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Positron Emission Tomography. Outline. PET Examples Imaging Goal Reconstruction/Data Requirements Method of Data Acquisition in PET Positron Decay/Annihilation Detectors/Scanner PET Tracers Data Acquisition Modes (2D/3D) Attenuation Degrading Effects Combined PET and CT.

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Outline
Outline

  • PET Examples

  • Imaging Goal

  • Reconstruction/Data Requirements

  • Method of Data Acquisition in PET

    • Positron Decay/Annihilation

    • Detectors/Scanner

  • PET Tracers

  • Data Acquisition Modes (2D/3D)

  • Attenuation

  • Degrading Effects

  • Combined PET and CT




Pet ct fdg
PET/CT FDG

Breast Cancer

Tracer: [F-18] FDG

A glucose analog, Goes to regions of high metabolic activity.

PET

CT


Colon cancer
Colon Cancer

10.9 mCi FDG

6 X ( 4 min Emission + 2.5 min Transmission) = 39 min


Positron emission tomography

FDG PET

FLT PET

(different patient)

MRI, T1+C

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
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 modeling1
Dynamic Imaging / Kinetic Modeling

Late time

(Tumor)

Early time

(Carotid Artery)


Dynamic imaging kinetic modeling2

K1

C1

k3

C2

Ca

k2

k4

Dynamic Imaging / Kinetic Modeling

Possible 2-Tissue Compartment Model for Fluorothymidine (FLT)

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.



Imaging goal
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 goal1
Imaging Goal

Example:

CT image of chest shows structure.

Nuclear Medicine (PET) image shows metabolic activity.

Tracer: [F-18] FDG

Overlaid PET /

CT image



Positron emission tomography

We treat as a 2-dimensional problem



Positron emission tomography

Constraint:

Have to work from outside (no slicing allowed).

Goal:

Obtain image or map of some property (for example radioactivity distribution) of this patient.


Positron emission tomography

A line transecting the object.

Definition:

Line of Response (LOR):


Positron emission tomography

With a complete set of LOR’s, every point in the object is intersected by lines in all directions.


Positron emission tomography

Summary intersected by lines in all directions.

Input: integral of desired quantity for all LOR’s in object

Output: map of quantity for entire object

Reconstruction

Algorithm

Nuclear Medicine

In: Line integrals of radioactivity concentration.

Out: Image of radioacitity concentration


Positron emission tomography

Example 1 - Internal Radioactivity intersected by lines in all directions.

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


Positron emission tomography

Example 1 - Internal Radioactivity intersected by lines in all directions.

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


Positron emission tomography

Example 1 - Internal Radioactivity intersected by lines in all directions.

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


Positron emission tomography

Example 1 - Internal Radioactivity intersected by lines in all directions.

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


Positron emission tomography

Reconstruction Result: intersected by lines in all directions.

Map of radioactivity concentration

Example 1 - Internal Radioactivity

-ray detector

(x,y) = Activity concentration

Rate of -ray emission along LOR*

Measure:

* emission rate is proportional to integral of activity concentration along LOR


Reconstruction
Reconstruction intersected by lines in all directions.

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

Method of Data Acquisition in PET intersected by lines in all directions.


Positron decay closeup

p intersected by lines in all directions.

n

Positron Decay Closeup

  • Beta Decay: +

e+

This decay is not allowed for a free proton (energy conservation)

Initial State

Final State


Positron emission tomography

PET intersected by lines in all directions.

: Positron Emission Tomography

  • Some neutron deficient nuclei decay by positron emission (+) decay.

Example:

F-18  O-18 + e+ + 

Half life: 109 minutes


Positron emission tomography

e- intersected by lines in all directions.

e+

Positron - Electron annihilation

PET

Positron comes to rest (total distance traveled ~ 1mm) and interacts with ambient electron


Positron emission tomography

Positron - Electron annihilation intersected by lines in all directions.

PET

Result: Two back-to-back 511 keV photons traveling along a line that contains the point at which the annihilation took place.


Positron emission tomography

PET intersected by lines in all directions.

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 timeτ of each other.

(typical τ: 10ns)


The pet scanner

The PET Scanner intersected by lines in all directions.


Positron emission tomography

PET intersected by lines in all directions.


Pet detectors
PET Detectors intersected by lines in all directions.

The PET scanner consists of a cylindrical grid of blocks, each containing a number individual detectors

15 cm (typical)


Block detector
Block Detector intersected by lines in all directions.

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
Example Block Detectors intersected by lines in all directions.

6.4 mm x 6.4 mm

8x8 crystals/block

4.0 mm x 4.0 mm

13x13 crystals/block

6.3 mm x 6.3 mm6x6 crystals/block

4.7 mm x 6.3 mm8x6 crystals/block

Most Common PET Scintillators:

Bismuth germanate (BGO)

Lutetium oxy-orthosilicate (LSO)


Positron emission tomography

Open PET Scanner. Block detector housings are visible. intersected by lines in all directions.


