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Basic Science Investigation |
1 Division of Nuclear Medicine, University Hospital Gasthuisberg and Katholieke Universiteit Leuven, Leuven, Belgium; 2 Bio-Imaging Laboratory, University of Antwerp, Antwerp, Belgium; 3 Laboratory for Neurobiology and Gene Therapy, Molecular Medicine, Katholieke Universiteit Leuven, Leuven, Belgium; and 4 Laboratory of Radiopharmaceutical Chemistry, Katholieke Universiteit Leuven, Leuven, Belgium
Correspondence: For correspondence or reprints contact: Cindy Casteels, MSc, Division of Nuclear Medicine, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. E-mail: cindy.casteels{at}uz.kuleuven.ac.be
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 (18F-FDG), dopamine transporter (DAT) (2'-18F-fluoroethyl(1R-2-exo-3-exe)-8-methyl-3-(4-chlorophenyl)-8-azabicyclo[3.2.1]-octane-2-carboxylate [18F-FECT]), and dopaminergic D2 receptor (11C-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 18F-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. 18F-FDG data were count normalized to the whole-brain uptake, whereas parametric DAT and D2 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 18F-FDG uptake, intersubject variation ranged from 1.7% to 6.4%. For 11C-raclopride and 18F-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 11C-raclopride and 7.7% for 18F-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.
Key Words: Paxinos atlas • SPM • VOI analysis • microPET • spatial normalization
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