Download Positron Emission Tomography

Positron Emission
Tomography
Outline
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PET Examples
Imaging Goal
Reconstruction/Data Requirements
Method of Data Acquisition in PET
– Positron Decay/Annihilation
– Detectors/Scanner
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PET Tracers
Data Acquisition Modes (2D/3D)
Attenuation
Degrading Effects
Combined PET and CT
PET Scan Examples
PET
PET/CT FDG
Breast Cancer
Tracer: [F-18] FDG
A glucose analog,
Goes to regions of
high metabolic
activity.
CT
PET
Colon Cancer
10.9 mCi FDG
6 X ( 4 min Emission + 2.5 min Transmission) = 39 min
SUV 
( radiotracer concentration )
(injected dose) /(body mass )
MRI, T1+C
FDG PET
FLT PET
(different patient)
FDG – Glucose metabolism. Normal gray matter tissue
has high glucose metabolism.
FLT – DNA synthesis/cellular proliferation. Normal
brain has low signal.
Dynamic Imaging / Kinetic Modeling
• During a scan, PET data can be acquired as
a function of time with ~ arbitrarily good time
resolution (limited by statistical/reconstruction
considerations)
• Can use time sequence of tracer uptake
(dynamic PET) coupled with blood pool tracer
measurements to determine parameters in a
model of tissue uptake.
• Leads to better understanding of mechanism
of tracer uptake.
Dynamic Imaging / Kinetic Modeling
Early time
(Carotid Artery)
Late time
(Tumor)
Dynamic Imaging / Kinetic Modeling
Possible 2-Tissue Compartment Model for Fluorothymidine (FLT)
K1
Ca
k2
C1
k3
C2
k4
Ca - Tracer concentration in blood
C1 - Unphosphorolated tracer concentration in tissue
C2 - Phosphorolated tracer concentration (preliminary step in the
incorporation of thymidine into DNA)
K’s:
•Model parameters
•Represent transfer rates between compartments (think pipe diameters)
Significance example: In brain, K1 is determined by BBB integrity whereas
k3 , the phosphorolation/proliferation rate is expected to better reflect tumor status.
These quantities cannot be cleanly disentangled with single time-point imaging.
Dynamic Imaging / Kinetic Modeling
Imaging Goal
• Main point: All nuclear medicine imaging studies
involve administration of a molecule tagged with a
radioactive atom (radiopharmaceutical or radio
tracer).
• Purpose: As opposed to some other modalities,
the purpose of nuclear medicine is to provide
functional information. Contrast this with, for
example, xray and CT procedures, in which we are
mainly looking at structure.
• The particular function that we examine in a
nuclear medicine mainly depends on the
radiopharmeceutical used.
Imaging Goal
Example:
CT image of chest
shows structure.
Nuclear Medicine
(PET) image shows
metabolic activity.
Tracer: [F-18] FDG
Overlaid PET / CT image
Overview of Image Reconstruction
We treat as a
2-dimensional
problem
“2-dimensional” slice
Goal:
Obtain image or map of some property
(for example radioactivity distribution)
of this patient.
Constraint:
Have to work from outside
(no slicing allowed).
Definition:
Line of Response
(LOR):
A line transecting
the object.
With a complete set
of LOR’s, every
point in the object is
intersected by lines
in all directions.
Summary
Input: integral of
desired quantity for
all LOR’s in object
Nuclear Medicine
In: Line integrals of
radioactivity concentration.
Out: Image of radioacitity
concentration
Output: map of
quantity for entire
object
Example 1 - Internal Radioactivity
An image of radioactivity distribution can be
reconstructed if gamma-ray count rates are
measured along “all” LOR’s.
This can be done by collimated detectors
(for example).
The measured count rates are proportional
to the total (integral) radioactivity along the
LOR
Example 1 - Internal Radioactivity
An image of radioactivity distribution can be
reconstructed if gamma-ray count rates are
measured along “all” LOR’s.
This can be done by collimated detectors
(for example).
The measured count rates are proportional
to the total (integral) radioactivity along the
LOR
Example 1 - Internal Radioactivity
An image of radioactivity distribution can be
reconstructed if gamma-ray count rates are
measured along “all” LOR’s.
This can be done by collimated detectors
(for example).
The measured count rates are proportional
to the total (integral) radioactivity along the
LOR
Example 1 - Internal Radioactivity
An image of radioactivity distribution can be
reconstructed if gamma-ray count rates are
measured along “all” LOR’s.
This can be done by collimated detectors
(for example).
