The influence of measurement uncertainties on the evaluation of the distribution volume ratio in rat studies on a microPET® R4: A phantom study

In small animal imaging the injectable radiotracer dose is often limited by the tracer mass effect. Biological considerations as opposed to the count rate capabilities of the scanner are thus often the limiting factor for the maximum allowed radiotracer dose, which in turn, together with the tracer kinetics and scanner sensitivity, dictates the statistical quality of the time activity curves (TACs) used to extract biologically significant parameters. We investigated the effect of measurement uncertainty on the determination of the distribution volume ratio (DVR) and binding potential (BP) as estimated using the tissue input Logan (DVR_L, BP_L) and the ratio (DVR _r, BP_r) methods for two different tracers, with the Concorde microPET® R4 camera. TAC templates extracted from rat studies and phantom data were used. We found that for a tracer with relatively fast kinetics, ¹¹C-dihydrotetrabenazine (DTBZ), the overall coefficient of variation (COV) was 11% for the BP_L and 13.4% for the BP _r, when the BP was calculated using TACs obtained from individual regions of interest (ROIs). The COVs were reduced to 7.5% (BP_L) and 8.6% (BP_r) when the striatal and cerebellar TACs were estimated as averages of 3 and 2 ROIs respectively. Similar results obtained for a tracer with slower kinetics ¹¹C-methylphenidate (MP), yielded approximately 30% higher COVs. The above values were obtained when segmented attenuation correction was applied to the data; with measured attenuation correction the COVs were on average 50% higher.