Abstract
High-resolution anatomical image data in preclinical brain PET and SPECT studies is often not available, and inter-modality spatial normalization to an MRI brain template is frequently performed. However, this procedure can be challenging for tracers where substantial anatomical structures present limited tracer uptake. Therefore, we constructed and validated strain- and tracer-specific rat brain templates in Paxinos space to allow intra-modal registration. PET [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195 and [11C]raclopride, and SPECT [99mTc]HMPAO brain scans were acquired from healthy male rats. Tracer-specific templates were constructed by averaging the scans, and by spatial normalization to a widely used MRI-based template. The added value of tracer-specific templates was evaluated by quantification of the residual error between original and realigned voxels after random misalignments of the data set. Additionally, the impact of strain differences, disease uptake patterns (focal and diffuse lesion), and the effect of image and template size on the registration errors were explored. Mean registration errors were 0.70±0.32mm for [18F]FDG (n = 25), 0.23±0.10mm for [11C]flumazenil (n = 13), 0.88±0.20 mm for [11C]MeDAS (n = 15), 0.64±0.28mm for [11C]PK11195 (n = 19), 0.34±0.15mm for [11C]raclopride (n = 6), and 0.40±0.13mm for [99mTc]HMPAO (n = 15). These values were smallest with tracer-specific templates, when compared to the use of [18F]FDG as reference template (p&0.001). Additionally, registration errors were smallest with strain-specific templates (p&0.05), and when images and templates had the same size (p≤0.001). Moreover, highest registration errors were found for the focal lesion group (p&0.005) and the diffuse lesion group (p = n.s.). In the voxel-based analysis, the reported coordinates of the focal lesion model are consistent with the stereotaxic injection procedure. The use of PET/SPECT strain- and tracer-specific templates allows accurate registration of functional rat brain data, independent of disease specific uptake patterns and with registration error below spatial resolution of the cameras. The templates and the SAMIT package will be freely available for the research community.
Highlights
Nuclear medicine imaging techniques are increasingly used for the study of rodent models of a variety of human brain diseases
The resolution that can be obtained in current small animal positron emission tomography (PET) and single-photon emission computed tomography (SPECT) scanners is a limiting factor during the analysis
The mean volumes of interest (VOI) uptake and right-to-left ratios, are displayed in Table 2 for [18F]FDG, [11C]flumazenil, [11C]MeDAS, [11C]PK11195, [11C]raclopride and [99mTc] HMPAO, which were calculated from the images used in the construction of the corresponding template
Summary
Nuclear medicine imaging techniques are increasingly used for the study of rodent models of a variety of human brain diseases The use of these functional images allows the researcher to measure physiological processes, biochemical pathways and neurotransmitters in vivo. A powerful and widely-used approach for the analysis of neuroimaging data is based on the adoption of a common reference space to which images from individual subjects and time points are spatially normalized [1]. This allows direct within- or between-subject comparisons and the application of standard, pre-defined reference maps and masks, including atlas structures. Group comparisons could be performed using a voxel-based and/or VOI-based (volume of interest) analysis
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