N. Belcari, M. Camarda, A. Del Guerra, A. Motta, S. Righi, A. Vaiano

Department of Physics, University of Pisa and INFN Sezione di Pisa,

Via F. Buonarroti 2, I-56127 Pisa (Italy)

SienaSiena20022002

8th Topical Seminar on Innovative Particle and Radiation Detectors 21 - 24 October 2002 Siena, Italy

G. Di Domenico, G. ZavattiniDepartment of Physics, University of Ferrara and

INFN Sezione di Ferrara, Via Paradiso 12, I-44100 Ferrara (Italy)

Novel high resolution detectors for Novel high resolution detectors for

Positron Emission Tomography (PET)Positron Emission Tomography (PET)

Outline of the talkOutline of the talk

Positron Emission Tomography (PET)

• Clinical PET

• Dedicated PET systems

Novel detectors for High Resolution PET

• Requirements

• PS-PMT

• Multi-Pixel HPD

Positron Emission Tomography (PET)

• Clinical PET

• Dedicated PET systems

Novel detectors for High Resolution PET

• Requirements

• PS-PMT

• Multi-Pixel HPD

Ring geometry Parallel plane geometry

511keV photon

511keV photon

PET principlePET principle• A + emitting radiotracer is injected to a “patient”

• The radiotracer marks a specific function (e.g. glucose metabolism) - Uptake process

•The positron annihilates with an electron and one pair of nearly collinear 511keV photons are emitted in opposite direction.

• A set of detectors surrounding the “patient” detects the pair of photons (time coincidence) (,Z or X,Y coordinates of the point of interaction)

• An algorithm performs the 3-D reconstruction of the activity density within the body.

Physical problem:Physical problem:

Position sensitive detection of both the 511 keV annihilation photons

Matrices of scintillators are usually used for the

photon detection

Fast, good energy resolution, high Z

Material Density[g/cm3]

Atomicnumbers

Light yield[%NaI(Tl)]

Decay time[ns]

Peak wavelength[nm]

Index ofrefraction

NaI(Tl) 3.76 11,53 100 230 410 1.85

BGO 7.13 83,32,8 15 300 480 2.15

LSO 7.4 71,32,8 75 40 480 1.82

CsI(Tl) 4.51 55,53 45 1000 565 1.80

YAP:Ce 5.37 39,13,8 55 27 370 1.95

YAP:Ce matrix4cm 4cm 3cm

(400 elements,2 2 30 mm3 each)

For the position determination we have to determine the crystal

where the interaction occurs Position Sensitive Photodetector

PIXEL IDENTIFICATION!PIXEL IDENTIFICATION!

• Higher spatial resolution ( <3mm FWHM for PEM) to reliably detect small tumors (< 5 mm Ø)

( <2mm FWHM for Small Animal PET) to detect very small structures (hot spots)

• Higher sensitivity to reliably detect very low specific activity (1Ci/cc) with a low uptake ratio

(hot spot/Background < 10) in a short time (10-20 min.)

• Better handling (easier positioning of the mouse or of the breast within the FoV)

• Application specific design (Rat or Mice for Small Animal PET), (Fit the breast for Axillary lymph

nodes scanning or compression mode PEM)

• Multimodality scanning (PET-SPECT, RX-PEM)

• Use of a reduced number of detectors reduction of cost

Needs of dedicated scannersNeeds of dedicated scanners

Whole body PET scanners

For specific application such as “small animal functional imaging” or “Positron Emission Mammography (PEM)” dedicated scanners are needed so as to offer:

• 2% Solid Angle Coverage• 4-8 mm spatial resolution• High cost for routine scanning

Spatial Resolution RequirementsSpatial Resolution Requirements

Human body: ~70 kgHeart mass: ~300 gAorthic cannula Ø: ~ 30 mm

Rat body: ~200 gHeart mass: ~1 gAorthic cannula Ø: 1.5 - 2.2 mm

Mouse body: ~20 gHeart mass: ~0.1 g Aorthic cannula Ø: 0.9 - 1.3 mm

4-8 mm FWHM 4-8 mm FWHM (60 - 500 mm(60 - 500 mm33))

2 mm FWHM 2 mm FWHM (8 mm(8 mm33))

1 mm FWHM 1 mm FWHM (( 1 mm 1 mm33))

Relative heart size heart size

Required spatial resolutionRequired spatial resolution

How to achieve this ?How to achieve this ?How to achieve this ?How to achieve this ?

