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

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.

Micro-Positron Emission Tomography Imaging of Rat Brain Metabolism during Expression of Contextual Conditioning

“…The within-subject test-retest variability of our imaging procedure is of comparable magnitude to human data (i.e., Ͻ5%) (Casteels et al, 2006).…”

“…After the session, food was returned. The fasting period preceding tracer injection ensured that the injected 18 F-fluorodeoxyglucose did not have to compete with high levels of normal blood glucose (Bailey, 2005;Casteels et al, 2006). For conditioning experiments, overnight fasting is not desirable because it may affect expression of contextual anxiety (L. Luyten, D. Vansteenwegen, K. van Kuyck, B. Nuttin, unpublished results).…”

“…Approximately 18 MBq (500 Ci; specific activity range, 100 -760 GBq/mol) of the radioligand was injected intraperitoneally. The tracer was administered in a sterile solution (injection volume, 500 l) of 5 mM sodium acetate buffer, pH 5.5, containing 6% of ethanol (Casteels et al, 2006).…”

“…FDG measurements were obtained during 30 min starting 1 h after injection. The acquisition timing rationale and kinetics of the radioligand in rats have been described previously (Casteels et al, 2006). Sinograms were reconstructed using filtered backprojection.…”

Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

“…To obtain maximal use of [ 18 F]MK-9470 image information, images were analysed on a voxel-by-voxel basis using SPM2 [27]. This methodology allows reporting results as coordinates directly corresponding to the Paxinos coordinate system of rat brain.…”