1. Nuclear and Radiological Engineering Summer 2006 DOE Practicum at the United States Transuranium and Uranium Registries Practicum Fellow: Deanna Hasenauer 4-Year DOE Health Physics Fellow Affiliation: University of Florida (2000 – Present) Advisors: Dr. Wesley Bolch (University of Florida) and Dr. Anthony James (USTUR)

2. Nuclear and Radiological Engineering Overview of Presentation Who am I? –Pre-college –Baccalaureate –Post – Baccalaureate Ongoing research at the University of Florida My current area of research at the University of Florida Planned research at the USTUR (Summer 2006 practicum)

3. Nuclear and Radiological Engineering A Bit of History: Pre-College Born in St. Petersburg, Florida –March 15, 1982 Mostly raised in Zephyrhills, Florida Zephyrhills High School (1996-2000) –Played the flute in marching and symphonic band Superior solo performances All-county band (1 st chair), All-district band, Festival of Winds (USF) –Swim Team Held 6 records (still hold 4!!!) – 50 m free, 100 m free, 50 m butterfly, various relays 1 st female to attend state competition –Valedictorian

4. Nuclear and Radiological Engineering A Bit of History: Baccalaureate University of Florida (2000-2004) –B.S. Nuclear and Radiological Engineering –Order of the Engineer –Alpha Nu Sigma –American Nuclear Society –Summa Cum Laude –Presented at 50 th Annual National HPS Conference (Spokane, WA) Summer Internship (2003) –Crystal River Unit 3 (Progress Energy) –Reactor Engineering GO GATORS!!!!!

5. Nuclear and Radiological Engineering A Bit of History: Post - Baccalaureate Once a Gator... Always a Gator! 2006 Men’s Basketball National Champs! DOE 4-year Health Physics Fellowship Award University of Florida (2004-2006) –M. S. Nuclear and Radiological Engineering –Alpha Nu Sigma –American Nuclear Society –Society of Health and Medical Physics Students President (2005-2006) –Present at 51 st Annual HPS Conference (Providence, RI) Summer DOE Practicum (2006) –US Transuranium and Uranium Registries (USTUR)/WSU –Voxel phantom modeling of Case #0102 –Human 241 Am Phantom –Advisor: Dr. Anthony James GO GATORS!!!!!

6. Nuclear and Radiological Engineering Overview of Current Research Projects at UF Bone Imaging and Dosimetry (BID) Project Group –Graduate Students: Deanna Hasenauer, Kayla Kielar, Carlos Pichardo, Matthew Hough, Wendy Kresge –Undergraduate Students: Laura Padilla (Senior), Lindsay Sinclair, Jessica Salazar –Post Doc: Vince Bourke –Advisor: Dr. Wesley Bolch Other projects at UF (Dr. Wesley Bolch) –Pediatric Organ Dose Project (POD) –Center for Disease Control Project (CDC)

7. Nuclear and Radiological Engineering My Research Area within the BID Group Development of image-based pediatric skeletal dosimetry models for electrons and betas

8. Nuclear and Radiological Engineering General Features of Bone Skeletal function –Support –Store minerals/lipids –Protection –Leverage –Produce blood cells Skeletal Structure: –Epiphysis (CB/TB) –Diaphysis (No TB) –2 types: Cortical bone Trabecular bone –Cortical (compact) bone Periosteum Osteon Haversian/Volksmann Canals –Trabecular (“spongy”) bone Network of irregular, interlacing bone along lines of stress Cavities with active (“red”) marrow and inactive (“yellow”) marrow 50 - 4000µm marrow cavities Age/skeletal site-specific; intersubject variability

9. Nuclear and Radiological Engineering Skeletal Development Static histomorphometry –Histos: Web or tissue –Morphe: Shape or form –Metrikos: To measure Limited studies from bone biopsies –Glorieux et al. Iliac Crest Tb. Th. increases first decade of life, then unchanged Increase in TBV and CBV Decrease in TBS/TBV Tb. N. invariant with age –Roschger et al. L4 Tb. width increase, then unchanged from adolescence on Decrease in Tb. N. after birth Thin, dense network to then thicker, looser network –Byer et al. (lumbar), Kneissel et al. (ribs), Beddoe et al. (various) Rapid increase in marrow cavity size during infancy Gradual increase in marrow cavity size throughout childhood Increase in Tb. Th. first decade of life

