brain… the final frontier…. lets go on a “fantastic voyage” blood flow metabolism...

Brain… The Final Frontier…

Lets go on a “Fantastic Voyage”

Blood FlowMetabolism

Permeability

Receptor Binding

Gene Expression

Neurotransmission

Transmitter Synthesis

Reuptake

With PET we can image at the site of “thinking”

15O-[H2O]18F-FDG

15O-[H2O]

11C-raclopride

(18)F-FBAU

11C-raclopride, etc

18F-FDOPA

11C-CFT

Dopaminergic synapse

OK.So what’s the problem?

What’s all this about models in PET?

Bound raclopride

Free raclopride

Plasma raclopride

‘stuck’ raclopride

Dopaminergic synapse

How can we tell which radioactivity comes from

Free tracerBound tracer

Plasma-borne tracer?

Tracer in each state has a unique temporal trajectory

Time (minutes)

trac

er c

onc

entr

atio

n

Plasma

Free

Bound

What the PET scanner sees

which is which ?

Divining the shape of each curve depends on kinetic modeling of

the data.

The modeling process

(b)

P F B

N

(c)

... )( )(

...( )(

... )()()(

5

'max

21

tFkdt

tdN

Bkdt

tdB

tFktPKdt

tdF

on

(d)

(a)

Imagine a living brain

Consider the relevant neurochemistry

Abstract the neurochemistry into a series of connected pools

Describe exchange between pools by a series of differential equations

Morris, E.D., C.J. Endres, K. Schmidt, B.T. Christian, R.F. Muzic, R.E. Fisher. Kinetic Modeling in PET. In Emission Tomography: The Fundamentals of PET and SPECT, ed. M. Wernick and N. Aarsvold. Academic Press. Amsterdam, Netherlands, 2004, pp. 499-540.

The modeling process

(b)

P F B

N

(c)

... )( )(

...( )(

... )()()(

5

'max

21

tFkdt

tdN

Bkdt

tdB

tFktPKdt

tdF

on

(d)

(a)