A statistical parametric mapping toolbox used for voxel-wise analysis of FDG-PET images of rat brain

Abstract

Purpose: PET (positron emission tomography) imaging researches of functional metabolism using fluorodeoxyglucose (18F-FDG) of animal brain are important in neuroscience studies. FDG-PET imaging studies are often performed on groups of rats, so it is desirable to establish an objective voxel-based statistical methodology for group data analysis.

Material and methods: This study establishes a statistical parametric mapping (SPM) toolbox (plug-ins) named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain, in which an FDG-PET template and an intracranial mask image of rat brain in Paxinos & Watson space were constructed, and the default settings were modified according to features of rat brain. Compared to previous studies, our constructed rat brain template comprises not only the cerebrum and cerebellum, but also the whole olfactory bulb which made the later cognitive studies much more exhaustive. And with an intracranial mask image in the template space, the brain tissues of individuals could be extracted automatically. Moreover, an atlas space is used for anatomically labeling the functional findings in the Paxinos & Watson space. In order to standardize the template image with the atlas accurately, a synthetic FDG-PET image with six main anatomy structures is constructed from the atlas, which performs as a target image in the co-registration.

Results: The spatial normalization procedure is evaluated, by which the individual rat brain images could be standardized into the Paxinos & Watson space successfully and the intracranial tissues could also be extracted accurately. The practical usability of this toolbox is evaluated using FDG-PET functional images from rats with left side middle cerebral artery occlusion (MCAO) in comparison to normal control rats. And the two-sample t-test statistical result is almost related to the left side MCA.

Conclusion: We established a toolbox of SPM8 named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain.

Figure 1. Schematic representation of the data analysis procedure in the spmratIHEP.

The procedures of spatial normalization showed in the red dashed pane could be accomplished automatically in this toolbox.

Figure 2. The constructed rat brain template.

(A) Axial, sagittal and coronal views of the standard FDG-PET template with extracranial tissues in Paxinos space; (B) axial, sagittal and coronal views of the corresponding FDG-PET canonical brain; and (C) axial, sagittal and coronal views of the corresponding intracranial mask image in Paxinos space. The cross point of red lines represent the origin point D3V. The origin point was the same in the images of template, canonical brain and intracranial mask.

Figure 3. The extraction results.

Panel A shows three planes from the standard FDG-PET template of rat brain, whose coordinates were Z_bregma 2.04 mm, Z_bregma −2.28 mm and Z_bregma −8.28 mm separately. Panel B shows the extraction result of a rat which is randomly selected from dataset obtained for template construction. Panel C and Panel D show the extraction results of two rats which are randomly selected for dataset obtained for the intracranial brain extraction evaluations. The original image of individual is shown on the left of Panels B, C, D separately. The extracted intracranial tissue of individual is shown on the right of Panels B, C, D separately, of which the left half shows the intracranial mask image superimposing on the extracted canonical brain and the right half shows the extracted canonical brain. The intracranial mask image is presented as a binary image with 25% transparency, while the extracted canonical brain is presented as a background.

Figure 4. The constructed synthetic FDG-PET images from atlas images in Paxinos & Watson space.

It was shown in pseudo-color scaled and the color-bar stands for the intensity of each voxel in synthetic FDG-PET image. The six main anatomy structures were labeled, in which (1) stands for the olfactory bulb, (2) stands for the cortex, (3) stands for the hippocampi, (4) stands for the mesencephalon, (5) stands for the thalamus and (6) stands for the cerebellar.

Figure 5. Superimposing the co-registered FDG-PET canonical brain on the MRI T2WI structural canonical brain in Paxinos & Watson space.

The co-registered FDG-PET canonical brain is presented with translucency and pseudo-color scaled. The MRI T2WI canonical brain is presented in gray-scale as a background. The color-bar stands for the intensity of each voxel in FDG-PET canonical brain, which is not translucent.

Figure 6. The result of two-sample t-test between the MCAO and healthy controls.

(A) The projection of all the blobs were shown in a figure of rat brain, in which the red vees point to the global maximal t-value. (B) The display of the statistical result overlaid on axial, sagittal and coronal views of a structural single brain in Paxinos & Watson space, which is the three-dimensional illustration of one blob. And the color bar stands for the t-value of each significant voxel in Paxinos & Watson space.