Construction and Evaluation of Multitracer Small-animal PET Probabilistic Atlases for Voxel-based Functional Mapping of the Rat Brain

Unlabelled: Automated voxel-based or predefined volume-of-interest (VOI) analysis of rodent small-animal PET data is necessary for optimal use of information because the number of available resolution elements is limited. We have mapped metabolic ((18)F-FDG), dopamine transporter (DAT) (2'-(18)F-fluoroethyl(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]-octane-2-carboxylate [(18)F-FECT]), and dopaminergic D(2) receptor ((11)C-raclopride) small-animal PET data onto a 3-dimensional T2-weighted MRI rat brain template oriented according to the rat brain Paxinos atlas. In this way, ligand-specific templates for sensitive analysis and accurate anatomic localization were created. Registration accuracy and test-retest and intersubject variability were investigated. Also, the feasibility of individual rat brain statistical parametric mapping (SPM) was explored for (18)F-FDG and DAT imaging of a 6-hydroxydopamine (6OHDA) model of Parkinson's disease.

Methods: Ten adult Wistar rats were scanned repetitively with multitracer small-animal PET. Registrations and affine spatial normalizations were performed using SPM2. On the MRI template, a VOI map representing the major brain structures was defined according to the stereotactic atlas of Paxinos. (18)F-FDG data were count normalized to the whole-brain uptake, whereas parametric DAT and D(2) binding index images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatching.

Results: Registration accuracy was between 0.24 and 0.86 mm. For (18)F-FDG uptake, intersubject variation ranged from 1.7% to 6.4%. For (11)C-raclopride and (18)F-FECT data, these values were 11.0% and 5.3%, respectively, for the caudate-putamen. Regional test-retest variability of metabolic normalized data ranged from 0.6% to 6.1%, whereas the test-retest variability of the caudate-putamen was 14.0% for (11)C-raclopride and 7.7% for (18)F-FECT. SPM analysis of 3 individual 6OHDA rats showed severe hypometabolism in the ipsilateral sensorimotor cortex (P </= 0.0004) and a striatal decrease in DAT availability (P </= 0.0005, corrected).

Conclusion: MRI-based small-animal PET templates facilitate accurate assessment and spatial localization of rat brain function using VOI or voxel-based analysis. Regional intersubject and test-retest variations found in this study, as well as registration errors, indicate that accuracy comparable to the human situation can be achieved. Therefore, small-animal PET with advanced image processing is likely to play a useful role in detailed in vivo molecular imaging of the rat brain.