1. 6: Positron Emission Tomography
What is the principle of PET imaging ?
Positron annihilation
Electronic collimation – coincidence detection
How 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 scan
Distinguish the principle of PET detection from that of SPECT
Understand the bases of scatter elimination.
Understand the factors affecting spatial resolution in PET.
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2. Positron Emission Tomography (PET) Cancer detection (metastasis) in patients
Transaxial
Coronal
PET/CT
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3. Positron Emission Tomography Scanner
Detector ring
Human scanner
PET is similar to SPECT but different
(detection principle and instrumentation)
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4. PET of animal models transgenic mice, cancer detection
micro PET scanner
Positioning of the rodent
Imaging gene expression (HSV)
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5. 6-1. What is Positron Emission Tomography ? PET
Positron Emission tomography: measured are x-rays emitted by annihilation of positrons
emitted by exogenous substance (tracer) in body
The principle is as emission tomography, but there is one major difference … (see later)
Two issues:
How to determine directionality of x-rays ?
Absorption is undesirable
Injection of positron emitter (tracer) -
Most widely used tracer for PET
18Fluoro-deoxy-glucose
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6. What does one want to measure with PET ? Annihilation photons
Question: Why are two photons are produced?
Conservation of linear momentum is not possible with one photon (p=E/c) → 2 photons
Energie of photons ?
hn=mec2=511keV
(1eV = 1.6·10-19 J) - +
p→n n
Unstable parent nucleus p
Annihilation coincidence detection :
two events detected at same time
→ annihilation event along a line (defined by detector)
 NO need for a collimator
NB. Light travels 1m in 3ns :
1[m]/3 108 [m/s]=3ns
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7. What defines simultaneity (coincidence) ?
What is coincidence detection ? electronic collimation (i.e. w/o physical collimators)
Electronic signal
What defines simultaneity (coincidence) ?
Crystal
Photomultiplier
Leading edge defines time of detection
(sharper, i.e. higher 1st derivative)
Bi4Ge3O12 (BGO): t~10ns.
Position logic electronics
Photomultipliers
PET-camera
Light guide
Scintillating crystal
Collimator
Elimination of collimator material is a major source of sensitivity increase (why?)
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8. What is really measured with PET ?b b
Random coincidences
True coincidence a a
Scattered coincidence
Trues )
Yab =
Nab
(Aab
Tab
+ Sab
+ Rab
What is measured
Scatter
Normalization
(Instrument imperfection)
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Attenuation
Randoms

9. 6-2. Why are Random and Scattered Events bad? mimic a true coincidence
emissions from unrelated nuclear transformations interact simultaneously with the detectors
Scatter
At least one annihilation photon is (Compton) scattered
Erroneous Line of incidence (LOI)
 assignment to wrong Radon transform
Rate of random coincidences :
S1 and S2 : count rates on the individual detectors (singles rates)
 : coincidence time window.
Reduce randoms by reducing t (coincidence interval)
Does not work for scattered events (why?)
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10. How can scattered events be distinguished from true coincidence
How can scattered events be distinguished from true coincidence ? Energy discrimination & background subtraction
Measure Ef → identify severely scattered photons
ENERGY WINDOW
ENERGY
WINDOW
425 – 650
511 keV photons
Counts
Energy (keV)
100
200
300
400
700
600
500
Some crystals (BGO) only allow 30% energy discrimination
Emission Transmission
LSO
Scatter
BGO
Other approaches are needed:
Scatter Corrected
350 – 650
Most scattering is by Compton
Subtract background (= scatter + randoms) measured in signal void regions → polynomial interpolation ÷ ø ö ç è æ - + = i e f c m E 2 )
cos 1 ( q
2000
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11. 6-3. How is attenuation correction performed
6-3. How is attenuation correction performed ? simpler for PET than SPECT
Probability P1:
S1=CT(x)*e-m(d-x)
 P1=S1/CT*(x)
CT*(x)
Probability P2: S2 = CT*(x)e-mx  P2=S2/CT*(x)
Attenuation :
Probability of detecting the photon pair
Compare to geometric average of SPECT (Lesson 5)
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uncorrected
corrected

