Compton Imaging for In-Situ Verification of Particle ...

Compton Imaging for In-Situ Verification of Particl e Therapy

From Concept to Demonstration

Kai VetterDepartment of Nuclear Engineering, UC Berkeley

Nuclear Science Division, LBNL

2nd Workshop on Hadron Beam Therapy of Cancer

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2nd Workshop on Hadron Beam Therapy of Cancer

Erice, Sicily, Italy

May 20 - 27, 2011

Outline

• What we normally do in Berkeley …

• Goal of gamma-ray imaging for particle therapy (bri ef reminder…)� State-of-the art detection and imaging: PET imaging of ββββ+ emitters

• Other signatures – The potential …� Discrete lines from many levels of several radioiso topes� Bone vs. Tissue� Excitation functions

• Imaging of prompt gamma rays – The challenge …

� Concept and Implementations of Compton imaging

� Advantages and Challenges

� Image reconstruction – limited angle “tomography”

• Status of first simple demonstration experiment – The reality …

• Summary and outlook – The future …

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What we actually do in Berkeley …

Applications

BeARINGNuclear EngineeringUC Berkeley

Applied Nuclear PhysicsNuclear Science DivisionLBNL

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Research

Radiation Detection

A few examples …

• Fundamental and Nuclear Physics� Gamma-ray tracking arrays for nuclear physics appli cations� Ultra-low noise radiation detection

� Neutrino-less double beta decay in 76Ge – MAJORANA PROJECT

� Coherent neutrino-nucleus scattering

• Gamma-ray imaging� Nuclear physics� Nuclear physics� Astrophysics� Nuclear nonproliferation and safeguards� Homeland security

• Fukushima� Research – Nuclear forensics … understand “fallout” and

distribution of radio-tracers from Japan in environ ment …� Education of general public …

� http://www.nuc.berkeley.edu/UCBAirSampling

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Gamma-Ray Imaging: From µµµµm2 to m 2

50µm

Electron-Tracking based Compton imaging� High-resolution CCD w/ 10 µµµµm pixel size

ier

eer

ger

Large-area coded-aperture imaging� Standoff detection � Machine vision and visual and gamma- ray

image information in 3D

2.5 m

Scientific CCD

5

pixe

l ene

rgy

(keV

)

E = 372 keV

50µm

Compton-scatter induced electron track

Full Cone Back-projection

θ

Φ

Partial Cone Back-projection

2.5 m

100 10x10x10cm 3

NaI detectors

3D object tracking

The “Nuclear Street View”

Goal: Detect weak signal out of complex and changing background• Challenge in all imaging applications: Medical imaging, astrophysics, nuclear safeguards, etc.• Merge gamma-ray spectral and location information with visual and object information in 3D!• Create a data base of 3D radiation “backgrounds” (“clickable” objects, returning spectra on 5-

10 m grid

Examples – Cont’d: MISTI!

• MISTI characteristics– Mobile system w/ communication

and GPS capabilities– Optical and infrared cameras– 100 (4”)3 NaI(Tl) detectors + passive

coded aperture– 28 100% HPGe detectors

➥Excellent identification,

MISTI: Mobile Imaging and Spectroscopic Threat Identification, developed by NRL

� Many useful tools and instruments for research and education at UCB-NE!

➥Excellent identification, localization, and object capture

– Extensive and systematic measurements of backgrounds

– Analysis and modeling of background

– Provide background data and models to DNDO and user community

Goal of Gamma-Ray Imaging for Particle Therapy

• Goal: In-vivo treatment verification� Verify actual beam location in object in-situ� Determine range of particles

� Better translation of gamma-ray emission distributi on to dose distribution in 3D

� Reduce systematic uncertainties in comparative stud ies � Reduce systematic uncertainties in comparative stud ies

• Ideally: Instantaneous verification of irradiation field and particle range!� May be even tracking moving beam for dynamic

treatment?

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Approach and Challenges for Imaging

• Approach: Gamma-ray imaging� Observe annihilation radiation from β+ decay: Positron Emission Tomography (PET) of nuclei

decaying by β+ decay resulting in the emission of two 511 keV photons: C-10, C-11, N-13, O-15, …; β+ emitter are either delivered as a beam or are produced in nuclear reactions induced by protons or heavy ions

� Observe “direct” and prompt gamma-ray decay in situ: Single-Photon Emission Computed Tomography (SPECT) by imaging de-excitation of nuclear states populated in nuclear beam-target reactions; Radioisotope-specific gamma-ray imaging (C-12, O-16, Ca-40, …)

• Challenge:• Challenge:� Convert 3D gamma-ray distribution into 3D dose distribution - Modeling� In situ measurements: Very complex and high flux radiation field, particularly for E/u > 100

MeV/u!

