Construction and Evaluation of Quantitative Small-Animal PET Probabilistic Atlases for [18F]FDG and [18F]FECT Functional Mapping of the Mouse Brain

Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([F-18]FDG) and dopamine transporter ([F-18]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [F-18]FDG and [F-18]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice. Methods: Twenty-three adult C57BL6 mice were scanned with [F-18]FDG and [F-18]FECT. Registrations and affine spatial normalizations were performed using SPM8. [F-18]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMR(glc)), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [F-18]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination. Results: Registration accuracy was between 0.21-1.11 mm. Regional intersubject variabilities of cMR(glc) ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [F-18]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMR(glc) positively correlated to SUVglc measured within the 45-60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT availability. Conclusion: MRM-based small-animal PET templates facilitate accurate assessment and spatial localization of mouse brain function using VOI or voxel-based analysis. Regional intersubject- and test-retest variations indicate that for these targets accuracy comparable to humans can be achieved.