PET: An Overview

1
PET An Overview

• Psychiatric Neuroimaging Program
• Vanderbilt University
• Didactic Session
• 7/24/07
• James Wantuck

2
PET Outline

• Basic Science
• Particle Physics
• Sources of error
• Experimental Design
• Our methods
• Overview
• Setoperone
• Types of inquiry
• Chemistry
• Metabolism
• Pharmacology

• Data Analysis
• Tracer Modeling
• Binding Potential Map/ Compartmental Analysis
• Reference Tissue Method
• Format Wars
• Preproccesing
• Cluster Analysis
• Region of Interest Analysis
• MNI to Talairach

3
Positron Emission Tomography

• Coincidence
• Background Radiation

• Radiotracer Technique
• Pos Ele Gamma Ray

• Image from http//dels.nas.edu/ilar_n/ilarjournal
  /42_3/4203_Positron.shtml

4
Sources of Noise 1

• Problem - Radioactive Decay as a Poisson
  Distribution and spatial separation

• Solution - Collect More Counts, limit on spatial
  resolution

Image from http//wlap.physics.lsa.umich.edu/umic
h/phys/satmorn/2003/20030322/real/sld011.htm
5
Sources of Noise 2

• Problem Photon Attenuation with Distance and
  Density

• Solution - Distance Density accounted for

Images from http//imd-www.es.hokudai.ac.jp/gnis
hi/scatt.html
6
Sources of Noise 3

• Problem -Photon Scatter

• Solution - Measure Photon E, but overlap persists

Image from http//www.petnm.unimelb.edu.au/pet/det
ail/nucphysics.html
7
Sources of Noise 4

• Problem - Spatial Resolution - FWHM

• Solution - Incorporate Structural Info

8
Types of measurements with PET

• Neuronal Metabolism
• rCGM or rCBF
• Oxygen-15 labeled water, or fluorine-18 labeled
  fluorodeoxyglucose
• Pharmacology
• Most drugs are organic and thus can be labeled
  with Carbon-11
• Brain Chemistry
• Neurotransmitter synthesis, receptors,
  transporters, and release (sensitive down to
  10-12M!)

Kaufman, M.J. Brain Imaging in Substance Abuse.
New Jersey Human Press Inc., 2001
9
Serotonin Overview

• 5-HTTLPR is promoter region of SERT gene
• SS causes less SERT, LaLa causes more SERT
• ? in serotonin in synapse should alter
  postsynaptic receptor, 5-HT2A

http//www.humanillnesses.com/images/hdc_0000_0001
_0_img0054.jpg
10
Setoperone v. Serotonin

• (18F)-Setoperone is an agonist at the 5-HT2A
  receptor with Ka 1nM

Seeman P Receptor Tables Drug Dissociation
Constants for Neuroreceptors and Transporters,
vol 2. Toronto, SZ Research, 1993
11
Tracer Modeling

• The basis for most Pet studies numerical value
• Time activity curves ? Parametric Images 3
  methods
• Kinetic non linear least squares
• Graphical linear
• Equilibrium no change over time

Kaufman, M.J. Brain Imaging in Substance Abuse.
New Jersey Human Press Inc., 2001
12
Compartmental Analysis
Reference Tissue Method - A variant of the
equilibrium method - Uses a region that is
devoid of the object of interest
Cp Plasma Cr Reference Cf Free Cb
Bound
A A Lammertsma, C J Bench, S P Hume, S Osman,
K Gunn, D J Brooks and R S J Frackowiak. 1995.
Comparison of Methods for Analysis of Clinical
11CRaclopride Studies. Journal of Cerebral
Blood Flow Metabolism (1996) 16, 4252
13
The Math
Parametric Map of BP BP Bmax/Kd k3/k4
Cp Metabolite-corrected plasma concentration
(kBq ml-1) Cr Concentration in reference
tissue (kBq ml-1) Cf Concentration of free
(i.e. not specifically bound) ligand (kBq ml-1)
Cb Concentration of specifically bound ligand
(kBq ml-1) K1 Rate constant for transfer from
plasma to free compartment (ml ml-1 min-1) k2
Rate constant for transfer from free to plasma
compartment (min-1) k3 Rate constant for
transfer from free to bound compartment (min-1)
k4 Rate constant for transfer from bound to
free compartment (min-1) K1' Rate constant for
transfer from plasma to reference compartment (ml
ml-1 min-1) k2' Rate constant for transfer
from reference to plasma compartment (min-1)
A A Lammertsma, C J Bench, S P Hume, S Osman,
K Gunn, D J Brooks and R S J Frackowiak. 1995.
Comparison of Methods for Analysis of Clinical
11CRaclopride Studies. Journal of Cerebral
Blood Flow Metabolism (1996) 16, 4252
14
Obtaining Binding Potential

• Measure binding in Rref and binding in ROI, and
  subtract out Rref to get BP in ROI.

A A Lammertsma, C J Bench, S P Hume, S Osman,
K Gunn, D J Brooks and R S J Frackowiak. 1995.
Comparison of Methods for Analysis of Clinical
11CRaclopride Studies. Journal of Cerebral
Blood Flow Metabolism (1996) 16, 4252
15
Reference Tissue Method

• Advantages
• No arterial cannulation
• Independent of plasma curve and hence the tracer
  , so there is no error in measurement of
  metabolites
• Disadvantages
• Reference tissue must be assumed to be void of
  object of interest and to be modeled by only one
  compartment

A A Lammertsma, C J Bench, S P Hume, S Osman,
K Gunn, D J Brooks and R S J Frackowiak. 1995.
Comparison of Methods for Analysis of Clinical
11CRaclopride Studies. Journal of Cerebral
Blood Flow Metabolism (1996) 16, 4252
16
Drawing Reference Regions
17
Drawing Reference Regions

• Draw in the cerebellum about 10 levels
• Avoid edges, spurious activation, midline
• Encompass equal gray and white

18
Preprocessing

• Data must be converted into format that SPM can
  read. Use MRIcro
• Convert from raw data format into NIFTI files by
  using your known image dimensions, voxel size,
  and orientation information
• Our data is 256x256x170 voxels, 1mmx1mmx1mm voxel
  size, and 2byte/pixel volume

19
Preprocessing Normalization and Smoothing

• Normalize the data to MNI (ICBM-152) space using
  the T1.nii SPM template
• Do the structural, then BP image
• Then smooth the data using 8mm Gaussian kernel

20
ROI Analysis

• Using a completely automated parametric approach
  within SPM

21
ROI Analysis

• Cluster Analysis
• SPM utilizes t-test to look for difference
  between groups in all voxels
• Subjects grouped by genetics (SS or LL)
• No regard to structure or function
• Once difference found, we must determine
  structures involved

22
ROI Analysis

• Brodmanns Areas ROI approach
• MarsBar SPM add-on looks for statistical
  difference in ROIs, inputed by user
• Allows some structural significance to be
  ascertained

23
MNI to Talairach?

• Uses the ICBM2TAL method described by Lancaster
  et al.
• 4x4 Affine Transform
• MTT Algorithm for conversion embedded into
  GingerALE, a program developed by brainmap.org

Lancaster et al. 2007. Bias between MNI and
Talaraich coordinates analyzed using the ICBM-152
brain template. Human Brain Mapping.
24
The End

• Thank you for listening. Please enjoy this
  animation of 5-HT pathways

http//www.brainchannels.com/evolution/evolutionme
dia/serotonin.gif