• Small size detectors (high pixellization)

• Individual detectors or “perfect” coding

Sensitivity RequirementsSensitivity Requirements

• Imaging of low activity sources • low uptake processes such as in small cancers

• Imaging of small hot spots

• discrimination of small regions with a low spot/background ratio

How to achieve this ?How to achieve this ?How to achieve this ?How to achieve this ?

• High geometry efficiency (large solid angle covered by detectors)

• High detection efficiency (e.g. for crystals: high Z, high density)

Detectors for High Resolution PETDetectors for High Resolution PET

Detector configuration- Detector configuration- Light sharingLight sharing

BA

DC

CDBA

BADCY

CDBA

DBCAX

X

Y

*Casey & Nutt, IEEE TNS 33 (1986) 460-463

CTI Exact HRdetector block*

A BGO block is saw at different depth. The cuts are filled with a reflective material and provide a light guide to the PMTs.

The light distribution is measured by 4 PMTs

Center of gravity calculation for X and Y

Identification from a LUT

Advantages

• Reduction of the number of PMT • Cheap• Easy to pack

Drawbacks

• Loss of resolution

- Statistical light sharing

- Distortion

- Pileup at high count rate

Detector configuration- Detector configuration- Individual couplingIndividual coupling

Early PET detector elementEarly PET detector element

Single PMT

Scintillator block(BGO)

+ Simple coding

(“parallel” operation)

- Difficult to pack

- Expensive

Novel configurationNovel configuration

Matrix ofscintillators(BGO/LSO)

Array or independentphotodiodes (APD)

+ Simple coding

(“parallel” operation)

+ High spatial resolution

with no distortion

+ Small size

+ High count rate

- Quite difficult to pack

- Tricky tuning

- Gain dependence on

bias & temperature

- Expensive

Si APD array (8×4)Hamamatsu S8550

A detector module made of a 8×4 LSO matrix couped to a

Hamamatsu S8550 (Pichler B., IEEE TNS 45

(1998) 1298-1302)

Electronic codingElectronic coding - PS-PMT readout (Single tube) - PS-PMT readout (Single tube)

Flood field irradiation(122 keV) of a 20 × 20 crystals(2 mm × 2 mm each)

YAP:Ce matrix read by a Hamamatsu R2486 (resistive readout)

A single position sensitive PMT is used for the identification of the hit crystal in a scintillator matrix

Advantages• Large active area (up to 100 mm Ø)• Good spatial resolution (up to 0.5 mm FWHM)• Good uniformity• Limited number of channels (up to 28 x + 28 y

crossed wire anodes) • Easy to use with a resistive chain (4 channels)

Drawbacks• Distortion at the borders• Low packing fraction (limited active area) • Round shape (difficult to pack)

The PS-PMT R2486 by Hamamatsu.• Active area 50 mm Ø• 16 x + 16 y anodes

Electronic codingElectronic coding -- PS-PMT readout (Multi tube)PS-PMT readout (Multi tube)

An array of densely packed small and square position sensitive PMT is used to build a large areaphotodetector for the readout of a scintillator matrix

Flood field irradiation(122 keV) of a matrix of scintillators read by a Hamamatsu R8520-C12

(single tube, resistive readout)

The PS-PMT R8520-C12 by Hamamatsu.