� Photons: Many reaction channels, Bremsstrahlung

� Neutrons

� PET: Long half lives of β+ decay, e.g. in C-11; So far, mainly post-treatment measurements, limited spatial resolution and image quality (e.g. limited angle tomography), washout effects

� SPECT: Sensitivity and resolution at 1-7 MeV?

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Count-rate capabilities, neutron-gamma ray discrimination?

Compare Prompt Gamma (PG) w/ PET (MGH)

M. Moteabbed et al, PMB 56 (2011) 1063“Monte Carlo patient study on the comparison of prompt gamma and PET imaging for range verification in proton therapy”

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Signatures: The Potential …

• Discrete lines from many levels of several radioiso topes

• Protons + PMMA

4,E-03

5,E-03

6,E-03

7,E-03

# o

f G

am

ma

s p

er

Pro

ton 100 MeV 200 MeV 300 MeV

GEANT-4.9

C-12, O-16, H

C-12

4439 keV2+

11

0,E+00

1,E-03

2,E-03

3,E-03

4,E-03

0 0,5 1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 8,5 9 9,5 10

# o

f G

am

ma

s p

er

Pro

ton

Energy (MeV)

4439 keV

0 keV0+

O-16

6049 keV

0 keV

0+

0+

6130 keV

6917 keV7117 keV

3-

2+1-


0,001

0,0015

0,002

0,0025

# o

f G

am

ma

s p

er

Pro

ton

200 MeV 100 MeV 50 Mev

5

7 8


• Protons + PMMA

12

0

0,0005

0,6 1,6 2,6 3,6 4,6 5,6 6,6 7,6 8,6 9,6

# o

f G

am

ma

s p

er

Pro

ton

Energy (MeV)

3 4

6

910

11

131

2

1415

17 1819

7 816

1: .718 MeV

• p + 12C � 2p + n + 10B

2: 1.02 MeV

• p + 12C � 2p + n + 10B

• p + 12C � p + n + 11C

3: 1.4 MeV

• p + 12C � p + n + 11C

4: 1.61 MeV

• n + 12C � p + 12B

5: 2.01 MeV

• p + 12C � p + n + 11C

6: 2.13 MeV

• p + 12C � p + n + 11C

• p + 12C � 2p + 11B

7: 2.23 MeV

• p + 12C � 2p + 11B

8: 2.3 MeV

• p + 12C � 2p + 11B

• p + 16O � n + 2p + 14N

• P + 16O � α + 13N

9: 2.88 MeV

• p + 12C � 2p + 11B

10: 3.33 MeV

• P + 12C � p + n + 11C

• P + 12C � 2p + 11B

11: 4.33 MeV

• p + 12C � p + n + 11C

12: 4.78 MeV

• p + 12C � 2p + 11B

13: 5.02 MeV

• P + 12C � 2p + 11B

14: 5.21 MeV

• p + 16O � 2p + 15N

15: 6.05 MeV

• p + 16O� p + 16O

16: 6.13 MeV

• p + 16O� p + 16O

• p + 16O � 2p + 15N

• P + 16O � p + n + α + 11C

17: 6.48 MeV

• P + 12C � p + n + 11C

18: 6.92 MeV

• p + 16O � p + 16O

19: 7.12 MeV

• p + 16O � p + 16O



• Protons + PMMA GEANT-4.9

0,0015

0,002

# o

f G

am

ma

s p

er

Pro

ton

100 MeV 200 MeV 300 MeV

DetectorDoppler Broadening

13

0

0,0005

0,001

1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8 8,5 9 9,5 10

# o

f G

am

ma

s p

er

Pro

ton

Energy (MeV)


• Bone vs. TissueCan we “track” beam through different materials? GEANT-4.9

Bone

0,004

0,005

0,006

# o

f G

am

ma

s p

er

Pro

ton

300 MeV 200 MeV 100 MeV

14

0

0,001

0,002

0,003

1 1,5 2 2,5 3 3,5 4 4,5 5 5,5 6 6,5 7 7,5 8

# o

f G

am

ma

s p

er

Pro

ton

Energy (MeV)


• Bone vs. TissueCan we “track” beam through different materials? GEANT-4.9

Bone0,0008

0,001

# o

f G

am

ma

s p

er

Pro

ton

Acrylic Bone 6 mm Bone with AcrylicTissue(PMMA)

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0

0,0002

0,0004

0,0006

1 1,5 2 2,5 3 3,5 4

# o

f G

am

ma

s p

er

Pro

ton

Energy (MeV)


• Excitation Functions …Is there complementary information in the gamma-ray emission ?

