ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Parkinson’s Disease and Aging-related Movement Disorders
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1569302
This article is part of the Research TopicAdvancing Neurodegenerative Disease Biomarkers: The Role of Neuroimaging in TDP-43 and Tau ProteinopathiesView all articles
Diffusion tensor imaging of sequential neuropathological patterns in progressive supranuclear palsy
Provisionally accepted
Lavinia Barlescu1
Günter U Höglinger2Heiko Volkmann1
Albert Ludolph1Kelly Del Tredici1Heiko Braak1
Hans-Peter Müller1
Jan Kassubek1*- 1Dept. of Neurology, University of Ulm, Ulm, Germany
- 2LMU Munich University Hospital, Munich, Bavaria, Germany
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Background and objective: A neuropathological cerebral staging concept for progressive supranuclear palsy (PSP) has been proposed that tau inclusions in PSP may progress in a sequential regional pattern. The objective was to develop a hypothesis-guided region/tract of interest-based (ROI/TOI) approach to use diffusion tensor imaging (DTI) targeted to analyze in vivo the regions that are prone to be involved at each neuropathological stage of PSP. Methods: Two data cohorts were analyzed: cohort A of 78 PSP patients (55 Richardson’s syndrome (PSP-RS) and 23 PSP with predominant parkinsonism (PSP-P)) and 63 controls, recorded at 3.0T at multiple sites, and a single-site cohort B constituted by 1.5T data of 66 PSP patients (46 PSP-RS and 20 PSP-P) and 44 controls. In cohort A, 21 PSP patients (13 PSP-RS and 8 PSP-P) and 17 controls obtained a follow-up scan after 17 months. Whole brain-based spatial statistics (WBSS) was used to identify the alterations in PSP patients vs. controls. The combined ROI- and TOI-based approach targeted structures that are prone to be involved during the course of PSP. Results: WBSS demonstrated alterations predominantly in brainstem/midbrain, basal ganglia, and frontal lobe, more pronounced in the longitudinal data. Statistical analyses of the ROIs/TOIs showed a sequential pattern of structures that were assigned to previously defined neuropathological steps. Conclusion: The combined ROI- and TOI-based DTI approach was able to map the disease stages of PSP in vivo cross-sectionally and longitudinally, lending support to DTI as a technical marker for imaging disease progression according to PSP stages. This approach might be useful as a tool for stratification of PSP patients´ MRI with respect to its proposed neuropathological progression in future longitudinal and autopsy-controlled studies.
Keywords: Progressive Supranuclear Palsy, sequential pattern, Diffusion tensor imaging (DTI), Neuropathology, tau protein
Received: 31 Jan 2025; Accepted: 07 May 2025.
Copyright: © 2025 Barlescu, Höglinger, Volkmann, Ludolph, Del Tredici, Braak, Müller and Kassubek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jan Kassubek, Dept. of Neurology, University of Ulm, Ulm, D-89081, Germany
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