Positron Emission Tomography Outline PET Examples Imaging Goal Reconstruction/Data Requirements Method of Data Acquisition in PET –Positron Decay/Annihilation

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

PET Scan Examples

PET

PET/CT FDG

Breast Cancer

CT PET

Tracer: [F-18] FDG

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

Colon Cancer

10.9 mCi FDG6 X ( 4 min Emission + 2.5 min Transmission) = 39 min

)/()(

)(

massbodydoseinjected

ionconcentratrradiotraceSUV

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.


Early time(Carotid Artery)

Late time(Tumor)


Possible 2-Tissue Compartment Model for Fluorothymidine (FLT)

CaC1 C2

K1

k2

k3

k4

Ca - Tracer concentration in bloodC1 - Unphosphorolated tracer concentration in tissueC2 - Phosphorolated tracer concentration (preliminary step in the

incorporation of thymidine into DNA)

• Model parameters• Represent transfer rates between compartments (think pipe diameters)

K’s:

2413

241321

2

1 )(

CkCk

CkCkkCK

dtdC

adtdC

Significance example: In brain, K1 is determined by BBB integrity whereask3 , the phosphorolation/proliferation rate is expected to better reflect tumor status. These quantities cannot be cleanly disentangled with single time-point imaging.


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

CT imageOverlaid PET /

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).

Line of Response (LOR):

Definition:

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

Output: map of quantity for entire

object

Nuclear Medicine

In: Line integrals of radioactivity concentration.

Out: Image of radioacitity concentration

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










Example 1 - Internal Radioactivity -ray detector

Reconstruction Result:

),( yxMap of

radioactivity concentration

Measure:Rate of -ray

emission along LOR*

jj dlyxI ),(

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

(x,y) = Activity 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

Initial State

p

n

e+

Final State

Positron Decay Closeup

• Beta Decay: +

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

PET

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

Example:

F-18 O-18 + e+ +

: Positron Emission Tomography

Half life: 109 minutes

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

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 PMTsHead 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

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)

Open PET Scanner. Block detector housings are visible.

PET Nuclides and Tracers

Nuclide half-lifeC-11 20.3 minN-13 10 minO-15 124 secF-18 110 minRb-82 75 sec

e.g., 18F 18O + e+ +

Positron Decay

ZAXN Z 1

AYN1 e+

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 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

direct slices (n)

For n detector rings:

crossslices (n-1)

total slices = 2n-1

2D 3D

septa

3D- More counts

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 MatterFor 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:

x

dxx

eIxI 0

')'(

0)(

Photon survival probability

μ

I0 x

Attenuation of Radiation by Matter

x

dxx

e 0

')'(

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

21PPPc

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

2

1)(

21

x

xdxx

c ePPP

0

1

')'(

1

x

x

dxx

eP

1x

2x

0x

2

0

')'(

2

x

x

dxx

eP

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

positron (511 keV photon) source

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.

Attenuation Corrected

Not Attenuation Correction x-ray CT

Atte

nuat

ion

Effe

cts

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

• Scatter • Randoms• Limited Spatial Resolution • Limited Counts -> Image Noise

Scattered Coincidence EventIn-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

RR=2RaRb

a

b

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

)//1(

2

TRTS

T

P

TNEC

RSPT

RSTP randomsscattertruesprompts

More background more statistical image noise.

“Background”

What you measure

What you want

Spatial Resolution Limits

Detector SizeSmaller crystal elements yield better

resolution.


Positron RangePositron moves before annihilation

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


Opening AngleGamma 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

FDG-PET

PET/CT CT

PET

Findings: Two foci of intense FDG uptake in soft tissue adjacent to bonesconsistent with malignancy.

NHL-Better LocalizationCase: 53 y/o male with hx of NHL s/p chemotherapy with c/o

weight loss and pain for follow-up PET/CT

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

Documents

Positron Emission Tomography Outline PET Examples Imaging Goal Reconstruction/Data Requirements Method of Data Acquisition in PET –Positron Decay/Annihilation