Diffusion tensor imaging of sequential neuropathological patterns in progressive supranuclear palsy

Lavinia A Bârlescu; Günter U Höglinger; Heiko Volkmann; Albert C Ludolph; Kelly Del Tredici; Heiko Braak; DESCRIBE-PSP Study Group; Hans-Peter Müller; Jan Kassubek

doi:10.3389/fnagi.2025.1569302

Diffusion tensor imaging of sequential neuropathological patterns in progressive supranuclear palsy

Front Aging Neurosci. 2025 Jun 6:17:1569302. doi: 10.3389/fnagi.2025.1569302. eCollection 2025.

Authors

Lavinia A Bârlescu¹, Günter U Höglinger^{2

3

4}, Heiko Volkmann¹, Albert C Ludolph^{1

5}, Kelly Del Tredici^{1

6}, Heiko Braak^{1

6}; DESCRIBE-PSP Study Group; Hans-Peter Müller^#¹, Jan Kassubek^#¹

Collaborators

DESCRIBE-PSP Study Group:
Moritz Brandt⁷, Katharina Buerger⁷, Emrah Düzel⁷, Björn Falkenburger⁷, Agnes Flöel⁷, Wenzel Glanz⁷, Günter U Höglinger⁷, Daniel Janowitz⁷, Sabrina Katzdobler⁷, Ingo Kilimann⁷, Okka Kimmich⁷, Johannes Levin⁷, Oliver Peters⁷, Josef Priller⁷, Johannes Prudlo⁷, Luisa-Sophie Schneider⁷, Annika Spottke⁷, Eike Jakob Spruth⁷, Matthis Synofzik⁷, Stefan Teipel⁷, Carlo Wilke⁷

Affiliations

¹ Department of Neurology, University Hospital Ulm, Ulm, Germany.
² Department of Neurology, LMU University Hospital, Ludwig-Maximilians-Universität (LMU), Munich, Germany.
³ German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.
⁴ Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
⁵ German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany.
⁶ Clinical Neuroanatomy, Department of Neurology, University of Ulm, Ulm, Germany.
⁷ Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University, Magdeburg, Germany; Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Department of Neurology, University Medicine Greifswald, Greifswald, Germany; Clinic for Neurology, Medical Faculty, University Hospital Magdeburg, Magdeburg, Germany; Department of Neurology, University Hospital, LMU Munich, Munich, Germany; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Department of Neurology, University Hospital of Munich, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany; Department of Neurology, University of Bonn, Bonn, Germany; Department of Neurology, University Hospital of Munich, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin-Institute of Psychiatry and Psychotherapy; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany; Department of Neurology, University Medical Centre, Rostock, Germany; Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin-Institute of Psychiatry and Psychotherapy; Department of Neurology, University of Bonn, Bonn, Germany; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany; Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany; Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen, Germany.

^# Contributed equally.

Abstract

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: diffusion tensor imaging (DTI); neuropathology; progressive supranuclear palsy; sequential pattern; tau protein.