• Active area 22 mm × 22 mm

• 6 x + 6 y anodes

Advantages• Higher packing fraction with respect to round tubes

(up to 73%)• Good spatial resolution • Good uniformity• Easy to use with a resistive chain (4 channels)Drawbacks• Dead area between adjacent PMTs• Small active area for each tube

CsI:Tl matrix, 8 × 8 crystals (2.8 mm × 2.8 mm each)

YAP:Ce matrix, 11 × 11 crystals (2mm × 2mm each)

PS-PMT readout - Multi tubePS-PMT readout - Multi tuberecovery of dead area - light sharingrecovery of dead area - light sharing

Transparentwindow

Flood field (122 keV) image of a matrix of a NaI(Tl) crystals (2 × 2 × 6 mm3 each) coupled to an array of four R7600-C12 via the transparent window of the NaI matrix*

*Courtesy of R. Pani, University of Rome, La Sapienza

+ Simple and cheap - Resolution worsening

- Requires enough light

yield

Matrix of scintillators

FWHM1.4 mm

FWHM pixel (1.0 mm)

Hamamatsu R8520-C12 readout Hamamatsu R8520-C12 readout Effect of: Quartz window - White reflectorEffect of: Quartz window - White reflector

Direct contact (optical grease)

3mm quartz window (optical grease)

White reflector(about 15% more light with a white reflector)

NO

FWHM0.7 mm

FWHM 1.1 mm

FWHM0.8 mm

YES

Direct contact (optical grease)

3mm quartz window (optical grease)

YAP:Ce Matrix25 crystals

2230 mm3 eachYAP:Ce Matrix

121 crystals2230 mm3 each

White reflector

YAP:Ce matrix

Quartz window

Hamamatsu R8520-C12 (resistive readout)

NO

511 keV source

Two Hamamatsu R8520-C12

(resistive readout)

Quartz window 3 mm thick

Hamamatsu R8520-C12 readout - Multi tubeHamamatsu R8520-C12 readout - Multi tuberecovery of dead area - Quartz windowrecovery of dead area - Quartz window

Flood field irradiation of the YAP matrix 1124 crystals (511 keV). All crystals can be identified

YAP matrix 1124 crystals(2mm 2mm 30mm each)

White reflector

22Na source

BGO crystal + PMTfor selecting 511keV annihilation photons

22mm

22m

m

Two rows of crystals (2 mm +2 mm) outsidethe active area

FOP(Fiber Optic

Plate)

+ Linear demagnification of the image

- Expensive

PS-PMT readout - Multi tubePS-PMT readout - Multi tube

recovery of dead area - fibersrecovery of dead area - fibers

Matrix of scintillators

Matrices of scintillators

Fiber optic bundle (individual coupling)

+ No demagnification

- Only for ring configuration

Example: the detector element of the MicroPET®

8×8 LSO matrix

8 × 8 array of 2 mm square fibres by Kuraray

PS-PMT Hamamatsu R7600-C8

Hamamatsu Flat Panel Multi Anode PMTHamamatsu Flat Panel Multi Anode PMT

Hamamatsu R8500Hamamatsu R8500

See next talk at this conference

“Flat Panel PMT: advances in position sensitive photodetection”

R. Pani, University of Rome

Array of 4 R8520 R8500 Flat PanelR2486

ComparisonComparison

Application: readout of a 5 cm × 5 cm matrix of scintillating crystals

77%77%(better than 92% with a quartz window)(better than 92% with a quartz window)

96%96%78%78%Active area

See next talk

What is an HPD (Hybrid Photo Diode)* ?What is an HPD (Hybrid Photo Diode)* ?

Main characteristicsMain characteristics

• Good quantum efficiency• Low noise • Single photon counting capabilities• Single or Multi - pixel structure

•Very low output signal (Low noise and high gain readout electronics is crucial)• HV (up to tens kV required)

Picture from: http://ssd-rd.web.cern.ch/ssd-rd/Pad_HPD/Principle/HPD_principle.htm

Available HPD structures:

Proximity focusedProximity focused: Electrons reach the Si sensor by straight lines (no demagnification) (multi-pixel: up to 73 pixel, up to ~1” Ø, good spatial resolution)

Fountain focusedFountain focused: Electrons are focused on the Si sensor (linear demagnification)(multi pixel: up to 73 pixel, up to ~ 3” Ø, poorer spatial resolution, spherical entrance window)

*R. de Salvo et al. NIM A315 (1992) 375-384

Multi Anode HPD - WLS Fibres readoutMulti Anode HPD - WLS Fibres readout

To 61 Pixel HPD

Scintillator matrix

WLS fibres

To 61 Pixel HPD

• Large number of crystals and large area crystal read out

• Separation of scintillating crystal from detector and read out electronics

• No dead zone around the detector

• Possibility of Z coordinate

measurement

YAP:Ce matrix

WLS fibres by Kuraray61 pixel HPD proximityfocusing by DEP ~1”

~10 p.e. for 511keV (22Na source) (photopeak event)*

Not enough light yield!

2.5 p.e. for 122keV (57Co source)*

*N. Belcari et al. NIM A461 (2001) 413-415

DEP HPD 61 PIXEL

HAMAMATSUPMT R-5900

4 4 YAP:Ce MATRIX

2 mm 2 mm

12 mm12 mm

2 mm2 mm

Four peaks of the second row: the peak-to-valley ratio is about 4.

3-D profiles of 4 2 crystals of a YAP:Ce matrix (2 mm side each ). Pixels are clearly separated.*

*N. Belcari et al. Presented at the conference “New Developments in Photodetection” Beaune, June 17-21, 2002 (NIM 2002)

Multi Anode HPD - Direct readoutMulti Anode HPD - Direct readout

Larger HPD with higher pixellization will be soon available.A 5” HPD is producedat CERN**A. Braem et al., NIM A 478 (2002) 400-403

Multi anode HPDs can be used as a PS-PMT for the direct readout of a matrix of scintillating crystals and readout by electronic coding.

Overall diameter 5" = 127 mmActive diameter 114 mmEntrance window Borosilicate glass, cut off < 250 nmField configuration Fountain shape, defined by 3 ring electrodesDemagnification 2.3<D<2.7Photocathode Bialkali (K2CsSb), semi-transparentSilicon sensor 300 mm thick, 50 mm diam., 2048 pads, 1 x 1 mmCurrent electronics 16 Viking VA3 chips, ENC <300 eFinal electronics (?) 16 Viking VATAGP, self-triggeringMax. HV ca. 20 kV

Multi Anode Large area HPD - Direct readoutMulti Anode Large area HPD - Direct readout

• 5” Pad HPD produced @ CERN

• Optimized for medical applications

• Spherical window + bundled small fibers or Fiber Optic Plate (FOS)

• K2CsSb photocatode

Near ?? future Near ?? future

Still a dream*Still a dream*

Further developments are needed in order to make this technology available. New devices and new front-end electronics (low noise-high gain-fast triggering preamplifiers) are necessary.

*C. Joram et al. Presented at the conference “New Developments in Photodetection” Beaune, June 17-21, 2002 (NIM 2002)

• To fulfil the spatial resolution and sensitivity requirements dedicated To fulfil the spatial resolution and sensitivity requirements dedicated instruments are needed.instruments are needed.

• Many different technologies are actually used in these scanners.Many different technologies are actually used in these scanners.

• Scintillator crystals (BGO, LSO, YAP)Scintillator crystals (BGO, LSO, YAP)

• Position sensitive PMT (electronic coding)Position sensitive PMT (electronic coding)

• Avalanche Photo Diode (individual coding)Avalanche Photo Diode (individual coding)

• Multi Wire Proportional Chambers (charge sharing)Multi Wire Proportional Chambers (charge sharing)

• Review of Small Animal PET Scanners*Review of Small Animal PET Scanners*

*(A. Del Guerra, N. Belcari. Q. J. Nucl. Med. 46(1) (2002) 35-47)*(A. Del Guerra, N. Belcari. Q. J. Nucl. Med. 46(1) (2002) 35-47) . .

