Position-Sensing Photon Position-Sensing Photon Detectors (for Positron Detectors (for Positron Emission Tomography)Emission Tomography)

Simon R. Cherry

Department of Biomedical Engineering

Center for Molecular and Genomic Imaging

University of California, Davis

In Vivo Biomedical Imaging Technologies

Anatomic Physiologic Metabolic Molecular

PET/SPECT

x-ray CT

MRI

ultrasound

optical imaging

Positron Emission Tomography

PET quantitatively and non-destructively measures the 3-D distribution of radiolabeled biomolecules in vivo

Primary tasks for imaging physics/engineering:–detect as many events as possible (sensitivity)–put events in the right place (spatial resolution)–make corrections and reconstruct quantitative

images (Bq/cc)

+ Decay and Annihilation

QuickTime™ and aSorenson Video 3 decompressorare needed to see this picture.

Positron Emission Tomography• Inject radiotracer• Detect (scintillation detectors) two

annihilation photons in coincidence• Defines line along which

annihilation lies• Collect ~107-108 events• Use reconstruction algorithms to

compute image of radiotracer distribution using all the different angular views

• Analyze data– Lesion detection

– Quantify radiotracer distribution

– Tracer kinetics

PET Radionuclides and Labeled ProbesSmall molecules

• enzyme substrates, ligands, drugs…

Peptides• receptor targeted…

Antibodies• fragments, minibodies, diabodies

Reporter Genes• enzyme-based, receptor-based

Cells• T-cells, stem cells…

Particles• Liposomes, lipospheres, nanoparticles…

T1/2

11C 20.4 mins18F 110 mins64Cu 12.6 hrs68Ga 68 mins89Zr 3.3 days124I 4.2 days

PET Radionuclides

PET Imaging in Cancer18F-Fluorodeoxyglucose

Images courtesy of GE Medical Systems

[18F]-fluoro-2-deoxy-D-glucose

Preclinical In Vivo Imaging Bridging the Divide

GENOMICS/PROTEOMICSCOMBINATORIAL CHEM

IN VITRO, EX VIVO IN VIVO

In Vivo

Imaging

MEDICAL DIAGNOSTICS AND THERAPEUTICS

Small Animal Imaging

Requires both:High spatial resolution - mouse organs ~1000-fold smaller volume than humanHigh sensitivity - number of targets also smaller, radiation dosimetry can be limiting

Spatial Resolution and Sensitivityspatial resolution determined by detector width

Spatial Resolution and Sensitivitysmaller detectors yield better resolution and better sampling

Spatial Resolution and SensitivityThicker detectors improve sensitivity, but spatial resolution degrades due to parallax effects

€

sensitivity∝ (1−e−μd )2

Spatial Resolution and SensitivityThicker detectors improve sensitivity, but spatial resolution degrades due to parallax effects

€

sensitivity∝ (e−μd )2

Requirements

• High Sensitivity– High efficiency (thick) detectors– High solid angle coverage

• Small Detector Ring Diameter • Long axial extent

• High Spatial Resolution– Very small cross-section detector elements– Depth-Encoding Detectors

Approaches

• Scintillation Detector– Photomultiplier tube (PMT)– Avalanche photodiode (APD)– Silicon photomultiplier (SiPM)

• High Density Semiconductors– CdTe or CZT– Ge– TlBr

PET Scintillators

Scintillator 90% efficiency (cm)

Light output

(photons/MeV)

Decay time

(nsecs)

BGO 2.4 7,000 300

BaF2 5.1 2,000 0.8

CsF 5.4 1,900 4

LSO, LYSO 2.6 25,000 42

LaBr3 4.9 60,000 27

LuI3 4.1 100,000 30

Factors Determining Spatial Resolution

Crystal width

Positron range

Scanner geometry

Non-colinearity

Depth of interaction

Detector scatter

How narrow should the crystals be?

What is the best resolution achievable

with PET?

Positron Range

511 keV

positron range

511 keV

Positron Range

fluorine-18(0.64 MeV) carbon-11

(0.97 MeV)

nitrogen-13(1.19 MeV)

oxygen-15(1.72 MeV)1 mm

Exponential distribution, range depends on energy of emitted positrons

Non-Colinearity

511 keV

511 keV180 ± 0.25°

Non-colinearity

• Annihilation photons emitted with angle of 180° ± 0.25°

• Non-colinearity blurring given by 0.022 x detector separation at center of scanner

D= 80 cm

R180° = 1.8 mm

D= 12 cm

R180° = 0.26 mm

Spatial Resolution in PET

Detector Interactions2 cm LSO (log scale)

Small Animal Scanner (D = 8 cm)

Human Whole-Body Scanner (D = 80 cm)

Positron Range18F

1 mm

Total

R~2.0 mm

R~0.4 mm

Non-Colinearity

Effect of Detector Size in Small Animal PET

“best” achievable resolution

detector size 1.5 mm1.0 mm0.5 mm0.25 mm

1 mm

Resolution versus Detector Size18F tracer, 8 cm diameter scanner

FWTM

Manufacturing of LSO ArraysStart off with a solid LSO crystal1

Slice the crystal to a desirable thickness (i.e. 0.5 mm) and glue reflector between the slices of scintillator

2

Glue the slices of scintillator together with the reflector between the scintillator slices.

