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

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

Moscoso, A; Grothe, MJ; Schöll, M; Alzheimer’s Disease Neuroimaging Initiative; (2021) Reduced [¹⁸F]flortaucipir retention in white matter hyperintensities compared to normal-appearing white matter. European Journal of Nuclear Medicine and Molecular Imaging , 48 pp. 2283-2294. 10.1007/s00259-021-05195-5. Green open access

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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.

Type:	Article
Title:	Reduced [¹⁸F]flortaucipir retention in white matter hyperintensities compared to normal-appearing white matter
Location:	Germany
Open access status:	An open access version is available from UCL Discovery
DOI:	10.1007/s00259-021-05195-5
Publisher version:	http://dx.doi.org/10.1007/s00259-021-05195-5
Language:	English
Additional information:	This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords:	Hyperintensity, Longitudinal, Myelin, Reference region, Tau PET, White matter
UCL classification:	UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI:	https://discovery.ucl.ac.uk/id/eprint/10120049