Dedicated Scanners forDedicated Scanners forSmall Animal PETSmall Animal PET

Gene expression in mouse liver

Imaging dopamine receptors in the ratFDG in rat myocardium

FDG in rat brain

microPETmicroPET®®4 - Images4 - ImagesCourtesy of S. Cherry, UCLA, 2002

YAP-(S)PETYAP-(S)PETUniversity of FerraraUniversity of Ferrara

3000

2500

2000

1500

1000

500

0

Con

cent

ratio

n (A

. U.)

40003000200010000

Time (s)

In vivo dynamic imaging of rat brain with 11C-Flumazenil

The rat was injected with 500 µCi of 11C-Flumazenil.Sagittal section through the center of the brain. (Nose towards the left. Upper skull towards top)

Ex vivo images of a rat brain injected with 18F-FDG (left) and 18F-FESP (right)

A. Del Guerra et al. IEEE-MIC Seattle, 1999, M10-45

Dedicated scanners for Dedicated scanners for Positron Emission Mammography (PEM)Positron Emission Mammography (PEM)

Pisa YAP-PEM prototype*Pisa YAP-PEM prototype*YAP:Ce crystal matrix

6cm × 6cm × 3cm2mm × 2mm × 3cm each

(900 elements)

PS-PMTR8520-C12

(Hamamatsu)2.2cm × 2.2 cm

active area

Optical diffuser (Quartz)

Variable distance

for compression(5 - 8 - 10 cm)

SNR values as a function of tumor size.

The tumor is embedded in an active breast tissue, with specific activity ratio 10:1 between cancer (1.0 Ci/cc) and tissue (0.1 Ci/cc). The distance between detectors is 5 cm.

Monte Carlo Simulation

Profiles of the images a,b,c

Reconstructed images of simulated tumors in active breast tissue. Tumors have different size (diameter/volume): (a) 12.4 mm / 1.0 cc; (b) 9.8 mm / 0.5 cc; (c) 5.8 mm / 0.1 cc; (d) 5.0 mm / 0.065 cc

A. Del Guerra et al. To be presented at IEEE-MIC, Norfolk, November 2002

Tumor diameter 5.0 mm (in breast tissue)Tumor / background activity:

1 Ci /cc / 0.1 Ci /cc (10:1)Moderate compression (5 cm) Events 3×106 (~10 min.) - Threshold 50keV

1 detector 6.0 6.0 cm2

4 detectors2.2 2.2 cm2

2.3%9.3 106 countsSNR = 10.7 1.0

0.8%3.0 106 countsSNR = 6.0 0.9

Scintillator: YAP:Ce 30 30 crystals 2 2 30 mm3 each

YAP-PEM simulationYAP-PEM simulation Results with YAP-PET Results with YAP-PET (2 heads)(2 heads)

The simulated breast is a specially designed 68Ge solid phantom.

A tumor is simulated by a cylinder 0.5 cm Ø and 0.5 cm height with an activity of 44 nCi.

The breast tissue is simulated by an active cylinder with diameter of 10.8 cm and height of 6 cm with a distributed 68Ge planar source of 25 mCi . The specific activity tumor/breast ratio is about 10:1 for all sources.

The image of the 5.0 mm source after the subtraction

of the backprojection of the planar source.

Experimental Monte Carlo

ConclusionsConclusions

• Dedicated scanners for small animalsDedicated scanners for small animals

Needs well establishedNeeds well established Commercially availableCommercially available Further developments required Further developments required

• Dedicated scanners for Positron Emission MammographyDedicated scanners for Positron Emission Mammography

Needs under scrutinyNeeds under scrutiny Few research prototypes availableFew research prototypes available

• Similarities between these two types of scannersSimilarities between these two types of scanners

• A high density / medium Z scintillator (such as YAP) coupled to novel A high density / medium Z scintillator (such as YAP) coupled to novel

PS-PMTs could be a very successful detector for these apparatus (e.g. PS-PMTs could be a very successful detector for these apparatus (e.g.

YAP-(S)PET and YAP-PEM)YAP-(S)PET and YAP-PEM)