Voxelwise relationships between distribution volume ratio and cerebral blood flow: Implications for analysis of b-amyloid images

Quantification of β-amyloid (Aβ) in vivo is often accomplished using the distribution volume ratio (DVR), based on a simplified reference tissue model. We investigated the local relationships between DVR and cerebral blood flow (CBF), as well as relative CBF (R1), in nondemented older adults. Methods: Fifty-five nondemented participants (mean age, 78.5 y) in the Baltimore Longitudinal Study of Aging underwent 15O-H2O PET CBF and dynamic 11C-PiB PET. 15O-H2O PET images were normalized and smoothed using SPM. A simplified reference tissue model with linear regression and spatial constraints was used to generate parametric DVR images. The DVR images were regressed on CBF images on a voxel-by-voxel basis using robust biologic parametric mapping, adjusting for age and sex (false discovery rate, P 5 0.05; spatial extent, 50 voxels). DVR images were also regressed on R1 images, a measure of the transport rate constant from vascular space to tissue. All analyses were performed on the entire sample, and on high and low tertiles of mean cortical DVR. Results: Voxel-based analyses showed that increased DVR is associated with increased CBF in the frontal, parietal, temporal, and occipital cortices. However, this association appears to spare regions that typically show early Aβ deposition. A more robust relationship between DVR and CBF was observed in the lower tertile of DVR, that is, negligible cortical Aβ load, compared with the upper tertile of cortical DVR and Aβ load. The spatial distributions of the DVR-CBF and DVR-R1 correlations showed similar patterns. No reliable negative voxelwise relationships between DVR and CBF or R1 were observed. Conclusion: Robust associations between DVR and CBF at negligible Aβ levels, together with similar spatial distributions of DVR-CBF and DVR-R1 correlations, suggest that regional distribution of DVR reflects blood flow and tracer influx rather than pattern of Aβ deposition in those with minimal Aβ load. DVR-CBF associations in individuals with a higher DVR are more likely to reflect true associations between patterns of Aβ deposition and CBF or neural activity. These findings have important implications for analysis and interpretation of voxelwise correlations with external variables in individuals with varying amounts of Aβ load.