.29E 04 4.41E 03 3.86E 02 9.45E 02 1.45E 01 1.86E 01 9.86E 01 1.17E+00 Salivary glands (ling.) c 3.60E 04 1.70E 03 1.47E 02 3.67E 02 5.64E 02 7.06E 02 3.83E 01 4.58E 01 Breast (R) n/a n/a n/a n/a n/a n/a 3.21E 02 4.13E 02 Ovary (R) 6.57E 04 5.45E 03 3.57E 02 8.69E 02 8.75E 02 9.26E 02 1.07E 01 1.42E 01 c Cranium 1.02E 01 7.80E 01 8.09E+00 1.62E+01 2.57E+01 3.18E+01 3.42E+01 4.11E+01 c Mandible 1.28E 02 7.79E 02 2.93E 01 5.79E 01 7.70E 01 8.83E 01 1.13E+00 2.23E+00 c Scapulae 1.93E 02 9.81E 02 4.32E 01 8.0 5E 01 9.25E 01 1.31E+00 1.80E+00 2.91E+00 c Clavicles 1.73E 02 8.49E 02 1.12E 01 3.33E 01 3.17E 01 3.86E 01 5.52E 01 7.26E 01 c Sternum 2.62E 03 2.32E 02 1.46E 01 2.74E 01 4.48E 01 5.90E 01 6.61E 01 8.04E 01 c Rib s 3.03E 02 1.98E 01 5.50E 01 1.11E+00 1.49E+00 1.98E+00 3.52E+00 5.94E+00 c Cervical discs n/a n/a 1.12E 01 2.33E 01 3.35E 01 3.96E 01 9.83E 02 1.24E 01 c Thoracic discs n/a n/a 2.67E 01 5.53E 01 8.11E 01 9.49E 01 4.28E 01 3.54E 01 c Lumbar discs n/a n/a 1.47E 01 3.06E 01 4.47E 01 5.26E 01 3.46E 01 2.67E 01 c Sacrum 1.48E 02 1.17E 01 7.65E 01 1.58E+00 2.20E+00 2.48E+00 3.55E+00 5.09E+00 c Os coxae 2.07E 02 1.36E 01 1.35E+00 2.93E+00 3.12E+00 4.56E+00 4.93E+00 7.06E+00 c Femora 1.82E 02 1.70E 01 2.29E+00 4.22E+00 5.56E+00 7.22E+00 1.06E+01 1.68E+01 c Tibiae 1.05E 02 8.74E 02 1.07E+00 2.07E+00 2.56E+00 3.93E+00 4.71E+00 6.55E +00 c Fibulae 9.74E 04 6.65E 03 1.87E 01 3.61E 01 4.53E 01 7.11E 01 1.59E+00 2.69E+00 c Patellae 1.67E 03 1.39E 02 1.63E 01 3.00E 01 1.43E+00 1.88E+00 2.09E+00 2.31E+00 c Feet 5.47E 04 3.93E 03 1 .08E+00 1.66E+00 2.14E+00 3.68E+00 4.10E+00 7.71E+00 c Humeri 1.43E 02 1.39E 01 1.01E+00 1.87E+00 2.38E+00 3.85E+00 5.59E+00 8.17E+00 c Radii 1.97E 03 1.63E 02 1.73E 01 3.21E 01 4.36E 01 6.30E 01 1.03E+00 1.03E+00 c Ulnae 2.43E 03 1.74E 02 2. 54E 01 4.76E 01 6.44E 01 9.65E 01 1.28E+00 1.50E+00 c Hands & wrists 1.88E 03 1.42E 02 9.93E 01 2.06E+00 2.30E+00 3.08E+00 4.54E+00 7.14E+00 c Cranial fontanelles n/a n/a n/a n/a n/a n/a 6.06E+00 7.28E+00 c Costal cartilage 1.42E 02 1.48E 01 6.47E 01 1.18E+00 1.83E+00 2.31E+00 2.51E+00 4.81E+00

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50 Table 3 4 Continued Fetal Tissue Fetal tissue mass (g) SOLO08WK SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK c Cerv. vertebrae 2.50E 02 1.69E 01 1.22E+00 2.53E+00 3 .55E+00 3.98E+00 5.68E+00 8.58E+00 c Thor. vertebrae 4.76E 02 2.99E 01 2.72E+00 5.65E+00 8.21E+00 9.58E+00 1.10E+01 1.68E+01 c Lumb. vertebrae 2.62E 02 1.79E 01 1.54E+00 3.19E+00 4.52E+00 5.03E+00 6.31E+00 1.02E+01 sp Cranium n /a 1.04E 01 6.13E+00 1.00E+01 2.00E+01 2.82E+01 4.23E+01 7.62E+01 sp Mandible n/a 3.37E 02 3.06E 01 6.21E 01 1.14E+00 1.63E+00 2.49E+00 4.07E+00 sp Scapulae n/a 6.46E 02 5.68E 01 1.10E+00 1.59E+00 2.61E+00 3.90E+00 7 .59E+00 sp Clavicles n/a 4.73E 02 8.80E 02 2.68E 01 2.88E 01 4.19E 01 7.46E 01 1.26E+00 sp Sternum n/a n/a n/a 7.93E 03 2.21E 02 4.28E 02 7.92E 02 1.84E 01 sp Ribs n/a 7.36E 02 3.57E 01 5.48E 01 1.15E+00 1.88E+00 3.45E+00 7.58E+00 sp Cerv. vertebrae n/a 3.66E 02 2.90E 01 6.24E 01 1.15E+00 1.50E+00 3.64E+00 9.31E+00 sp Thor. vertebrae n/a 9.99E 02 6.14E 01 1.32E+00 2.10E+00 2.70E+00 5.99E+00 1.67E+01 sp Lumb. vertebrae n/a 3.98E 02 3.91 E 01 8.36E 01 1.46E+00 1.99E+00 4.33E+00 1.06E+01 sp Sacrum n/a 5.22E 03 7.20E 02 1.55E 01 3.78E 01 5.81E 01 1.35E+00 4.82E+00 sp Os coxae n/a 3.74E 02 1.06E+00 2.37E+00 2.70E+00 5.18E+00 8.18E+00 1.79E+01 sp Femo ra n/a 6.85E 02 1.38E+00 2.64E+00 4.29E+00 6.04E+00 9.38E+00 1.75E+01 sp Tibiae n/a 3.90E 02 8.21E 01 1.63E+00 2.30E+00 3.95E+00 5.45E+00 1.13E+01 sp Fibulae n/a 7.35E 03 1.38E 01 2.75E 01 3.12E 01 5.35E 01 1.83E +00 2.53E+00 sp Patellae n/a n/a n/a n/a n/a n/a n/a n/a sp Ankle & feet n/a 4.42E 03 2.18E 01 3.45E 01 4.54E 01 2.02E+00 4.89E+00 9.51E+00 sp Humeri n/a 5.52E 02 7.06E 01 1.36E+00 1.82E+00 3.16E+00 4.9 1E+00 9.19E+00 sp Radii n/a 1.23E 02 1.89E 01 3.62E 01 5.62E 01 9.21E 01 1.65E+00 3.12E+00 sp Ulnae n/a 1.59E 02 2.84E 01 5.56E 01 8.61E 01 1.38E+00 2.14E+00 4.05E+00 sp Hands & wrists n/a 2.31E 02 2.01E 01 4.31E 01 4 .90E 01 2.01E+00 3.63E+00 5.83E+00 Total fetal mass 3.58E+00 4.19E+01 3.71E+02 6.37E+02 1.07E+03 1.41E+03 2.05E+03 3.41E+03 a Only whole o rgan modeled for 8 30 weeks; o rgan partitioned into sub regions for 35 38 weeks. b Small intestine wall and contents m odeled as single homogenous volume for 8 30 weeks; explicitly modeled for 35 38 weeks. c Salivary glands partitioned into parotid, submandibular and sublingual regions. n/a: Tissue is not explicitly modeled, not present at given fetal age, or partitioned in to sub regions (e.g. colon, small intestine, kidney). c : Indicates cartilage/fibrous tissue region of bone site.

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51 sp : Indicates spongiosa/homogenous ossified region of bone site.

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52 Table 3 5 Target bone and fetus masses (g) and percent error of modele d values for the SOLO fetal phantom series. SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Fetal tissue Mass % Error Mass % Error Mass % Error Mass % Error Mass % Error Mass % Error Cranium n/a n/a 26.1 0.38 45.5 0.49 60.0 0.03 82.0 0.67 124.7 0.15 Mandible n/a n/a 1.2 0.01 1.9 0.47 2.5 0.46 3.6 0.62 6.3 0.06 Vertebrae & s acrum n/a n/a 16.9 0.43 25.1 0.26 29.8 0.34 42.7 0.16 83.0 0.15 Ribs & s ternum n/a n/a 3.1 0.69 4.9 0.83 6.8 0.01 10.3 0.69 19.3 0.04 Scapula n/a n/a 1.9 0.01 2.5 0.46 3.9 0.47 5.7 0.13 10.5 0.00 Clavicles n/a n/a 0.6 0.22 0.6 0.70 0.8 0.69 1.3 0.16 2.0 0.80 Humerus n/a n/a 3.2 0.81 4.2 0.10 7.0 0.19 10.5 0.04 17.4 0.25 Ulna & r adius n/a n/a 1.7 0.97 2.5 0.12 3.9 0.02 6.1 0.24 9.7 0.09 Hands & wrists n/a n/a 2.5 0.16 2.8 0.39 5.1 0.10 8.2 0.46 13.0 0.25 Femur & patella n/a n/a 7.1 0.74 11.3 0.13 15.1 0.30 22.1 0.01 36.7 0.22 Tibia & fibula n/a n/a 4.3 0.81 5.6 0.36 9.1 0.30 13.6 0.12 23.2 0.41 Feet & ankles n/a n/a 2.0 0.39 2.6 0.13 5.7 0.02 9.0 0.11 17.3 0.48 Pelvis n/a n/a 5.3 0.01 5.8 0.39 9.7 0.42 13.1 0.05 24.9 0.22 Whole s keleton 39.3 0.30 75.9 0.43 115.3 0.32 159.4 0.05 228.2 0.22 388.0 0.16 Whole f etus 378.0 1.84 640.0 0.53 1067.0 0.07 1408.0 0.19 2059.0 0.22 3429.0 0.46 Mass data adapted from Borisov. 25 No data reported for 8 and 12 weeks. n/a: No data reported.

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53 Table 3 6 Ratio of ossified bone mass to whole bone mass for several bone sites in the SOLO fetal phantom series. Bone site(s) SOLO 12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK %Diff Femur & patella 0.27 0.36 0.37 0.38 0.40 0.42 0.48 0.11 Tibia & fibula 0.33 0.43 0.44 0.46 0.49 0.54 0.60 0.15 Humerus 0.28 0.41 0.42 0.43 0.45 0.47 0.53 0.15 Ulna & radius 0.46 0.53 0. 54 0.57 0.59 0.62 0.74 0.41 Scapula 0.40 0.57 0.58 0.63 0.67 0.68 0.72 0.11 Pelvis 0.22 0.44 0.45 0.46 0.53 0.62 0.72 0.90 Percent diff for SOLO38WK calculated using target data adopted from Borisov. 25 Similar data not provided for other ages.

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54 Table 3 7 Comparison of whole bone masses for common ages of SOLO and UF fetal phantom series. 30 weeks 38 weeks Bone site(s) SOLO UF SOLO UF Cranium 60.0 98.4 124.5 181.1 Mandible 2.5 6.4 6.3 13.2 Vertebra e & sac rum 29.7 24.4 82.9 69.8 Ribs & sternum 6.8 24.2 19.3 49.7 Scapula 3.9 5.9 10.5 10.3 Clavicles 0.8 0.6 2.0 3.7 Humerus 7.0 6.5 17.4 14.3 Ulna & radius 3.9 3.5 9.7 10.4 Hands & wrists 5.1 1.5 13.0 8.6 Femur & patella 15.1 11.6 36.6 27.1 Tibi a & fibula 9.1 8.7 23.1 19.4 Feet & ankles 5.7 1.0 17.2 10.7 Pelvis 9.7 8.9 25.0 25.3 Whole skeleton 159.5 203.2 387.4 460.7 SOLO mass data adapted from Borisov. 25

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55 Table 3 8. Soft tissue mass comparisons betw een SOLO and UF fetal phantom series. 30 weeks 38 weeks Tissue SOLO UF SOLO UF Brain 198.2 206.4 312.9 367.8 Liver 34.4 61.1 89.4 129.8 Lungs 17.4 31.0 34.8 50.5

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56 Figure 3 1 Comparison of 50% volume reduction of 38 week fetal mandible ac hieved through various scaling methods A) original mandible. B) uniform 3D scaling. C) 2D scaling in XY plane. D) 1D scaling along X axis. E) offset mesh and control point smoothing. Grid dimensions equal to 1 cm.

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57 Figure 3 2 M esh face intersection s produced by inward offset mesh of simple cone. A) original cone. B) cone after 0.5 Grid dimensions equal to 1 cm.

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5 8 Figure 3 3 To scale sagittal size compa rison of Urals based computational fetal pha n toms A) SOLO08WK. B) SOLO12WK. C) SOLO18WK. D) SOLO22WK. E) SOLO26WK. F) SOLO30WK. G) SOLO34WK. H) SOLO38WK.

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59 Figure 3 4 Sagittal view of voxelized SOLO38WK fetal phantom.

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60 CHAPTER 4 HYBRID COMPUTATIONA L PREGNANT FEMALE PHANTOMS Overview Any efforts to assess in utero radiation doses and related quantities to the developing fetus should account for the presence of the surrounding materna l tissues. Maternal tissues can provide varying levels of protection to the fetus by shielding externally emitted radiation or alternatively, can become sources of internally emitted radiation following the biokinetic uptake of medically administered radiopharmaceuticals or radionuclides located in the surrounding environ ment This chapter details the efforts undertaken to account for the maternal components of fetal radiation exposure geometry through Research Aims 5 and 6: the construction of two hybrid computational phantom series representing Western and Urals pregnant female populations at various stages of fetal gestation. Phantom Construction Methods Summary of Methods and Design Criteria A cornerstone of phantom development within the ALRADS research group is the use of medical image sets (e.g. CT or MRI) of human o r animal anatomy as bases for constructing anatomically accurate computational phantoms 22 29 35 The powerful, flexible nature of the NURBS/polygon mesh format of these phantoms allows tissue volumes and morphology to be adjusted to match target data (e.g. mass, length, etc.). This general methodology w as adopted for constructing a reference series of phantoms repr esenting the Western pregnant female at various fetal ages. P regnant female abdominal anatomy was captured from segmented (contoured) medical CT image sets a nd systematically combined with the UF adult non pregnant

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61 computational phantom 32 a nd the eight 50 th percentile UF reference fetal computational series 22 to produce a series of pregnant female computational phantoms that faithfully represent s the geometry of the maternal organs that encompass the devel oping fetus. T he following general design criteria were also adopted to yield a more representative phantom series: 1. A single, reference fetal orientation within the gravid uterus 2. A ge dependent target masses for the uterine wall, placenta, b r east tissue and total body mass 3. Preservation of original non pregnant female reference tissue masses where appropriate, i.e. tissues not listed in (2). 4. A single, reference maternal circumference, skin contour and muscle contour at each gestational age Usi ng a simplified procedure, a n additional series of eight computational phantoms representing the Urals pregnant female population was constructed by systematically altering the completed reference UF (Western) pregnant female series. The details of the co nstruction of both series of phantoms are presented in the following sections. Image Acquisition and Segmentation CT image sets of pregnant females were obtained from two sources: 1) the Picture Archiving and Communication System (PACS) archive at the Univ ersity of Florida and 2) twenty four publically available, anonymized images provided by Angel et al. 19 Images were acquired and anonymized from the UF PACS archi ve under an approved Institutional Review Board (IRB) protocol. Images were screened for two specific criteria: 1) coverage of the entire fetus and 2) no visibly significant physical abnormalities of the mother and fetus. I mages provided by Angel et al 19 included

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62 coverage of the entire fetus and had been screened for anatomical normalcy of mother and fetus as part of that study. A total of seventy one screened imag es were obtained from either the UF PACS archive or the Angel et al. 19 study. The fetal outer body contour as visualized in each screen ed image set was segmented u sing the software 3D DOCTOR TM (Able Software Corp., Lexington, MA). The resulting fetal volumes were compared against the volumes of each UF reference fetal phantom Phantoms aged 20 weeks and older (five total) were each assigned a representative pregnant female image set based on these fetal volume comparisons. Image sets were not assigned to phantoms aged 15 weeks and younger based on the assumption that maternal organ displacement caused by their presence in the abdomen would be limited due to their sma ller volumes (max: ~140 cm 3 ) and could be sufficiently modeled without additional image sets. The largest fetal volume observed in the screened pregnant female CT images closely matched that of the 35 week UF reference fetus. This image set aged approxima tely 36 weeks PC, was thus assigned to both the 35 week and 38 week UF reference fetuses. Additional segmentation was performed on the assigned image sets to capture the geometrical configuration of the major maternal soft tissues, specifically the outer b oundaries of the uterus, placenta, liver, stomach, spleen, large intestine and small intestine. Figure 4 1 presents a representative image slice showing a portion of the additional segmentation. Native surface rendering functions in 3D DOCTOR TM were used t o generate 3D polygon mesh representations (Wavefront objects) of the individual organ contours of each segmented image set. The Wavefront object file format is an

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63 industry standard and compatible with practically all major 3D modeling software packages N URBS and Polygon Mesh Modeling UF phantom series 38 weeks Importing maternal anatomy. Construction of the 38 week UF reference pregnant female computational phantom was undertaken first as it represented the most restrictive geometry The polygon mesh r epresentation (Wavefront object) of the maternal CT image set assigned to 38 weeks was directly imported in the 3D modeling software Rhinoceros TM (McNeel North America, Seattle, WA ) The UF reference adult non pregnant female phantom, in its native NURBS/p olygon mesh format, was also imported into Rhinoceros TM The major soft tissue organs comprising the maternal abdomen were removed from the non pregnant female and the polygon mesh representations of the pregnant abdomen were roughly positioned in the appr opriate locations. Figure 4 2A ,B, and C present the polygon mesh representations of the pregnant female abdomen and their subsequent insertion into the vacated abdomen of the non pregnant female. Generating NURBS surfaces. To facilitate future matching o f target organ mass data, deformable NURBS surfaces representing each maternal tissue were manually created using various native Rhinoceros TM commands and tools. NURBS surfaces of non tubular organs (i.e. not the small and large intestines) were created us ing the contour and loft commands. The contour command generates a set of cross sectional surface contours of a given polygon mesh object along a user defined axis. The set of surface contours then acts as a frame or skeleton for the loft command, which wr The

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64 original polygon mesh object is no longer required and is therefore deleted. Figure 4 3 illustrates this procedure for the uterus. Figures 4 2D and E show the 38 week uterus in the NURBS f ormat after additional modeling. NURBS surfaces defining tubular organs were created using a separate procedure involving the pipe command. The pipe command creates a uniform cylindrical NURBS surface with a user defined radius whose long axis is defined b y a curve or central track. The polygon mesh representations of the large and small intestines were used as guides to manually define the ir respective central tracks. Figure 4 4 illustrates the manually defined central tracks of the large and small intesti nes of the 38 week phantom with respect several other major organs. For each tubular organ, the pipe command was used twice: once to define the lumen and a second time to define the wall thickness. The exact location and shape of the central tracks of thes e organs could not be finalized until the locations and volumes of the other internal organs had been finalized. For this reason, creation of the NURBS surfaces defining the small and large intestines was deferred until the final modeling stages of the int ernal anatomy. Reference fetal position. For t he reference series of Western pregnant female computational phantoms a single representative fetal orientation was desired. The left occiput anterior (LOA) configuration was adopted as the reference fetal pos ition as it is the ideal at term configuration among the possible vertex presentations, which account for the vast majority of fetal presentations during birth. 36 37 Figure 4 5 demonstrat es the approximate LOA position of the 38 week fetus This general configuration was adopted for all eight fetal ages. The section Phantom Series Limitations in Results and Discussion addresses the limitations of this approach.