• Plot #specific gamma rays vs. location/ depth of em ission GEANT-4.9

Tissue (PMMA)

4.4 MeV gamma ray emission vs. depth

Not just C-12 but also B-10 and others6.050 MeV gamma ray emission vs. depth

Depth of penetration

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5.2 MeV gamma ray emission vs. depth718 keV gamma ray emission vs. depth867 keV gamma ray emission vs. depth

�Plenty of physics to be explored and to be used to improve in-beam verification

Imaging of Prompt Gamma Rays: The Challenge …

• Efficiency and resolution achievable in the imaging of 1 MeV – 7 MeV gamma rays?� Challenge: Highly penetrating and only multiple int eractions in detection

process� Collimator-based systems?

� Very limited sensitivity due to thick absorbers (at tenuation and scatter)

� Optical systems?� Optical systems?

� Limited opening angle, very small FOV, multiple int eractions in detections,…

� Compton imaging?

� In principle, very high angular resolution at MeV ga mma rays possible (<< 1 deg)

� Highest sensitivity of all imaging modality

� BUT:

� Range of secondary particles?

� Efficiency and resolution that can actually be achi eved?

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Concept of Gamma-Ray Tracking based Compton Imaging

2cmE

r1

r2r3

r4

θ

1E

γE

12rr

sourcesource� Gamma rays interact several times with detector via Compton

interaction (e.g. until it is stopped by the photo-electrical effect)

� The interaction pathway is determined from the measured positions and energies of individual interactions (tracking)

� Energies and positions of first two interactions define cone of incident angles (electron path is not measured)

� Cones are projected on plane or sphere (one circle per event) for 2D or into cube (one cone per event) for 3D imaging

( )1

2011cos

EEEcmE−

−=γγ

θThe Compton scattering formula gives θ:

4321 EEEEE +++=γ

source

3 components critical for Compton imaging:

� Position Resolution

(distance between first two interactions)

� Energy Resolution

(energy deposition/ scattering angle)

� Intrinsic Electron Momentum

(scattering angle, gamma-ray energy)

� Tracking allows us to distinguish between

gamma rays and neutrons

Advantages and Implementations

• General Benefits of Gamma-Ray Tracking based Compto n imaging� No collimator-based trade-off between efficiency and resolution� No image degradation due to collimator scattering and penetration� 3D tomographic information with limited view (1-2 views)� Compact and flexible systems possible � Excellent spatial resolution for E > 500 keV� Scalable sensitivity� Differentiation of neutrons and photons by gamma-ray tracking� Large Field-of-View

• Implementations• Implementations� Gas detectors, Scintillators, and Semiconductors… � However, combine high sensitivity and 3D position resolution?

⇒ Semiconductor-based instruments� E.g. Si, Ge, CdZnTe, CdTe, …� Energy resolution: ≤ 2%� Position resolution: Combination of 2D segmentation and signal processing⇒ < 1 mm in 3D (high granularity in 3D)

� Efficiency: Density of solid: 2-7 g/cm3; Volumes: 1 - >100 cm3

� Count rate capabilities? Granularity and digital signal processing helps

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Achievable Spatial Resolution

• Determined by Doppler broadening, energy resolution, and position resolution

• Doppler broadening � Angular resolution of 0.5 deg � Angular resolution of 0.5 deg

translates into < 1mm spatial resolution at distances of up to 20 cm

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The Compact Compton Imager CCI

� 2 HPGe +2 Si(Li) large and segmented detectors in two cryostats & 2nd generation digital DAQ� Si(Li): Each 32+32 strips w/ 2 mm pitch size; 10 mm

thickness; 1.9 keV at 60 keV� HPGe: Each 37+37 strips w/ 2 mm pitch size; 15 mm

thickness; 1.7 keV at 60 keV

� Compact, high-bandwidth and resolution preamplifiers� Fully digital data acquisition system� State-of-the art graphical user interface to setup,

monitor, display, and analyze data.

Assembled CCI-2 instrument

Si+Ge detectors

Photo camera

Pre-amplifiers

monitor, display, and analyze data.� Realtime imaging and gating capabilities

detectors

Dewar 20 cm

Si-II Ge-II Ge-ISi-I

“Static” Tomographic Compton Imaging

• Compton imaging enables 3D or tomographic imaging for objects in near field (Distance < Detector dimension/2)

• Experimental demonstration using CCI-1 and iterative image reconstruction:

4 mm

10 mm2 spherical 113Sn sources (391 keV):Diameter: Each 4 mm

DSSD-Si(Li)

CCI-1

Distance: 10 mm

DSSD-HPGe

3D reconstruction to ~ 1 mm with one view!