10. Nuclear and Radiological Engineering Internal/External Dosimetry Applications Medical applications (bone marrow is dose-limiting organ – marrow toxicity) –University of Florida –Radioimmunotherapy (RIT) Tag tissue-specific antibody to beta-particle emitting radionuclide Cancers outside hematopoietic system (e.g. osteosarcomas, liver cancer, tumor growths) –Radiotherapy Bone marrow ablation using external beam or bone-seeking radiopharmacuticals Localization of radiation within hematopoietic system Hodgkin’s or non-Hodgkin’s lymphoma; leukemia Radiation protection/epidemiological risk assessments –USTUR and University of Florida –Techa River contamination (about 30,000 people exposed) Mayak Production Association in Southern Urals of Russia (1949-1956) Waste management failures and radioactive waste storage facility exposion 10 17 Bq (~27 MCi) liquid waste (Sr, Cs, Y, Ba, La, I) US – Russian JCCRER (Joint Coordinating Committee on Radiation Effects Research) –Chernobyl accident (~5 million living in contaminated areas at time of release) Ukraine (1986) I-131 and Cs-137 (10 18 Bq  about half biologically inert noble gases) Increase in thyroid cancer in children –Leukemia risks from multiple CT exams and IVF

11. Nuclear and Radiological Engineering Introduction – Historical Approach to Skeletal Dosimetry –Historic perspective 40+ years of skeletal dosimetry research –FW Spiers and colleagues at the University of Leeds »1949 - 1981 »Development of chord distributions used today –Keith Eckerman and Michael Stabin at ORNL »1980s to present »Development of current stylized (mathematical) Reference Man model »Development of ICRP pediatric age series models (currently used in clinic – OLINDA and MIRDOSE) –UF Bone Imaging and Dosimetry (BID) Group (late 1990s to now) »Development of first “image-based” male tomographic model »Development of first “image-based” female model (in progress) »Development of first tomographic pediatric models (in progress)

12. Nuclear and Radiological Engineering Historical Perspective – The ‘Founders’ University of Leeds, UK –Frederick “Bill” Spiers, Joan Whitwell, Philip Darley, and Alan Beddoe –First to assess modeling the complex microstructure of trabecular bone –Majority of microstructural data acquired in 1976 (Beddoe and colleagues) –Chord-length or path-length distributions 1.7 Y - Iliac crest, femur head, parietal bone, rib, and 3 rd lumbar vertebra 9 Y - 4 th cervical vertebra, humerus, rib, femur head and neck, iliac crest, and femu shaft 44 Y - Parietal bone, femur head and neck, iliac crest, cervical vertebra, and lumbar vertebra –Known as infinite “chord-based” modeling through trabecular bone Electron energy completely expended in trabecular bone Used in current skeletal electron dosimetry models

13. Nuclear and Radiological Engineering Research Initiatives at UF Image-based approach to skeletal modeling –Voxel models to replace chord-based models Anatomically realistic skeletal shape/dimension Internally consistent masses –First comprehensive adult male (Amish Shah) –First comprehensive adult female (Kayla Kielar) –In-vivo CT Some mass data –Ex-vivo CT 3D shape and dimension of skeletal sites –microCT 3D trabecular microstructure –PIRT (Paired-Image Radiation Transport) Developed by Amish Shah Simultaneously couples macro-image and micro- image to account for electron escape

14. Nuclear and Radiological Engineering In-House Transport Codes

15. Nuclear and Radiological Engineering Paired-Imaged Radiation Transport (PIRT) Amish Shah, HPJ 2005 66-Y male complete skeletal voxel model Simultaneous electron transport simulation within: –Macrostructure (cortical bone, soft tissue, spongiosa) Ex-vivo CT imaging; 3D contour of true skeletal structure –Microstructure (TAM 50, TAM, TIM, TBV) microCT imaging; 3D image of skeletal spongiosa