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65 Matching target masses. Onc e the 38 week fetus was properly positioned and oriented in the maternal abdomen the surrounding maternal organ NURBS surfaces were fine adjusted (or created in the case of the intestines) to 1) accommodate the fetus and 2) match target reference mass data Because the computational phantoms are volume based, mass densities were necessary to converted between organ volumes and organ masses. Tissue mass densities of the UF adult non pregnant female 32 were adopted for all fetal ages of both the UF and SOLO pregnant female series. Those mass densities are summarized in Table A 3. Organ adjustments began with those in close proximity to the fetus and proceeded outward ly i. e. placenta, inner uterine boundary, outer uterine boundary, neighboring organs such as the urinary bladder and liver, and finally the small and large intestines and ovaries. Masses of non walled organs not directly involved with pregnancy were re matched to within 1% of their ICRP Publication 89 9 reference adult female masses. Wall masses of walled organs were re matched to their reference ICRP Publication 89 9 reference masses; however any associated content masses or reference lengths were left as free variables to ease geometric modeling constraints. Age dependent reference masses for the uterine wall and placenta were derived from data presented in ICRP Publication 89 9 which tabulates the individual contributions of various tissues to the age dependent mass gain of the pregnant female Linear interpolation was used when necessary to obtain data at intermediat e fetal ages. Uterine wall and placenta masses were matched within 1% of their target value. The completed internal anatomy of the 38 week pregnant female was reviewed for accuracy by a clinical obstetrician and suggested corrections were implemented.

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66 Pend ing adjustments to external anatomy. Along with uterine wall and placenta masses, age dependent breast and whole body masses were also derived from ICRP Publication 89 9 The breast contours of the UF family of reference phantoms were recently delineated into adipose and glandular tissues. C oordination with ALRADS colleagues is underway to ensure breast modeling uniformity prior to publication of the UF pregnant female series. Subsequently, the skin and muscle contours of the pregnant female series have been adjusted to approximate configurat ions and will undergo fine adjustments prior to publication. UF phantom series r emaining ages Generating NURBS surfaces with the contour and loft commands and defining central tracks of tubular organs are time consuming processes. Rather than repeat thos e procedures for the remaining seven fetal ages the decision was made to utilize the flexibility of the NURBS format to adjust the 38 week surfaces and central tracks as needed, using the segmented abdominal anatomy as design guides. The above procedures w ere adopted for positioning the fetus (LOA), adjusting maternal tissues to accommodate the fetus, and matching target organ mass data. In each case the resulting internal anatomy was reviewed and corrected as necessary. As with the 38 week pregnant female phantoms, efforts are underway to finalize breast, skin and muscle contours prior to publication. SOLO phantom series Several radionuclides of interest to SOLO have biokinetic proprieties that cause some maternal tissues to become sources of radiation expo sure to the developing fetus. Unlike fetal target tissues, which are of critical importance, UF and SOLO colleagues agreed that variations in maternal tissue masses between Western and Urals

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67 populations would likely have little effect on the fetal do ses an d related quantities produced by radioactivity originating within maternal source organs For this reason the Urals based SOLO pregnant female phantom series was generated by simply selecting a similarly aged UF reference pregnant female phantom and repla cing the fetus with the corresponding SOLO fetal phantom and adjusting the maternal skin, muscle and organ contours as needed. No additional maternal mass data were targeted. Because the 8 week UF fetal phantom and the 8 week SOLO fetal phantom are identic al, the 8 week UF pregnant female phantom was simply adopted into the SOLO pregnant female phantom series. Conversion to Voxel Format Voxelization of NURBS/polygon mesh phantoms was discussed in detail in Chapter 3 as it pertained to the series of Urals ba sed SOLO fetal phantom series. The same general procedure which is applicable to the entire UF phantom library was applied to the UF and SOLO pregnant female phantom series, but with some unique exceptions An important consideration in the voxelization pr ocess is the physical dimensions or r esolutions of the voxels. Voxel resolution must be high enough to represent the phantom anatomy with sufficient fidelity yet maintain a minimal level of computer memory burden, i.e. minimize the number of total voxels c omprising the voxel array. The pregnant female phantoms developed in this work represent a novel challenge with respect to the voxelization process. The fetus must be represented at finer voxel resolutions, typically fractions of millimeters, compared to t he UF reference adult non pregnant female 32 which is typically represented at voxel resolutions >1mm. Voxelizing the entire pregnant female phantom at the finer feta l resolution is not a feasible solution.

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68 R esulting files would theoretically range from ~10 9 to ~10 12 voxels in size, require between ~2 gigabytes to ~2 terabytes of hard drive space, and command wait times of several weeks using the current ALRADS voxeliz ation algorithm. Voxelization would likely fail prior to completion, however, by exhausting the RAM resources of a typical desktop computer. T hese issues were circumvented by represent ing each pregnant female phantom with two separate voxel voxelization comprising the pregnant female without the fetus and a second comprising the fetus and nearby maternal organs. As detailed in Chapter 5, radiation transport simulations were ntom by virtually combining the coarse and fine voxel binaries in the radiation transport software. The coarse voxel resolutions and matrix sizes of the UF and SOLO pregnant female phantoms are presented in Tables 4 1 and 4 2. The coarse voxel resolutions of the UF and SOLO pregnan t females were identical (0.126 cm x 0.126 cm x 0.27 cm) and equivalent to resolutions for the UF adult non pregnant female derived by Wayson 38 in his doctoral dissertation These voxel resolutions represen ted a comprom ise between matrix size and the faithful representation of thin anatomica l structures The X Y dimensions were set at the skin thickness of the UF adult non pregnant female while the Z dimension was allowed to vary to allow the total matrix size to remain near approximately 50 x 10 6 voxels. These voxel dimensions were adopted f or both UF and SOLO pregnant female series. The increased size of the pregnant female phantoms compared to their non pregnant counterpart drove t he total coarse matrix size slightly beyond the ideal 50 x 10 6 voxels However, the number of additional voxels (~20 x 10 6 )

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69 was not a major concern from a computational perspective. The voxel resolutions derived in Chapter 3 for the UF and SOLO fetal phantom series (Table A 5 and Table 3 2 respectively ) were adopted as the fine voxel resolutions for the correspo nding pregnant fetal phantom series. Results and Discussion Completed Phantom Series The completed UF pregnant female phantom series is presen ted in Figure 4 6 to Figure 4 13 Clearly visible in each figure is the fetus positioned approximately in a left occiput anterior (LOA) configuration, surrounded by the expected maternal tissues, including the placenta, uterus, ovaries and other maternal organs. The completed SOLO pregnant female phantom series is nearly indistinguishable from the UF series and exhib its the same visual trends. A complete listing of the UF maternal organ masses is presented in Table 4 3. Table 4 4 summarizes the percent differences of UF maternal organ masses compared to their targeted values. All target masses were matched within 1%. The completed SOLO pregnant female series is presented in Figure 4 14 through a series of to scale sagittal views showing the increasing size of the fetus and maternal abdominal perimeter. The UF pregnant female series exhibits the same general trends. As discussed, no specific maternal mass data were targeted in the SOLO pregnant female series. SOLO pregnant female phantom masses are presented in Table 4 5. Figure 4 1 5 illustrates the concept of representing the pregnant female phantom using two separate voxel binaries. Figure 4 1 5 A presents a sagittal view of the coarse voxel ization of the SOLO 38 week pregnant female phantom with an empty uterus. Figure 4 1 5 B shows the fine voxel ization of the SOLO 38 week fetus, illustrating its

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70 intended overlap onto th e coarse maternal voxelization. As stated previously, the voxel overlap was successfully realized within the radiation transport software and is discussed in detail in Chapter 5. Phantom Series Limitations While the pregnant female computational phantom se ries presented in this work represent significant advancements in the state of the art they are certainly not wit hout their limitations, particularly in accounting for variations in 1) fetal position and mass and 2) maternal organ size and maternal abdomi nal perimeter. A single, reference LOA fetal position was adopted throughout both UF and SOLO pregnant female phantom series. While sufficient for the first iteration of reference pregnant female phantoms, wide variations in fetal presentation are observed in normal pregnancies, particularly in younger fetal ages. 36 37 In addition, a range of fetal whole body masses is observed for a given fetal age. 39 40 The UF pregnant f emale series presented in this work accounts for only the 50 th weight and biometry percentiles however, the series could be updated in the future to include the 10 th and 90 th percentile fetal phantoms presented by Maynard et al. 22 While not critical to the successful fulfillment of SOLO grant deliverables, data are available that would all ow the SOLO pregnant female series to be expanded to include additional wei ght and biometry percentiles of the Urals populations. 24 25 The UF pregnant female computational series also did not account for var iations in maternal organ mass or position. Although these variations contribute less to fetal doses and related quantities than variations in the fetus itself, their quantification could be accounted for through the statistical analysis an appropriately s ized set of maternal abdominal CT images. Similarly, variations in the maternal abdominal perimeter which

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71 can be considered a measure of maternal shielding were not accounted for in this work. Variations in this parameter affect fetal doses imparted from e xternally emitted ionizing radiation, e.g. a pregnant female undergoing a CT examination. 19 Another limitation of the pregnant female phantom series pertains to di screpancies in the center of gravity of the two eldest fetal phantoms compared to expected observations. The UF 35 week and 38 week fetal phantoms and the SOLO 34 week and 38 week fetal phantoms are all derivatives of the UF reference newborn phantom. 22 The UF newborn was originally modeled in a supine position 29 32 and was re positioned as best as possible into an approximate fetal position before constructi ng derivative phantoms. 22 For multiple r easons the UF newborn could not be repositioned perfectly, causing the spine to be slightly too elongated, i.e. exhibiting less curvature than observed in utero The elongated spines of the two eldest UF and SOLO fetal phantoms resulted in noticeable devia tions in the center of gravity of the maternal abdomens from expected (see Figure 4 16 ). Center of gravity deviations are not observed for the younger fetal ages as those phantoms were derived from specimens who were imaged in a fetal position. F igure 4 17 qualitatively compares the spinal curvatures of the UF 20 week and 38 week phantoms. While some modeling adjustments can provide some correction to the centers of gravity of the affected maternal abdomens, true correction would require significant redesig ns of the eldest fetal phantoms.

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72 Table 4 1 Voxel dimensions and matrix sizes of voxelized UF pregnant female phantoms Voxel Resolution (cm) Number of Voxels Phantom X Y Z X Y Z Total (x10 6 ) UFPF 08WK a 0.126 0.126 0.270 391 236 610 56.29 UFPF10 WK 0.126 0.126 0.270 391 236 610 56.29 UFPF15 WK 0.126 0.126 0.270 391 236 610 56.29 UFPF20 WK 0.126 0.126 0.270 391 240 610 57.24 UFPF25 WK 0.126 0.126 0.270 391 280 610 66.78 UFPF 30WK 0.126 0.126 0.270 391 295 610 70.36 UFPF35 WK 0.126 0.126 0.270 391 303 610 72.27 UFPF 38WK 0.126 0.126 0.270 391 307 610 73.22 a UFPF08WK and SOPF08WK are identical

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73 Table 4 2 Voxel dimensions and matrix sizes of voxelized SOLO pregnant female phantoms Voxel Resolution (cm) Number of Voxels Phantom X Y Z X Y Z Total (x10 6 ) SOPF 08WK a 0.126 0.126 0.270 391 236 610 56.29 SO PF 12WK 0.126 0.126 0.270 391 236 610 56.29 SOPF 18WK 0.126 0.126 0.270 391 248 610 59.15 SOPF 22WK 0.126 0.126 0.270 391 266 610 63.44 SOPF 26WK 0.126 0.126 0.270 391 288 610 68.69 S OPF 30WK 0.126 0.126 0.270 391 308 610 73.46 SOPF 34WK 0.126 0.126 0.270 391 312 610 7 4 4 1 SOPF 38WK 0.126 0.126 0.270 391 326 610 77.75 a SOPF08WK and UFPF08WK are identical

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74 Table 4 3 UF pregnant female phantom tissue masses Tissue mass (g) Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF35WK UFPF38WK Adipose tissue 1.488 E E+04 1.462E+04 1.294E+04 1.371E+04 1.590E+04 1.453E+04 1.512E+04 1.552E+04 Adrenal ( L ) 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.5 02E+00 Adrenal (R ) 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 Brain 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 Breast (adipose) 3.337E+02 3.337E+02 3.337E+02 3.337E+02 3.337E+02 3. 337E+02 3.337E+02 3.337E+02 Bronchi 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 Right colon wall 1.443E+02 1.443E+02 1.443E+02 1.452E+02 1.452E+02 1.452E+02 1.451E+02 1.451E+02 Right colon cont. 1.814E+01 1.814E+01 1. 814E+01 6.199E+01 6.199E+01 6.199E+01 5.344E+01 5.344E+01 Ears 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 Esophagus 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 External nose 1.502E +01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 Eye balls 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 Gall bladder wall 8.023E+00 8.023E+00 8.023E+00 7.743E+00 7.743E+00 7.743E+00 7.743E+00 7. 743E+00 Gall bladder cont. 4.788E+01 4.788E+01 4.788E+01 4.773E+01 4.773E+01 4.774E+01 4.774E+01 4.774E+01 Heart wall 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 Heart cont. 3.688E+02 3.688E+02 3.688E+02 3.688E+02 3.6 88E+02 3.688E+02 3.688E+02 3.688E+02 Kidney cortex (L ) 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 Kidney cortex (R ) 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 Kidney medulla (L ) 3 .619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 Kidney medulla (R ) 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 Kidney pelvis (L ) 7.237E+00 7.237E+00 7.237E+00 7.237E+00 7.237E+00 7.237E+0 0 7.237E+00 7.237E+00 Kidney pelvis (R ) 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 Larynx 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 Lens 4.587E 01 4.587E 01 4.587E 01 4.587E 01 4 .587E 01 4.587E 01 4.587E 01 4.587E 01 Liver 1.396E+03 1.396E+03 1.396E+03 1.394E+03 1.394E+03 1.394E+03 1.394E+03 1.394E+03 Lung (L ) 4.163E+02 4.163E+02 4.163E+02 4.164E+02 4.164E+02 4.164E+02 4.164E+02 4.164E+02 Lung (R ) 5.131E+02 5.131E+02 5.131E+02 5.132E+02 5.132E+02 5.132E+02 5.132E+02 5.132E+02 Nasal layer (ant.) 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01

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75 Table 4 3 Continued Tissue mass (g) Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF 35WK UFPF38WK Nasal layer (post.) 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 Oral cavity layer 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 Ovaries 1.096E+01 1.092E+01 1.090E+01 1.0 95E+01 1.091E+01 1.091E+01 1.091E+01 1.091E+01 Pancreas 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 Penis 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Pharynx 1.453E+00 1.453E+00 1.4 53E+00 1.453E+00 1.453E+00 1.453E+00 1.453E+00 1.453E+00 Pituitary gland 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 Prostate 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Rectosigmoi d wall 7.021E+01 7.021E+01 7.021E+01 7.013E+01 7.012E+01 7.009E+01 7.009E+01 7.009E+01 Rectosigmoid cont. 2.561E+01 2.561E+01 2.561E+01 1.370E+01 1.370E+01 1.370E+01 1.370E+01 1.370E+01 Saliva ry glands (parot.) a 4.084E+01 4.084E+01 4.084E+01 4.084E+01 4. 084E+01 4.084E+01 4.084E+01 4.084E+01 Scrotum 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Si wall 5.978E+02 5.978E+02 5.978E+02 5.938E+02 5.934E+02 5.942E+02 6.019E+02 6.013E+02 Si cont. 1.990E+02 1.990E+02 1.990E+02 4.154E+02 3.747E+02 2.611E+02 2.572E+02 2.572E+02 Skin 1.883E+03 1.882E+03 1.870E+03 1.883E+03 1.923E+03 1.926E+03 1.946E+03 1.955E+03 Spinal cord 4.742E+01 4.742E+01 4.742E+01 4.740E+01 4.740E+01 4.740E+01 4.740E+01 4.740E+01 Spleen 1.278E+02 1.278E+02 1.278E+02 1.278E+02 1.278E+02 1.278E+02 1.300E+02 1.300E+02 Stomach wall 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 Stomach cont. 2.309E+02 2.309E+02 2.309E+02 2.309E+02 2.309E+02 2.309E+02 2.309E+02 2.309E+02 Teste s 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Thymus 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 Thyroid 1.703E+01 1.703E+01 1.703E+01 1.703E+01 1.703E+01 1.703E+01 1.703E+01 1.703E+ 01 Tongue 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 Tonsil 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 Trachea 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.068E+0 0 8.068E+00 Urinary bladder wall 3.970E+01 3.970E+01 4.003E+01 4.001E+01 4.001E+01 4.001E+01 4.042E+01 4.042E+01 Urinary bladder cont. 4.864E+01 6.785E+01 2.590E+01 4.231E+01 0.000E+00 0.000E+00 9.126E+00 9.126E+00 Uterine wall 1.914E+02 2.193E+02 3.087 E+02 3.985E+02 5.437E+02 6.833E+02 9.091E+02 1.046E+03

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76 Table 4 3 Continued Tissue mass (g) Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF35WK UFPF38WK Air (in body) 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 Left colon wall 1.442E+02 1.442E+02 1.442E+02 1.442E+02 1.442E+02 1.442E+02 1.449E+02 1.449E+02 Left colon cont. 2.089E+01 2.089E+01 2.089E+01 2.089E+01 2.089E+01 2.089E+01 3.750E+01 3.750E+01 Salivary glands (mand.) a 2.036E+01 2.036E+01 2 .036E+01 2.036E+01 2.036E+01 2.036E+01 2.036E+01 2.036E+01 Salivary glands (ling.) a 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 Arteries 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 Veins 2.204E+02 2.204E+02 2.204E+02 2.203E+02 2.203E+02 2.203E+02 2.203E+02 2.203E+02 Muscle 3.303E+04 3.292E+04 3.228E+04 3.289E+04 3.415E+04 3.403E+04 3.408E+04 3.393E+04 Breast (glandular) 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1. 837E+02 1.837E+02 Amniotic fluid 6.528E+01 1.393E+02 4.314E+02 1.168E+03 2.139E+03 3.709E+03 5.140E+03 5.769E+03 Placenta 1.593E+01 1.976E+01 9.467E+01 1.693E+02 2.988E+02 4.281E+02 5.650E+02 6.475E+02 Costal cartilage 3.830E+01 3.830E+01 3.830E+01 3.79 7E+01 3.797E+01 3.797E+01 3.797E+01 3.797E+01 Cervical discs 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 Thoracic discs 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 Lumbar discs 1.51 4E+01 1.514E+01 1.514E+01 1.513E+01 1.513E+01 1.513E+01 1.513E+01 1.513E+01 cb Cranium 5.812E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 cb Mandible 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925 E+01 cb Scapulae 2.220E+02 2.221E+02 2.220E+02 2.223E+02 2.223E+02 2.223E+02 2.223E+02 2.223E+02 cb Clavicles 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 cb Sternum 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1. 919E+01 1.919E+01 1.919E+01 cb Ribs 2.502E+02 2.502E+02 2.502E+02 2.515E+02 2.515E+02 2.515E+02 2.518E+02 2.518E+02 cb Vertebrae cervical 4.409E+01 4.409E+01 4.409E+01 4.409E+01 4.409E+01 4.409E+01 4.409E+01 4.409E+01 cb Vertebrae thoracic 8.543E+01 8.5 43E+01 8.543E+01 8.537E+01 8.537E+01 8.537E+01 8.537E+01 8.537E+01 cb Vertebrae lumbar 8.333E+01 8.333E+01 8.333E+01 8.328E+01 8.328E+01 8.328E+01 8.328E+01 8.328E+01 cb Sacrum 9.614E+01 9.614E+01 9.614E+01 9.663E+01 9.663E+01 9.663E+01 9.663E+01 9.663E+ 01 cb Os coxae 2.787E+02 2.787E+02 2.787E+02 2.731E+02 2.731E+02 2.731E+02 2.731E+02 2.731E+02 cb Femur proximal 3.395E+01 3.395E+01 3.395E+01 3.180E+01 3.180E+01 3.180E+01 3.180E+01 3.180E+01 cb Femur upper shaft 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02

