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PET in the detection of breast cancerThe ClearPEM Project

Encontro Nacional de Ciência — Ciência 2009Fundação Calouste Gulbenkian

29-30 de Julho de 2009

Joao VarelaIST/LIP, Lisbon, Portugal

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Breast Cancer•Most common type of cancer

among women•Second deadliest cancer•One out of 9 women develop a

form of breast cancer throughout her life

MammographyAdvantages

• Low cost• Good sensivity/specificity

Disadvantages• Based in structural tissue changes• Less reliable in dense breasts• High false-positive rates

Breast Cancer

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PET •Based on the decay of a positron

emitting radionuclide (tracer)•18F-FDG most commonly used

radiotracer•Based on histological and

metabolical changes of the tissue

PET vs. MammographyAdvantages

• Not dependent on tissue density• Very good sensivity

Disadvantages• More expensive• Low sensivity for small lesions (Whole Body-PET)

P.E.T. (Positron Emission Tomography)

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PET and breast cancer• PET demonstrated good sensitivity

to breast cancer

Radiotracer• FDG (fluoro-deoxyglucose):

glucose labeled with the positron emitter F-18

• FDG has strong affinity to cancer cells

• Other tracers under investigation

Dedicated PEM scanners• One commercial scanner

(Naviscan, USA)• Two research prototypes in USA

PET Mammography

Dedicated Breast-PET Imaging

Randolph Cancer CenterWest Virginia University

X-ray mammogram

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GoalHigh performance scanner, to

approach the limits allowed by tracer physiology

Framework• Project developed in the framework

of the Crystal Clear Collaboration, CERN

• Funded by the Portuguese Innovation Agency (AdI)

• 6 years development• 4.5 M€ investiment

Status•IP licensend to PETsys, SA•Scanner in clinical trials

The ClearPEM Project

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Requirements•High counting sensitivity •Detector capable of image resolution of 1

mm •Detector capable to sustain a large flux of

single photons (up to 10 MHz)•On-line coincidence trigger with few ns

resolution•No data acquisition dead-time (up to 1 M

coincidence events/s)•Measurement of individual hits of Compton

events in the detector•Movable and compact dual-head detector

plates with large active area•No parallax effect

The ClearPEM Project

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The ClearPEM Scanner

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Crystals•Material: LYSO:Ce•Density: 7.4g.cm-3

•Emission Peak: 420nm•Light Yield: 27000 photons/MeV•Time Constant: 40ns•Geometry: 2x2x20 mm3

Avalanche Photodiodes•Operating Voltage: 350-450V•Dark Current: ≤10nA•Gain uniformity (sub-array):

±15%

Detector Plates•6144 crystals•12288 readout channels•160x180 mm2 surface area•Front-back readout for DoI

measurement

Detector Technology

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CharacteristicsTechnology: CMOS 0.35μmArea: 70mm2

Input: 192 channels Output: 2 highest channelsMax Input Charge: 90 fCNoise: ENC ~ 1300 e-

Shaping: 40nsAnalog Memories: 10 samples

Clock Frequency: 50-100MHzPower: 3.6 mW/channel

Frontend ASIC

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Frontend Board•Processes 384 APD channels•Contains 2 ASICs for signal

selection•2 High-speed ADCs (10bit,

100MHz)•1 LVDS transmitter (600Mbps)

Supermodule•Comprises 2 FE Boards•Processes 768 APD channels

Detector Plate•Comprises 8 Supermodules•Processes 6144 APD channels•Contains one Service Board to

control 192 high-voltage lines as well as power supply and clock distribution

Frontend (FE) Electronics

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Pulse Shape•Amplifier response rise time:

20ns•Variation in baseline <0.5%

Noise•ENC = 1300 e- r.m.s.•Inter-channel dispersion ~ 8%

(2.2 ADC Counts = 5keV)(Noise measurements obtained with

full electronics chain)

FE Electronics Performance

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DAE Crate System• DAE housed in a single 19” rack

crate• Uses two cPCI backplanes• 1 TGR/DCC Board• 4 DAQ Boards

• FE - DAE bandwidth up to 19.2Gbps• Sophisticated coincidence trigger

(36k calibration constants)• DAE-Acq Server bandwidth up to

6.4Gbps

Data Acquisition Electronics

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Trigger Performance•Events in coincidence up to

2.5MHz(This involves computation of

energy and time and Compton grouping and transmission to the trigger processor)

•Acquisition rate up to 0.8MHz(This involves readout of the event

dataframe after the issueing of a trigger)

•Disk storage > 300MBps

Data Acquisition Electronics Performance

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Performance results

• Dispersion of channel gain 15.3%

• Energy resolution at 511 keV 15.9%

• Dispersion of energy resolution 8.8%

• Single photon time resolution 1.5 ns (RMS)

• Coincidence time resolution 5.2 ns (FWHM)

• Resolution in DoI 2 mm

Detector Performance

Resolution ~12.5%

137Cs

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Image Setup• 1mm Na-22 source• Grid with 5mm pitch• Two acquisitions with orthogonal

plate orientations for each source location (400-600 keV)

• Simultaneous reconstruction of 16 source positions

Results•Horizontal FWHM: 1.3mm•Vertical FWHM: 1.2mm

ClearPEM Image Resolution

OSEM-2DOSEM-3D

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ClearPEM Image Resolution

5 mm

1 mm

Parallax effect

• Measurement of 3D photon interaction coordinates eliminates parallax effect

• ClearPEM is unique in this respect (DoI resolution of 2mm)

• Images without parallax correction show considerable blurring

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ClearPEM Image Uniformity

Images of uniform Ge-68 source

• Image artifacts due to detector effects are corrected

• Absorption and scatter corrections are not applied (less intensity at the center)

• Reconstruction with 4 orientations of the detector plates

•Very good uniformity

Cylinder filled with positron emitter Ge-68

2 mm slices

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SimulationsSimulation Model

•NURBS CArdiac Torso (NCAT) Phantom•Detector detailed description•Standard injection of 10mCi (370MBq)

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Scanner Installation• Hospital Garcia Orta at Almada not

available • Obliged fall back solution at IPO, Porto

Phase 1• Tuning the image reconstruction with

real cases• Patients indicated for PET/CT (other

disease)• Normally negative breast exams• Started in June 2009

Phase 2• Assessment of PEM sensitivity /

specificity • Comparison to mammography and MRI• Patients with positive indication from

x-rays mammography

Clinical Trials

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Clinical Images

Tuning image reconstruction

• Phase 1• Normalization correction• Correction of the effect of

background radiation• Effect of scattered radiation• Measure detector sensitivity• Evaluate FDG uptake in the breast• Validate simulation results

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Multimodal PET – US

CERIMED and University Hospital Marseille

Ultra-sound probe with elastography capabilities coupled to ClearPEM

Cross-reference system and PET-US image fusion

Construction of second ClearPEM machine well advanced

ClearPEM and Ultrasound

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• ClearPEM technological developments were

successfully completed• The detector performance is excellent• ClearPEM is one of the most innovative APD-based

PET systems in clinical• Scanner is presently installed at IPO, Porto• Clinical Phase 1 is on-going

Conclusions

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