Radiobiology at SCIPP
Hartmut F.-W. SadrozinskiSanta Cruz Inst. for Particle Physics SCIPP
Loma Linda University Medical Center
UCSC Santa Cruz Institute of
Particle Physics
INFN Florence& Catania
Actvities
Project Science Impact
SCIPP Role Funding Impact within UC
Long-term Prospects
ND “niche” ~5 papers
Undergrads + techs
small ?
PTSM 1 paper (instrument only)
Undergrads + M.S.
LLUMC Large “worm community”
NASA “vision”
pCT Interesting >10 papers
Undergrads, M.S. (Postdoc) + techs
Appl. to NIH for ~$125k/y 3y grant
Commercial-ization?
If funded, expansion to larger grant likely
• 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)
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.
Particle Tracking Silicon Microscope PTSM
• Localization of Radiation Damage in living cells (C. elegans)
“C.” elegans live!
Proton Computed Tomography
Loma Linda University Medical Center
State University of New York at Stony Brook
UCSC Santa Cruz Institute of
Particle Physics
INFN Florence& Catania
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
http://scipp.ucsc.edu/pCT/
•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
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
Computed Tomography (CT)
X-ray tube
Detector array
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
Proton CT System (Final & prototype)
CollaboratorsBrookhaven National Laboratory
Steve Peggs, PhDTodd Satogata, PhDCraig Woody, PhD
Florence U. Mara Bruzzi, PhDDavid Menichelli, PhDMonica Scaringella (grad student)Martha Bucciulini, PhD
Santa Cruz Institute of Particle PhysicsHartmut Sadrozinski, PhDAbe Seiden, PhDDavid C Williams, PhDZhan Lang, PhDBrian 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)
KEKTakashi Sasaki
SLACJoe PerlNorman Graf
LLUMCReinhartd Schulte, MDVladimir Bashkirov, PhDGeorge Coutrakon, PhDPeter Koss, MS
SUNY Stony BrookJerome Z. Liang, PhDKlaus Mueller, PhDTianfang Li (grad student)
INFN CataniaPablo Cirrone, PhDGiacomo Cuttone, PhDNunzio Randazzo, PhDDomenico Lo Presti, EngineerValeria Sipali (grad student)
Comparison pCT - X-ray CT
2
2
~ Dd
E
⋅∆ ρσ
b
a
Challenge One: Calorimeter Resolution
• Can achieve proton energy resolution much better than energy straggling (~1%)
52
2
~ Dd
E
⋅∆ ρσ
• Dose to the patient during imaging depends on the square of the effective energy resolution (including beam straggling)
“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.
Challenge Two: High-speed DAQ
SSDPFME
FPGA
Hardware:Modular Commercial
Hartmut Sadrozinski et al., IEEE TRANS ON NUCL. SCIE., VOL. 51, NO. 5, 1
(NI 6534).
Challenge Four: Low-Dose Image reconstruction3
mm
2 m
m
1.5
mm
0.5
mm
4 m
m
1 m
m0.
75 m
m
b
a
0.1
1
10
100
0.1 1 10
Object diameter (mm)
Obj
ect c
ontr
ast (
%)
5.48 mGy1.37 mGy
Fig. 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. The 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 of (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 contrast of the top, center, and bottom row of holes was 30%, 20%, and 10%, respectively, and in the left images
Challenge Four: Image of Al AnnulusSubdivide SSD area into pixels1. Strip x strip 194um x 194um2. 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
Challenge Three: The most likely path (“banana”)
Measurement of entrance and exit anglesconstrain the most likely path
The most likely path of an energetic charged particle through a uniform mediumD C Williams Phys. Med. Biol. 49 (2004) 2899–2911
200 MeV Protons, 20 cm water, most likely, 1 σ and 2 σ path’
Goal of the Beam Test:
Verify the MLP Predictions
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
UCSC Santa Cruz Institute of
Particle Physics
Loma Linda University Medical Center
Florence & Catania
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. 2nd rotated by 90o
GLAST GTFE32 readout chips, 32 channels each, serial data flow.
Replace large scale GLAST readout (VME, Vxworkssoftware) by commercial FPGA and NI 6534 PCI card
First Data: Beam Profile
Measured Beam profileAngle-position correlation:θx = -0.005+0.0002*x/mmθy = -0.003+0.0002*y/mm
“Fuzzy”Source at L= 1/0.0002= 5mBeam Divergence σB = 0.005
Prot
on A
ngle
Proton PositionTranslate and rotate coordinates such that
entrance is at (0,0) with zero angleMeasure outside parameters: Displacement y
exit angle θMeasure inside parameter: Displacement yl
in roving module vs. absorber depth
MCS at Work
Correlation between exit displacement and angle
• Without Absorber
Map out Beam Dispersion Limited by Beam Spread
• With Absorber
Angular Spread given by multiple scattering ~ 3 degreesStrong correlation between angle and displacement due to multiple scattering
Displacement
Exit
Ang
le
Exit Displacement & Angle CorrelationsD
ispl
acem
ent i
n A
bsor
ber
Dis
plac
emen
t in
Abs
orbe
rExit Displacement Exit Angle
Displacement in Roving Module is correlated with exit displacement Y
Displacement in Roving Module is anti-correlated with exit angle blue:
First Results: < 500 µm Localization within Absorber
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
-0.5-0.4-0.3-0.2-0.1
00.10.20.30.40.5
0 2 4 6 8 10 12 14 16 18 20Depth inside Absorber [cm]
Dis
plac
emen
t [cm
]
RMS = 490um
MLP width = 380 um
Angle Cut improves Localization
0
0.05
0.1
0.15
0.2
0.25
0 5 10 15 20 25Depth inside Absorber [cm]
Dis
plac
emen
t [cm
]
0.018 rad0.036 rad0.00 rad
z [cm] All 0.018 rad 0.036 rad 0.0 rad MLP5 0.038 0.033 0.029 0.034 0.0277.5 0.049 0.043 0.041 0.041 0.03814 0.054 0.039 0.035 0.038 0.031
Selection on Angles
Displacement in the “roving” modules for an exit displacement of 2 mm, Select 3 narrow exit angle bins :Mean Mean + 1 σMean –1 σ
Observe expected negative correlationRefine banana localization by ~ 200 um Resolution improves wrt no angle selection
Spread in Roving Module [cm]
pCT design validated:
measure both exit displacement AND angle
with high precision
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
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)