Objective: To compare cortical microstructural measures in Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS) using cortical diffusion magnetic resonance imaging (MRI).

Background: Differential diagnosis between PSP and CBS can be challenging due to the overlap in symptoms and the absence of discriminative biomarkers. Neuroimaging techniques, such as microstructural MRI, can provide valuable information to aid differential diagnosis.

Method: Two hundred and five T1-structural and diffusion-weighted MRI data of individuals diagnosed with PSP (n=46) and CBS (n=35), along with a cognitively normal (CN) group (n=124) [Table 1] were obtained from the frontotemporal lobar degeneration neuroimaging initiative (FTLDNI) and the 4-Repeat Tau Neuroimaging Initiative (4RTNI). Structural and diffusion scans were used to calculate cortical volume fraction (CVfr) and three neuropathology-inspired cortical diffusivity measures: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD⁺) [1-4]. Group differences in whole-brain and regional metrics were tested with a linear model, adjusted for age, sex, head motion, and variations in scanner software or protocol, with false discovery rate correction (pFDR<0.05).

Results: At the whole brain level, groups show significant differences in CVfr (η_p² = 0.197; pFDR<0.0001) PerpPD⁺ (η_p² = 0.279; pFDR<0.0001) and AngleR (η_p² = 0.129; pFDR<0.0001).

Figure 1 summarizes distinctive patterns of macrostructural alterations in PSP and CBS compared with the control group and between disease groups, involving mainly precentral, postcentral and superior frontal cortex [Figure 1].

In comparison to cortical volume, measures of cortical diffusivity show more extensive patterns of alteration involving mainly frontal and parietal regions, consistent with patterns described in the literature [5-6]. PerpPD⁺ emerged as the most sensitive measure in capturing differences among all groups [Figure 2].

Conclusion: These findings highlight the utility of cortical diffusivity measures in understanding the pathophysiological characteristics of PSP and CBS, and in providing valuable information for the early and accurate clinical identification of these syndromes.

Table 1 Demographic and clinical characteristics

Figure 1 Regional cortical volume patterns

Figure 2 Regional cortical diffusivity patterns

References: 1- McKavanagh, R., Torso, M., Jenkinson, M., Kolasinski, J., Stagg, C. J., Esiri, M. M., … & Chance, S. A. (2019). Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis. Human brain mapping, 40(15), 4417-4431.

2- Torso, M., Bozzali, M., Zamboni, G., Jenkinson, M., Chance, S. A., & Alzheimers Disease Neuroimage Initiative. (2021). Detection of Alzheimer’s Disease using cortical diffusion tensor imaging. