Radiobiology at SCIPP

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1 Radiobiology at SCIPP Hartmut F.-W. Sadrozinski Santa Cruz Inst. for Particle Physics SCIPP Loma Linda University Medical Center UCSC Santa Cruz Institute of Particle Physics INFN Florence & Catania

2 Actvities Studies with the 250 MeV Proton Synchrotron at the Loma Linda University Medical Center (LLUMC). Nanodosimetry (ND), Particle Tracking Silicon Microscope (PTSM) Proton computed tomography (pct) Funded by Opportunity funds (Calspace, LLUMC funds) Project Science Impact SCIPP Role Funding Impact within UC ND niche Undergrads small? ~5 papers + techs PTSM 1 paper Undergrads + LLUMC Large (instrument M.S. worm only) community pct Interesting Undergrads, Appl. to NIH Commercialization? >10 papers M.S. for ~$125k/y (Postdoc) 3y grant + techs Long-term Prospects NASA vision If funded, expansion to larger grant likely

3 Nanodosimetry ND ND aims at determining the amount of large ionization clusters in relatively low LET (Linear Energy Transfer) interaction of protons in cells. Large ionization clusters are associated with double-strand breaks in DNA, which lead to irreparable damage. Our introduction of high-precision silicon strip detectors in the low-pressure gas target area to determine the tracks of the protons within the Nanodosimetry set-up has allowed a new level of precision and reliability in the cluster determination.

4 Particle Tracking Silicon Microscope PTSM Localization of Radiation Damage in living cells (C. elegans) C. elegans live!

5 Proton Computed Tomography State University of New York at Stony Brook Loma Linda University Medical Center UCSC Santa Cruz Institute of Particle Physics INFN Florence & Catania

6 The Proton CT Collaboration Proton Treatment: LLUMC Particle Tracking Systems: SCIPP, INFN Firenze Energy Detectors: BNL, LLUMC, INFN Catania Monte Carlo Simulation (GEANT 4): BNL, SCIPP, INFN, SLAC Image Reconstruction: SUNY Stony Brook Goal Develop proton CT for applications in proton therapy Specific Aims Design, construct and test components of a modular proton CT system Develop, test, and optimize a dose-efficient image reconstruction algorithm Evaluate performance of proton CT prototype

7 Why Proton CT? Major advantages of proton beam therapy: Finite range in tissue (protection of critical normal tissues) since cross section fairly flat and low away from peak Maximum dose and effectiveness at end of range (Bragg peak effect) Major uncertainties of proton beam therapy: range uncertainty due to use of X-ray CT for treatment planning (up to several mm) patient setup variability Goal of pct Collaboration Develop proton CT for applications in proton therapy

8 Computed Tomography (CT) XCT: Based on X-ray absorption Faithful reconstruction of patient s anatomy Stacked 2D maps of linear X-ray attenuation Coupled linear equations Invert matrices and reconstruct z- dependent features Proton CT: replaces X-ray absorption with proton energy loss reconstruct mass density (ρ) distribution instead of electron distribution X-ray tube Detector array

9 Proton CT System (Final & prototype)

10 Collaborators KEK Takashi Sasaki SLAC Joe Perl Norman Graf LLUMC Reinhartd Schulte, MD Vladimir Bashkirov, PhD George Coutrakon, PhD Peter Koss, MS SUNY Stony Brook Jerome Z. Liang, PhD Klaus Mueller, PhD Tianfang Li (grad student) INFN Catania Pablo Cirrone, PhD Giacomo Cuttone, PhD Nunzio Randazzo, PhD Domenico Lo Presti, Engineer Valeria Sipali (grad student) Brookhaven National Laboratory Steve Peggs, PhD Todd Satogata, PhD Craig Woody, PhD Florence U. Mara Bruzzi, PhD David Menichelli, PhD Monica Scaringella (grad student) Martha Bucciulini, PhD Santa Cruz Institute of Particle Physics Hartmut Sadrozinski, PhD Abe Seiden, PhD David C Williams, PhD Zhan Lang, PhD Brian Keeney (M.S.) Jason Feldt (M.S.) Jason Heimann (B.S.) Dominic Lucia (undergrad student) Nate Blumenkrantz (undergrad student) Eric Scott (undergrad student) Maureen Petterson (undergrad student)

11 Comparison pct - X-ray CT D ~ 2 σ E 2 ρ d a b

12 Challenge One: Calorimeter Resolution Dose to the patient during imaging depends on the square of the effective energy resolution (including beam straggling) D ~ 2 σ E 2 ρ d 5 Can achieve proton energy resolution much better than energy straggling (~1%) First Experimental Calorimeter Studies for Proton CT at LLUMC, M. C. L. Klock, R. W. Schulte, V.Bashkirov, et al., submitted to Nucl. Inst. Meth.

