Introduction au cours

Fund BioImag 20136-16: Positron Emission TomographyWhat is the principle of PET imaging ?Positron annihilation Electronic collimation coincidence detectionHow are the effects of scatter and attenuation corrected for ? What factors can affect resolution ?Examples: PET tracers in oncology and neuroscience

After this course you are capable of Describing the essential elements of a PET scanDistinguish the principle of PET detection from that of SPECT Understand the bases of scatter elimination. Understand the factors affecting spatial resolution in PET. Fund BioImag 20136-2

PET/CTTransaxialCoronal

Positron Emission Tomography (PET)Cancer detection (metastasis) in patients

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Positron Emission Tomography Scanner

Human scanner Detector ring PET is similar to SPECT but different(detection principle and instrumentation)

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PET of animal modelstransgenic mice, cancer detection

micro PET scannerPositioning of the rodentImaging gene expression (HSV)

Fund BioImag 20136-56-1. What is Positron Emission Tomography ? PETPositron Emission tomography: measured are x-rays emitted by annihilation of positrons emitted by exogenous substance (tracer) in bodyThe principle is as emission tomography, but there is one major difference (see later)Most widely used tracer for PET18Fluoro-deoxy-glucose-Two issues:How to determine directionality of x-rays ?Absorption is undesirableInjection of positron emitter (tracer)

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What does one want to measure with PET ?Annihilation photonspUnstable parent nucleuspn+-nAnnihilation coincidence detection : two events detected at same time annihilation event along a line (defined by detector) NO need for a collimator Conservation of linear momentum is not possible with one photon (p=E/c) 2 photonsQuestion: Why are two photons are produced?Energie of photons ?hn=mec2=511keV(1eV = 1.610-19 J)NB. Light travels 1m in 3ns :1[m]/3 108 [m/s]=3ns6Fund BioImag 20136-7

What is coincidence detection ?electronic collimation (i.e. w/o physical collimators) PhotomultiplierCrystalWhat defines simultaneity (coincidence) ?Electronic signalLeading edge defines time of detection (sharper, i.e. higher 1st derivative)

Bi4Ge3O12 (BGO): t~10ns.

CollimatorPhotomultipliersLight guideScintillating crystalPET-cameraPosition logic electronicsElimination of collimator material is a major source of sensitivity increase (why?)7Fund BioImag 20136-8abWhat is measuredTruesTrue coincidenceRandom coincidencesNormalization(Instrument imperfection)AttenuationRandomsScatterWhat is really measured with PET ?abTabYab=+ Sab+ Rab(Aab)NabScattered coincidence

Fund BioImag 20136-96-2. Why are Random and Scattered Events bad? mimic a true coincidenceRandomemissions from unrelated nuclear transformations interact simultaneously with the detectorsRate of random coincidences :

S1 and S2 : count rates on the individual detectors (singles rates) : coincidence time window. Erroneous Line of incidence (LOI) assignment to wrong Radon transform

ScatterAt least one annihilation photon is (Compton) scatteredReduce randoms by reducing t (coincidence interval)Does not work for scattered events (why?)9Fund BioImag 20136-10How can scattered events be distinguished from true coincidence ? Energy discrimination & background subtractionMost scattering is by ComptonMeasure Ef identify severely scattered photons

Some crystals (BGO) only allow 30% energy discriminationOther approaches are needed:ENERGY WINDOW350 650ENERGYWINDOW425 650Scatter511 keV photonsBGOLSOCountsEnergy (keV)0100200300400700600500

Emission Transmission Scatter Corrected

2000

Subtract background (= scatter + randoms) measured in signal void regions polynomial interpolation -+=ieiifcmEEE2)cos1(1q

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6-3. How is attenuation correction performed ? simpler for PET than SPECTAttenuation : Probability of detecting the photon pair

Compare to geometric average of SPECT (Lesson 5)Probability P1:S1=CT(x)*e-m(d-x) P1=S1/CT*(x)Probability P2: S2 = CT*(x)e-mx P2=S2/CT*(x)CT*(x)uncorrectedcorrected

Fund BioImag 20136-12Comparison with blank scan i.e. subject removedWhat are the steps in Attenuation Correction for PET ?Mass attenuation coefficient /r in soft tissue = 0.095cm2/g (511keV)

Average path length for the photon pairlonger than for a single photon different lines of response attenuate to varying degrees

Lsingle photon emitter

HVL7cm

More attenuation (x4)

Less attenuationPET imaging of the body

Correction factor for each Radon transform( homogeneous)

Attenuation correction in practice:Spatially uniform attenuation coefficient assumed Transmission technique using e.g. Cs source (662keV, why is this good enough ?)