16. Nuclear and Radiological Engineering Chord-Based Infinite Spongiosa Transport (CBIST) Developed by Chris Watchman Macrostructure: None; infinite spongiosa Microstructure: University of Leeds chord distributions –Infinite trabecular bone, active/inactive marrow 3D-CBIST: Cellularity dependence during transport Adipocyte (yellow marrow)  -track < sampled marrow chord Buffer region (120  m) Transport radius (380  m) Active (red) marrow B*B* B A C D 70% 40% 20%

17. Nuclear and Radiological Engineering Single-Image Radiation Transport (SIRT) Developed by Amish Shah Macrostructure: Ex-vivo CT imaging; 3D contour of true skeletal structure Microstructure: None Coupled with EGSnrc (Electron-Gamma-Shower)

18. Nuclear and Radiological Engineering Voxel-Based Infinite Spongiosa Transport (VBIST) Developed by Amish Shah Macrostructure: None; infinite spongiosa Microstructure: MicroCT imaging; 3D image of skeletal spongiosa (coupled with EGSnrc)

19. Nuclear and Radiological Engineering Limitations of Current Pediatric Electron Skeletal Dosimetry Models: (Health Physics 2000, 2003) Transports through an infinite medium (infinite chord-based models) – Does not account for particle escape from microstructure Accounts for cellularity after transport and not during transport –Only valid at high electron energies (greater than 1 MeV) –Bolch et al. (J Nucl Med – 2002) 10 micron endosteal layer model for osteogenic cells –Recommended extension to 50 microns –Gossner et al. (Radiation Protection Dosimetry – 2000, 2003) Skeletal masses are tied to stylized (mathematical) models –Anatomically unrealistic Skeletal-averaged absorbed fraction data –Significant changes in shape, size, and trabecular microstructure –Beddoe et al. (Phys. Med. Biol. – 1976), Kneissel et al. (Calcif Tissue Int – 1997), Glorieux et al. (Bone – 2000), Byers et al. (Bone – 2000), Roschger et al. (J of Structural Biology – 2001)

20. Nuclear and Radiological Engineering Pediatric Skeleton: Reasons for Model Improvements Pediatric Skeleton –Smaller skeletal macrostructure Increased electron energy escape  Reduced absorbed fraction –Varying skeletal microstructure Higher % active marrow  Increased radiobiological effects –Active bone marrow one of most radiosensitive tissues in the body »ICRP 60 w T = 0.12 »Rapid cellular division »Low cellular differentiation »Long dividing future Smaller marrow cavities  More electron energy escape Thinner bone trabeculae  Less energy deposition in TBV –Age at exposure Longer life expectancy after exposure  Increased probability of secondary cancer inductions Law of Bergonie and Tribondeau

21. Nuclear and Radiological Engineering Pediatric Skeletal Modeling PIRT is ideal model for transport –Microstructure (No 3D microCT data) What we do have... –Macrostructure (UF pediatric series CT data) 9-month male, 4-year female, 8-year female, 11-year male, and 14-year male Scaled dimensions for each skeletal site –Microstructure (studies at the University of Leeds in 1976) Cervical vertebra: 9-y, 44-y Lumbar vertebra: 1.7-y, 44-y Femur head and neck: 1.7-y (head only), 9-y (and shaft), 44-y Humerus: 9-y Iliac crest: 1.7-y, 9-y, 44-y Parietal bone: 1.7-y, 44-y Rib: 1.7-y, 9-y, 44-y These are the only microstructural data for pediatric subjects

