Radiopharmaceuticals used for Brain Perfusion SPECT

A number of commercially available and experimental pharmaceuticals have been applied to SPECT studies of cerebral perfusion. The radiotracer accumulates in different areas of the brain proportional to the rate of delivery of the blood to that volume of brain tissue. Accumulation is described in units of ml/min/100 g (differing from the flow of blood in vessels, which is described in units of ml/min).

Perfusion may also be referred to as regional blood flow or, in the brain, regional cerebral blood flow (rCBF)". Implicit in the use of those tracers that remain in the brain is the notion of a multicompartment clearance (the microsphere model). This model assumes that :

• injected isotope is freely diffusible from the blood pool into the brain
• the brain extracts all or nearly all of the available isotope by the blood
• once in the brain tissue, the isotope is fixed, or "trapped", or that backflux from the brain into the blood can be accounted for, and
• following initial tracer uptake, its initial redistribution is nil.

This approach also assumes that all compartments --including the blood pool and the brain tissue --are accounted for in the model and that forward (and reverse) transport of the tracer are predictable throughout the brain, as are potentially confounding influences such as inhomogenecities in flow, extraction, and potential receptor binding. Many if not all of these assumptions are violated to greater or lesser degrees by virtually all available flow tracers.

Despite these caveats, work in animals and humans has demonstrated that, under properly controlled conditions, SPECT data obtained with perfusion agents approximates perfusion closely enough to be meaningful in clinical and research studies.

Furthermore, most routine clinical applications of brain-perfusion SPECT do not require quantitation of rCBF and rely exclusively on the generation of images that reflect tracer uptake and retention only.

Tracer activity in the brain correlates well with independent measures of rCBF over a wide range of flow, but achieving this determination requires arterial sampling, scrupulous technique and highly accurate instrumentation.

Regional blood flow measurement (functional brain imaging)

For radiotracers that have a very slow clearance from the brain, estimates of regional cerebral blood flow (rCBF) are based on the microsphere model, which assumes that:

the radiotracer is freely diffusible from the blood pool,

it is completely extracted from the blood into the blood brain barrier, and

it remains fixed within the brain without redistribution.

Quantitative blood flow measurment

Blood flow can also be measured quantitatively from the clearance of the inert blood gas Xenon-133 with highly sensitive instrumentation that can image its distribution repeatedly during its rapid clearance from the brain.

Most routine clinical applications of brain perfusion SPECT do not require quantitation of rCBF and rely on the generation of images which reflect tracer uptake and retention only. Quantitation of regional cerebral blood flow using these radiotracers requires arterial sampling and careful modeling to account for incomplete extraction, back flux from the brain and other deviations from the theoretical model.

Despite such constraints, intravenous injection of brain perfusion radiotracers results in regional brain activity which correlates well with independent measures of rCBF over a wide range of flows.

• Iodine-123 ligands
• 99m-Technitium ligands
• Xenon-133
• Neuroreceptor ligands

Safety of the procedure

Brain perfusion SPECT imaging is a safe procedure. The whole body effective dose equivalent (EDE) received from the administration of Tc-99m HMPAO (exametazime) is 0.7 rem per 20 mCi dose. This EDE value is similar to that received during a radionuclide bone scan, is 1.5 times that received from a CT of the abdomen and the pelvis, and is 43% of the annual average background radiation in the United States.

Patients must remain still during the study, which usually lasts 20 to 30 minutes. Most state-of-the-art imaging systems are designed to reduce head motion and patient discomfort. Most clinical applications do not require arterial sampling.