Planimetric and Linear MRI Markers for Progressive Supranuclear Palsy Classification: A Large Multicohort International Study

Background Differentiating progressive supranuclear palsy (PSP) from Parkinson disease and other parkinsonisms is challenging. MRI measures have been investigated, but most studies included small samples, limiting result reliability. Purpose To compare the performance of planimetric and linear MRI measurements in differentiating PSP from other parkinsonisms and identify an optimized linear marker. Materials and Methods Participants with PSP and non-PSP parkinsonisms and controls were included in this secondary analysis of multiple international prospective studies (enrollment: 2006-2024). The previously established midbrain line, midbrain area, pons to midbrain area ratio, and MR parkinsonism index were compared with a new simple linear marker based on two midbrain measures performed on midsagittal T1-weighted sections (dual-line midbrain PSP index [DMPI]). Logistic regression including DMPI, age, and sex was used to differentiate participants with PSP (PSP-Richardson syndrome, PSP variants) from those with non-PSP parkinsonisms and controls in two large independent cohorts and in a small cohort of participants with pathologically proven diagnoses. Results A total of 2111 participants (mean age, 67.8 years ± 8.4 [SD]; 54% male) were included (Italian: 136 PSP, 238 non-PSP, 85 controls; international: 520 PSP, 564 non-PSP, 525 controls). All markers were compared in a subcohort (PSP [n = 161]; non-PSP parkinsonisms [n = 203]) representative of the overall cohort. All measures showed area under the receiver operating characteristic curve (AUC) values over 0.90 for differentiating PSP from non-PSP parkinsonisms, with the DMPI and midbrain area performing best (AUCs, 0.97 [95% CI: 0.95, 0.98] and 0.95 [95% CI: 0.93, 0.97], respectively) and the DMPI showing the smallest percentage of uncertain cases (gray zone, 29 of 364 participants [7.97%]). In the entire Italian and international cohorts, the DMPI distinguished participants with PSP from those with non-PSP, with AUCs of 0.97 (95% CI: 0.97, 0.98) and 0.96 (95% CI: 0.95, 0.97), respectively. Excellent DMPI performance was also observed in participants with early-stage disease (AUC, 0.97 [95% CI: 0.95, 0.99]) and those with pathologically confirmed diagnoses (n = 43) (AUC, 0.94 [95% CI: 0.86, 1.00]). Conclusion The DMPI and midbrain area performed well for differentiating PSP from other neurodegenerative parkinsonisms. Clinical trial registration nos. NCT03068468, NCT01110720, NCT01049399, NCT01804452 © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article.