Reduced [18F]flortaucipir retention in white matter hyperintensities compared to normal-appearing white matter.

Abstract

PURPOSE:

Recent research has suggested the use of white matter (WM) reference regions for longitudinal tau-PET imaging. However, tau tracers display affinity for the β-sheet structure formed by myelin, and thus WM lesions might influence tracer retention. Here, we explored whether the tau-sensitive tracer [18F]flortaucipir shows reduced retention in WM hyperintensities (WMH) and how this retention changes over time.

METHODS:

We included 707 participants from the Alzheimer's Disease Neuroimaging Initiative with available [18F]flortaucipir-PET and structural and FLAIR MRI scans. WM segments and WMH were automatically delineated in the structural MRI and FLAIR scans, respectively. [18F]flortaucipir standardized uptake value ratios (SUVR) of WMH and normal-appearing WM (NAWM) were calculated using the inferior cerebellar grey matter as reference region, and a 3-mm erosion was applied to the combined NAWM and WMH masks to avoid partial volume effects. Longitudinal [18F]flortaucipir SUVR changes in NAWM and WMH were estimated using linear mixed models. The percent variance of WM-referenced cortical [18F]flortaucipir SUVRs explained by longitudinal changes in the WM reference region was estimated with the R2 coefficient.

RESULTS:

Compared to NAWM, WMH areas displayed significantly reduced [18F]flortaucipir SUVR, independent of cognitive impairment or Aβ status (mean difference = 0.14 SUVR, p < 0.001). Older age was associated with lower [18F]flortaucipir SUVR in both NAWM (- 0.002 SUVR/year, p = 0.005) and WMH (- 0.004 SUVR/year, p < 0.001). Longitudinally, [18F]flortaucipir SUVR decreased in NAWM (- 0.008 SUVR/year, p = 0.03) and even more so in WMH (- 0.02 SUVR/year, p < 0.001). Between 17% and 66% of the variance of longitudinal changes in cortical WM-referenced [18F]flortaucipir SUVRs were explained by longitudinal changes in the reference region.

CONCLUSIONS:

[18F]flortaucipir retention in the WM decreases over time and is influenced by the presence of WMH, supporting the hypothesis that [18F]flortaucipir retention in the WM is partially myelin-dependent. These findings have implications for the use of WM reference regions for [18F]flortaucipir-PET imaging.

• Authors: Alexis Moscoso, Michel J Grothe, Michael Schöll, Alzheimer’s Disease Neuroimaging Initiative
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 48 Issue 7 Pg. 2283-2294 (07 2021) ISSN: 1619-7089 [Electronic] Germany
• PMID: 33475761 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbolines
• 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

Topics

• Aged
• Alzheimer Disease (diagnostic imaging)
• Carbolines
• Cognitive Dysfunction (diagnostic imaging)
• Humans
• Positron-Emission Tomography
• White Matter (diagnostic imaging)