22. Nuclear and Radiological Engineering Proposed Pediatric Skeletal Models: Overview of SIRT-3DCBIST Model SIRT –Accounts for particle escape from 3D voxelized macrostructure –Skeletal masses, elemental compositions, densities are more anatomically refined and applicable to tomographic phantoms (PEGS4 – Material dependent cross section data for spongiosa, cortical bone, and soft tissue) –Spongiosa self dose and cortical bone cross dose to spongiosa 3D-CBIST –TAM, TBV, TBS, TIM sources to TAM D, TAM 50 (TAM S ), TAM, TIM 50 (TIM S ), TIM D, TIM, TBV targets –Accounts for cellularity during transport from 10 keV to 100 keV –50 micron “shallow marrow” for osteogenic cell targets –Curve-fit using hillslope in SigmaPlot between 100 keV and 1 MeV –Scale by cellularity from 1 MeV to 10 MeV SIRT-3DCBIST –Mathematically combine AF results from SIRT and 3D-CBIST to imitate “true” PIRT results

23. Nuclear and Radiological Engineering SIRT-3DCBIST Validation TAM Targets TBV Targets TBE Targets

24. Nuclear and Radiological Engineering φ(TAM  TBV) SIRT SIRT-3DCBIST 3D-CBIST In House Transport Model Comparisons 9-Month Sternum (96% Cellularity)

25. Nuclear and Radiological Engineering φ(TAM  CBV) Cranium Sternum Fibular heads Tibial heads Mandible SIRT-3DCBIST Absorbed Fraction Results 9-month Male (96% Cellularity)

26. Nuclear and Radiological Engineering φ(TAM  TBS) 51% Skeletal-Averaged Absorbed Fraction Comparisons between Current Model and SIRT-3DCBIST Model 9-Month Male (ICRP Reference Cellularity)

27. Nuclear and Radiological Engineering Overall Conclusions Movement toward image (voxel)-based approaches in Medical and Health Physics fields –Anatomical accuracy (real 3D images) –Realistic electron pathlength simulations (non-linear pathlengths) –No chord-dependence (straight-line pathlength) EGSnrc interface used with SIRT, VBIST, and PIRT –Allows user defined subroutines for any geometry and scoring options without touching physics –Preferred over MCNP with voxel-based images due to memory SIRT (macrostructure) and 3D-CBIST (microstructure) mathematical combination for pediatric electron dosimetry models –More anatomically accurate (electron escape and internally consistent skeletal masses) –Accounts for cellularity DURING transport

28. Nuclear and Radiological Engineering My Research Area within the USTUR Development of VOXEL phantom and mathematical modeling of detector configuration response for low energy photons ( 241 Am – 59.5 keV; 239 Pu - 17 keV) for USTUR case #0102

29. Nuclear and Radiological Engineering USTUR Case # 0102: DOE’s Human 241 Am Phantom Half skeleton – encased in tissue equivalent plastic – with simulated lungs. Died 1979 – age 50 – malignant melanoma. Lawrence Livermore Laboratory. Skeletal burden approx. 2 kBq (50 nCi) 241 Am. Phantom distributed to DOE “in vivo” labs – and internationally. Develop VOXEL phantom model from in-vivo CT scanning (approximately 1mm axial slices) – Kadlec Medical Center; Richland, WA – G.E. CT/PET scanner for data acquisition

30. Nuclear and Radiological Engineering Mathematical Modeling of Detector Response USTUR Case # 0990: October 2005 Whole Body Donor PNNL low- background “in vivo” counting facilities (thin planar Ge). Rocky Flats “Follow-up Program ” participant – died at age 82. Pu inhalation (1960s) – with 30,000 ppm 241 Am. Counters positioned for liver.

31. Nuclear and Radiological Engineering For More Information... Dr. Anthony James (USTUR/WSU) –tjames@tricity.wsu.edu United States Transuranium and Uranium Registries –www.ustur.wsu.edu Dr. Wesley Bolch (Univ. of Florida) –wbolch@ufl.edu Deanna Hasenauer (USTUR/Univ. of Florida) –ufdeanna@ufl.edu –dhasenauer@tricity.wsu.edu Advanced Laboratory for Radiation Dosimetry Studies (ALRADS) at the University of Florida –alrads.nre.ufl.edu Department of Nuclear and Radiological Engineering at the University of Florida –www.nuceng.ufl.edu