The measured count rates are proportional
to the total (integral) radioactivity along the
LOR
Example 1 - Internal Radioactivity
(x,y) = Activity concentration
Measure:
I j    ( x, y )dl j
-ray
detector
Rate of -ray
emission along
LOR*
* emission rate is proportional to integral of activity concentration along LOR
Reconstruction
Result:
 ( x, y )
Map of
radioactivity
concentration
Reconstruction
The point of this is –
The data we need require that we know:
1. where an emitted gamma ray hits the detector;
2. the direction from which the gamma ray came.
In SPECT we use collimators.
PET uses a different technique to get the same information.
Method of Data Acquisition in
PET
Positron Decay Closeup
• Beta Decay: +

e+
p
This decay is not allowed
for a free proton (energy
conservation)
Initial State
n
Final State
PET : Positron Emission Tomography
•Some neutron deficient nuclei decay by
positron emission (+) decay.
Example:
F-18  O-18 + e+ + 
Half life: 109 minutes
PET
Positron - Electron annihilation
Positron comes to rest (total distance
traveled ~ 1mm) and interacts with
ambient electron
PET
Positron - Electron annihilation
Result: Two back-to-back 511 keV
photons traveling along a line that
contains the point at which the
annihilation took place.
PET
In PET, the LOR upon which an annihilation took
place is defined by the coincident observation of
two 511 keV photons
Gamma detectors
Coincidence:
Look for events within
time τ of each other.
(typical τ: 10ns)
The PET Scanner
PET
PET Detectors
The PET scanner consists of a
cylindrical grid of blocks, each
containing a number individual
detectors
15 cm (typical)
Block Detector
Photomultiplier(s)
Scintillation Crystals
•Gamma ray hits crystal
•It may interact producing scintillation light
•Scintillation light is detected by
photomultiplier tubes (PMTs)
•Struck crystal determined by light
distribution in PMTs
Head on view
Example Block
Detectors
6.4 mm x 6.4 mm
8x8 crystals/block
4.0 mm x 4.0 mm
13x13 crystals/block
Most Common PET
Scintillators:
Bismuth germanate (BGO)
Lutetium oxy-orthosilicate
(LSO)
6.3 mm x 6.3 mm
6x6 crystals/block
4.7 mm x 6.3 mm
8x6 crystals/block
Open PET Scanner. Block detector housings are visible.
PET Nuclides and Tracers
Positron Decay
A
A
Z X N  Z1Y N 1
+
e 
Nuclide half-life
C-11
20.3 min
N-13
10 min
O-15
124 sec
F-18
110 min
Rb-82
75 sec
e.g., 18F  18O + e+ + 
PET Compounds Routinely Produced
and Approved for Animal/Human Use
[O-15]H2O
[O-15]O2
[N-13]NH3
(perfusion)
(oxygen metabolism)
(myocardial perfusion)
[F-18]FDG
(glucose metabolism, cell viability)
[C-11]raclopride
[C-11]PMP
[carbonyl-C-11]WAY100635
[C-11]flumazenil
(+)[C-11]McN5652
(-)[C-11]McN5652
[C-11]PK-11195
[C-11]β-CFT
[C-11]PIB
[C-11]3-O-methylglucose
[C-11]DASB
[F-18]FLT
[F-18]altanserin.
[F-18] FMISO
(dopamine D2 receptor ligand)
(acetylcholinesterase substrate)
(serotonin 5-HT1A receptor ligand)
(central benzodiazepine receptor ligand)
(serotonin transporter ligand, active)
(serotonin transporter ligand, inactive)
(peripheral benzodiazepine receptor ligand)
(dopamine transporter ligand)
(beta amyloid imaging agent)
(glucose transport)
(serotonin transporter ligand)
(thymidine kinase substrate, cell proliferation)
(serotonin 5HT2A receptor ligand)
(tumor cell hypoxia)
PET Compounds Routinely Produced
and Approved for Animal/Human Use
[F-18]FDG
(glucose metabolism, cell viability)
FDG – FluoroDeoxyGlucose - a glucose analog
FDG is now comercially available most places in the
USA and throughout much of the world.
PET Data Acquisition Modes
Multiple Rings, 2D – 3D
For n detector rings:
2D
direct
slices (n)
3D
cross
slices (n-1)
3D- More counts
septa
total slices = 2n-1
2D- Better ratio of
good to bad
counts
Notice!
We are always going to produce a 3D
image of radiotracer distribution in PET
2D and 3D PET refer to the method of
acquiring the raw data used to produce
the final image.
Attenuation and Attenuation
Correction
The Problem: Attenuation of radiation by the
patient
•In a nuclear medicine study a gamma-ray emitted within the
patient may be reabsorbed. Thus the quantities that we
measure for each LOR are not just integrals of the radioactivity
distribution. Instead they are a complicated function of both the
activity distribution and the patient attenuation properties.