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77 Table 4 3 Continued Tissue mass (g) Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF35WK UFPF38WK cb Femur lower shaft 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1.3 08E+02 cb Femur distal 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 cb Tibiae proximal 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 cb Tibiae shaft 1.684E+02 1.684E+02 1.684E+02 1.684 E+02 1.684E+02 1.684E+02 1.684E+02 1.684E+02 cb Tibiae distal 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 cb Fibulae proximal 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 cb Fibulae shaft 3.298E+01 3.298E+01 3.298E+01 3.298E+01 3.298E+01 3.298E+01 3.298E+01 3.298E+01 cb Fibulae distal 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 cb Patellae 7.004E+00 7.004E+00 7.004E+00 7.004E+00 7.004E+00 7.004E+0 0 7.004E+00 7.004E+00 cb Ankle+feet 2.184E+02 2.184E+02 2.184E+02 2.184E+02 2.184E+02 2.184E+02 2.184E+02 2.184E+02 cb Humerus proximal 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 cb Humerus upper shaft 8.408E+01 8.40 8E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 cb Humerus lower shaft 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 cb Humerus distal 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+ 01 3.507E+01 cb Radii proximal 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 cb Radii shaft 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 cb Radii distal 7.770E+00 7.770E+00 7.770E+00 7 .770E+00 7.770E+00 7.770E+00 7.770E+00 7.770E+00 cb Ulnae proximal 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 cb Ulnae shaft 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 cb Ulnae di stal 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 cb Hand 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 cb Teeth 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1. 705E+01 sp Cranium 4.438E+02 4.438E+02 4.438E+02 4.438E+02 4.438E+02 4.729E+02 4.438E+02 4.438E+02 sp Mandible 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 sp Scapulae 1.945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 sp Clavicles 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 sp Sternum 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 sp Ribs 1.921E+02 1.921E+02 1.921E+02 1 .919E+02 1.919E+02 1.919E+02 1.920E+02 1.920E+02

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78 Table 4 3 Continued Tissue mass (g) Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF35WK UFPF38WK sp Vertebrae cervical 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.79 6E+01 4.796E+01 sp Vertebrae thoracic 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 sp Vertebrae lumbar 2.569E+02 2.569E+02 2.569E+02 2.568E+02 2.568E+02 2.568E+02 2.568E+02 2.568E+02 sp Sacrum 1.630E+02 1.630E+02 1.630 E+02 1.633E+02 1.633E+02 1.633E+02 1.633E+02 1.633E+02 sp Os coxae 5.109E+02 5.109E+02 5.109E+02 5.056E+02 5.056E+02 5.056E+02 5.056E+02 5.056E+02 sp Femora proximal 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 mc Femo ra upper shaft 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 mc Femora lower shaft 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 sp Femora distal 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 sp Tibiae proximal 1.866E+02 1.866E+02 1.866E+02 1.866E+02 1.866E+02 1.866E+02 1.866E+02 1.866E+02 mc Tibiae shaft 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 sp Tibiae distal 6 .559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 sp Fibulae proximal 1.432E+01 1.432E+01 1.432E+01 1.432E+01 1.432E+01 1.432E+01 1.432E+01 1.432E+01 mc Fibulae shaft 7.891E+00 7.891E+00 7.891E+00 7.891E+00 7.891E+00 7.891E+0 0 7.891E+00 7.891E+00 sp Fibulae distal 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 sp Patellae 2.516E+01 2.516E+01 2.516E+01 2.516E+01 2.516E+01 2.516E+01 2.516E+01 2.516E+01 sp Ankle+feet 2.705E+02 2.705E+02 2.705E+ 02 2.705E+02 2.705E+02 2.705E+02 2.705E+02 2.705E+02 sp Humera proximal 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 mc Humera upper shaft 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 mc Humera lower shaft 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 sp Humera distal 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 sp Radii proximal 1.003E+01 1.003E+01 1.003E+01 1.003E +01 1.003E+01 1.003E+01 1.003E+01 1.003E+01 mc Radii shaft 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 sp Radii distal 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 sp Ulnae proximal 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 mc Ulnae shaft 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 sp Ulnae distal 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.8 00E+00 6.800E+00 sp Hands 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01

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79 a Salivary glands partitioned into parotid, submandibular and sublingual regions. cb Indicates cortical bone. sp Indicates spongiosa. mc Indicates medullary cavity.

PAGE 80

80 Table 4 4. Percent differences of relevant tissue masses to target masses in UF pregnant female phantom series Tissue UFPF08WK UFPF10WK UFPF15WK UFPF20WK UFPF25WK UFPF30WK UFPF35WK UFPF38WK Liver 0.27 0.27 0.27 0.44 0.44 0.44 0.44 0.44 Small intestine w all 0.36 0.36 0.36 0.90 0.92 0.96 0.31 0.21 Left colon wall 0.53 0.53 0.53 0.53 0.53 0.53 0.10 0.10 Right colon wall 0.50 0.50 0.50 0.14 0.14 0.14 0.07 0.07 Recto sigmoid colon wall 0.31 0.31 0.31 0.19 0.17 0.13 0.13 0.13 Urinary bladder wall 0.75 0.75 0.08 0.01 0.01 0.01 0.92 0.94 Uterine w all 0.32 0.32 0.41 0.37 0.68 0.48 0.23 0.39 Placenta 0.41 0.89 0.34 0.42 0.39 0.45 0.44 0.38

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81 Table 4 5 SOLO pregnant female phantom tissue masses Tissue Tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Adipose tissue 1.447E+04 1.548E+04 1.570E+04 1.599E+04 1.682E+04 1.547E+04 1.641E+04 Adrenal (L) 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+00 6.502E+0 0 Adrenal (R) 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 6.480E+00 Brain 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 1.302E+03 Breast(adipose) 3.337E+02 3.337E+02 3.337E+02 3.337E+02 3.337E+02 3.337E+02 3.337E+02 Bronch i 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 8.994E+00 Right colon wall 1.690E+02 1.690E+02 1.691E+02 1.691E+02 1.691E+02 1.691E+02 1.691E+02 Right colon cont. 1.814E+01 5.344E+01 5.344E+01 5.344E+01 5.344E+01 5.344E+01 5.344E+01 Ears 6 .780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 6.780E+00 Esophagus 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 3.475E+01 External nose 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 1.502E+01 Eye balls 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 1.478E+01 Gall bladder wall 8.023E+00 7.743E+00 7.743E+00 7.743E+00 7.743E+00 7.743E+00 7.743E+00 Gall bladder cont. 4.788E+01 4.773E+01 4.773E+01 4.773E+01 4.774E+01 4.774E+01 4.774E+01 Heart wall 2.491 E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 2.491E+02 Heart cont. 3.688E+02 3.688E+02 3.688E+02 3.688E+02 3.688E+02 3.688E+02 3.688E+02 Kidney cortex (l) 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 Kidney cortex (r) 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 1.010E+02 Kidney medulla (l) 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 3.619E+01 Kidney medulla (r) 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 3.611E+01 Kidne y pelvis (l) 7.237E+00 7.237E+00 7.237E+00 7.237E+00 7.237E+00 7.237E+00 7.237E+00 Kidney pelvis (r) 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 7.260E+00 Larynx 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 Lens 4.587E 01 4.587E 01 4.587E 01 4.587E 01 4.587E 01 4.587E 01 4.587E 01 Liver 1.396E+03 1.394E+03 1.394E+03 1.394E+03 1.394E+03 1.394E+03 1.394E+03 Lung (L) 4.163E+02 4.164E+02 4.164E+02 4.164E+02 4.164E+02 4.164E+02 4.164E+02 Lung (R) 5.131E+02 5.132E+02 5.132E+02 5.132E+02 5.132E+02 5.132E+02 5.132E+02 Nasal layer (ant.) 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01 5.203E 01

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82 Table 4 5 Continued Tissue Fetal tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38W K Nasal Layer (Post.) 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 8.828E+00 Oral Cavity Layer 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 1.749E+00 Ovaries 1.090E+01 1.095E+01 1.098E+01 1.098E+01 1.085E+01 1.087E+01 1.087 E+01 Pancreas 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 1.191E+02 Penis 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Pharynx 1.453E+00 1.453E+00 1.453E+00 1.453E+00 1.453E+00 1.453E+00 1.453E+00 Pituitary Glan d 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 5.422E 01 Prostate 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Rectosigmoid w all 7.021E+01 7.013E+01 7.012E+01 7.012E+01 7.009E+01 7.009E+01 7.009E+01 Rectosigmoid c ont. 2.561E+01 1.370E+01 1.370E+01 1.370E+01 1.370E+01 1.370E+01 1.370E+01 Salivary Glands (p arot.) a 4.084E+01 4.084E+01 4.084E+01 4.084E+01 4.084E+01 4.084E+01 4.084E+01 Scrotum 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Si W all 5.978E+02 5.938E+02 5.934E+02 5.934E+02 5.942E+02 6.019E+02 6.019E+02 Si Cont. 1.990E+02 4.154E+02 3.747E+02 3.747E+02 2.611E+02 2.572E+02 2.572E+02 Skin 1.883E+03 1.901E+03 1.919E+03 1.929E+03 1.950E+03 1.951E+03 1.972E+03 Spinal Cord 4.742E+01 4.7 40E+01 4.740E+01 4.740E+01 4.740E+01 4.740E+01 4.740E+01 Spleen 1.278E+02 1.278E+02 1.278E+02 1.278E+02 1.278E+02 1.300E+02 1.300E+02 Stomach Wall 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 1.397E+02 Stomach Cont. 2.309E+02 2.309E+02 2. 309E+02 2.309E+02 2.309E+02 2.309E+02 2.309E+02 Testes 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Thymus 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 2.012E+01 Thyroid 1.703E+01 1.703E+01 1.703E+01 1.703E+01 1.7 03E+01 1.703E+01 1.703E+01 Tongue 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 5.993E+01 Tonsil 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 3.047E+00 Trachea 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.068E+00 8.06 8E+00 Urinary Bladder Wall 4.003E+01 4.001E+01 3.987E+01 3.989E+01 3.986E+01 4.038E+01 4.042E+01 Urinary Bladder Cont. 2.590E+01 4.231E+01 2.011E+01 2.008E+01 2.011E+01 9.126E+00 9.126E+00 Uterine Wall 2.512E+02 3.970E+02 4.490E+02 5.367E+02 6.681E+02 5 .229E+02 6.671E+02

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83 Table 4 5 Continued Tissue Fetal tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Air (in body) 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 6.572E 02 Left colon wall 1.442E+02 1.446E+0 2 1.446E+02 1.446E+02 1.449E+02 1.449E+02 1.449E+02 Left colon cont. 2.089E+01 3.750E+01 3.750E+01 3.750E+01 3.750E+01 3.750E+01 3.750E+01 Salivary glands (mand.) a 2.036E+01 2.036E+01 2.036E+01 2.036E+01 2.036E+01 2.036E+01 2.036E+01 Salivary glands (li ng.) a 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 7.547E+00 Arteries 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 7.383E+01 Veins 2.204E+02 2.203E+02 2.203E+02 2.203E+02 2.203E+02 2.203E+02 2.203E+02 Muscle 3.317E+04 3.302 E+04 3.415E+04 3.425E+04 3.501E+04 3.527E+04 3.542E+04 Breast(glandular) 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1.837E+02 1.837E+02 Amniotic fluid 2.122E+02 1.191E+03 1.803E+03 2.554E+03 3.454E+03 5.068E+03 2.531E+03 Placenta 4.657E+01 1.466E +02 2.442E+02 3.413E+02 4.005E+02 5.652E+02 6.522E+02 Cranial cartilage 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 0.000E+00 Costal cartilage 3.830E+01 3.797E+01 3.797E+01 3.797E+01 3.797E+01 3.797E+01 3.797E+01 Cervical discs 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 2.740E+00 Thoracic discs 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 3.469E+01 Lumbar discs 1.514E+01 1.513E+01 1.513E+01 1.513E+01 1.513E+01 1.513E+01 1.513E+01 cb Cranium 5.812E+02 5.8 12E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 5.812E+02 cb Mandible 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 3.925E+01 cb Scapulae 2.220E+02 2.223E+02 2.224E+02 2.223E+02 2.223E+02 2.223E+02 2.223E+02 cb Clavicles 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 4.244E+01 cb Sternum 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 1.919E+01 cb Ribs 2.502E+02 2.515E+02 2.515E+02 2.515E+02 2.518E+02 2.518E+02 2.518E+02 cb Vertebrae cervical 4.409E+01 4.409E+01 4 .409E+01 4.409E+01 4.409E+01 4.409E+01 4.409E+01 cb Vertebrae thoracic 8.543E+01 8.537E+01 8.537E+01 8.537E+01 8.537E+01 8.537E+01 8.537E+01 cb Vertebrae lumbar 8.333E+01 8.328E+01 8.328E+01 8.328E+01 8.328E+01 8.328E+01 8.328E+01 cb Sacrum 9.614E+01 9. 663E+01 9.663E+01 9.663E+01 9.663E+01 9.663E+01 9.663E+01 cb Os Coxae 2.787E+02 2.731E+02 2.731E+02 2.731E+02 2.731E+02 2.731E+02 2.731E+02 cb Femur P roximal 3.395E+01 3.180E+01 3.180E+01 3.180E+01 3.180E+01 3.180E+01 3.180E+01

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84 Table 4 5 Continued Tis sue Fetal tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK cb Femur Upper Shaft 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 1.131E+02 cb Femur Lower Shaft 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1.308E+02 1 .308E+02 1.308E+02 cb Femur Distal 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 6.237E+01 cb Tibiae Proximal 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 4.238E+01 cb Tibiae Shaft 1.684E+02 1.684E+02 1.684E+02 1.684E+02 1.6 84E+02 1.684E+02 1.684E+02 cb Tibiae Distal 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 2.206E+01 cb Fibulae Proximal 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 5.050E+00 cb Fibulae Shaft 3.298E+01 3.298E+01 3.298E+01 3. 298E+01 3.298E+01 3.298E+01 3.298E+01 cb Fibulae Distal 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 7.819E+00 cb Patellae 7.004E+00 7.004E+00 7.004E+00 7.004E+00 7.004E+00 7.004E+00 7.004E+00 cb Ankle+Feet 2.184E+02 2.184E+02 2.184E+02 2 .184E+02 2.184E+02 2.184E+02 2.184E+02 cb Humerus Proximal 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 2.743E+01 cb Humerus Upper Shaft 8.408E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 8.408E+01 cb Humerus Lower Shaft 7.270E+0 1 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 7.270E+01 cb Humerus Distal 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+01 3.507E+01 cb Radii Proximal 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 5.668E+00 cb Radii Shaft 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 5.882E+01 cb Radii Distal 7.770E+00 7.770E+00 7.770E+00 7.770E+00 7.770E+00 7.770E+00 7.770E+00 cb Ulnae Proximal 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 1.401E+01 cb Ulnae Shaft 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 6.990E+01 cb Ulnae Distal 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 2.688E+00 cb Hand 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 1.426E+02 cb Teeth 1.70 5E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 1.705E+01 sp C ranium 4.438E+02 4.438E+02 4.438E+02 4.438E+02 4.438E+02 4.438E+02 4.438E+02 sp M andible 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 2.806E+01 sp S capulae 1.945E+02 1. 945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 1.945E+02 sp C lavicles 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 3.071E+01 sp S ternum 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01 3.130E+01

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85 Table 4 5 Continued Tissue Fe tal tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK sp Ribs 1.921E+02 1.919E+02 1.919E+02 1.919E+02 1.920E+02 1.920E+02 1.920E+02 sp Vertebrae cervical 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.796E+01 4.796E+01 sp Vertebrae thoracic 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 2.055E+02 sp Vertebrae lumbar 2.569E+02 2.568E+02 2.568E+02 2.568E+02 2.568E+02 2.568E+02 2.568E+02 sp Sacrum 1.630E+02 1.633E+02 1.633E+02 1.633E+02 1.633E+02 1.633E+02 1.633E+02 sp Os coxae 5.109E+02 5.056E+02 5.056E+02 5.056E+02 5.056E+02 5.056E+02 5.056E+02 sp Femora proximal 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 1.963E+02 mc Femora upper shaft 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 6.443E+01 mc Femora lower shaft 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 7.305E+01 sp Femora distal 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 2.371E+02 sp Tibiae proximal 1.866E+02 1.866E+02 1.866E+02 1.866 E+02 1.866E+02 1.866E+02 1.866E+02 mc Tibiae shaft 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 7.734E+01 sp Tibiae distal 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 6.559E+01 sp Fibulae proximal 1.432E+01 1.432E+01 1.432 E+01 1.432E+01 1.432E+01 1.432E+01 1.432E+01 mc Fibulae shaft 7.891E+00 7.891E+00 7.891E+00 7.891E+00 7.891E+00 7.891E+00 7.891E+00 sp Fibulae distal 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 1.315E+01 sp Patellae 2.516E+01 2.516E+01 2 .516E+01 2.516E+01 2.516E+01 2.516E+01 2.516E+01 sp Ankle+feet 2.705E+02 2.705E+02 2.705E+02 2.705E+02 2.705E+02 2.705E+02 2.705E+02 sp Humera proximal 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 1.209E+02 mc Humera upper shaft 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 2.344E+01 mc Humera lower shaft 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 2.057E+01 sp Humera distal 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 7.046E+01 sp Radii prox imal 1.003E+01 1.003E+01 1.003E+01 1.003E+01 1.003E+01 1.003E+01 1.003E+01 mc Radii shaft 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 1.592E+01 sp Radii distal 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 2.035E+01 sp Ulna e proximal 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 4.280E+01 mc Ulnae shaft 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 1.857E+01 sp Ulnae distal 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.800E+00 6.800E+00

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86 T able 4 5 Continued Tissue Fetal tissue mass (g) SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK sp H ands 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 4.309E+01 a Salivary glands partitioned into parotid, submandibular and sublingual regions. cb Indicates cortical bone. sp Indicates spongiosa. mc Indicates medullary cavity.

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87 Figure 4 1 Representative segmented CT image slice of 36 week pregnant female.

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88 Figure 4 2 Incorporation of segmented 36 week maternal abdominal organs into UF adult non pregnant female. A) Segmented 36 week maternal abdominal organs (polygon mesh B) UF adult non pregnant female with abdominal organs removed. C) UF adult non pregnant female with segmented organs inserted into abdomen. D) Segmented organs following NURBS conversion as modeled in 38 week UF pregnant female (uterus opaque). E) Segmented organs following NURBS conversion as modeled in 38 week UF pregnant female (uterus hidden).

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89 Figure 4 3 Conversion of 36 week polygo n mesh uterus to NURBS format. A) Segmented 36 week uterus (polygon mesh). B) Showing 2D surface contour frame (uterus translucent). C) Uterus NURBS surface wrapped around contour frame.

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90 Figure 4 4. Central tracks of small intestine (silver) and la rge intestine (blue) in the 38 week UF pregnant female phantom. A) Right oblique view. B) Left oblique view.

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91 Figure 4 5 Approximate left occiput anterior (LOA) fetal orientation in 38 week UF pregnant female phantom.

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92 Figure 4 6 Completed 8 week UF pregnant female phantom (UFPF08WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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93 Figure 4 7 Completed 10 week UF pregnant female phantom (UFPF10WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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94 Figure 4 8 Completed 15 week UF pregnant female phantom (UFPF15WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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95 Figure 4 9 Completed 20 week UF pregnant female phantom (UFPF20WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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96 Figure 4 10 Completed 25 week UF pregnant female phantom (UFPF25WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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97 Figure 4 11 Completed 30 week UF pregnant female phantom (UFPF30WK). A) Frontal view. B) Zoomed right oblique view of ab domen.

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98 Figure 4 12 Completed 35 week UF pregnant female phantom (UFPF35WK). A) Frontal view. B) Zoomed right oblique view of abdomen.

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99 Figure 4 13 Completed 38 week UF pregnant female phantom (UFPF38WK). A) Frontal view. B) Zoomed right obliqu e view of abdomen.

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100 Figure 4 14 To scale left side comparison of completed Urals based (SOLO) pregnant female phantom series. A) SOPF08WK (equiv. to UFPF08WK). B) SOPF12WK. C)SOPF18WK. D)SOPF22WK. E)SOPF26WK. F)SOPF30WK. G)SOPF34WK. H)SOPF38WK.

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101 Figure 4 15 Voxel representation of 38 week Urals based (SOLO) pregnant female phantom. A) Coarse resolution maternal tissues (empty uterus). B) Fine resolution fetal tissues overlaying section of maternal abdomen.