3

Rotate the block 90°4

Again, slice the crystal to a desirable thickness (i.e. 0.5 mm) and glue reflector between the slices of scintillator

5

Glue the slices of scintillator together with the reflector between the scintillator slices.

6in collaboration with Agile Engineering

LSO Arrays

• 56 x 56 array• 0.22 x 0.22 x 20 mm elements• 90:1 aspect ratio• Vikuiti ESR specular reflector

in collaboration with Agile Engineering

• Down to ~220 micron pixels• Up to 20 mm thick• Diffuse or specular reflectors

– Vikuiti ESR (3M) (65 µm)– Lumirror E20 (Toray) (50 µm)

Photomultiplier Tubes

• PMTs (arrays of individual PMTs, MC-PMTs or PS-PMTs) struggle to resolve LSO arrays with element sizes much less than 0.5 mm.

0.5 x 0.5 x 10 mm elements Hamamatsu M64 MC-PMT

Flood Histogram

Limitations• Resolution limited by

– brightness of scintillator– light transport to PMT– quantum efficiency of PMT (~20%)– Size of anode structures (~ 2-4 mm)

• Solution - solid state detectors?– Finer feature sizes– Higher quantum efficiency– Considerations

• Gain, noise, timing, area, # of channels…

Depth-Encoding Detectors

“phoswich” design

photo-detector

photo-detector photodetector

photodetector

“offset” design “dual-ended” design

discrete depth informationcontinuous

depth information

Avalanche Photodiodes• compact Si devices• electric field high enough for

multiplication of e-h pairs• magnetic field insensitive• range of sizes• monolithic arrays available

– but need lots of electronics

• compared with PMTs– lower gain– sensitive to temperature and bias

voltage

p+ drift region

avalanche regionn+ Si substrate +V

Position-Sensitive Avalanche Photodiodes

Si avalanche photodiode with position-

sensitive resistive anode - only four

readouts from entire surface

Active area: 8x8 to 28x28 mm

Gain ~ 1000 at 1750 V

Noise = 200 e– (FWHM)

Q. E. ≥ 60 % (400-700 nm)

Rise time ~ 1 ns

Capacitance 0.7 pf/mm2

Depth-Encoding PET Detectors

13 x 13 LSO array(0.5 x 0.5 x 20 mm3

elements)

PSAPD 1 (8 x 8 mm2)

PSAPD 2(8 x 8 mm2)

Flood Histograms and Energy Resolution

room temperature 10°C 0°C –10°C

Crystal Size Reflector Energy Resolution (%)

0.5 x 0.5 x 20 mm3 Specular (ESR) 19.8 +/- 3.0

Diffuse (Toray) 21.1 +/- 4.9

Depth of Interaction ResolutionPSAPD

Average DOI resolution

1.9 mm +/– 0.2 mm

Energy ratio = E1/E1+E2

Intrinsic Spatial ResolutionRectangle, all events

0

1000

2000

3000

4000

5000

6000

1 4 7 10 13 16 19 22 25 28 31 34 37

Source position

Counts

MeasurementGaussian fit

FWHM: All events: 0.674 mm Photopeak: 0.681 mm Compton: 0.662 mm

New Small Animal PET Scanner Design with Depth-Encoding Detectors

1.6 x higher sensitivity

Beyond APDs - SiPMs

• Silicon Photomultipliers– Higher gain– Faster response time– Low bias voltage (tens of volts)– Less dependence on bias and temperature

– Non-linearity at higher light levels– Dark noise a problem at very low light levels– Less mature technology

SiPM Structure

“low” light level

“high” light level

Solid State Photomultipliers (SSPMs)• CMOS process

– Lower cost for mass production

– On-chip integration with electronics possible

Position-Sensitive SPPMs

Pixel Level PS-SPPMs

Summary• LSO arrays with pixel sizes as low as 0.22 mm and

as thick as 20 mm can be fabricated for high resolution PET

• Dual-ended readout of these arrays with PSAPDs provides good crystal identification and depth encoding ability

• PS-SPPMs in a similar design may provide even better performance in the future

• Such detectors provide a pathway to constructing small animal PET scanners at or close to the physical resolution and sensitivity limits.

AcknowledgmentsInstrumentation & Preclinical Molecular ImagingSimon CherryYongfeng YangGregory MitchellYibao WuChangqing LiEmilie RoncaliSara St. JamesMelissa FreedenbergBo PengRuby GillJulien Bec

Computational Molecular ImagingJinyi QiGuobao WangNannan CaoLin FuMichel TohmeJinxiu Liao

Clinical Molecular Imaging PhysicsRamsey BadawiAbhijit ChaudhariJonathan PoonSpencer BowenFelipe Godinez

Radiation Monitoring Devices Inc.Kanai ShahRichard FarrellPurushottam DokhaleMickel McClishChristopher StapelsErik JohnsonJames Christian

Keith Vaigneur (Agile Engineering)

Recent Lab MembersCiprian Catana (MGH/Harvard)Bernd Pichler (U. Tübingen)Martin Judenhofer (U. Tübingen)Jennifer StickelHongjie Liang (Philips Medical)Huini Du (Toshiba Medical)Shrabani Sinha

Funding:National Institutes of Health R01 EB000993 R01 EB006109 R01 CA134632Department of Energy DE-FG02-08ER64677