Positron Emission Tomography

Charles Laymon CML14@pitt.edu

Outline •  PET Examples •  Imaging Goal •  Reconstruction/Data Requirements •  Method of Data Acquisition in PET

–  Positron Decay/Annihilation –  Detectors/Scanner

•  PET Tracers •  Attenuation •  Degrading Effects •  Combined Modalities: PET, CT, MR

Starting Point / Overview • Patient administered radioactive drug or tracer that follows a metabolic pathway of interest.

• Emitted gamma rays detected using PET scanner.

• Acquired data reconstructed into 3D image of tracer distribution (perhaps as function of time).

àThus PET = Tracer + Scan

--Example: F-18 labeled Fluoro DeoxyGlucose (FDG) is a glucose analog that traced the first steps of glycolysis

PET Scan Examples

PET/CT FDG

Breast Cancer

CT PET

Tracer: [F-18]fluordeoxyglucose_ ( [F-18] FDG)

A glucose analog, Goes to regions with high glycolitic rate.

(Extent and location)

Colon Cancer

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

(Extent and location)

Lymphoma Pre/Post treatment FDG-PET MIP Images

Initial Exam Follow up (3 month)

FDG-PET MIP Images

Initial Exam Follow up (3 month)

MRI, T1+C FDG PET FLT PET (different patient)

FDG – Glucose metabolism. Normal gray matter tissue has high glucose metabolism.

FLT –(fluorothymidine) DNA synthesis/cellular proliferation. Normal brain has low signal.

Example of Different Tracers

Example of Different Tracers

F-18- labeled PET apoptosis (programmed cell death tracer

PET images (color) overlaid on MR (gray)

Example of Different Tracers

Raclopride binds to dopamine receptors

(D2/3 antagonist)

Narendran et al. Synapse 63:574–584 (2009)

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 image Overlaid PET /

Overview of Image Reconstruction

We treat as a 2-dimensional

problem

We treat as a 2-dimensional

problem

Transaxial plane

Axial direction

We treat as a 2-dimensional

problem

Transaxial plane

“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.

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

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+ ν

Final State

Positron Decay Closeup •  Beta Decay: β+

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

PET

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

Example:

F-18 → O-18 + e+ + ν

: Positron Emission Tomography

Half life: 110 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 (energy and momentum

conservation)

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: few ns)

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

6.3 mm x 6.3 mm 6x6 crystals/block

4.7 mm x 6.3 mm 8x6 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-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+ + ν

Positron Decay

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 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. In which the source orbits about the subject.

Sources were an integral part of a PET scanner.

Modern day PET/CT scanners accomplish this using the CT data.

Attenuation Corrected

Not Attenuation Corrected x-ray CT

Atte

nuat

ion

Effe

cts

Degrading Effects

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

Scattered Coincidence Event In-Plane Out-of-Plane

Scatter Fraction S/(S+T) ~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

±τ

RR=2τRaRb 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

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 and MR

PET/CT

PET/CT Systems

All new systems sold in the USA are now PET/CT (or PET/MR).

Hardware fusion: function + anatomy

FDG-PET

PET/CT CT

PET

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

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"

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

• Note that for practical* and technical reasons PET and CT are basically separate units within a single gantry. Thus the PET and CT scans are acquired sequentially.

*PET scans are generally much longer than CT scans

PET MR •  Emerging technology combining PET and MR

•  Data processing/reconstruction issues: How do we get a 511 keV mu map (required for PET reconstruction) from MR? •  This issue is still being addressed

àImproved pulse sequences allowing improved identification of tissue types àPost acquisition image processing methods to identify tissue types and assign appropriate µ-value

PET MR Despite challenges commercial systems are becoming available

•  Philips •  Two separate back-to-back units •  Scans are acquired sequentially (Similar to PET/CT)

PET MR Despite challenges commercial systems are becoming available

•  Siemens •  Integrated units •  PET and MR fields of

view overlap •  True simultaneous

acquisitions possible

PET MR •  Emerging technology combining PET and MR

•  Technological difficulties: •  Distortion of magnetic field (B) by PET components •  Effect of high B field on PET

(Example : photomultiplier tubes, a main component of traditional PET scanners are useless in a high B field)

àReplace photomultipliers with solid state avalanche photo diodes