Topography of 11C-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions

Abstract

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in 11C-PIB binding to white matter.

Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM).

Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule.

Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Figure 1. Findings of increased carbon-11 labeled Pittsburgh compound B (¹¹C-PIB) uptake in patients with Alzheimer’s disease (n=17) in comparison with healthy elderly controls (n=19) after cerebellum gray-matter normalization, highlighted in yellow (at the z >3.09 cutoff, corresponding to p < 0.001 uncorrected for multiple comparisons, and using an extent threshold of 10 voxels). Findings are overlaid on axial brain slices spatially normalized into an approximation to the Talairach and Tournoux stereotactic atlas, and the numbers associated with each frame represent standard coordinates in the z -axis. Clusters of increased ¹¹C-PIB uptake are shown throughout the cerebral cortex. R = right side.

Figure 2. Findings of increased carbon-11 labeled Pittsburgh compound B (¹¹C-PIB) uptake in patients with Alzheimer’s disease (n=17) in comparison with healthy elderly controls (n=19) after global brain normalization, highlighted in yellow (at the z > 3.09 cutoff, corresponding to p < 0.001 uncorrected for multiple comparisons, and using an extent threshold of 10 voxels). Findings are overlaid on axial brain slices spatially normalized into an approximation to the Talairach and Tournoux stereotactic atlas, and the numbers associated with each frame represent standard coordinates in the z-axis. Clusters are shown in several portions of the cerebral cortex, with the greatest size and statistical significance in the orbitofrontal cortex (Table 3). R = right side.

Figure 3. Illustrative positron emission tomography (PET) with carbon-11 labeled Pittsburgh compound B (¹¹C-PIB) images (top) are shown for a healthy control subject (left-side) and an AD patient (right-side) with regional tracer uptake data normalized either to total PIB uptake in the brain (A) or to cerebellar grey-matter uptake (B). The respective time-activity curves are shown at the bottom. AD = Alzheimer’s disease; R = right side.

Figure 4. Findings of decreased carbon-11 labeled Pittsburgh compound B (¹¹C-PIB) uptake in patients with Alzheimer’s disease (n=17) compared with healthy elderly controls (n=19) after global brain uptake normalization, highlighted in yellow (at the z > 3.09 cutoff, uncorrected for multiple comparisons and using an extent threshold of 10 voxels). Findings are overlaid on axial brain slices spatially normalized into an approximation to the Talairach and Tournoux stereotactic atlas, and the numbers associated with each frame represent standard coordinates in the z-axis. Clusters are shown throughout the cerebral white matter. R = right side.