13 Challenge Two: High-speed DAQ Hardware: Modular Commercial SSD PFME FPGA (NI 6534). Hartmut Sadrozinski et al., IEEE TRANS ON NUCL. SCIE., VOL. 51, NO. 5, 1

14 Challenge Four: Low-Dose Image reconstruction mgy 4 mm 3 mm 2 mm 1.5 mm 1 mm 0.75 mm 0.5 mm a b Object contrast (%) 1.37 mgy Object diameter (mm) ig. 7. Reference system for the simulation study. The phantom is centered at u =15 cm, t = 3.5 cm. The protons arrive along the u direction at plane u = 0 cm. he entry and exit detector planes are at u = 0 cm and u = 30 cm respectively. Images of the phantom shown in Fig. 7 reconstructed from a simulated data set f (a) 35,000 proton histories and (b) 8,750 proton histories per projection. In the left images all holes had an object contrast of 100%, in the center images the ontrast of the top, center, and bottom row of holes was 30%, 20%, and 10%, respectively, and in the left images

15 Challenge Four: Image of Al Annulus Subdivide SSD area into pixels 1. Strip x strip 194um x 194um 2. 4 x 4 strips (0.8mm x 0.8mm) Image corresponds to average energy in pixel Initial studies on proton computed tomography using a silicon strip detector telescope, L. Johnson et al., NIM. A 514 (2003) 215

16 Challenge Three: The most likely path ( banana ) The most likely path of an energetic charged particle through a uniform medium D C Williams Phys. Med. Biol. 49 (2004) Measurement of entrance and exit angles constrain the most likely path 200 MeV Protons, 20 cm water, most likely, 1 σ and 2 σ path Goal of the Beam Test: Verify the MLP Predictions

17 Beam Test for Proton Computed Tomography PCT (aka Mapping out The Banana ) Most likely Path MLP Beam Test Set-up Comparison with MLP Localization Accuracy Florence & Catania Loma Linda University Medical Center UCSC Santa Cruz Institute of Particle Physics

18 Beam Test setup In and out telescopes measure entrance and exit location and angle Roving module in between absorbers measures the 2-D displacement wrt beam = banana Move roving module through the segmented absorber GLAST BT 97 Silicon Telescope single-sided SSD, pitch = 236 µm. 2 nd rotated by 90 o GLAST GTFE32 readout chips, 32 channels each, serial data flow. Replace large scale GLAST readout (VME, Vxworks software) by commercial FPGA and NI 6534 PCI card

19 Measured Beam profile First Data: Beam Profile Angle-position correlation: θ x = *x/mm θ y = *y/mm Fuzzy Source at L= 1/0.0002= 5m Beam Divergence σ B = Proton Angle Proton Position Translate and rotate coordinates such that entrance is at (0,0) with zero angle Measure outside parameters: Displacement y Measure inside parameter: exit angle θ Displacement yl in roving module vs. absorber depth

20 MCS at Work Correlation between exit displacement and angle Exit Angle Displacement Without Absorber Map out Beam Dispersion Limited by Beam Spread With Absorber Angular Spread given by multiple scattering ~ 3 degrees Strong correlation between angle and displacement due to multiple scattering

21 Exit Displacement & Angle Correlations Displacement in Absorber Displacement in Absorber Exit Displacement Displacement in Roving Module is correlated with exit displacement Y Exit Angle Displacement in Roving Module is anti-correlated with exit angle blue:

22 First Results: < 500 µm Localization within Absorber Displacement [cm] RMS = 490um MLP width = 380 um Depth inside Absorber [cm] Displacement from incoming direction in the Roving planes as a function of exit displacement bins of 500 µm (all angles). Analytical calculation of the most likely path MLP (open symbols: the size of the symbol is close to the MLP spread). Fairly good agreement data - MLP, but systematically growing difference with larger displacements: need to incorporate absorber-free distance (M.C.) Resolution inside Absorber better than 500 µm vs. MLP width of 380 µm Resolution ultimately limited by Beam Spread

23 Angle Cut improves Localization Displacement in the roving modules for an exit displacement of 2 mm, Select 3 narrow exit angle bins : Mean Mean + 1 σ Mean 1 σ Observe expected negative correlation Refine banana localization by ~ 200 um Resolution improves wrt no angle selection Displacement [cm] rad rad 0.00 rad Spread in Roving Module [cm] Selection on Angles z [cm] All rad rad 0.0 rad MLP Depth inside Absorber [cm] pct design validated: measure both exit displacement AND angle with high precision

24 Beam Test Conclusions Si tracker affords compact, high resolution position and angle measurement First results show localization within phantom to better than 400 um Simple analysis confirms prediction of MLP on the < 200 um level (improvement expected when air gaps are included) Improvements: Increased precision of input parameters (entrance angle) to correct for beam divergence Calorimeter DAQ Geant4 description of data Banana in non-uniform medium Next Steps: NON-uniform phantom (non-uniform density and/or shape, small animal) pct Reconstruction: FBP, Layer-by-layer deconvolution

25 SCIPP Radiobiology Conclusions Valuable Technology Transfer Perfect small-scale Project for Students Funding in US a problem Opportunity funds and Student projects (Master s and Senior Theses) Growing Interest in Medical and GEANT4 Community INFN has started PRIMA Project (Gruppo V) with LNS-Catania, Florence (Energy Dept., Medical School)