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)