Using Prompt gamma ray emission to address uncertainties in proton therapy

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Using Prompt gamma ray emission to address uncertainties in proton therapy Jerimy C. Polf, PhD, DABR Department of Radia9on Oncology University of Maryland School of Medicine AAPM 2013

Disclosures and Announcements Funding: IRG-08-061-01, American Cancer Society R21CA137362, National Institute of Health Therapy Scientific Session: Proton Range Uncertainty, Thursday, 10:30-12:30 pm, Room 144 Experimental Study of Discrete Prompt Gamma Lines for In-Vivo Proton Range Verification J. Verburg*, K. Riley, J. Seco Characterizing Prompt Gamma Signal During Proton Radiotherapy J. Polf*, D. Mackin, E. Lee, S. Avery, D. Dolney, S. Beddar On the Feasibility of Prompt Gamma Imaging in Heterogeneous Patient Anatomy E. Sterpin*, G. Janssens, J. Smeets, D. Prieels, F. Stichelbault, F. Roellinghoff, E. Clementel, A. Benilov, S. Vynckier

Goal of radiation therapy Maximize the dose of ionizing radiation to malignant (cancer) cells Minimize the dose of ionizing radiation to healthy tissue 3

Proton vs. x-ray dose delivery X-Rays This gives many pictures of how wonderful Protons are (in a perfect world). PROTONS In reality there are many uncertain9es in Proton treatment delivery due to a wide range of factors: 4 - - - - - Treatment setup, CT# conversion, Tumor mo9on, Tissue response to proton irradia9on Etc.

Uncertainties in Proton Therapy Dose delivery errors: - setup errors, - tumor motion, - changes to internal anatomy Treatment CT 2 week re- CT 5

Uncertainties in Proton Therapy - Tumor and normal tissue response Why does one pa,ent respond adversely, while another does not? Pre- treatment 6 month follow- up 6

Prompt gamma imaging (PGI) concept Prompt Gamma Ray Emission (a) (b) - occurs within 10-9 sec of interac9on - i.e. real- 9me signal (c) - each element emits characteris9c gamma- rays with different energies - gamma rays only emized where proton beam interacts in the pa9ent (i.e where dose is deposited)

Polf et al, AIP conf. proceed. 2011 Prompt Gamma Monte Carlo Studies Moteabbed et al, Phys. Med. Biol., 2011 By measuring PG emission, it may be possible to address uncertain9es in: - delivered proton beam range - (changes to) elemental composi9on of irradiated 9ssue.

Prompt Gamma Measurements PG emission vs. depth shown to correlate well to Bragg Peak. Min et al., Appl. Phys. Let., 89:183517 (2006) Polf et al., (2013).

Prompt Gamma detec9on systems Early Monte Carlo studies and measurements Have led to the design and development of PG detec9on and imaging systems. These include: courtesy of M. Fatyga and M. Bues, Mayo Clinic, Phoenix AZ - Pinhole/slit cameras - Linear detector arrays - Compton cameras - Energy- 9me resolve detec9on

Prompt Gamma range verifica9on Knife edge slit camera Bom et al., Phys. Med. Biol., 57 (2012) 297-308. Prompt Gamma Dose

Prompt Gamma range verifica9on Knife edge slit camera Correla9on between range shid and PG profile shid Smeets et al., Phys. Med. Biol., 57 (2012) 3371-3405. - Es9mated that, determina9on of 1-2 mm shid in BP possible

Prompt Gamma range verifica9on Compton Camera 13

Prompt Gamma range verifica9on Compton Camera Itera,ve Image Reconstruc,on 1. Choose point on surface of cone inside phantom 3. Does image meet Figure of Merit? No Yes Final Image r i H 2. Voxelize phantom to produce 3D image space Mackin et al, Phys. Med. Biol., 57:3537-3553 (2012). 14

Compton Camera Prompt Gamma range verifica9on Itera,ve reconstruc,on of 3D image of PG emission Mackin et al, Phys. Med. Biol., 57:3537-3553 (2012). 15

Prompt Gamma range verifica9on Reconstructed images from PG emission Measured with prototype Compton camera

Prompt Gamma range verifica9on Energy- and 9me- resolved gamma detec9on Prompt gamma spectra before And ader the Bragg peak show Measureable differences. Courtesy of: Joost Verburg, Kent Riley, Thomas Borleld, Joao Seco, MassachuseUs General Hospital and Harvard Medical School

Prompt Gamma range verifica9on Using energy and 9me resolved measurement of PG: - Can measure PG depth profile from individual elemental PG emission. Courtesy of: Joost Verburg, Kent Riley, Thomas Bor]eld, Joao Seco, MassachuseUs General Hospital and Harvard Medical School

Prompt gamma spectroscopy - Measurements (symbols) - 40 MeV proton beam, ~2 Gy dose Water sample Beam pipe Lead shielding Ge detector Polf et al, Phys. med. Biol., 54:N519-N527, (2009)

Prompt gamma spectroscopy Determina9on of elemental composi9on from PG spectra Mixed up samples of water + sugar with 25g, 75g, and 130g of sugar added to 130 g of water. The phantom (130 cc) was then filled with the water+sugar solu9on. Polf et al., Phys. Med. Biol., 58: in press (2013). 20

Prompt gamma spectroscopy gammas / incident proton 1.0E- 07 8.0E- 08 6.0E- 08 4.0E- 08 2.0E- 08 water 25g sucrose 75g sucrose 130g sucrose Irradiated samples with proton beam, And measured PG spectra. As carbon increased (oxygen decreased): - - 6.13 MeV 16O PG emission decreased 5.21 MeV 16O PG emission decreased 0.0E+00 0 2 4 6 Gamma energy (MeV) - 4.44 MeV 12C PG emission remained constant. 21

Prompt gamma spectroscopy From emized 16O PGs emized: - - Calibrated #PGs / gram of oxygen 1.64 x 10 7 PGs/gram of oxygen/gy Polf et al., Phys. Med. Biol., 58: in press (2013). - By measuring PG emission, may be possible to determine concentra9on of oxygen in irradiated volume of 9ssue. 22

Conclusions PG emission correlates well to Bragg peak total PG and elemental PG Measuring 1-2 mm shift in BP position may be possible Elemental PG intensity proportional to concentration in irradiated tissue.

How to get to the clinic Experimental detectors need to be further developed into clinical systems Robust method to determine BP shift from PG emission profile Fast method to reconstruct image and overlay onto patient CT data for real-time evaluation.