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102 Figure 4 16 C enter of grav ity discrepancy in the UF and SOLO pregnant female phantoms. Dashed lines indicate the planes that bound the skin contours of the maternal abdomen in a more realistic center of gravity.

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103 Figure 4 17 Qualitative comparison of spinal curvatures of tw o UF fetal phantoms (not to scale) A) 20 weeks. B) 38 weeks. Dashed lines emphasize spinal curvature.

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104 CHAPTER 5 RADIATION S VALUES F OR THE SOLO RADIONUCLIDES Overview Several radionuclides are of interest to the in utero dose subproject of SOLO due to the many by products of nuclear we a pons development and their release into the surrounding Urals environment, specifically Sr 90 /Y 90 Sr 89, I 131, Cs 137 / Ba 137m and Pu 239 The presence of these radi onuclides in the water, air, and soil in and around p opulated villages led to their uptake into the organs and tissues of pregnant women and their unborn children. Biokinetic modeling of the movement of these radionuclides throughout the body can provide an estimate of the distribution of radiation activity throughout the individual organs of the mother and fetus. However, this type of analysis only provides an estimate of whe re radiation is being emitted from in the body; it does not provide a measure of energy deposition occurring in neighboring organs and tissues. If the time integrated activity (total number of nuclear transformations) in a source tissue is known, a dose coefficient or S value can link that quantity to the radiation doses to target biological tissues as a result of that activity distrib ution throughout the body. An S value is defined, using the International System of Units, as the ratio of 1) the radiation dose (Gy) deposited in a specific target per radioactive transformation (Bq s) occurring in a specific source and 2) the target mass ( k g) S values are therefore dependent on the source target combination. The following equation, based on the MIRD schema, illustrates the relationship between the total number of nuclear transformations in a source tissue and the resulting radiation dose s to a target:

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105 (Eq. 5 1) where is the time integrated activity (total nuclear transformations), T D is the integration period, r T is the target tissues, r S is th e source tissue and is the radiation S value. The goal of the efforts in this chapter was to estimation these radionuclide dependent S values for all source and target combinations of interest to the SOLO project. The computational fetal and pregnant female phantoms presented earlier in this work provide excell ent surrogates with which to s imulate the radiation exposures from the SOLO radionuclides and estimate the associated S values for any a wide range of source target combination s Radiation Transport Methods and S Value Calculations Summary of Methods All radiation transport simulations were performed with the software Monte Carlo N Particle eXtended ( MCNPX ) version 2.7. The MCNPX software transports radiation particle physics i nteractions using random number generation and is a powerful, popular tool for problems related to radiation shielding, nuclear engineering, detector design, and even medical applications like radiography simulation. In an MCNPX simulation, the code reads in a user defined input file that contains descriptions of 1) the physical geometry of the problem, 2) the regions for which radiation radiation source. For this work, the tallie s generated by MCNPX required further manual processing in order to obtain S values. The following sections describe the principal components of the MCNPX input files assembled for this work, the sub investigations

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106 performed to determine or verify any crit ical physics parameters, and the manual post processing of the transport data to calculate S values. Radiation Transport Phantom geometry Methods for representing a single, voxelized phantom in MCNPX and other radiation transport code s have been well established by many authors and research groups. 20 21 29 32 34 35 41 43 Several recent conference presentations have discussed efforts to represent multiple voxel resolutions simultaneously in a single MCNPX input file geometry. As discussed in Chapter 4, due to a number of computational limitations each UF and SOLO pregnant female phantom had to be represented by a pai r of voxel models representing the fetal tissues and nearby maternal tissues As a result, a novel method was needed for simultaneously represent ing those voxel models in MCNPX. Each v oxel model was first imported in the MCNPX code using the established method, which represents each phantom voxel as a unique element within a three dimensional, cubic ommon point in both lattices were visually id entified various regions of the uterus were used in this work, depending on fetal age, however any common point would suffice. Using native MCNPX Boolean operations and the coordinates of the common point represent ing the fetal tissues of the pregnant female phantom was overlaid onto the coarse lattice representing the maternal tissues. The position of each overlay was visually confirmed using the MCNPX integrated geometry plotter. Figure 5 1 illustrates the success ful dual lattice representation of the 38 week SOLO pregnant female in MCNPX.

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107 Some additional components required in the MCNPX geometry definition input file are mass densities and elemental compositions of the materials comprising the geometry. This info calculations. Tables A 1 through A 3 summarize the mass densities while Tables A 6 through A 9 summarize the elemental compositions. Elemental compositions of fetal soft tissues (Table A 6) w ere adopted from a combination of relevant literature sources. 9 44 Elemental compositions of SOL O and UF fetal spongiosa (Tables A 7 and A 8) were derived by linearly interpolating between the 38 week cranium and lumbar vertebrae elemental compositions reported by Pafundi et al. 35 and the ICRU46 reference adult cartila ge elemental composition. 44 This approximation mirrored the spongiosa mass density approximation performed by Maynard et al. 22 The elemental compositions of the maternal tissues of the UF and SOLO pregnant females (Table A 9) were assumed to be equivalent to the blood inclusive elemental compositions of the UF adult non pregnant female phantom derived by Wayson 38 in his doctoral dissertation. Target tissues MCNPX offers a comprehensive set of tallies for measuring various radiation related quantities for target regions of interest within the user defined geometry. For this work the *F8 tally was utilized for all transport simulations and subsequent S value calculations. The *F8 tally provides a measure of the mean energy deposition within a volume of interest per starting source particle history (MeV particle 1 ) Using the r adionuclide spectrum sampling methods discussed in the next section the *F8 tally of a target tissue can be directly converted to the corresponding S value. All radiation transport simulations performed in this work tallied the same set of target tissues o f interest to the SOLO project. Those targets are summarized in Table B 1.

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108 Source definitions Source geometry and source tissues In order to transport radiation emitted internally within a voxel phantom, MCNPX requires a list of lattice elements (source file) from which to sample its starting particle locations. The list of lattice elements corresponds to a source tissue of interest to the problem. For example, a radiation source located within the femur is defined by a list of all the lattice elements as sociated with the femur. Groups of different lattice elements can form a combined source, e.g. all the ossified regions of the fetal skeleton. Individual source files were generated for the fetal and maternal source tissues of interest to SOLO. Those tissu es are summarized in Tables B 2 and B 3, respectively. The volumes of select source organs or groups of organs were sampled non uniformly in order to simulate the non uniform distribution of certain sources of radiation One such radiation source was bloo d, which is not distributed evenly among all tissues. The non uniform distributions provided in Table B 4 were adopted to computationally simulate the distribution of blood throughout the maternal tissues. Distribution data were assembled from Wayson 38 and ICRP Publication 89 9 Another such radiation source was the mineral bone of the maternal skeleton. A portion of the volume of skeletal spongiosa regions is occupied by ossified trabecular bone, which is frequently a source of interest in radiation dosimetry. Although the microscopic structure of skeletal spongiosa is not explicitly modeled in the UF ad ult female skeleton, the sampling distributions presented in Table B 5 provide a method for sampling the macroscopic regions of spongiosa to account for the bone by bone variations in trabecular bone volume. The distributions are sub divided into the trabe cular volume and surfaces sources. Sampling distributions for cortical bone surfaces are also provided, which are

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109 assumed to be equivalent to the uniform volume sampling distributions for cortical bone volume. Skeletal sampling distributions were adapted f Lindsay Sinclair. Direct energy spectrum sampling Another requirement of the MCNPX source definition is a description of the particle type (e.g. electron ) and corresponding starting energy or energies. Because radionuclide specific S values were the desired result of the radiation transport simulations, the MCNPX source definitions were written to sample directly from the associated radionuclide decay spectrum. This direct spectrum sampling is what ultimately allowed to the *F8 to be later directly converted to the corresponding S value. Typically, a given radionuclide will undergo nuclear transformations (radioactive decay) through several different pathways. Pathways were grouped by type (e.g. beta electrons or monoenerget ic photons) transported separately, and the results mathematically combined later during S value calculation. Radionuclide d ecay spectra were adopted from ICRP Publication 107. 45 Verification of transpor t physics Electron energy indexing. Electron energy indexing is a process which MCNPX undergoes when estimating electron energy loss straggling. 46 MCNPX offers two energy indexing options: the MCNPX default algor ithm and the ITS (Integrated TIGER Series) algorithm. The two options differ in how they bin the electron energy : the MCNP algorithm proach. These differing approaches result in the ITS algorithm relying significantly less on the linear interpolation of non linear interaction data, making it the superior algorithm in terms of electron energy loss modeling. 46

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110 ESTEP. When transporting electrons through a medium, MCNPX divides the random path of an electron into energy steps and sub steps. The se steps and sub steps are intended to divide the st atistical treatment of the electron interactions with the surrounding medium through the history of the particle. 47 The ESTEP card defines the sub steps per energy step for a given material. The default value (usually 3 6) is typically sufficient fo r problem geometry dimensions of a few millimeters, however, discrepancies in electron tallies can occur when smaller physical dimensions are considered. 47 Methods electron transport within the smallest anatomical structures observed in t he SOLO pregnant female phantom series, specifically the spleen of the 8 week fetus and the ossified bone sites of the 12 week fetus. Suggested ESTEP variations were calculated and tested for the highest electron energy observed in this work (ESTEP=~75 240 ), specifically the maximum theoretical Y 90 beta energy (E=2.28 MeV). The maximum observed discrepancy was approximately 1%. Considering the computer run time increases approximately linearly with increasing ESTEP, this small discrepancy was considered ac ceptable and the default ESTEP values were used. Photon and electron energy cutoff values By default, MCNPX transports photon and electrons until they reach energies of 1 keV, upon which the code assumes their remaining energy is deposited locally. Addit ional output table options allow the MCNPX user to examine the range of electrons in the materials defined in the geometry. Because a 1 keV photon has practically a 100% probability of undergoing a photoelectric absorption event 47 the range of the resulting photoelectron was examined

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111 to ensure it would not travel beyond the distance of the smallest l attice (voxel) dimension (0.0065 cm) The range of a 1keV electron was over 1000x smaller than the smallest lattice dimension, confirming the validity of the default photon and electron energy cutoff value s Variance r eduction For many deep penetration transport problems direct (analog) simulation in MCNPX will not provide acceptable tally results in a reasonable amount of computer time. Such is the case for certain SOLO pregnant female phantom source and target combina tions. For example, when simulated directly, I 131 photons emitted isotropically (i.e. in all directions with equal probability) from the maternal thyroid will not register sufficient tally results in the younger fetuses in reasonable time due to the incre dibly small solid angle between source and target. For this and other similar cases, certain techniques, called variance reduction, were proactively utilized to increase the simulation efficiency and improve results for certain simulations where inefficie ncy was anticipated. Specifically, those methods were source directional biasing, importance weighting, and non analog bremsstrahlung sampling. The I 131 photon example given above was an example of a source/target simulation that was vastly improved by so urce directional biasing. This variance reduction technique was useful for photon emitters located in far off maternal source tissues. Source directional biasing involves defining a reference vector and the half angle of an acceptance cone within which 100 % of the source are emitted. The statistical weight of the source particle is properly adjusted by MCNPX so no bias is introduced to the tally result. Figure 5 2 illustrates the concept for the thyroid example in the SOLO 38 week pregnant female phantom. R hinoceros TM was used to measure the

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112 limiting (largest) half angle for several I 131 and Ba 137m photon sources in which directional biasing was utilized. Those half angles are provided in Table B 6 Another simple yet effect variance reduction technique is importance weighting, which is used to maintain a good population of statistically significant particles along the path from the source to the target. As particles enter materials with a higher importance they are split into multiple particles based on th e ratio of the importance of the two materials. The statistical weights of the new particles are adjusted so that no bias is introduced into the tally results. Figure 5 3 illustrates this concept in a simple, one dimensional set of materials. Suggestions i n the MCNPX user manual were followed in defining importance ratios of neighboring materials, specifically that a ratio of six was never exceeded. Importances in the SOLO pregnant female phantoms were adjusted for the uterine wall, amniotic fluid, residual soft tissue of the fetus and unossified cartilage of the fetus. The final variance reduction method used in this work centered on the production of bremsstrahlung photons from relatively energetic beta electrons. When an electron particle is accelerated b y an atomic electric field it undergoes radiative energy loss, transfer a fraction or all of its energy to a so called bremsstrahlung photon. The neutral, massless photon can then carry that energy to targets further away than the range of the original ele ctron. Although bremsstrahlung production is rare in soft tissues at the electron energies of interest to the SOLO radionuclides (<1% yield in water for maximu m Y 90 beta energy) their production does occur on occasion and can affect tallies of interest. The B B suggestions to increase the non analog sampling of higher energy bremsstrahlung

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113 emissions. As with the previous variance reduction techniques, the statistical weights of the generated particles ar e adjusted so that no bias is introduced to the tally results Source particle histories The final MCNPX parameter of interest was the NPS card or number of source particle histories. The NPS card is one of the most influential parameters in the MCNPX inpu t file as it tells the software how many source particle histories to track to completion with each source particle hopefully producing a strong cascade of statistically significant particles that reach the tally region For basic geometries the NPS card can be set relatively low (~1 x 10 5 to ~1 x 10 6 ) and yield excellent tally statistics. However, for voxel phantom simulations (e.g. SOLO intra fetal sources and targets) typically the user must run several million particle histories. The situation is furt her exacerbated in the present work, where many small maternal tissues lie relatively large distances fro m even smaller fetal targets (e.g. SOLO pregnant female maternal sources irradiation fetal targets) When coupled with certain radionuclide decay modes that generate relatively short range beta electrons, the problem efficiency is further worsened. An on going trial and evaluation procedure yielded NPS card values between 100 million and 650 million, depending on the source particle type. Beta electron e mitting radionuclides required NPS values near the higher end of the range. Transport simulation runs The University of Florida High Performance Computing Center (UF HPC) provides exceptionally powerful computing resources which allow the successful execut ion of cumbersome MCNPX transport simulations. This valuable resource was heavily utilized in the completion of the large of number source and target combinations.

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114 The total number of simulations was dependent on the pro duct of the number of phantoms, sour ces tissues, radionuclides, and simulated radionuclides decay modes. The number of individual MCNPX simulations performed was slightly greater than one thousand Each simulation was typically r un in parallel using 24 processor cores distributed over 6 nod es. RAM usage per core range from 4 6 gigabytes. Wall clock times varied between 45 minutes and 3.5 hours. Data Processing and S value Calculation MATLAB TM scripts were written and utilized to 1) parse *F8 tally data from all input files, 2) perform the ne cessary conversions from *F8 tally to S value and 3) export and tabulate all S values data into formatted Microsoft Excel workbooks and spreadsheets. This process saved not only time but significantly minimized the possibility for human error in such exten sive data manipulation. Recall the mathematical definition of the radiation S value per the MIRD, time independent formulation 48 : (Eq. 5 2) where E i Y i is the product of the mean energy of the i th nuclear transition and the nu mber of i th transitions per nuclear transformation and m T is the target mass Because the MCNPX simulations directly sampled the decay spectrums of the associated radionuclides of interest, Eq uation 5 2 can be re written in terms of the *F8 tally. (Eq. 5 3) where *F8 n and are the MCNPX *F8 tally measured for the n th decay type e.g. beta electron monoenergetic electrons, monoenergetic photons, et c. Y n is the corresponding absolute yield and k is simply a unit conversion constant to Gray (J kg 1 )

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115 per nuclear transformation ( J kg 1 Bq 1 s 1 ) For the case where the target mass is units of grams (g) and the MCNPX default *F8 tally units are used (Me V per starting source particle), the conversion constant is equivalent to 1.602 x 10 10 Gy g MeV 1 As expected, despite proactive efforts to minimize these cases, certain source/target/radionuclide combinations did not yield sufficient tally results to be considered reliable. In calculating S values via Equation 5 3, if a tally did not meet the specified tally uncertainty criteria then it was artificially presumed t o be equal to zero and not therefore not included in the summation. The acceptable uncertain ty criteria for fetal source and maternal sources were set at <=3% and <= 10%, respectively. The rationale behind the selection of these criteria was largely personal preference. Shi et al. 42 performed similar radiation transport simulations to estimate mono energetic photon specific absorbed fractions in a set of pregnant female phantoms. The acceptable uncertainty criteria cutoff in that study was 40% to balance reasonable simulation results with acceptable computer run time. 43 Results and Discussion Several hundred Excel worksheet s of data were parsed from the post processed radiation transport simulations. A subset of those data is presented here in graphica l form to illustrate several points of interest the two principle ones being the magnitudes and trends of intra fetal irradiation vs. contributions from maternal crossfire. Comparisons were also performed with previous studies to confirm the orders of mag nitude of the simulated and calculated data sets were indeed reasonable.

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116 Intra fetal Irradiation Fetal whole body source skeletal average Figure 5 4 illustrates age dependent trends of fetal whole body self irradiation. Two significant trends in particul ar were noted : particle type and energy dependence and target mass dependence As expected, fetal self irradiation was dependent on the particle type and energy of the emitted radiation. A clear trend was observed where, for a given fetal age, the S value increases as the particle energy of the emitted radiation increases, beginning first with Ba 137m photon s and continuing through the increasing average beta energies of Cs 137 to Y 90. A substantial increase was observed for Pu 239, an alpha emitter, due to its higher linear energy transfer (LET) within the fetal tissue medium. The second trend involved a given radionuclide and the observed decrease in S value with increasing fetal age. As the fetus grows and its bones, tissues, and body increase in size, undoubtedly the absolute magnitude of deposit ed energy from internally emitted radiation is likewise increasing. However, as observed, the mass component in the denominator of the S value definition is increasing at a greater rate than the magnitude of rad iation energy deposition term in the numerator. The result is a decrease in S value as a function of age for all radionuclides. Also of n ote was the asymptotic trend of the of the S value d ata with increasing fetal age, a result of the increasing absorbed fraction being offset by the increasing target mass. Fetal whole body source individual bone sites Figures 5 5, 5 6 and 5 7 provide bone site and tissue specific S values for the 12 week, 26 week and 38 week SOLO fetal phantoms for the fetal whole body irradiating fetal whole body. Data are provided for a photon emitter (Ba137m), a beta

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117 emitter (Sr 90) and an alpha emitter (Pu 239). The variation of S values among the different skeletal sites and major soft tissues was relatively minor for all three feta l ages Also observed were the previous trends of decreasing S value with increasing age and S value magnitude dependence on particle charge and energy. Maternal Crossfire I rradiation Maternal whole body source Figure 5 8 compares age dependent fetal skele tal average S values from irradiation by fetal whole and maternal whole body. The previously discussed S value trends regarding intra fetal irradiations are observed. In contrast to intra fetal irradiation the variations in maternal source S values trends for a given age are exactly reversed. The same physics principles that previously allowed for the high energy beta electrons and Pu 239 to deposit large doses intra fetally also prevent those same particles from effectively traversing the maternal tissues between the source and fetus. As a result, the photons of I 131 and Ba 137m deposit orders of magnitude greater energy in the fetal targets. The maternal whol e body Y 90 source in Figure 5 8 exhibited some statistical noise across the different fetal ages This statistical noise is likely due to a combination of the relatively short range beta electron (with respect to the dimensions of the mother) and the rare but statistically significant production of bremsstrahlung photons. As discussed previously, a n umber of variance reduction techniques were proactively implemented in an attempt to limit such statistical noise. The techniques adopted in this work are not cure all solutions nor are they particularly powerful. Other more sophisticated variance reductio n techniques are available in MCNPX and could be

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118 explored more thoroughly in the future to help improve this type of statistical noise in upcoming projects. Maternal urinary bladder contents source Figures 5 9, 5 10, and 5 11 provide a measure of the mater nal cross fire from a nearby organ, in this case the urinary bladder. The urinary bladder was considered for metabolic removal of ingested radionuclides. Immediately clea r is the substantial relative variations in S values for a given radionuclide across different bones sites. Average variations range from ~15% to ~40%, with maximum variations peaking 100% in some cases. Variations increase with increasing age. These wide variations can be attributed to self shielding of the fetus from radiation emitted within the maternal urinary bladder. There is a clear correlation with the orientation of the fetus in the gravid uterus. Bone sites such as the cranium, cervical spine and humerus all lie within close proximity of the maternal urinary bladder due to the reference LOA fetal orientation adopted during the development of the pregnant female phantom series. Similarly, bone sites such as the sacrum and os coxae lie much further a way and their corresponding S values convey that accordingly This clear dependence on fetal orientation is not unexpected, especially at the oldest fetal age where the most fetal self shielding could occur. Although the variations for a given radionuclide in a given fetal age are somewhat striking, the overall contribution of maternal crossfire remains low. The maternal urinary bladder S values are comparable in order of magnitude to those of the maternal whole body source, which are overshadowed by the in tra fetal whole body source by one to two orders of magnitude.