Two 113Sn Spheres, Iterative Reconstruction

Maximum Likelihood EM algorithm

z [mm]

x [m

m]

-10 -5 0 5 10 15 20

-5

0

5

10

15

20

25


z [mm]

x [m

m]

-10 -5 0 5 10 15 20

-5

0

5

10

15

20

25


-5

0


-5

0

Experimental ResultMaximum Likelihood Expectation Maximization

X vs. Z

X vs. Y


y [mm]

z [m

m]

-55 -50 -45 -40 -35 -30 -25

-10

-5

0

5

10

15

20


y [mm]

z [m

m]

-55 -50 -45 -40 -35 -30 -25

-10

-5

0

5

10

15

20

y [mm]

x [m

m]

-55 -50 -45 -40 -35 -30 -25

5

10

15

20

25

y [mm]

x [m

m]

-55 -50 -45 -40 -35 -30 -25

5

10

15

20

25

X

Y

Z vs. Y

MLEM Reconstruction of line source on background

• Simulated reconstruction results of a 1 mm x 40 mm l ine source on top of background (SNR = 1:5)

Cs-137 line source40 mm long, 1 mm diameter rod

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DSSD-Si(Li)

CCI-1

DSSD-HPGe

� 3D reconstruction of extended source in background w/ ~mm

resolution at 392 keV and 662 keV.

� Imaging at > 2 MeV (4.4 MeV, 6.1 MeV,…) ?

1st Simple Experiment: The (Current) Reality …

• Recent experiment at LBNL to evaluate challenges and opportunities:� Beam: 88” cyclotron to provide “pencil” beam of

protons at 50 MeV� Target: Tissue-equivalent plastic to create

radiation (gamma rays, neutrons, …) + Dosimetry

� Detector: CCI� Challenges: 1mm pencil beam, high-energy

Compact Compton

Imager CCIBeam collimator

(1mm)

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gamma rays, …

Target(1”x1”x2.5” Lucite)

CCI

Reference Ge detector

Measured Photon Spectra from Protons @ 50 MeV in PMM A

Measured Gamma-Ray Spectrum in Reference Ge Detector

C-12: 4.44 MeV

Double-Escape

O-16: 6.30 MeV

• Escape lines – only full-energy deposition is useful for gamma-ray imaging

• Doppler-broadened lines in C-12 due to emission of gamma rays in flight

• Narrow lines e.g. in O-16 due to emission after stopping

• Continuum background

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Single-Escape

Double-Escape • Continuum background

1st Simple Experiment: The (Current) Reality …

�Preliminary, Online Spectrum

�No refined energy calibration

�No event reconstruction yet

• Multiple strip hits

• Charge loss corrections

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Simulated Ge Detector Spectrum

• Protons + PMMA @ 50 MeV• No other materials, collimators, support,…

B10 (p, 3He)B11 (p,2pn)C11 (p,d)

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Energy [MeV]

C-12

O-16

Summary & Outlook: The future …

• Gamma-ray imaging is potentially a very useful tool for beam and dose verification

• PET instruments imaging 511 keV photons are already being used

• Prompt gamma-ray imaging promises additional benefi ts� In-situ imaging – no washout, fast feedback,…� Radioisotope – specific imaging (C, O, N, Ca, …)� Excitation function measurements (additional handle on activity-dose

conversion)� Semiconductor-based Compton imaging promises high s patial

resolution (<1mm) with compact systems and limited views

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Acknowledgements

• UC Berkeley� Joe Miller, Daniel Bond, Department of Nuclear Engineering

• LBNLLucian Mihailescu, Nuclear Science Division� Lucian Mihailescu, Nuclear Science Division

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Questions?

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Comparison PG vs. PET

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Gamma-ray fluxes… (very preliminary)

• Is there enough or too much information?

• For example, 200 Gp (or 2x10 11 protons)/ treatment in 60 s, or about 10 5 p/ mm 3 /min

• Too much?� E.g. ~20% of protons at 200 MeV produce photons resu lting ~ MHz in

detectordetector

• Enough ?� E.g. ~ 1% of protons at 200 MeV produce full energy detection of

usable gamma rays at ~ kHz

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Prompt emission spectra

C-12

N-14

Relative gamma-ray production as a function of proton energy for carbon (triangle), nitrogen (square), oxygen (diamond) and calcium

(circle). Gamma-ray production for all proton energies is normalized to the maximum production for each element.

O-16

Ca-40

JC Polf et al. Phys.

Med. Biol. 54

(2009) 731–743

Proton beams – difference between gamma-ray activity and dose

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Positron emission of C -12 beams

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