Attenuation of Radiation by Matter
For Photons ( and x radiation)
– Total interaction probability is expressed by
Linear Attenuation Coefficient:
  --> Units = 1/cm
  is a function of material and gamma energy
– Transmitted beam intensity (# of photons)
decreases exponentially with distance:
I0
x
μ
Photon survival probability
Attenuation of Radiation by Matter
If a photon is
emitted here
traveling along
the indicated
LOR
then the probability that it
will survive attenuation is
The integral is taken along the
LOR starting at the emission
point to the exit point.
Thus the probability of attenuation depends on the point
of emission along the LOR.
Coincidence Attenuation
Remember – in PET both photons have to be
detected for an event to be registered. If you lose
one photon you lose the event!
Probability of the event surviving attenuation is the
product of the individual survival probabilities.
This makes attenuation a serious effect in PET, however …
Coincidence Attenuation
Observe that Pc is independent of where
along the LOR the annihilation took place.
Thus – each LOR has a particular attenuation factor!
This is a very important difference from the single photon case.
Attenuation Correction
In PET, we can make an “exact” attenuation correction by
dividing the counts recorded on each LOR by the
coincidence attenuation probability (or attenuation factor
[AF]) for that particular LOR.
Corrected Counts= (Recorded Counts)/AF
(This is not true in SPECT.)
Notice that the correction is applied to the raw data before or
as part of the reconstruction.
Attenuation Correction
The required AF’s can be
determined by performing a
transmission measurement
using an external radiation
source.
Sources are an integral part of
a PET scanner.
positron (511 keV
photon) source
Attenuation Effects
Attenuation
Corrected
Not Attenuation
Correction
x-ray CT
PET Imaging Attenuation Effects
• Incorrect regional image intensity
• Distortion of shape
• Streaking from large hot objects can mask less
intense structure
Uncorrected
Corrected
Degrading Effects
Degrading Effects
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•
•
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Scatter
Randoms
Limited Spatial Resolution
Limited Counts -> Image Noise
Scattered Coincidence
Event
In-Plane
Out-of-Plane
Scatter Fraction S/(S+T)
With septa ~10-20%
w/o septa ~30-80%
Scatter Control
1. Scattered events have energies less
than 511 keV. Using a tight energy
window eliminates some scatter events.
However the energy resolution of
scintillators used in PET (BGO, LSO,
etc.) is not so great. Therefore if we
make the windows too tight, we lose
good events.
Scatter Control
2. There are several procedures for
estimating the distribution of scatter in
the PET raw data or images. The
estimated scatter is then subtracted.
Images for quantitative use must have
a scatter subtraction performed.
Random Coincidence
Event
b

RR=2RaRb
a
Random Compensation
Very good estimates of randoms can be made.
• Method 1: monitor the rates in the detectors to
deduce the randoms rates.
•Method 2 – Delayed coincidence : For each
detector hit, look for coincidences after a delay (i.e.
look at the wrong time). There will be no true
coincidences, only randoms.
Noise
• Due to counting statistics including the
effects of scatter and random
compensation
More counts
Fewer counts
Correcting Background:
Noise Equivalent Counts
Pprompts  Ttrues  S scatter  Rrandoms
What you
measure
What you
want
“Background”
T   P  S   R
2
T
T
NEC 

P (1  S / T  R / T )
More background  more statistical image noise.
Spatial Resolution Limits
Detector Size
Smaller crystal elements yield better
resolution.
Spatial Resolution Limits
Positron Range
Positron moves before annihilation
Size of effect depends on nuclide, typically
on the order of a millimeter
Spatial Resolution Limits
Opening Angle
Gamma rays emerge with angles slightly
different than 180o due to center-of-mass
motion of positron/electron pair.
Angular blurring of few tenths of a degree. Effect
on resolution proportional to ring diameter.
Typical Resolution in a modern PET scanner 4-6 mm.
(Not uniform throughout the field-of-view)
Combining Modalities
PET and CT
PET/CT
PET/CT Systems
All new systems sold in the
USA are now PET/CT
Hardware fusion: function + anatomy
PET
PET/CT
FDG-PET
CT
NHL-Better Localization
Case: 53 y/o male with hx of NHL s/p chemotherapy with c/o
weight loss and pain for follow-up PET/CT
Findings: Two foci of intense FDG uptake in soft tissue adjacent to bones
consistent with malignancy.
Hardware fusion: function + anatomy
• A combined PET/CT scanner allows automatic
correlation of functional image (PET) with anatomy
(CT)
•The CT data can be used for producing the
attenuation correction