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119 Maternal stomach contents source Variations in individual bone S values were observed to a lesser extent in Figures 5 1 2 5 1 3 and 5 1 4 which present the irradiation of individual fetal bones s ites and tissues by the maternal stomach contents. Similar to the maternal bladder contents source, those fetal bone sites which lie closes to the stomach exhibit the higher S values. Fetal bone sites located near the fundus of the uterus, e.g. femur, tibi a and feet, show a slight increase over neighboring bone sites. As expected, for both cases of maternal cross fire the two energetic photons yielded S values several orders of magnitude greater than their beta emitting counterpart. Comparisons with previo us studies Stabin et al. 16 designed three stylized pregnant female phantoms at 3 months, 6 months, and 9 months gestation. Similarly, Guo et al. 41 calculated monoenergetic electron SAFs for the 3 month, 6 month and 9 month NURBS based pregnant female ages presented by Xu et al. 21 Finally, Shi et al. 43 also calculated monoenergetic photon SAFs for the Xu et al 21 pregnant phantom series. Those SAF data were estimated from the cited publications and weighted using the MIRD schema 48 to estimate fetal 12 week, 26 week and 38 week S values for Y 90, I131 and Ba 137 for the following sources, r espectively: fetal whole body, maternal thyroid and maternal urinary bladder contents. Comparisons are presented in Figures 5 15, 5 16 and 5 17. All studies agreement in terms of order of magnitude. Admittedly some variation was likely introduced into the comparisons due to difficulties in estimating numerical values from small, published figures. There are likely some inherent differences to the fact that the fetus in each phantom series is largely undifferentiated. 16 18 21

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120 Previously, Sr 90, Sr 89 and Y 90 S values were calculated for the UF fetal phantom series. Wit h corresponding S values having been calculated for the derivative SOLO fetal phantom series, a simple comparison was made to determine whether the differences in S values between the two series were due solely to mass difference or if the absorbed fractio n and/or other parameters had significantly changed. The two fetal ages that were compared were 30 weeks and 38 weeks, due to their equivalent age. The UF S values for 30 weeks and 38 weeks were multiplied by the ratio of the UF target mass with the SOLO t arget mass. This mass weighting removed any dependence on target mass and isolated any differences to other reasons. Table 5 1 summaries % differences between the weight UF S values. Clearly the UF mass weighting did not provid e good agreement with the SOLO fetal series. Extensive individual bone modeling occurred during the construction of the 30 week phantom which caused significant changes geometry (and absorbed fraction) of each bone site. Recall the ribs and sternum were pa rticularly difficult bone sites to contend with from a modeling stand point and both required significant modeling changes. Contrastingly the 38 week phantom showed generally good agreement as this phantom underwent far less drastic edits during the constr uction of its 38 week SOLO cousin. Interestingly, the skeletal average of both ages showed generally good agreement. Besides the changes in bone geometry and, hence, absorbed fraction, there is another competing process, related to source volume sampling, that affects the S values of the individual bone sites. Changes in relative volume fractions have a direct effect on the MCNPX volume source sampling if the target is also part of a composite volume source e.g. whole

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121 skeleton irradiating individual bone sites Because the MCNPX tallies are normalized per starting particle, the relative number of starting particles being sampled in a particular source will be affected by changes in relative volume fractions because the relative volume fractions, by nature, exactly equivalent to the sampling probabilities. two identical volumes (e.g. two spheres). The targets of interest are the two spheres individually and the source is the combined volume of the two spheres. Presume the radiation being simulated has a low range and sphere cross fire is non existent. If 100 particle histories were to be simulated and emitted uniformly throughout the volumes of the two identical spheres, then each sphe re would the oretically be sampled 50 times due to their equal volumes. However, if one of the spheres were to increase in volume while the other remained unchanged, the number of particle histories sampled in the enlarged volume would increase proportional ly while the sampled histories in the unchanged sphere would decrease. The tally associated with the sphere, say a *F8 tally, would report a lower magnitude then before. In the case where the *F8 is subsequently converted to an S value, the magnitude of th e S value is now lower due to relative phantom volume changes that are completely independent of the radiation physics. Due to the significant changes in bone geometry in the 30 week UF fetal phantom during the construction of the 30 week fetal volume, rel ative volume fractions between bone sites necessarily changed, if only slightly, and contributed to the observed disagreement between the weight UF phantom and the SOLO phantom. The observed disagreement between individual phantoms of the UF fetal series a nd the SOLO fetal series, be they caused by mass differences, changes in absorbed

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122 fraction, or changes in relative volume fractions, it appears the development of a Urals based series of fetal computational phantoms was warranted.

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123 Table 5 1. Percent d ifference in S values of mass weighted UF fetal phantoms compared to Urals fetal phantoms. Source: whole ossified bone source irradiating ossified bone 30 weeks 38 weeks Ossified bone site Sr 90 Sr 89 Y 90 Sr 90 Sr 89 Y 90 Cranium 40% 53% 56% 2% 7% 9 % Mandible 66% 77% 88% 3% 9% 15% Scapulae 2% 2% 4% 0% 0% 1% Clavicles 52% 54% 54% 3% 12% 19% Sternum 549% 887% 1012% 9% 37% 53% Ribs 273% 411% 462% 12% 42% 58% Vertebrae cervical 44% 45% 45% 0% 2% 3% Vertebrae thoracic 45% 46% 47% 1% 3% 4% Vertebrae lumbar 44% 44% 45% 0% 1% 2% Sacrum 7% 3% 0% 1% 2% 2% Os Coxae 42% 43% 43% 0% 0% 0% Femora 36% 36% 36% 0% 1% 2% Tibiae 30% 30% 29% 0% 0% 0% Fibulae 30% 29% 28% 0% 0% 0% Ankles & f eet 83% 86% 87% 2% 5% 7% Humera 28% 28% 27% 0% 1% 2% Radii 44% 45% 46% 0% 1% 2% Ulnae 43% 44% 45% 0% 1% 2% Hands 73% 77% 79% 1% 5% 8% Skeletal average 3% 7% 8% 1% 3% 5%

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124 Figure 5 1. Dual lattice representation of the 38 week SOLO pregnant fe male phantom in MCNPX. A) Sagittal view of SOPF38WK torso. B) Zoomed display of SOPF38WK abdomen (no lattice grid). C) Zoomed display of SOPF38WK abdomen (with lattice grid)

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125 Figure 5 2. Directional biasing half angle for the SOPF38WK thyroid photon source

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126 Figure 5 3. Example of importance weighting variance reduction. Note each particle entering a neighboring material is split into the number of particle s equal to the ratio of the material importance.

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127 Figure 5 4. Irradiation of whole f etal body by whole fetal body for all radionuclides for all SOLO fetal phantoms.

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128 Figure 5 5 Skeletal average S values for all radionuclides including fetal and maternal contributions

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129 Figure 5 6. 12 week individual bone site S value variatio ns for Ba 137, Sr 90 and Pu 239 fetal whole body source (No ossified sternum at 12 weeks)

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130 Figure 5 7. 26 week individual bone site S value variations for Ba 137, Sr 90 and Pu 239 fetal whole body source

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131 Figure 5 8. 38 week individual bone si te S value variations for Ba 137, Sr 90 and Pu 239 fetal whole body source

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132 Figure 5 9. 12 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source

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133 Figure 5 10. 26 week individual bone s ite S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source

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134 Figure 5 1 1 38 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal urinary bladder content source

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135 Figure 5 12. 12 week in dividual bone site S value variations for Ba 137, I 131, and Y 90 maternal stomach content source

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136 Figure 5 13. 26 week individual bone site S value variations for Ba 137, I 131, and Y 90 maternal stomach content source

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137 Figure 5 1 4 38 week in dividual bone site S value variations for Ba 137, I 131, and Y 90 maternal stomach content source

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138 Figure 5 15. Comparisons of Y 90 fetal whole body irradiating fetal whole body S values for several phantoms

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139 Figure 5 16. Comparisons of Ba 137 m maternal urinary bladder content irradiating fetal whole body S values for several phantoms

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140 Figure 5 17. Comparisons of I 131 maternal thyroid irradiating fetal whole body S values for several phantoms

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141 CHAPTER 6 CONCLUSION S AND FUTURE WORK I n c ases where cancer and other diseases are induced by exposure to ionizing radiation, dose estimates to individual affected organs are necessary to mathematically quantify organ specific health risks. One method for obtaining dose estimates is to computation al ly simulate radiation exposures and their effects on virtual human computational T he work presented here represents significant advanc ement to the state of the art in fetal and pregnant female computational radiation dosimetry thro ugh the successful completion of the following major goals: 1) the construction of high anatomical resolution hybrid computational phantoms representing the devel oping human fetus and pregnant mother and 2) the generation of a comprehensive library of popu lation specific intra fetal and maternal radionuclide S values to be incorporated into the Epidemiological Studies of Exposed Southern Urals Populations to be used in part to estimate excess health risks associated low dose rate, chronic in utero radiation exposure. Urals Based Hybrid Computational Fetal Phantoms The successful construction of a series of hybrid computational phantoms representing the fetal population of the Urals region of modern Russia was an important goal for the funding grant (SOLO) i n order to maintain cohesion between the biokinetic models assumed within the project and the future radiation dosimetry data eventually obtained using the phantom series. A series of eight computational phantoms were developed, each matching within 1% of targeted values, representative Russian skeletal masses whole body mass es and biometry data. The phantoms were

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142 successfully converted to voxel format for representation in modern radiation transport software. Hybrid Computational Pregnant Female Phantoms An important consideration in any fetal radiation exposure scenario is the presence of the surrounding maternal tissues, which can act as a protective shield for radiation emitted towards the fetus or as sources of radiation following the biokinetic uptak e of radioactive material by the mother. A major goal of this work was the construction of a comprehensive, anatomically accurate series of hybrid computational phantoms representing the pregnant mother. This goal was achieved by virtually combining the Un iversity of Florida reference adult non pregnant female phantom with the University of Florida high resolution reference 50 th percentile fetal phantom series. The anatomical fidelity of the mother was ensured through the use of CT images of pregnant female patients. Other pregnant female computational phantoms provide only a simplistic representation of the developing fetus, either through the use of simple mathematically shapes or low resolution medical CT images. The pregnant female phantom series created in this work is superior in that aspect. Extensive efforts ensured the mother represente d the Western female pop ulation by matched reference maternal organ masses within 1% of their target values. In addition, Urals based derivatives of the pregnant femal e phantom series were constructed by replacing the fetal tissues with Urals based fetal phantom series. Radiation S values for the SOLO Radionuclides The Urals based pregnant female phantom series was successfully visualized and represented in the popular radiation transport code MCNPX as a dual lattice configuration of maternal and fetal tissues. The successful representation of this

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143 geometry permitted the simulation of a comprehensive set of radionuclide source and target combinations of interest to SOLO project for the purposes of calculation radiation S values. All simulations were performed successfully and the S values were compared, with a focus on intra fetal self dose and maternal cross fire. The completed library of Urals based S values has been i ncorporated into ongoing SOLO project efforts to improve estimates of the risks of long term health effects associated with protracted external and internal radiation exposures Intra fetal S values ranged from ~10 14 to ~10 10 Gy Bq 1 s 1 depending on fe tal age and radionuclide S values generally decreased with increasing fetal age due to increasing target masses. However the relative magnitudes of S values between different radionuclides appeared relatively constant likely due to the competing increase in absorbed fraction with increasing fetal age. For a given fetal age, changes in S value as a function of radionuclide followed expected trends, with higher S values being produced by higher LET emissions For intra fetal sources, l ittle variation in S va lue was observed among individual fetal targets for a given radionuclide and fetal age Maternal cross fire S values ranged from ~10 1 8 to ~10 14 Gy Bq 1 s 1 depending on fetal age and radionuclide. In most cases, for a given fetal age and radionuclide, t he maternal cross fire contribution was approximately two orders of magnitude lower than the intra fetal contribution. Similar to intra fetal S values, maternal cross fire S values in general decreased with increasing fetal age. In contrast, large S value variations were observed, in some cases ~100%, among individual fetal targets for maternal sources near the fetus. In addition, the variations in S values for individual fetal targets were

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144 clearly dependent on fetal position. Overall S value magnitudes and variations reduced with increasing distance of the maternal source organ from the fetus. Future Work Several immediate refinements are planned for this work. The six younger UF reference hybrid fetal phantoms currently do not include many soft tissue orga ns which are present in the older two ages, e.g. two region small intestine (wall and contents). NURBS based modeling efforts will be applied to these phantoms to bring the complete series into better anatomical agreement. In addition, the breast and outer body contours of the pregnant female phantom series are currently not finalized and will be completed prior to submission for publication. Several exciting medical and non medical applications and revisions of this work are planned One such plan is to co nstruct a comprehensive library of fetal CT dose s fo r various scan types, x ray energies maternal abdominal perimeters and fetal orientations for the purposes of quantifying CT doses for medical dose tracking. Recent advancements at the University of Flor ida have improved the accuracy of computational modeling of CT tube current modulation, a critical dose limiting component of modern radiography practices. In addition, ALRADS is currently developing software to aid clinicians in tracking real time skin an d organ doses during fluoroscopy procedures. The incorporation of the reference pregnant female phantom series into these studies could assist with fetal dose reconstructions and long term medical dose tracking. A proposal is currently be ing considered by the Radiation Effects Research Foundation (RERF), a bi national organization which studies the health effects of atomic bomb radiation. The work would involve adapting the computational pregnant female phantom series to the Japanese population for the purp oses of simulating radiation

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145 dose s received from the atomic bomb detonations. As with the SOLO project, the resulting data would be incorporated into studies investigating the health effects associated with in utero exposure to ionizing radiation. Finally, a proposal is currently under consideration by the Environmental Protection Agency (EPA) to greatly expand the radiation transport sim ulations performed in this work specifically to produce a robust library of photon and electron specific absorbed fracti on s (SAFs) for the UF pregnant female series. The completed library would allow the derivation of S values for any radionuclide or radiopharmaceutical of interest. The study would heavily incorporate the methods and findings of this work, particularly the transport methods and the observations of sensitivity of simulated radiation quantities on the orientation s of the fetus and maternal source organs. Those observations would be further investigated to include additional fetal positions beyond the reference LOA considerations of different dwell times of the fetus in those positions and variations in maternal organ morphology and distance from the fetus

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146 APPENDIX A ADDITIONAL PHANTOM DATA This ap pendix serve s to present the following tables of fetal and p regnant female phantom data that are pertinent to the research aims but are not critical to the flow of the main text: 1. Mass densities of SOLO fetal phantom tissues 2. Mass densities of UF 50 th percentile fetal phantom tissues 3. Mass densities of UF and SOLO pre gnant female tissues 4. Masses of UF 50 th percentile fetal phantom tissues 5. Voxel resolutions of the UF 50 th percentile fetal phantoms 6. Elemental compositions of UF and SOLO fetal soft tissues 7. Elemental compositions of UF spongiosa tissues 8. Elemental composition s of SOLO spongiosa tissues 9. Elemental compositions of UF and SOLO pregnant female tissues

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147 Table A 1. Mass densities (g cm 3 ) of SOLO fetal phantom tissues. Tissue SOLO08WK d SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Residual soft t issue 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Adrenal (L) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Adrenal (R) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Brain 1.02 1.02 1.02 1.02 1.02 1.02 1.03 1.03 Breast (L) n/a n/a n/a n/a n/a n/a 0.99 0.99 Bronchi 1. 07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Whole colon wall 1.03 1.03 1.03 1.03 1.03 1.03 n/a n/a Whole colon cont. 1.00 1.00 1.00 1.00 1.00 1.00 n/a n/a Right colon wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Right colon cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Esophagus 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Eye balls 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Gall bladder wall 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Gall bladder cont. n/a n/a n/a n/a n/a n/a 1.03 1.03 Whole heart 1.04 1.04 1.04 1.04 1.04 1.0 4 1.04 1.04 Whole kidney (L) n/a n/a n/a n/a n/a n/a n/a n/a Whole kidney (R) n/a n/a n/a n/a n/a n/a n/a n/a Kidney cortex (L) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Kidney cortex (R) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Kidney medulla (L) n/a n/ a n/a n/a n/a n/a 1.03 1.03 Kidney medulla (R) n/a n/a n/a n/a n/a n/a 1.03 1.03 Kidney pelvis (L) n/a n/a n/a n/a n/a n/a 1.03 1.03 Kidney pelvis (R) n/a n/a n/a n/a n/a n/a 1.03 1.03 Larynx n/a n/a n/a n/a n/a n/a 1.07 1.07 Lens n/a n/a n/a n/a n/a n/a 1.07 1.07 Liver 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Lung (L) 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Lung (R) 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Nasal layer (ant.) n/a n/a n/a n/a n/a n/a 1.03 1.03

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148 Table A 1. Continued Tissue SOLO08WK d S OLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Nasal layer (post.) n/a n/a n/a n/a n/a n/a 1.03 1.03 Oral cavity layer n/a n/a n/a n/a n/a n/a 1.03 1.03 Ovary (L) 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 Pancreas 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Penis n/a n/a n/a n/a n/a n/a 1.05 1.05 Pharynx n/a n/a n/a n/a n/a n/a 1.03 1.03 Pituitary gland n/a n/a n/a n/a n/a n/a 1.03 1.03 Prostate n/a n/a n/a 1.03 1.03 1.03 1.03 1.03 Rectosigmoid wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Recto sigmoid cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Salivary glands (parot.) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Scrotum n/a n/a n/a n/a n/a n/a 1.03 1.03 SI wall and cont. 1.03 1.03 1.03 1.03 1.03 1.03 n/a n/a SI wall n/a n/a n/a n/a n/a n/a 1.03 1.03 SI cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Skin 1.02 1.02 1.02 1.02 1.02 1.10 1.10 1.10 Spinal cord 1.02 1.02 1.02 1.02 1.02 1.02 1.03 1.03 Spleen 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Stomach wall 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Stomach c ont. 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Testes 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Thymus 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Thyroid 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 Tongue n/a n/a n/a n/a n/a n/a 1.05 1.05 Tonsil n/a n/a n/a n/a n/a n/a 1.03 1.03 Trachea 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Urinary bladder wall 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Urinary bladder cont. 1.01 1.01 1.01 1.01 1.01 1.01 1.01 1.01 Uterus 1.03 1.03 1.03 1.03 1.03 1.03 1.05 1.05

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149 Table A 1. Con tinued Tissue SOLO08WK d SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK Fluid (in body) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Left colon wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Left colon cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Salivary glands (mand.) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Salivary glands (ling.) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Breast (R) n/a n/a n/a n/a n/a n/a 0.99 0.99 Ovary (R) 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 c Cranium 1.10 1.10 1.10 1.10 1.10 1. 10 1.10 1.10 c Mandible 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Scapulae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Clavicles 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Sternum 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Ribs 1.10 1.10 1.10 1.10 1.10 1. 10 1.10 1.10 c Cervical discs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Thoracic discs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Lumbar discs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Sacrum 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Os coxae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Femora 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Tibiae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Fibulae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Patellae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Feet 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Humeri 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Radii 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Ulnae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Hands & wrists 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Cranial fontanelles 1 .10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Costal cartilage 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10

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150 Table A 1. Continued Tissue SOLO08WK d SOLO12WK SOLO18WK SOLO22WK SOLO26WK SOLO30WK SOLO34WK SOLO38WK c Cerv. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Thor. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Lumb. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 sp Cranium n/a 1.15 1.22 1.27 1.32 1.36 1.41 1.46 sp Mandible n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Scapulae n/a 1.14 1.19 1.2 3 1.26 1.30 1.33 1.37 sp Clavicles n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Sternum n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Ribs n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Cerv. vertebrae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Thor. vertebrae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Lumb. vertebrae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Sacrum n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Os coxae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Femora n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Tibia e n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Fibulae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Patellae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Ankle & feet n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Humera n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Ra dii n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Ulnae n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 sp Hands & wrists n/a 1.14 1.19 1.23 1.26 1.30 1.33 1.37 a Only whole organ modeled for 8 30 weeks; organ partitioned into sub regions for 3 4 38 weeks. b Small inte stine wall and contents modeled as single homogenous volume for 8 30 weeks; explicitly modeled for 3 4 38 weeks. c Salivary glands partitioned into parotid, submandibular and sublingual regions. d SOLO 8 week phantom (SOLO08WK) identical to UF 8 week 50 th per centile phantom (UFHF08WK) n/a Tissue is not explicitly modeled, not present at given fetal age, or partitioned into sub regions (e.g. colon, small intestine, kidney). c Indicates cartilage/fibrous tissue region of bone site. sp Indicates spongiosa/homog enous bone region of bone site.

