AUTHOR=Bârlescu Lavinia A. , Höglinger Günter U. , Volkmann Heiko , Ludolph Albert C. , Del Tredici Kelly , Braak Heiko , Müller Hans-Peter , Kassubek Jan ,  the DESCRIBE-PSP Study Group , Brandt Moritz , Buerger Katharina , Düzel Emrah , Falkenburger Björn , Flöel Agnes , Glanz Wenzel , Höglinger Günter U. , Janowitz Daniel , Katzdobler Sabrina , Kilimann Ingo , Kimmich Okka , Levin Johannes , Peters Oliver , Priller Josef , Prudlo Johannes , Schneider Luisa-Sophie , Spottke Annika , Spruth Eike Jakob , Synofzik Matthis , Teipel Stefan , Wilke Carlo 

TITLE=Diffusion tensor imaging of sequential neuropathological patterns in progressive supranuclear palsy

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 17 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2025.1569302

DOI=10.3389/fnagi.2025.1569302

ISSN=1663-4365

ABSTRACT=Background and objectiveA 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.MethodsTwo 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.ResultsWBSS 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.ConclusionThe 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.