Reference tissue
Reference tissue is a region without specific binding of the ligand.
Reference tissue vs arterial plasma input
| Reference tissue | Arterial plasma |
|---|---|
|
+ noninvasive - available only for a few brain receptor tracers - radioactivity spillover from adjacent tissues or due to scatter |
- invasive - not accessible from all subjects or small animals - labor-intensive and error-prone metabolite analysis |
If reference tissue has specific binding
If the reference region has specific binding, the binding potential will be underestimated [Gunn et al. 1997]:
Specific binding in reference region will also lead to bias in Scatchard analysis (Litton et al. 1994).
Extracerebral reference region
When no suitable cerebral reference region is available, it may be possible to quantify brain receptors using muscle as reference region (Le Foll et al. 2007). However, there are several caveats in using this approach:
- Radioactive label carrying metabolites that can not penetrate the blood brain barrier may well enter extracellular tissues and prevent their use as reference region
- Blood flow is much lower in muscle than in the brain, therefore becoming the limiting factor for K1 in the reference tissue
- Furthermore, blood flow in muscle is highly variable in awake state
- Non-displaceable distribution volume is probably different in the brain and in extracerebral reference region; therefore it has to be measured, and only if proven to be constant the binding potentials can be corrected for it (Le Foll et al. 2007)
- Additional requirements may be set by the model, for example, SRTM requires that reference region kinetics can be reasonably well described by 1-tissue compartment model
See also:
- Reference tissue input compartmental models
- Calculation of reference tissue input compartment models for regional data
- Calculation of BPND images