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151 Table A 2. Mass densities (g cm 3 ) of the UF 50 th percentile fetal phantom tissues. Tissue UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK Residual soft tissue 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1. 03 Adrenal (L) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Adrenal (R) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Brain 1.02 1.02 1.02 1.02 1.02 1.02 1.03 1.03 Breast (L) n/a n/a n/a n/a n/a n/a 0.99 0.99 Bronchi 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Whol e colon wall 1.03 1.03 1.03 1.03 1.03 1.03 n/a n/a Whole colon cont. 1.00 1.00 1.00 1.00 1.00 1.00 n/a n/a Right colon wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Right colon cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Esophagus 1.03 1.03 1.03 1.03 1.03 1.03 1. 03 1.03 Eye balls 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Gall bladder wall 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Gall bladder cont. n/a n/a n/a n/a n/a n/a 1.03 1.03 Whole heart 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Whole kidney (L) n/a n/a n/a n /a n/a n/a n/a n/a Whole kidney (R) n/a n/a n/a n/a n/a n/a n/a n/a Kidney cortex (L) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Kidney cortex (R) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Kidney medulla (L) n/a n/a n/a n/a n/a n/a 1.03 1.03 Kidney medulla (R) n/a n/a n/a n/a n/a n/a 1.03 1.03 Kidney pelvis (L) n/a n/a n/a n/a n/a n/a 1.03 1.03 Kidney pelvis (R) n/a n/a n/a n/a n/a n/a 1.03 1.03 Larynx n/a n/a n/a n/a n/a n/a 1.07 1.07 Lens n/a n/a n/a n/a n/a n/a 1.07 1.07 Liver 1.04 1.04 1.04 1.04 1. 04 1.04 1.04 1.04 Lung (L) 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Lung (R) 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Nasal layer (ant.) n/a n/a n/a n/a n/a n/a 1.03 1.03

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152 Table A 2. Continued Tissue UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK Nasal layer (post.) n/a n/a n/a n/a n/a n/a 1.03 1.03 Oral cavity layer n/a n/a n/a n/a n/a n/a 1.03 1.03 Ovary (L) 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 Pancreas 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Penis n/a n/a n/a n/a n/a n /a 1.05 1.05 Pharynx n/a n/a n/a n/a n/a n/a 1.03 1.03 Pituitary gland n/a n/a n/a n/a n/a n/a 1.03 1.03 Prostate n/a n/a n/a 1.03 1.03 1.03 1.03 1.03 Rectosigmoid wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Rectosigmoid cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Salivary glands (parot.) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Scrotum n/a n/a n/a n/a n/a n/a 1.03 1.03 SI wall and cont. 1.03 1.03 1.03 1.03 1.03 1.03 n/a n/a SI wall n/a n/a n/a n/a n/a n/a 1.03 1.03 SI cont. n/a n/a n/a n/a n/a n/a 1.00 1.0 0 Skin 1.02 1.02 1.02 1.02 1.02 1.10 1.10 1.10 Spinal cord 1.02 1.02 1.02 1.02 1.02 1.02 1.03 1.03 Spleen 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Stomach wall 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Stomach cont. 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.0 0 Testes 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Thymus 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Thyroid 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 Tongue n/a n/a n/a n/a n/a n/a 1.05 1.05 Tonsil n/a n/a n/a n/a n/a n/a 1.03 1.03 Trachea 1.07 1.07 1.07 1 .07 1.07 1.07 1.07 1.07 Urinary bladder wall 1.04 1.04 1.04 1.04 1.04 1.04 1.04 1.04 Urinary bladder cont. 1.01 1.01 1.01 1.01 1.01 1.01 1.01 1.01 Uterus 1.03 1.03 1.03 1.03 1.03 1.03 1.05 1.05

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153 Table A 2. Continued Tissue UFHF 08WK d UFHF10 WK UFHF15 WK U FHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK Fluid (in body) 1.00 1.00 1.00 1.00 1.00 1.00 1.00 1.00 Left colon wall n/a n/a n/a n/a n/a n/a 1.03 1.03 Left colon cont. n/a n/a n/a n/a n/a n/a 1.00 1.00 Salivary glands (mand.) 1.03 1.03 1.03 1.03 1.03 1. 03 1.03 1.03 Salivary glands (ling.) 1.03 1.03 1.03 1.03 1.03 1.03 1.03 1.03 Breast (R) n/a n/a n/a n/a n/a n/a 0.99 0.99 Ovary (R) 1.05 1.05 1.05 1.05 1.05 1.05 1.05 1.05 c Cranium 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Mandible 1.10 1.10 1.10 1.1 0 1.10 1.10 1.10 1.10 c Scapulae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Clavicles 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Sternum 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Ribs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Cervical discs 1.10 1.10 1. 10 1.10 1.10 1.10 1.10 1.10 c Thoracic discs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Lumbar discs 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Sacrum 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Os coxae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Femora 1. 10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Tibiae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Fibulae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Patellae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Feet 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Humeri 1.10 1. 10 1.10 1.10 1.10 1.10 1.10 1.10 c Radii 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Ulnae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Hands & wrists 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Cranial fontanelles 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c C ostal cartilage 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10

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154 Table A 2. Continued Tissue UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK c Cerv. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Thor. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 c Lumb. vertebrae 1.10 1.10 1.10 1.10 1.10 1.10 1.10 1.10 sp Cranium n/a 1.12 1.18 1.24 1.30 1.36 1.42 1.46 sp Mandible n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Scapulae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Clavicles n/a 1.1 2 1.16 1.21 1.25 1.30 1.34 1.37 sp Sternum n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Ribs n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Cerv. vertebrae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Thor. vertebrae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Lum b. vertebrae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Sacrum n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Os coxae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Femora n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Tibiae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 s p Fibulae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Patellae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Ankle & feet n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Humera n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Radii n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Ulnae n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 sp Hands & wrists n/a 1.12 1.16 1.21 1.25 1.30 1.34 1.37 a Only whole organ modeled for 8 30 weeks; organ partitioned into sub regions for 35 38 weeks. b Small intestine wall and contents modeled as single h omogenous volume for 8 30 weeks; explicitly modeled for 35 38 weeks. c Salivary glands partitioned into parotid, submandibular and sublingual regions. d UF 8 week 50 th percentile phantom (UFHF08WK) identical to 8 week SOLO phantom (SOLO08WK) n/a Tissue is no t explicitly modeled, not present at given fetal age, or partitioned into sub regions (e.g. colon, small intestine, kidney). c Indicates cartilage/fibrous tissue region of bone site. sp Indicates spongiosa/homogenous bone region of bone site.

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155 Table A 3 Mass densities (g cm 3 ) of UF and SOLO pregnant female phantom maternal tissues (all fetal ages). Tissue Density (g cm 3 ) Tissue Density (g cm 3 ) Tissue Density (g cm 3 ) Adipose tissue 0.960 Testes 1.040 cb Humerus proximal 1.900 Adrenal (L) 1.02 0 Thymus 1.030 cb Humerus upper shaft 1.900 Adrenal (R) 1.020 Thyroid 1.050 cb Humerus lower shaft 1.900 Brain 1.040 Tongue 1.050 cb Humerus distal 1.900 Breast(adipose) 0.940 Tonsil 1.020 cb Radii proximal 1.900 Bronchi 1.070 Trachea 1.070 c b Radii shaft 1.900 Right colon wall 1.030 Urinary bladder wall 1.040 cb Radii distal 1.900 Right colon cont. 1.020 Urinary bladder cont. 1.010 cb Ulnae proximal 1.900 Ears 1.100 Uterine wall 1.050 cb Ulnae shaft 1.900 Esophagus 1.030 Air (in bo dy) 0.001 cb Ulnae distal 1.900 External nose 1.050 Left colon wall 1.030 cb Hand 1.900 Eye balls 1.020 Left colon cont. 1.020 cb Teeth 3.000 Gall bladder wall 1.020 Salivary glands (mand.) a 1.020 sp Cranium 1.600 Gall bladder cont. 1.020 Saliv ary glands (ling.) a 1.020 sp Mandible 1.131 Heart wall 1.050 Arteries 1.060 sp Scapulae 1.047 Heart cont. 1.060 Veins 1.060 sp Clavicles 1.067 Kidney cortex (L) 1.050 Muscle 1.050 sp Sternum 1.086 Kidney cortex (R) 1.050 Breast (glandular) 1.05 0 sp Ribs 1.093 Kidney medulla (L) 1.050 Amniotic fluid 1.000 sp Vertebrae cervical 1.170 Kidney medulla (R) 1.050 Placenta 1.030 sp Vertebrae thoracic 1.114 Kidney pelvis (L) 1.050 Costal cartilage 1.100 sp Vertebrae lumbar 1.126 Kidney pelvis (R) 1.050 Cervical discs 1.100 sp Sacrum 1.138 Larynx 1.070 Thoracic discs 1.100 sp Os coxae 1.046 Lens 1.070 Lumbar discs 1.100 sp Femora proximal 1.199 Liver 1.060 cb Cranium 1.900 mc Femora upper shaft 0.989 Lung (l) 0.340 cb Mandible 1.900 mc Femora lower shaft 0.981 Lung (r) 0.340 cb Scapulae 1.900 sp Femora distal 1.164 Nasal layer (ant.) 1.020 cb Clavicles 1.900 sp Tibiae proximal 1.123

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156 Table A 3 Continued Tissue Density (g cm 3 ) Tissue Density (g cm 3 ) Tissue Density (g c m 3 ) Nasal layer (post.) 1.020 cb Sternum 1.900 mc Tibiae shaft 0.981 Oral cavity layer 1.020 cb Ribs 1.900 sp Tibiae distal 1.135 Ovaries 1.050 cb Vertebrae cervical 1.900 sp Fibulae proximal 1.091 Pancreas 1.020 cb Vertebrae thoracic 1.900 mc Fibulae shaft 0.981 Penis 1.050 cb Vertebrae lumbar 1.900 sp Fibulae distal 1.144 Pharynx 1.030 cb Sacrum 1.900 sp Patellae 1.149 Pituitary gland 1.020 cb Os coxae 1.900 sp Ankle+feet 1.063 Prostate 1.030 cb Femur proximal 1.900 sp Humera prox imal 1.080 Rectosigmoid wall 1.030 cb Femur upper shaft 1.900 mc Humera upper shaft 0.989 Rectosigmoid cont. 1.020 cb Femur lower shaft 1.900 mc Humera lower shaft 0.981 Salivary glands (parot.) a 1.020 cb Femur distal 1.900 sp Humera distal 1.135 Scrotum 1.030 cb Tibiae proximal 1.900 sp Radii proximal 1.089 Si wall 1.030 cb Tibiae shaft 1.900 mc Radii shaft 0.981 Si cont. 0.520 cb Tibiae distal 1.900 sp Radii distal 1.101 Skin 1.100 cb Fibulae proximal 1.900 sp Ulnae proximal 1.223 Sp inal cord 1.040 cb Fibulae shaft 1.900 mc Ulnae shaft 0.981 Spleen 1.060 cb Fibulae distal 1.900 sp Ulnae distal 1.016 Stomach wall 1.030 cb Patellae 1.900 sp Hands 1.062 Stomach cont. 1.020 cb Ankle+feet 1.900 a Salivary glands partitioned in to parotid, submandibular and sublingual regions. cb Indicates cortical bone. sp Indicates spongiosa. mc Indicates medullary cavity.

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15 7 Table A 4. UF 50 th percentile fetal phantom voxel masses Fetal Tissue Fetal tissue mass (g) UFHF08WK d UFHF10WK UFHF 15WK UFHF20WK UFHF25WK UFHF30WK UFHF35WK UFHF38WK Residual soft tissue 1.773E+00 1.220E+01 8.026E+01 2.745E+02 6.185E+02 1.077E+03 1.491E+03 1.904E+03 Adrenal (L) 9.414E 03 4.582E 02 3.190E 01 8.628E 01 1.284E+00 1.568E+00 3.24 1E+00 2.950E+00 Adrenal (R) 1.040E 02 5.329E 02 3.194E 01 8.638E 01 1.289E+00 2.496E+00 3.210E+00 4.799E+00 Brain 6.984E 01 3.193E+00 2.282E+01 6.377E+01 1.180E+02 2.064E+02 3.188E+02 3.678E+02 Breast (L) n/a n/a n/a n/a n/a n/a 3.658E 02 4.434E 02 Bronchi 3.790E 04 2.460E 03 1.220E 02 4.610E 02 8.906E 02 1.298E 01 3.654E 01 4.574E 01 Whole colon wall a 3.593E 03 2.852E 02 1.293E 01 4.248E 01 8.231E 01 1.202E+00 n/a n /a Whole colon cont. a 2.760E 03 2.175E 02 1.000E 01 3.282E 01 6.346E 01 9.262E 01 n/a n/a Right colon wall a n/a n/a n/a n/a n/a n/a 5.129E+00 6.487E+00 Right colon cont. a n/a n/a n/a n/a n/a n/a 1.120E+01 1.411E+01 Esophagus 2.616E 03 1.651E 02 8.982E 02 2.972E 01 5.750E 01 8.359E 01 1.544E+00 1.982E+00 Eye balls 1.555E 02 7.111E 02 3.426E 01 9.773E 01 1.868E+00 3.030E+00 4.974E+00 5.857E+00 Gall bladder wall 1.311E 03 8.654E 03 5.727E 02 1.881E 01 3.644E 01 5.310E 01 3.942E 01 4.960E 01 Gall bladder cont. n/a n/a n/a n/a n/a n/a 2.216E+00 2.794E+00 Whole heart 6.846E 02 1.485E 01 1.098E+00 3.373E+00 6.259E+00 1.078E+01 1.755E+01 2.025E+01 Whole kidney (L) a 5.778E 03 6.859E 02 6.475E 01 2.107E+00 4.246E+00 6.803E+00 n/a n/a Whole kidney (R) a 7.784E 03 9.097E 02 6.496E 01 2.119E+00 4.261E+00 8.130E+00 n/a n/a Kidney cortex (L) a n/a n/a n/a n/a n/a n/a 7.898E+00 9.009E+00 Kidney cortex (R) a n/a n/a n/a n/a n/a n/a 7.839E +00 8.956E+00 Kidney medulla (L) a n/a n/a n/a n/a n/a n/a 2.800E+00 3.204E+00 Kidney medulla (R) a n/a n/a n/a n/a n/a n/a 2.781E+00 3.171E+00 Kidney pelvis (L) a n/a n/a n/a n/a n/a n/a 5.667E 01 6.525E 01 Kidney pelv is (R) a n/a n/a n/a n/a n/a n/a 5.627E 01 6.465E 01 Larynx n/a n/a n/a n/a n/a n/a 1.025E+00 1.300E+00 Lens n/a n/a n/a n/a n/a n/a 1.123E 01 1.259E 01 Liver 3.964E 0 1 1.009E+00 7.133E+00 2.256E+01 3.776E+01 6.112E+01 1.039E+02 1.298E+02 Lung (L) 2.751E 02 2.087E 01 2.227E+00 5.849E+00 1.002E+01 1.504E+01 2.178E+01 2.345E+01 Lung (R) 3.673E 02 2.875E 01 2.434E+00 6.052E+00 1.041E+01 1.593E+01 2.514E+01 2.700E+01 Nasal layer (ant.) n/a n/a n/a n/a n/a n/a 5.944E 02 9.890E 02

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158 Table A 4. Continued Fetal Tissue Fetal tissue mass (g) UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK Nasal laye r (post.) n/a n/a n/a n/a n/a n/a 8.954E 01 1.096E+00 Oral cavity layer n/a n/a n/a n/a n/a n/a 6.257E 01 7.276E 01 Ovary (L) 6.559E 04 4.350E 03 2.017E 02 6.603E 02 8.386E 02 1.006E 01 1.174E 01 1.503E 01 Pancreas 4.034E 04 2.762E 02 1.955E 01 5.989E 01 1.006E+00 1.761E+00 2.836E+00 3.640E+00 Penis n/a n/a n/a n/a n/a n/a 4.816E 01 6.111E 01 Pharynx n/a n/a n/a n/a n/a n/a 2.636E 01 3.679E 01 Pituitary gla nd n/a n/a n/a n/a n/a n/a 8.340E 02 1.001E 01 Prostate n/a n/a n/a 3.062E 03 5.640E 03 8.287E 03 6.289E 01 7.985E 01 Rectosigmoid wall a n/a n/a n/a n/a n/a n/a 2.823E+00 3.562E+00 Rectosigmoid cont. a n/a n/a n/a n/a n/a n/a 8.685E+00 1.101E+01 Salivary glands (parot.) c 1.797E 03 8.201E 03 5.237E 02 2.942E 01 5.622E 01 9.132E 01 2.957E+00 3.475E+00 Scrotum n/a n/a n/a n/a n/a n/a 9.741E 01 1.237E+00 SI wall and cont. b 1.861E 02 3.540E 01 1.017E+00 3.204E+00 6.538E+00 1.105E+01 n/a n/a SI wall b n/a n/a n/a n/a n/a n/a 2.267E+01 2.861E+01 SI cont. b n/a n/a n/a n/a n/a n/a 2.389E+01 3.011E+01 Skin 8.688E 02 6.326E 01 3.827E+00 1.157E+01 2.372E+ 01 4.692E+01 8.601E+01 1.071E+02 Spinal cord 3.322E 03 2.190E 02 1.863E 01 6.140E 01 1.237E+00 1.729E+00 4.404E+00 6.586E+00 Spleen 8.507E 04 1.000E 02 1.495E 01 6.598E 01 1.771E+00 4.374E+00 8.086E+00 1.018E+01 Stomach wall 5.72 9E 03 3.788E 02 8.841E 02 2.907E 01 5.629E 01 8.146E 01 5.529E+00 6.979E+00 Stomach cont. 7.625E 03 5.044E 02 1.096E 01 3.604E 01 6.977E 01 1.018E+00 1.947E+01 2.457E+01 Testes 1.427E 03 9.455E 03 1.174E 02 3.829E 02 7.414E 02 1 .087E 01 6.718E 01 8.455E 01 Thymus 5.415E 04 9.983E 03 1.998E 01 9.177E 01 2.366E+00 4.905E+00 8.953E+00 1.019E+01 Thyroid 3.323E 03 2.192E 02 7.648E 02 1.785E 01 3.596E 01 6.365E 01 9.956E 01 1.293E+00 To ngue n/a n/a n/a n/a n/a n/a 2.961E+00 3.493E+00 Tonsil n/a n/a n/a n/a n/a n/a 8.505E 02 9.800E 02 Trachea 1.005E 03 6.498E 03 3.702E 02 1.219E 01 2.367E 01 3.430E 01 3.899E 01 5.057 E 01 Urinary bladder wall 9.680E 04 6.402E 03 5.103E 02 1.688E 01 3.264E 01 4.763E 01 3.149E+00 3.985E+00 Urinary bladder cont. 5.271E 04 3.496E 03 6.211E 02 2.035E 01 3.951E 01 5.726E 01 7.541E+00 9.502E+00 Uterus 1 .055E 03 6.994E 03 4.162E 02 1.369E 01 2.648E 01 3.838E 01 3.162E+00 3.987E+00