Why is PET/CT the industry standard ?PET-Attenuation correction using CT-DataFund BioImag 20136-13Fund BioImag 20136-13

100200300400500Energy (keV)00.10.20.30m/r(cm/g)

BoneSoft tissueCT

Soft tissueBone

511 keVPET/CT: Two separate scanners in one package

CTPET

CT + PET = PET/CTscatter & attenuation correction

extrapolationPET 511 keVCT ~70 keVFund BioImag 20136-146-4. Why is Resolution never perfect ?Annihilation Range and photon non-collinearityIsotopeHalf-life (min)Max. Energy (MeV)Range in H2O (FWHM, mm)18F1100.6111C211.01.215O21.71.513N101.21.468Ga681.91.782Rb13.21.7Range: limits spatial resolution (In air, b+ range ~ several m)

Mean free path length (range) conservation of momentumBackground: At time of annihilation, e-p pair has non-zero kinetic energyCollinearity: Assumed for Reconstructionnucleuse-+511 keV511 keV~ 0.25x = 0.5 D tan(0.25)D (cm) x (mm) 601.3801.71002.2} xqD (detector distance)pe+ppPhoton momentum w/zero momentum e-pFund BioImag 20136-15

Example: BGO Block DetectorCoincidence window: 12 nsEnergy resolution: ~ 25%Photomultiplier tubescintillatorHow does the detector affect PET spatial resolution ? True coincidence count rate RTRT=2C*TG2CT* - tissue activity of a voxel : the intrinsic detector efficiency (1-e-x)G : the geometric efficiency (solid angle defined by the detector surface/4).NB. = 0.9 81% of photon pairs emitted towards detectors produce coincidenceThis is a reason for the 3cm thick crystals used for PET detection.3 cm

Crystal thicknessResolution is best at the center15Fund BioImag 20136-1618Fluoro-Deoxyglucose (FDG)Glucose metabolismH215OBlood flow18Fluoroethyl-Tyrosine (FET)Amino acid transport11C-MethionineAmino acid transport and metabolismDeoxy-18fluoro-thymidine (FLT)Proliferation18Fluoromisonidazole (FMISO)Hypoxia6-5. What are typical PET tracers ?Oncology and neuroscienceOncologyNeuroscience15O-ButanolBlood Flow18FDOPAPresynaptic dopaminergic function11C-FlumazenilBenzodiazepine-receptor mapping

FDG orF18 fluorodeoxyglucose

O15 WaterFund BioImag 20136-17PET: NeurosciencePseudo-color display:red, yellow: high activitygreen, blue: low activity

RawNormalAlzheimers

Fund BioImag 20136-18FDG PET Stomach carcinomaEarly detection of response to treatment

Before CTxDay 143 M. after CTxResponse-Prediction

respondernon-responder186This is just one of many studies that shows that FDG PET is able to predict response to chemotherapy early after start of the treatment. This is a responding patient with advanced gastric cancer showing increased FDG uptake before treatment and a dramatic decrease of glucose metabolism 2 weeks after the start of treatment. 3 months after chemotherapy, CT verifies the success of neoadjuvant treatment.Fund BioImag 20136-19Whole-body FDG PETBrainKidneyBladder

Malignant Lymphomanormal

Fund BioImag 20136-20X-ray imaging modalities. OverviewCT, SPECT, PETCTSPECTPETProjection EncodingDefined by incident x-ray(collimation to reduce scatter)Collimator essentialCoincidence detection (electronic collimation)Spatial Resolution

(rodent)100m-mm

(m)Typical 10mm (Variable and complex)(1.5-3 mm)4.5-5mm at center

(1mm)Attenuation= measurement variable(Varies with energy) Complex correction (Varies with photon energy)Accurate correction (transmission method)RadionuclidesNone (contrast agents)Any with hn= 60-200keVPositron emitters onlyMeasurement of signal integrated along line of incidence (LOI) (Radon transform)CT: attenuated incident x-ray beam (direction of beam given by source)SPECT: emitted single photon (need collimation to determine ray direction)PET: annihilation photon pair (directionality by electronic collimation)Apply correction to measured Radon transform (attenuation, scatter, etc.) Backprojection or central slice theorem:

Finally an image! 20Sheet1theta/Ei100140511(keV)209913848245951303959084110256110791022181807290170

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