A Standardized Method for the Construction of Tracer Specific PET and SPECT Rat Brain Templates: Validation and Implementation of a Toolbox

High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain-and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [F-18]FDG, [C-11]flumazenil, [C-11]MeDAS, [C-11]PK11195 and [C-11]raclopride, and SPECT [Tc-99m]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70 +/- 0.32mm for [F-18] FDG (n = 25), 0.23 +/- 0.10mm for [C-11]flumazenil (n = 13), 0.88 +/- 0.20 mm for [C-11]MeDAS (n = 15), 0.64 +/- 0.28mm for [C-11]PK11195 (n = 19), 0.34 +/- 0.15mm for [C-11] raclopride (n = 6), and 0.40 +/- 0.13mm for [Tc-99m] HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [F-18] FDG as reference template (p&0.001). Additionally, registration errors were smallest with strain-specific templates (p&0.05), and when images and templates had the same size (p