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159 Table A 4. Continued Fetal Tissue Fetal tissue mass (g) UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK Fluid (in body) 8.560E 04 5.810E 03 2.630E 02 8.961E 02 1.730E 01 2.522E 01 1.575E+00 1.949E+00 Left colon wall a n/a n/a n/a n/a n/a n/a 5.267E+00 6.609E+00 Left colon cont. a n/a n/a n/a n/a n/a n/a 1.393E+01 1.756E+01 Salivary glands (mand.) c 9.286E 0 4 4.247E 03 2.681E 02 1.518E 01 2.898E 01 4.662E 01 1.525E+00 1.797E+00 Salivary glands (ling.) c 3.602E 04 1.643E 03 1.060E 02 5.955E 02 1.132E 01 1.827E 01 5.876E 01 6.872E 01 Breast (R) n/a n/a n/a n/a n/a n/a 3.523E 02 4.376E 02 O vary (R) 6.575E 04 4.333E 03 2.007E 02 6.606E 02 8.403E 02 1.008E 01 1.202E 01 1.503E 01 c Cranium 1.016E 01 4.505E 01 8.722E+00 1.659E+01 2.776E+01 4.021E+01 4.792E+01 5.443E+01 c Mandible 1. 278E 02 4.478E 02 3.877E 01 9.416E 01 1.542E+00 2.228E+00 3.372E+00 3.781E+00 c Scapulae 1.928E 02 8.850E 02 2.618E 01 7.251E 01 1.257E+00 1.968E+00 2.522E+00 3.186E+00 c Clavicles 1.733E 02 8.162E 02 3.832E 02 1.20 4E 01 2.222E 01 3.095E 01 1.216E+00 1.376E+00 c Sternum 2.619E 03 1.529E 02 2.406E 01 7.596E 01 1.422E+00 2.315E+00 1.146E+00 1.449E+00 c Ribs 3.034E 02 1.428E 01 6.323E 01 1.918E+00 3.101E+00 4.641E+00 7.810E +00 6.282E+00 c Cervical discs n/a n/a 3.726E 02 1.233E 01 2.379E 01 3.426E 01 8.054E 02 1.005E 01 c Thoracic discs n/a n/a 8.885E 02 2.946E 01 5.656E 01 8.231E 01 5.543E 01 6.911E 01 c Lumbar discs n/a n/a 4. 963E 02 1.641E 01 3.125E 01 4.555E 01 4.306E 01 5.532E 01 c Sacrum 1.484E 02 9.499E 02 2.612E 01 8.445E 01 1.548E+00 1.878E+00 3.059E+00 2.804E+00 c Os coxae 2.069E 02 1.190E 01 5.994E 01 1.715E+00 3.261E+00 4.14 1E+00 7.257E+00 7.797E+00 c Femora 1.820E 02 1.522E 01 9.761E 01 2.937E+00 5.260E+00 4.946E+00 6.941E+00 5.911E+00 c Tibiae 1.054E 02 7.954E 02 4.470E 01 1.376E+00 2.549E+00 3.209E+00 3.480E+00 3.774E+00 c Fibulae 9.737 E 04 7.889E 03 8.128E 02 2.419E 01 4.600E 01 6.364E 01 1.520E+00 1.797E+00 c Patellae 1.667E 03 1.113E 02 6.341E 02 2.102E 01 4.071E 01 5.930E 01 2.160E 01 2.715E 01 c Feet 5.470E 04 3.139E 03 4.180E 02 1.399E 01 2.668E 01 3.879E 01 3.788E+00 4.769E+00 c Humeri 1.434E 02 1.245E 01 4.408E 01 1.270E+00 2.324E+00 2.966E+00 3.831E+00 3.943E+00 c Radii 1.967E 03 1.416E 02 7.926E 02 2.202E 01 4.046E 01 5.654E 01 1.368E+00 1.660E+00 c Ulnae 2.430E 03 1.79 6E 02 1.079E 01 3.275E 01 5.966E 01 8.626E 01 1.707E+00 2.150E+00 c Hands & wrists 1.883E 03 1.134E 02 6.495E 02 2.221E 01 4.190E 01 6.026E 01 3.735E+00 4.630E+00 c Cranial fontanelles n/a n/a n/a n/a n/a n/a 1.344E+01 1.577E+01 c Costal cartilage 1.422E 02 8.272E 02 8.028E 01 2.643E+00 5.044E+00 7.623E+00 9.519E+00 1.199E+01

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160 Table A 4. Continued Fetal Tissue Fetal tissue mass (g) UFHF 08WK d UFHF10 WK UFHF15 WK UFHF20 WK UFHF25 WK UFHF 30WK UFHF35 WK UFHF 38WK c Cerv. vertebrae 2.496 E 02 1.562E 01 4.351E 01 1.345E+00 2.482E+00 3.521E+00 3.950E+00 4.933E+00 c Thor. vertebrae 4.761E 02 3.021E 01 9.622E 01 3.013E+00 5.771E+00 8.285E+00 7.538E+00 9.474E+00 c Lumb. vertebrae 2.618E 02 1.640E 01 5.486E 01 1.702E+00 3.182E+00 4.451E+ 00 4.490E+00 5.636E+00 sp Cranium n/a 1.455E 02 1.861E+00 1.198E+01 3.163E+01 5.821E+01 1.017E+02 1.267E+02 sp Mandible n/a 1.408E 02 2.732E 01 9.964E 01 2.259E+00 4.128E+00 7.632E+00 9.386E+00 sp Scapulae n/a 4.012E 02 2.451E 01 9.826E 01 2.147E+00 3.954E+00 5.511E+00 7.123E+00 sp Clavicles n/a 3.353E 02 2.593E 02 9.467E 02 2.021E 01 3.231E 01 1.673E+00 2.359E+00 sp Sternum n/a n/a n/a 3.184E 02 1.079E 01 3 .192E 01 5.425E 01 7.031E 01 sp Ribs n/a 3.480E 02 4.552E 01 1.747E+00 4.156E+00 9.280E+00 1.926E+01 2.927E+01 sp Cerv. vertebrae n/a 8.322E 03 6.865E 02 3.288E 01 7.967E 01 1.322E+00 8.181E+00 1.053E+01 sp Thor. vertebrae n/a 1.2 86E 02 1.543E 01 6.930E 01 1.467E+00 2.335E+00 1.471E+01 1.898E+01 sp Lumb. vertebrae n/a 8.839E 03 9.443E 02 4.393E 01 1.018E+00 1.753E+00 9.291E+00 1.199E+01 sp Sacrum n/a 3.173E 03 1.788E 02 8.091E 02 2.623E 01 8.384E 01 3.1 97E+00 5.463E+00 sp Os coxae n/a 1.821E 02 3.120E 01 1.363E+00 2.797E+00 4.714E+00 1.221E+01 1.751E+01 sp Femora n/a 3.663E 02 4.680E 01 1.813E+00 4.149E+00 6.073E+00 1.501E+01 2.091E+01 sp Tibiae n/a 2.157 E 02 2.743E 01 1.074E+00 2.377E+00 4.312E+00 7.238E+00 1.131E+01 sp Fibulae n/a 1.524E 03 4.440E 02 1.802E 01 3.667E 01 5.882E 01 1.775E+00 2.544E+00 sp Patellae n/a n/a n/a n/a n/a n/a n/a n/a sp Ankle & feet n/a 3.464E 03 5.498E 02 1.880E 01 3.759E 01 5.695E 01 4.557E+00 5.883E+00 sp Humeri n/a 3.182E 02 2.294E 01 9.057E 01 2.000E+00 3.563E+00 7.097E+00 1.034E+01 sp Radii n/a 7.147E 03 6.865E 02 2.454E 01 5.213E 01 8.21 9E 01 2.225E+00 2.869E+00 sp Ulnae n/a 8.284E 03 9.385E 02 3.768E 01 7.964E 01 1.244E+00 2.883E+00 3.731E+00 sp Hands & wrists n/a 1.809E 02 8.730E 02 2.985E 01 5.960E 01 8.979E 01 3.082E+00 3.954E+00 Total fetal mass 3.58E+00 2.117E+ 01 1.460E+02 4.678E+02 9.857E+02 1.693E+03 2.645E+03 3.303E+03 a Only whole organ modeled for 8 30 weeks; organ partitioned into sub regions for 35 38 weeks. b Small intestine wall and contents modeled as single homogenous volume for 8 30 weeks; explicitl y modeled for 35 38 weeks. c Salivary glands partitioned into parotid, submandibular and sublingual regions. d UF 8 week 50 th percentile phantom (UFHF08WK) identical to 8 week SOLO phantom (SOLO08WK) n/a: Tissue is not explicitly modeled, not present at giv en fetal age, or partitioned into sub regions (e.g. colon, small intestine, kidney). c : Indicates cartilage/fibrous tissue region of bone site.

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161 sp : Indicates spongiosa/homogenous ossified region of bone site.

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162 Table A 5 Voxel resolutions and matrix si zes of voxelized UF 50 th percentile fetal phantoms Voxel Resolution (cm) Number of Voxels Phantom X Y Z X Y Z Total (x10 6 ) UFHF 08WK 0.0065 0.0065 0.0065 332 453 367 55.20 UFHF10 WK 0.01141 0.01141 0.01141 253 400 539 54.55 UFHF15WK 0.0206 0.0206 0.020 6 250 430 475 51.06 UFHF20WK 0.0301 0.0301 0.0301 258 427 487 53.65 UFHF25WK 0.0381 0.0381 0.0381 258 424 475 51.96 UFHF30WK 0.0471 0.0471 0.0471 304 409 437 54.33 UFHF35WK 0.0611 0.0611 0.0611 287 346 543 53.92 UFHF38WK 0.0664 0.0664 0.0664 282 343 5 36 51.85

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163 Table A 6. Elemental compositions of the UF and SOLO fetal soft tissues Elemental composition (% by mass) Tissue Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine Adrenals 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Tongue 10.80 4.90 1.30 82.10 0.20 0.00 0.10 0.10 0.30 0.00 0.20 0.00 0.00 0.00 Esophagus 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Stomach 10.60 11.50 2.2 0 75.10 0.10 0.00 0.10 0.10 0.20 0.00 0.10 0.00 0.00 0.00 Small Intestine 10.60 11.50 2.20 75.10 0.10 0.00 0.10 0.10 0.20 0.00 0.10 0.00 0.00 0.00 Large Intestine 10.60 11.50 2.20 75.10 0.10 0.00 0.10 0.10 0.20 0.00 0.10 0.00 0.00 0.00 Liver 10.50 9.10 2.10 77.40 0.20 0.00 0.20 0.10 0.20 0.00 0.20 0.00 0.00 0.00 Gall bladder 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Pancreas 10.60 16.90 2.20 69.40 0.20 0.00 0.20 0.10 0.20 0.00 0.20 0.00 0.00 0.00 Brain 10.90 7.30 2.20 79 .20 0.10 0.00 0.10 0.10 0.20 0.00 0.20 0.00 0.20 0.00 Heart 10.60 7.50 1.80 79.30 0.20 0.00 0.10 0.10 0.20 0.00 0.20 0.00 0.00 0.00 Eye 9.60 19.50 5.70 64.60 0.10 0.00 0.10 0.30 0.10 0.00 0.00 0.00 0.00 0.00 Residual Soft Tissue 10.60 16.30 2.00 71.00 0 .00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Skin 10.80 5.10 1.20 82.10 0.20 0.00 0.10 0.10 0.30 0.00 0.10 0.00 0.00 0.00 Pituitary gland 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Trachea 10.60 16.30 2.00 71.00 0.00 0. 00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Larynx 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 Lung 10.60 7.60 1.80 79.20 0.20 0.00 0.20 0.10 0.20 0.00 0.10 0.00 0.00 0.00 Spleen 10.50 8.60 2.40 77.60 0.20 0.00 0.20 0.10 0.20 0 .00 0.20 0.00 0.00 0.00 Thymus 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Thyroid 10.40 11.90 2.40 74.50 0.20 0.00 0.10 0.10 0.20 0.00 0.10 0.00 0.00 0.10 Tonsils 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0. 00 0.00 0.00 Kidney 10.70 6.40 1.60 80.40 0.20 0.00 0.20 0.10 0.00 0.20 0.20 0.00 0.00 0.00 Urinary 10.50 9.60 2.60 76.10 0.20 0.00 0.20 0.20 0.30 0.00 0.30 0.00 0.00 0.00 Breast 11.10 29.70 0.90 58.00 0.10 0.00 0.10 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Prostate 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Ovaries 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Uterus 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Cartilage 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 Water 11.20 88.80 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 Lens 9.60 19.50 5.70 64.60 0.10 0.00 0.10 0.30 0.10 0.00 0.00 0.00 0.00 0.00 Nasal layers 10.60 16.30 2. 00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Oral cavity layer 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Pharynx 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Sal glands 10.60 16.30 2.00 71.00 0.00 0.00 0.00 0.10 0.00 0.00 0.00 0.00 0.00 0.00 Spinal cord 10.80 5.50 1.10 81.60 0.20 0.00 0.30 0.10 0.20 0.00 0.20 0.00 0.00 0.00

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164 Table A 7. Elemental compositions of the SOLO fetal spongiosa Elemental composition (% by mass) Phanto m/Bone Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine SOLO08WK Cranium 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 Other 9.60 9.90 2.20 74. 40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 SOLO12WK Cranium 9.05 11.15 2.48 71.27 0.44 0.03 2.75 0.82 0.26 0.00 0.00 1.73 0.00 0.00 Other 9.16 11.55 2.46 71.19 0.44 0.03 2.63 0.82 0.26 0.00 0.00 1.46 0.00 0.00 SOLO18WK Cranium 8.24 13.02 2.89 66.58 0.34 0.09 3.59 0.70 0.21 0.00 0.01 4.34 0.00 0.00 Other 8.49 14.02 2.84 66.37 0.35 0.08 3.27 0.69 0.21 0.00 0.01 3.66 0.01 0.00 SOLO22WK Cranium 7.69 14.27 3.17 63.46 0.28 0.12 4.14 0.62 0.17 0.00 0.01 6.07 0.00 0.00 Other 8.05 15.67 3.10 63.16 0.29 0.12 3.69 0.61 0.17 0.00 0.01 5.12 0.01 0.00 SOLO26WK Cranium 7.15 15.52 3.44 60.33 0.22 0.16 4.70 0.53 0.13 0.00 0.01 7.81 0.01 0.00 Other 7.61 17.32 3 .36 59.95 0.22 0.15 4.12 0.52 0.13 0.00 0.01 6.59 0.02 0.00 SOLO30WK Cranium 6.60 16.77 3.72 57.20 0.16 0.19 5.25 0.45 0.09 0.00 0.01 9.54 0.01 0.00 Other 7.17 18.96 3.62 56.73 0.16 0.18 4.55 0.44 0.09 0.00 0.01 8.05 0.02 0.00 SO LO34WK Cranium 6.06 18.02 3.99 54.08 0.09 0.23 5.81 0.37 0.06 0.00 0.02 11.28 0.01 0.00 Other 6.72 20.61 3.87 53.52 0.10 0.22 4.97 0.35 0.06 0.00 0.02 9.52 0.03 0.00 SOLO38WK Cranium 5.51 19.27 4.27 50.95 0.03 0.26 6.36 0.29 0.02 0.00 0.02 13.01 0.01 0.00 Other 6.28 22.26 4.13 50.31 0.04 0.25 5.40 0.27 0.02 0.00 0.02 10.98 0.03 0.00

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165 Table A 8. Elemental compositions of the UF fetal spongiosa Elemental composition (% by mass) Phantom/Bone Hydrogen Ca rbon Nitrogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine UFHF08WK Cranium 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 Other 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 UFHF10WK Cranium 9.33 10.52 2.34 72.84 0.47 0.02 2.48 0.86 0.28 0.00 0.00 0.87 0.00 0.00 Other 9.38 10.72 2.33 72.79 0.47 0.02 2.41 0.86 0.28 0.00 0.00 0.73 0.00 0.00 UFHF15WK Cranium 8.65 12.09 2.68 68.93 0.39 0.06 3.17 0.76 0.23 0.00 0.00 3.04 0.00 0.00 Other 8.83 12.78 2.65 68.78 0.39 0.06 2.95 0.75 0.23 0.00 0.00 2.56 0.01 0.00 UFHF20WK Cranium 7.96 13.65 3.03 65.02 0.31 0.10 3.86 0.66 0.19 0.0 0 0.01 5.20 0.00 0.00 Other 8.27 14.84 2.97 64.76 0.32 0.10 3.48 0.65 0.19 0.00 0.01 4.39 0.01 0.00 UFHF25WK Cranium 7.28 15.21 3.37 61.11 0.23 0.15 4.56 0.55 0.14 0.00 0.01 7.37 0.01 0.00 Other 7.72 16.90 3.29 60.75 0.24 0.1 4 4.01 0.54 0.14 0.00 0.01 6.22 0.02 0.00 UFHF30WK Cranium 6.60 16.77 3.72 57.20 0.16 0.19 5.25 0.45 0.09 0.00 0.01 9.54 0.01 0.00 Other 7.17 18.96 3.62 56.73 0.16 0.18 4.55 0.44 0.09 0.00 0.01 8.05 0.02 0.00 UFHF35WK Cranium 5.92 18.33 4.06 53.30 0.08 0.23 5.94 0.35 0.05 0.00 0.02 11.71 0.01 0.00 Other 6.61 21.02 3.94 52.72 0.09 0.23 5.08 0.33 0.05 0.00 0.02 9.88 0.03 0.00 UFHF38WK Cranium 5.51 19.27 4.27 50.95 0.03 0.26 6.36 0.29 0. 02 0.00 0.02 13.01 0.01 0.00 Other 6.28 22.26 4.13 50.31 0.04 0.25 5.40 0.27 0.02 0.00 0.02 10.98 0.03 0.00

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166 Table A 9. Elem e ntal compositions of the UF and SOLO pregnant female phantoms Elemental composition (% by mass) Tissue Hydrogen Carbon Ni trogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine Adrenals 10.44 22.82 2.81 62.92 0.10 0.00 0.18 0.28 0.22 0.00 0.20 0.00 0.02 0.00 Tongue 10.20 14.30 3.40 71.00 0.10 0.00 0.20 0.30 0.10 0.00 0.40 0.00 0.00 0.0 0 Esophagus 10.43 22.15 2.84 63.58 0.10 0.00 0.18 0.28 0.22 0.00 0.20 0.00 0.02 0.00 Stomach 10.51 11.38 2.46 74.96 0.10 0.00 0.10 0.12 0.22 0.00 0.12 0.00 0.02 0.00 Small Intestine 10.50 11.37 2.49 74.94 0.10 0.00 0.10 0.13 0.23 0.00 0.13 0.00 0.03 0.0 0 Large Intestine 10.50 11.37 2.48 74.95 0.10 0.00 0.10 0.13 0.23 0.00 0.13 0.00 0.03 0.00 Liver 10.27 16.35 2.95 69.29 0.17 0.00 0.17 0.27 0.23 0.00 0.27 0.00 0.03 0.00 Gall bladder 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0. 00 Pancreas 10.52 15.68 2.43 70.45 0.18 0.00 0.18 0.12 0.22 0.00 0.20 0.00 0.02 0.00 Blood 10.20 11.00 3.30 74.50 0.10 0.00 0.10 0.20 0.30 0.00 0.20 0.00 0.10 0.00 Brain 10.68 14.37 2.24 71.33 0.20 0.00 0.39 0.20 0.30 0.00 0.30 0.00 0.00 0.00 Heart 10. 37 13.42 2.97 72.25 0.10 0.00 0.18 0.20 0.22 0.00 0.28 0.00 0.02 0.00 Eye 9.60 19.50 5.70 64.60 0.10 0.00 0.10 0.30 0.10 0.00 0.00 0.00 0.00 0.00 Fat 11.38 58.90 0.75 28.66 0.10 0.00 0.10 0.10 0.01 0.00 0.00 0.00 0.00 0.00 Skin 10.01 19.94 4.16 64.99 0. 20 0.00 0.10 0.20 0.30 0.00 0.10 0.00 0.00 0.00 Muscle 10.20 14.24 3.40 71.06 0.10 0.00 0.20 0.30 0.10 0.00 0.40 0.00 0.00 0.00 Pituitary gland 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Trachea 10.49 24.93 2.73 60.86 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Larynx 9.60 9.90 2.20 74.40 0.50 0.00 2.20 0.90 0.30 0.00 0.00 0.00 0.00 0.00 Lung 10.25 10.77 3.21 74.68 0.15 0.00 0.15 0.25 0.30 0.00 0.20 0.00 0.05 0.00 Spleen 10.26 11.17 3.24 74.28 0.10 0.00 0.21 0.20 0. 24 0.00 0.26 0.00 0.04 0.00 Thymus 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Thyroid 10.37 11.77 2.53 74.50 0.19 0.00 0.10 0.11 0.21 0.00 0.11 0.00 0.01 0.09 Tonsils 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.2 0 0.00 0.00 0.00 Kidney 10.27 12.54 3.09 73.03 0.17 0.00 0.17 0.20 0.23 0.00 0.20 0.07 0.03 0.00 Ureters 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Urinary 10.49 9.63 2.61 76.07 0.20 0.00 0.20 0.20 0.30 0.00 0.30 0.00 0.00 0.00 Urethra 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Testes 10.57 9.97 2.08 76.47 0.19 0.00 0.10 0.20 0.21 0.00 0.20 0.00 0.01 0.00 Prostate 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Breas t 11.60 51.90 0.00 36.50 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 Ovaries 10.48 24.50 2.75 61.27 0.10 0.00 0.19 0.29 0.21 0.00 0.20 0.00 0.01 0.00 Fallopian tubes 10.60 31.50 2.40 54.70 0.10 0.00 0.20 0.20 0.10 0.00 0.20 0.00 0.00 0.00 Uterus 1 0.60 31.50 2.40 54.70 0.10 0.00 0.20 0.20 0.10 0.00 0.20 0.00 0.00 0.00 Cartilage 9.61 9.92 2.22 74.40 0.49 0.00 2.17 0.89 0.30 0.00 0.00 0.00 0.00 0.00 Teeth 2.20 9.50 2.90 42.10 0.00 0.70 13.70 0.00 0.00 0.00 28.90 0.00 0.00 0.00 Soft Tissue (ICRP 89) 10.50 25.60 2.70 60.20 0.10 0.00 0.20 0.30 0.20 0.00 0.20 0.00 0.00 0.00 Water 11.20 0.00 0.00 88.80 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 Air 0.00 0.01 75.53 23.18 0.00 0.00 0.00 0.00 0.00 1.28 0.00 0.00 0.00 0.00 Lens 9.60 19.50 5.70 64.6 0 0.10 0.00 0.10 0.30 0.10 0.00 0.00 0.00 0.00 0.00

