Dosimetry comparison of orthovoltage x-ray and 137 Cs irradiation of the murine bone marrow compartment Matthew Belley

Transcription

1 Dosimetry comparison of orthovoltage x-ray and 137 Cs irradiation of the murine bone marrow compartment Matthew Belley NCHPS Fall Meeting October 9, 2015 Duke Medical Physics

2 Disclaimer Financial support for this work received from Precision X-ray Manufacturer of small animal x-ray irradiator systems

3 Background Current Method of Dose Prescription Dose calculated using ion chamber air-kerma measurement Time = Target dose Dose rate Time = 6 Gy 1 Gy/min = 6 min Many limitations: Homogeneity Differences in tissue f-factors

4 RELATIVE ABSORBED DOSE (f) Al Cu At 50 kev: Bone: Z eff = 12.6 Soft Tissue: Z eff = BONE 320 kvp X-rays F1 Filter HALF VALUE LAYER (mm) Photoelectric Probability: Z 3 /E 3 Source: Bushberg WATER MUSCLE 320 kvp X-rays F8 Filter 137 Cs -rays 60 Co -rays Photoelectric dominates at low energy PHOTON ENERGY (MeV)

5 RELATIVE ABSORBED DOSE (f) Increasing Use of X-ray Irradiators (Low Energy) Why do we care? Al Cu Photo-electrons BONE 320 kvp X-rays F1 Filter HALF VALUE LAYER (mm) kvp X-rays F8 Filter 137 Cs -rays 60 Co -rays 1.0 WATER MUSCLE PHOTON ENERGY (MeV)

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7 Need for Bone Marrow Dosimetry Center for Medical Countermeasures against Radiation (CMCR) Radiation biology studies, testing pharmaceuticals and radio-protectants Model radiation damage as expected from nuclear event Bone Marrow (BM) Primary site hematopoietic development Radiation sensitive ICRP 103: w T =0.12 Common target organ for small animal dosimetry Contains self-renewing stem cells Performing dosimetry to BM is challenging, especially in mice

8 Purpose of this Research Goal: To determine if photo-electrons from bone increase dose to BM i.e. dose enhancement and distribution within BM Calculate dose to BM compartment using Monte Carlo 137 Cs (662 kev) Orthovoltage x-rays (160 and 320 kv) Compare BM (progenitor) cell survival at 6 Gy dose 137 Cs (662 kev) Orthovoltage x-rays (320 kv at 1 mm and 4 mm Cu HVL)

9 Methods Monte Carlo

10 RELATIVE ABSORBED DOSE (f) Methods Monte Carlo Assess dose to BM and dose gradients in Vertebra and Femur Four different radiation beams Al Cu BONE 320 kvp X-rays F1 Filter HALF VALUE LAYER (mm) kvp X-rays F8 Filter 137 Cs -rays 60 Co -rays 1.0 WATER MUSCLE PHOTON ENERGY (MeV)

11 Scout Images, of Mouse Anatomy Femur Vertebrae

12 Axial CT Images of (a) Femur and (b) Vertebrae 1 micron voxel resolution

13 3 Region, Digital Virtual Phantoms 5 Micron Resolution

14 Software to Calculate Distance

15 Trabecular Rich Regions of Anatomy

16 Simulated X-ray Spectra Monte Carlo Three X-ray Beams

17 Methods Cell Survival Experiments Achieved equivalent dose rates for 320 kv beams and 137 Cs In-Vitro: 100 cgy/min In-Vivo: 140 cgy/min 3 different beam energies

18 Methods Cell Survival Experiments

19 Methods - Irradiations In-Vitro Harvested Cells Radiation, Various Energy In-Vivo Mice Radiation, Various Energy BM Cell Suspension Bone Equivalent Material BM Cell Suspension

20 137 Cs In-Vitro X-ray In-Vitro

21 Results Monte Carlo

22 Results Monte Carlo Dose enhancement vs. distance trends similar for all anatomy

23 Average Dose to BM Depends on Distribution P(x) Biology D(x) Dose

24 Lower Photon Energy, Higher Dose Enhancement Dose Gradients, D(x), Energy Dependent

25 Trabecular Rich Anatomy, Higher Dose Enhancement Biological Distribution, P(x), Anatomy Dependent

26 Highest HVL 320 kv Beam, Best Mimics 137 Cs

27 In-Vitro Results: Significantly Reduced Survival for Cells on Bone Equivalent Material, with 1 mm Cu HVL Beam

28 In-Vivo Results: Animals Exposed at Low Energy, Significant Increase in Cell Killing

29 Significance Need for dosimetry standardization We expect dose response curves or biological end points may be different: Institution X irradiations done to 6 Gy with low energy x-ray Institution Y irradiations done to 6 Gy with 137 Cs Recommend highest energy x-ray beams to best model radiation relevant for countermeasure studies

30 Conclusions Dose to BM dependent on Photon beam quality (energy) Anatomical structure Low energy x-rays cause significant dose enhancement to BM compartment for irradiation of live mice Highest filtered beam 320 kv beam (HVL=4 mm Cu), best mimics 137 Cs

31 Acknowledgements Kathleen A. Ashcraft, Chen-Ting Lee, Milton R. Cornwall-Brady, Jane-Jane Chen, Rathnayaka Gunasingha, Markus Burkhart, Mark Dewhirst, Terry T Yoshizumi, and Julian D. Down SCANCO Medical: Bruettisellen, Switzerland Precision X-ray: North Branford, CT

32 Thank you!

33 References Kurudirek M. Effective atomic numbers and electron densities of some human tissues and dosimetric materials for mean energies of various radiation sources relevant to radiotherapy and medical applications. Radiation Physics and Chemistry. 2014; 102: Bushberg JT, Boone JM. The essential physics of medical imaging. Lippincott Williams & Wilkins, Kiel MJ, Morrison SJ. Uncertainty in the niches that maintain haematopoietic stem cells. Nat Rev Immunol. 2008; 8(4): Fuchs E, Tumbar T, and Guasch G. Socializing with the neighbors: stem cells and their niche. Cell ; Spangrude G, Heimfeld S, Weissman I. Purification and characterization of mouse hematopoietic stem cells. Science. 1988; 241(4861):

34 Supporting Stem Cells Photoelectric Effect Compton Effect

35 CFU-GM: Colony forming: Granulocyte, Macrophage CFU-E: Colony forming: Erythrocyte CFU-C: Colony forming, in culture (in-vitro) [same as BFU-GM] BFU: Burst Forming (later form erythrocytes)

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38 Results Monte Carlo