12. What are the steps in Attenuation Correction for PET ?
Mass attenuation coefficient µ/r in soft tissue = 0.095cm2/g (511keV)
Average path length for the photon pair
longer than for a single photon different lines of response attenuate to varying degrees
PET imaging of the body
More attenuation (x4)
HVL7cm
Attenuation correction in practice:
Spatially uniform attenuation coefficient assumed
Transmission technique using e.g. Cs source (662keV, why is this good enough ?)
Less attenuation
single photon emitter
Comparison with blank scan
i.e. subject removed
Correction factor for each Radon transform
(µ homogeneous) L
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13. attenuation correction
Why is PET/CT the industry standard ? PET-Attenuation correction using CT-Data
0.1
0.2
0.3
m/r
(cm/g)
CT PET = PET/CT
CT ~70 keV
extrapolation
Bone
PET 511 keV
Soft tissue
100
200
300
400
500
Energy (keV)
PET/CT: Two separate scanners in one package
scatter &
attenuation correction CT
PET
Bone
511 keV CT
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6-13
Soft tissue

14. 6-4. Why is Resolution never perfect
6-4. Why is Resolution never perfect ? Annihilation Range and photon non-collinearity
Collinearity: Assumed for Reconstruction
Background: At time of annihilation, e-p pair has non-zero kinetic energy
Mean free path length (range)
 conservation of momentum
Photon momentum w/zero momentum e-p
Range: limits spatial resolution
(In air, b+ range ~ several m)
pe+pp
nucleus +
Isotope
Half-life (min)
Max. Energy (MeV)
Range in H2O (FWHM, mm)
18F
110
0.6 1
11C 21
1.0
1.2
15O 2
1.7
1.5
13N 10
1.4
68Ga 68
1.9
82Rb
3.2 e- q
~ 0.25
} ∆x
511 keV
511 keV
D (detector distance)
D (cm) ∆x (mm)
∆x = 0.5 D tan(0.25)
60 1.3
80 1.7
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15. How does the detector affect PET spatial resolution ?
Example: BGO Block Detector
Coincidence window: 12 ns
Energy resolution: ~ 25%
Photomultiplier tube
True coincidence count rate RT
RT=2C*TG2
CT* - 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 coincidence
3 cm
scintillator
Crystal thickness
Resolution is best at the center
This is a reason for the 3cm thick crystals used for PET detection.
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16. 6-5. What are typical PET tracers ? Oncology and neuroscience
18Fluoroethyl-Tyrosine (FET)
Amino acid transport
Deoxy-18fluoro-thymidine (FLT)
Proliferation
18Fluoromisonidazole (FMISO)
Hypoxia
Neuroscience
11C-Methionine
Amino acid transport and metabolism
H215O
Blood flow
18Fluoro-Deoxyglucose (FDG)
Glucose metabolism
18FDOPA
Presynaptic dopaminergic function
15O-Butanol
Blood Flow
11C-Flumazenil
Benzodiazepine-receptor mapping
FDG or
F18 fluorodeoxyglucose
O15 Water
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17. PET: Neuroscience Raw Normal Alzheimer’s Pseudo-color display:
red, yellow: high activity
green, blue: low activity
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18. FDG PET Stomach carcinoma Early detection of response to treatment
Response-Prediction
3 M. after CTx
Day 14
responder
Before CTx 6
This 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.
non-responder
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19. Whole-body FDG PET Brain Kidney Bladder normal Malignant Lymphoma
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20. X-ray imaging modalities. Overview CT, SPECT, PET
Measurement 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! CT
SPECT
PET
Projection Encoding
Defined by incident x-ray
(collimation to reduce scatter)
Collimator essential
Coincidence detection (electronic collimation)
Spatial Resolution
(rodent)
100µm-mm
(µm)
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)
Radionuclides
None (contrast agents)
Any with hn= keV
Positron emitters only
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