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167 Table A 9. Continued Elemental composition (% by mass) Tissue Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine Cortical bone 3.57 15.95 4.19 44.82 0.30 0.20 9.40 0.30 0.00 0.00 0.00 21.27 0.00 0.00 sp_Cranium 5.96 26.74 3.47 42.31 0.23 0.16 6.42 0.25 0.02 0.00 0.01 14.42 0.02 0.00 sp_Mandible 9.95 46.78 2.21 36.03 0.13 0.09 1.48 0.17 0.02 0.00 0.01 3.09 0.04 0.00 sp_Vertebrae cervical 8 .88 35.53 3.10 43.95 0.15 0.14 2.51 0.21 0.04 0.00 0.02 5.42 0.06 0.00 sp_Vertebrae thoracic 9.68 39.34 2.92 42.90 0.13 0.13 1.50 0.19 0.03 0.00 0.02 3.08 0.06 0.00 sp_Vertebrae lumbar 9.57 39.47 2.93 42.36 0.13 0.14 1.66 0.19 0.03 0.00 0.02 3.44 0.06 0. 00 sp_Sternum 9.83 38.69 2.91 44.13 0.12 0.13 1.28 0.19 0.04 0.00 0.03 2.59 0.07 0.00 sp_Ribs 9.46 38.67 2.96 42.80 0.13 0.14 1.79 0.20 0.03 0.00 0.02 3.74 0.06 0.00 sp_Scapulae 9.29 41.74 2.47 38.88 0.15 0.10 2.25 0.18 0.03 0.00 0.02 4.85 0.04 0.00 sp _Clavicles 9.69 46.12 2.20 35.71 0.14 0.09 1.86 0.17 0.02 0.00 0.01 3.96 0.03 0.00 sp_Os Coxae 9.77 43.18 2.49 39.15 0.13 0.10 1.58 0.18 0.03 0.00 0.02 3.31 0.05 0.00 sp_Sacrum 9.44 38.41 2.97 43.00 0.14 0.14 1.81 0.20 0.03 0.00 0.02 3.79 0.06 0.00 sp_H umera proximal 9.96 48.99 1.95 33.70 0.13 0.07 1.60 0.16 0.02 0.00 0.01 3.38 0.03 0.00 sp_Humera distal 9.49 50.91 1.64 29.87 0.15 0.05 2.42 0.15 0.01 0.00 0.01 5.30 0.00 0.00 sp_Radii proximal 10.25 55.61 1.30 27.72 0.13 0.03 1.53 0.13 0.01 0.00 0.01 3. 28 0.00 0.00 sp_Radii distal 9.91 53.57 1.45 28.62 0.14 0.04 1.93 0.14 0.01 0.00 0.01 4.19 0.00 0.00 sp_Ulnae proximal 9.38 50.25 1.69 30.16 0.15 0.05 2.55 0.15 0.01 0.00 0.01 5.60 0.00 0.00 sp_Ulnae distal 9.63 51.81 1.57 29.45 0.15 0.05 2.25 0.15 0.01 0.00 0.01 4.92 0.00 0.00 sp_Wrists and Hands 9.49 50.94 1.64 29.84 0.15 0.05 2.42 0.15 0.01 0.00 0.01 5.30 0.00 0.00 sp_Femora proximal 9.38 45.14 2.19 35.58 0.15 0.08 2.29 0.17 0.02 0.00 0.01 4.96 0.03 0.00 sp_Femora distal 9.55 51.19 1.62 29.80 0.15 0.05 2.34 0.15 0.01 0.00 0.01 5.13 0.00 0.00 sp_Patellae 9.55 51.04 1.62 29.96 0.15 0.05 2.34 0.15 0.01 0.00 0.01 5.11 0.00 0.00 sp_Tibiae proximal 9.91 53.52 1.45 28.69 0.14 0.04 1.92 0.14 0.01 0.00 0.01 4.17 0.00 0.00 sp_Tibiae distal 9.80 52.83 1.50 28.99 0.14 0.04 2.06 0.14 0.01 0.00 0.01 4.48 0.00 0.00 sp_Fibulae proximal 10.38 56.46 1.24 27.33 0.13 0.03 1.37 0.13 0.01 0.00 0.01 2.91 0.00 0.00 sp_Fibulae distal 9.54 51.12 1.62 29.83 0.15 0.05 2.36 0.15 0.01 0.00 0.01 5.16 0.00 0.00 sp_Ankles and Feet 9.55 51.14 1.62 29.86 0.15 0.05 2.34 0.15 0.01 0.00 0.01 5.13 0.00 0.00 sp_Humera upper shaft 11.17 55.37 1.52 31.46 0.10 0.05 0.12 0.13 0.02 0.00 0.01 0.00 0.03 0.00 sp_Humera lower shaft 11.47 63.26 0.76 24.19 0.10 0.00 0.10 0.10 0.01 0.00 0.00 0. 00 0.00 0.00 sp_Radii shaft 11.48 63.67 0.74 23.80 0.10 0.00 0.10 0.10 0.00 0.00 0.00 0.00 0.00 0.00 sp_Ulnae shaft 11.48 63.65 0.74 23.83 0.10 0.00 0.10 0.10 0.00 0.00 0.00 0.00 0.00 0.00 sp_Femora upper shaft 11.14 54.02 1.58 32.77 0.10 0.05 0.12 0.13 0.03 0.00 0.02 0.00 0.03 0.00 sp_Femora lower shaft 11.47 63.32 0.75 24.14 0.10 0.00 0.10 0.10 0.01 0.00 0.00 0.00 0.00 0.00 sp_Tibiae shaft 11.46 62.82 0.78 24.62 0.10 0.00 0.10 0.10 0.01 0.00 0.01 0.00 0.00 0.00 sp_Fibulae shaft 11.47 63.15 0.76 24.3 0 0.10 0.00 0.10 0.10 0.01 0.00 0.00 0.00 0.00 0.00 Ears 9.89 10.43 2.73 74.45 0.31 0.00 1.19 0.56 0.30 0.00 0.10 0.00 0.05 0.00 External nose 9.90 10.45 2.75 74.45 0.30 0.00 1.15 0.55 0.30 0.00 0.10 0.00 0.05 0.00 Nasal layers 10.34 18.06 3.01 67.59 0. 10 0.00 0.15 0.25 0.25 0.00 0.20 0.00 0.05 0.00 Oral cavity layer 10.34 18.06 3.01 67.59 0.10 0.00 0.15 0.25 0.25 0.00 0.20 0.00 0.05 0.00 Pharynx 10.34 18.06 3.01 67.59 0.10 0.00 0.15 0.25 0.25 0.00 0.20 0.00 0.05 0.00

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168 Table A 9. Continued Elemental composition (% by mass) Tissue Hydrogen Carbon Nitrogen Oxygen Sodium Magnesium Phosphorus Sulfur Chlorine Argon Potassium Calcium Iron Iodine Sal ivary glands 10.34 18.06 3.01 67.59 0.10 0.00 0.15 0.25 0.25 0.00 0.20 0.00 0.05 0.00 Spinal cord 10.45 12. 73 2.76 72.87 0.15 0.00 0.25 0.20 0.30 0.00 0.25 0.00 0.05 0.00 c : Indicates cartilage/fibrous tissue region of bone site. sp : Indicates spongiosa region of bone site.

PAGE 169

169 APPENDIX B ADDITIONAL RADIATION TRANSPORT DATA This appendix serve s to present the following tables of radiation transport data that are pertinent to the research aims but are not critical to the flow of the main text: 1. Target fetal tissues of interest to the SOLO project 2. Fetal source tissues of interest to the SOLO project 3. Maternal sourc e tissues of interest to the SOLO project 4. UF adult female skeletal source volume sampling distributions 5. UF adult female blood source volume sampling distributions 6. I 131 and Ba 137m radiation transport directional biasing half angles

PAGE 170

170 Table B 1. Fetal ta rget tissues of interest to the SOLO project Tissue Tissue Tissue All soft tissues (AST) c Lumbar discs sp Clavicles Brain c Sacrum sp Sternum Right c olon w all c Os Coxae sp Ribs Heart c Femora sp Vertebrae cervical Liver c Tibiae sp Vertebrae thoraci c Lungs c Fibulae sp Vertebrae lumbar Rectosigmoid w all c Patellae sp Sacrum Small intestine wall c Feet&ankles sp Os Coxae Spleen c Humeri sp Femora Stomach w all c Radii sp Tibiae Thyroid c Ulnae sp Fibulae Left c olon w all c Hands&wrists sp Patella e c Cranium c Cranial fontanelles sp Feet&ankles c Mandible c Costal cartilage sp Humera c Scapulae c Vertebrae cervical sp Radii c Clavicles c Vertebrae thoracic sp Ulnae c Sternum c Vertebrae lumbar sp Hands&wrists c Ribs sp Cranium sp Skeletal ave rage c Cervical discs sp Mandible c Thoracic discs sp Scapulae c : Indicates cartilage/fibrous tissue region of bone site. sp : Indicates spongiosa region of bone site.

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171 Table B 2. Fetal source tissues of interest to the SOLO project Source tissue Sr 90, Sr 89, Y 90 Cs 137, Ba 137m I 131 Pu 239 Blood/whole body X X X X Bone surface X X Bone volume X X Liver X Other tissues X X Thyroid X

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172 Table B 3. Maternal source tissues of interest to the SOLO project Source tissue Sr 90, Sr 89, Y 90 Cs 137, Ba 137m I 131 Amniotic Fluid X Bladder Contents X X X Blood X X X Cortical bone volume X ET1 X X X ET2 X X X Kidneys X Left Colon Contents X X X Lungs X X X Other Tissues X X Ovaries X Placenta X Rectosigmoid Colon Contents X X X Right Colon Contents X X X Salivary Glands X Small intestine contents X X X Stomach Contents X X X Stomach Wall X Thyroid X Trabecular bone surface X Trabecular bone volume X Trachea/Bronchi X X X Whole Body X X X Note: Pu 239 maternal sources not considered

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173 Table B 4 UF adult female blood source volume sampling distributions (% volume of total blood) Tissue % by volume Tissue % by volume Tissue % by volume Residual Soft Tissue 8.50E +00 Tonsil 1.10E 03 cb Radii distal 2.00E 03 Adrenal (L) 3.00E 02 Trachea 2.77E 03 cb Ulnae proximal 3.60E 03 Adrenal (R) 3.00E 02 Urinary bladder wall 2.00E 02 cb Ulnae shaft 1.80E 02 Brain 1.20E+00 Uterus 2.34E 01 cb Ulnae distal 6.91E 04 Bre ast(adipose) 1.31E 01 Air (in body) 2.01E 02 cb Hand 3.67E 02 Bronchi 2.00E+00 Left Colon W 5.17E 02 cb Teeth 2.78E 03 Right colon wall 6.04E 02 Salivary Glands (mand.) 7.34E 03 sp Cranium 5.72E 01 Ears 2.27E 03 Salivary Glands (ling.) 2.72E 03 sp Mandible 6.50E 02 Esophagus 8.00E 01 Arteries 6.00E+00 sp Scapulae 7.43E 01 External nose 5.26E 03 Veins 1.80E+01 sp Clavicles 7.40E 02 Eye balls 5.33E 03 Muscle 1.05E+01 sp Sternum 1.54E 01 Gall bladder wall 2.79E 03 Breast (glandular) 6.43E 02 sp Ribs 6.53E 01 Heart W 1.00E+00 Placenta 2.33E 01 sp Vertebrae cervical 1.86E 01 Heart C 9.00E+00 cb Cranium 1.49E 01 sp Vertebrae thoracic 7.38E 01 Kidney cortex (L) 7.40E 01 cb Mandible 1.01E 02 sp Vertebrae lumbar 8.35E 01 Kidney cortex (R) 7.40E 01 cb Scapulae 5.72E 02 sp Sacrum 5.38E 01 Kidney medulla (L) 2.60E 01 cb Clavicles 1.09E 02 sp Os coxae 1.78E+00 Kidney medulla (R) 2.60E 01 cb Sternum 4.93E 03 sp Femora proximal 4.16E 01 Kidney pelvis (L) 2.53E 03 cb Ribs 6.47E 02 mc Femora upper shaft 1.96E 01 Kidney pelvis (R) 2.54E 03 cb Vertebrae cervical 1.13E 02 mc Femora lower shaft 4.90E 02 Larynx 6.59E 03 cb Vertebrae thoracic 2.19E 02 sp Femora distal 2.32E 01 Lens 1.58E 04 cb Vertebrae lumbar 2.14E 02 sp Tibiae p roximal 1.72E 01 Liver 1.00E+01 cb Sacrum 2.48E 02 mc Tibiae shaft 7.50E 02 Lung (L) 4.70E+00 cb Os coxae 7.02E 02 sp Tibiae distal 6.10E 02 Lung (R) 5.80E+00 cb Femur proximal 8.17E 03 sp Fibulae proximal 1.30E 02 Nasal layer (anterior) 1.88E 04 cb Femur upper shaft 2.91E 02 mc Fibulae shaft 6.00E 03 Nasal layer (posterior) 3.18E 03 cb Femur lower shaft 3.36E 02 sp Fibulae distal 1.30E 02 Oral cavity layer 6.30E 04 cb Femur distal 1.60E 02 sp Patellae 2.70E 02 Ovaries 2.00E 02 cb Tibiae proximal 1.09E 02 sp Ankle+feet 3.02E 01

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174 Table B 4 Continued Tissue % by volume Tissue % by volume Tissue % by volume Pancreas 6.00E 01 cb Tibiae shaft 4.33E 02 sp Humera proximal 2.56E 01 Pharynx 5.18E 04 cb Tibiae distal 5.67E 03 mc Humera u pper shaft 4.90E 02 Pituitary Gland 1.95E 04 cb Fibulae proximal 1.30E 03 mc Humera lower shaft 1.40E 02 Rectosigmoid wall 9.70E 01 cb Fibulae shaft 8.48E 03 sp Humera distal 6.70E 02 Salivary Glands (parot.) 1.47E 02 cb Fibulae distal 2.01E 03 sp Radii proximal 9.00E 03 SI wall 3.80E+00 cb Patellae 1.80E 03 mc Radii shaft 7.00E 03 Skin 3.00E+00 cb Ankle+feet 5.61E 02 sp Radii distal 1.80E 02 Spinal Cord 1.68E 02 cb Humerus proximal 7.05E 03 sp Ulnae proximal 3.70E 02 Spleen 1.40E+00 cb Humerus upper shaft 2.16E 02 mc Ulnae shaft 9.00E 03 Stomach wall 2.00E 01 cb Humerus lower shaft 1.87E 02 sp Ulnae distal 7.00E 03 Thymus 7.18E 03 cb Humerus distal 9.01E 03 sp Hands 4.30E 02 Thyroid 6.00E 01 cb Radii proximal 1.46E 03 Distribut ion sum 1.00E+02 Tongue 2.10E 02 cb Radii shaft 1.51E 02

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175 Table B 5 UF adult female skeletal source volume sampling distributions Trabecular bone Cortical bone Skeletal site Surface Volume Surface/Volume Cranium 0.1805 0.3366 0.2014 Mandible 0.0040 0.0074 0.0144 Scapulae 0.0263 0.0207 0.0710 Clavicles 0.0060 0.0047 0.0132 Sternum 0.0062 0.0049 0.0060 Ribs 0.0418 0.0329 0.0786 Cervical vertebrae 0.0235 0.0190 0.0170 Thoracic vertebrae 0.0529 0.0428 0.0287 Lumbar vertebrae 0.0818 0.0604 0 .0243 Sacrum 0.0614 0.0453 0.0297 Os Coxae 0.0565 0.0478 0.0872 Promixal femora 0.0912 0.0767 0.0107 Femora upper shaft 0.0354 Femora lower shaft 0.0404 Distal femora 0.1011 0.0851 0.0203 Proximal tibiae 0.0670 0.0542 0.0130 Tibiae sh aft 0.0525 Distal tibiae 0.0257 0.0208 0.0061 Proximal fibulae 0.0041 0.0033 0.0015 Fibulae shaft 0.0105 Distal fibulae 0.0053 0.0043 0.0024 Patellae 0.0104 0.0084 0.0021 Ankles and feet 0.0579 0.0468 0.0696 Proximal humerus 0.0265 0.0214 0.0089 Humera upper shaft 0.0261 Humera lower shaft 0.0230 Distal humera 0.0270 0.0218 0.0113 Proximal radii 0.0029 0.0023 0.0019 Radii shaft 0.0184 Dista radii 0.0064 0.0051 0.0024 Proximal ulnae 0.0238 0.0193 0.0048 Ulnae shaf t 0.0219 Distal ulnae 0.0006 0.0005 0.0009 Wrists and hands 0.0092 0.0075 0.0445

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176 Table B 6. I 131 and Ba 137m radiation transport directional biasing half angles for the SOLO pregnant female series Half angle (degrees) SOPF08WK SOPF12WK SOPF1 8WK SOPF22WK SOPF26WK SOPF30WK SOPF34WK SOPF38WK ET1 4 8 25 25 25 25 35 35 ET2 4 8 25 25 25 25 35 35 Kidneys 90 90 145 145 145 145 145 145 Lungs 45 45 65 65 65 65 90 90 Salivary Glands 4 8 25 25 25 25 35 35 Thyroid 4 8 25 25 25 25 35 35 Trachea/Bron chi 18 18 45 45 45 45 50 50

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181 BIOGRAPHICAL SKET CH Matthew Ryan Maynard was born in Vincennes, Indiana to Pamela and Terry Maynard and raised in the suburbs of Indianapolis, Indiana. He received his Bachelor of Science degree in nuclear engineering from Purdue University in 2007 and his Master of Scienc e in nuclear engineering sciences (medical physics concentration) from the University of Florida in 2009. Matthew first became interested in engineering and physics as a high school student taking advanced placement (AP) courses. He was introduced specif ically to the field of medical physics when his grandmother, Patricia, was diagnosed with stage four cancer in late 2006 a bittersweet irony the two of them discussed fondly until her death in 2011 Matthew plans to continue his contributions to the fiel d of computation radiation dosimetry as a post doctoral associate under Dr. Wesley Bolch while simultaneously preparing for admission to medical school where he hopes to begin pursuing a career as radiation oncology physician In his free time, Matthew enj oys playing guitar, reading, playing flag football and riding his motorcycle. Matthew also treasures time spent with family and visits whenever life permits.