Abstract
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 ([18F]FDG) and dopamine transporter ([18F]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 [18F]FDG and [18F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice.MethodsTwenty-three adult C57BL6 mice were scanned with [18F]FDG and [18F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [18F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMRglc), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [18F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination.ResultsRegistration accuracy was between 0.21–1.11 mm. Regional intersubject variabilities of cMRglc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [18F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMRglc 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.ConclusionMRM-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.
Highlights
Neuroimaging studies are increasingly performed on mice as models for a variety of human diseases and genetic traits
Registrations and affine spatial normalizations were performed using SPM8. [18F]FDG data were quantified using (1) an image-derived-input function obtained from the liver, using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake
Regional values of cMRglc positively correlated to Standardized uptake value corrected for blood glucose (SUVglc) measured within the 45– 60 min time frame
Summary
Neuroimaging studies are increasingly performed on mice as models for a variety of human diseases and genetic traits. As in small-animal PET measurements of mouse brain, the number of available resolution elements is lower than in the human PET counterpart [3], optimal information usage is imperative for detailed regional analysis. An important step in functional neuroimaging analysis is the development of methods to combine data from different subjects in a common atlas space [4]. Spatial normalization can increase sensitivity of low-magnitude responses and facilitate group comparisons. This can be performed using either automated voxel-based or operator-independent volume-of-interest (VOI) analysis on probabilistic atlases which are oriented into a common stereotactic space, e.g. according to Paxinos for rodents [5]
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