Pet nuclides and tracers

PET Nuclides and Tracers intersected by lines in all directions.


Positron decay
Positron Decay intersected by lines in all directions.

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
PET Compounds Routinely Produced and Approved for Animal/Human Use

[O-15]H2O (perfusion)

[O-15]O2 (oxygen metabolism)

[N-13]NH3 (myocardial perfusion)

[F-18]FDG (glucose metabolism, cell viability)

[C-11]raclopride (dopamine D2 receptor ligand)

[C-11]PMP (acetylcholinesterase substrate)

[carbonyl-C-11]WAY100635 (serotonin 5-HT1A receptor ligand)

[C-11]flumazenil (central benzodiazepine receptor ligand)

(+)[C-11]McN5652 (serotonin transporter ligand, active)

(-)[C-11]McN5652 (serotonin transporter ligand, inactive)

[C-11]PK-11195 (peripheral benzodiazepine receptor ligand)

[C-11]β-CFT (dopamine transporter ligand)

[C-11]PIB (beta amyloid imaging agent)

[C-11]3-O-methylglucose (glucose transport)

[C-11]DASB (serotonin transporter ligand)

[F-18]FLT (thymidine kinase substrate, cell proliferation)

[F-18]altanserin. (serotonin 5HT2A receptor ligand)

[F-18] FMISO (tumor cell hypoxia)


Pet compounds routinely produced and approved for animal human use1
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

PET Data Acquisition Modes Animal/Human Use


Multiple rings 2d 3d

cross Animal/Human Useslices (n-1)

Multiple Rings, 2D – 3D

For n detector rings:

2D

3D

direct slices (n)

3D- More counts

2D- Better ratio of good to bad counts

septa

total slices = 2n-1


Notice
Notice! Animal/Human Use

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.



Positron emission tomography

The Problem: Attenuation of radiation by the patient Animal/Human Use

  • 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
Attenuation of Radiation by Matter Animal/Human Use

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:

μ

I0

x

Photon survival probability


Attenuation of radiation by matter1
Attenuation of Radiation by Matter Animal/Human Use

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
Coincidence Attenuation Animal/Human Use

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 attenuation1
Coincidence Attenuation Animal/Human Use

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.


Positron emission tomography

Attenuation Correction Animal/Human Use

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.


Positron emission tomography

Attenuation Correction Animal/Human Use

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 Effects Animal/Human Use

Attenuation Corrected

Not Attenuation Correction

x-ray CT


Positron emission tomography

Corrected Animal/Human Use

PET Imaging Attenuation Effects

  • Incorrect regional image intensity

  • Distortion of shape

  • Streaking from large hot objects can mask less intense structure

Uncorrected


Degrading effects

Degrading Effects Animal/Human Use


Degrading effects1
Degrading Effects Animal/Human Use

  • Scatter

  • Randoms

  • Limited Spatial Resolution

  • Limited Counts -> Image Noise


Scattered coincidence event
Scattered Coincidence Event Animal/Human Use

In-Plane

Out-of-Plane

Scatter Fraction S/(S+T)

With septa ~10-20%

w/o septa ~30-80%


Scatter control
Scatter Control Animal/Human Use

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 control1
Scatter Control Animal/Human Use

  • 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

 Animal/Human Use

Random Coincidence Event

b

RR=2RaRb

a


Random compensation
Random Compensation Animal/Human Use

  • 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
Noise Animal/Human Use

  • Due to counting statistics including the effects of scatter and random compensation

More counts

Fewer counts


Correcting background noise equivalent counts
Correcting Background: Animal/Human UseNoise Equivalent Counts

What you want

What you measure

“Background”

More background  more statistical image noise.


Spatial resolution limits
Spatial Resolution Limits Animal/Human Use

  • Detector Size

  • Smaller crystal elements yield better resolution.


Spatial resolution limits1
Spatial Resolution Limits Animal/Human Use

  • Positron Range

    • Positron moves before annihilation

Size of effect depends on nuclide, typically on the order of a millimeter


Spatial resolution limits2
Spatial Resolution Limits Animal/Human Use

  • 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

Combining Modalities Animal/Human Use

PET and CT


Pet ct
PET/CT Animal/Human Use


Pet ct systems
PET/CT Systems Animal/Human Use

All new systems sold in the USA are now PET/CT


Positron emission tomography

+ anatomy Animal/Human Use

Hardware fusion: function

PET

CT

PET/CT

FDG-PET


Nhl better localization

Case Animal/Human Use: 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.

NHL-Better Localization


Positron emission tomography

+ anatomy Animal/Human Use

Hardware fusion: function

  • 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