Physics & Instrumentation in Positron Emission Tomography Paul Vaska, Ph.D. Center for Translational Neuroscience Brookhaven National Laboratory July 21, 2006

Non-invasive Medical Imaging Techniques MRI Anatomical X-ray CAT MRI Ultrasound Functional “nuclear medicine” - SPECT, PET Optical fluorescence, … CAT X-Ray

Positron Emission Tomography Recent mainstream acceptance relatively expensive cyclotron for tracer production detectors must stop high-energy gamma-rays low resolution (>2 mm), limited counting statistics BUT unique functional capabilities Applications Diagnosis of disease cancer (WB), cardiac, … Research brain function animal studies

Technical Challenges in PET Imaging Radiochemistry - better tracers Imaging Physics - better images by Detector design Spatial resolution Sensitivity Image processing Corrections for physical effects Image reconstruction algorithms Data Analysis & Biological Modeling - better interpretation of images

PET Imaging Overview Synthesize radiotracer Inject radiotracer Measure gamma-ray emissions from isotope (~20-60 min) Reconstruct images of radiotracer distribution (nCi/cc)

Positron (+) Decay Nucleus Neutrons 18F-FDG + Protons Electrons

Neutron-deficient isotopes can decay by emitting positrons + anti-neutrino + positron Net effect: one proton replaced by neutron anti-neutrino positron

Positron annihilation Annihilation gives 2x 511 keV gamma rays 180 degrees apart Line of response Positron range & gamma noncollinearity Scanner is just a photon counter! Counts gamma-ray pairs vs. single gammas Time window ~ 1 ns 511 keV e+ e- 511 keV

Raw Data & Image Reconstruction “sinogram” 0 180 90 90 projection image reconstruction 0 projection

Important Detector Properties Spatial resolution Directly controls spatial resolution in reconstructed image Currently ~ 1 - 5 mm Depth-of-interaction? Reduces “parallax”

Important Detector Properties Detection efficiency (aka sensitivity, stopping power) Reduces noise from counting statistics Currently > ~ 30% (singles) 1M Events 55M Events

Important Detector Properties Time resolution Affects acceptance of random coincidences Currently ~ 1 - 10 ns Time-of-flight (TOF)? c = ~ 1 ft/ns Need << 1 ns resolution Random (accidental) coincidence

Important Detector Properties Energy resolution Scattered gammas change direction AND lose energy Affects acceptance of scattered coincidences Currently ~ 20% Deadtime Handle MHz count rates! 511 keV 400 keV 511 keV Scatter and Attenuation

Prototypical PET Detector Optical reflector light is converted to an electrical signal & amplified Gamma Ray Scintillation Crystal PMT Pre-Amplifier + Electronics Gamma photon converts to optical photons (proportional to gamma energy, typ. 1000’s) photons are collected at the end of the crystal Front-end electronics condition the signal for further processing

New Developments Detectors Multimodality imaging Specialized applications

New Developments: Detectors Scintillators No perfect choice - tradeoffs Also practical qualities Rugged? Hygroscopic? Cost? 175 25

New Developments: Detectors Photosensors Photomultiplier tubes Avalanche photodiodes Arrays, position-sensitive Compact but noisier Silicon photomultipliers Very new Best of both? PMT APD array SiPM

New Developments: Detectors Z2 Z1 Sa2 Sa1 Sc   Solid-state detectors Direct conversion, no photodetector Great dE/E & spatial resolution Poorer timing & stopping power CZT

New Developments: Detectors Pb converters & ionization HIDAC Pb-walled straws (50 cm long)

New Developments: Detectors 3D gamma-ray event positioning Depth of interaction Reduces parallax problem vs. LSO slab crystal holder APD decoupling capacitor HV filter capacitor Current-limiting resistor signal output connector SHV connector unused APD slot

New Developments: Detectors Time of flight using LaBr3 no TOF 300 ps TOF 1 Mcts 5 Mcts 10 Mcts

New Developments Multimodality imaging Specialized applications PET/CT PET/MRI Specialized applications Brain, breast, prostate Small animal - microPET Arterial input function Humans - wrist scanner Animals - microprobe Awake rat brain - RatCAP

RatCAP: Rat Conscious Animal PET Eliminate anesthesia in preclinical neuroscience using PET in order to: Remove confounding effects of anesthetic on neurochemistry Enable stimulation in animal PET Enable correlations of behavior and neuro-PET

Architecture Detector blocks x12 Timestamp & Signal Processing Module TSPM TDC PCI card ASIC optical differential RatCAP Detector blocks x12 LSO 2.2 x 2.2 x 5 mm in 4 x 8 array 1:1 coupling to APD ASIC - single all digital output Timestamp & Signal Processing Module Programmable real-time logic (FPGA) 1 ns bins (debugging, now 10 ns) Data acquisition PCI card in standard PC Up to 70 MB/s = ~10 Mcps singles Offline software for coincidences, corrections, recon, …

Architecture high voltage data, clock, power all interconnections LSO APD 18 mm axial FOV 38 mm FOV ASICs TSPM 72 mm OD optical links to PCI RatCAP 194 g

1st prototype: LLD = 150 keV average, variable Performance 1st prototype: LLD = 150 keV average, variable Spatial resolution (FWHM @ CFOV) FBP: 2.1 mm MLEM: <1.5 mm Energy resolution: 23% FWHM Time resolution: 14 ns FWHM window = 30 ns Sensitivity (point @ CFOV): 0.7% Peak Noise Equivalent Count rate: 14 kcps @ 5 Ci/cc

Imaging Conditions Anesthetized 250-350 g rats Limited DAQ livetime >> long scans for statistics Artifacts

F-18 Fluoride Bone Scan 1.3 mCi fluoride RatCAP microPET R4

C-11 Raclopride 1.8 mCi raclopride In the RatCAP

Time-activity curve for striatum C-11 Methamphetamine Time-activity curve for striatum

Thanks! DOE OBER funding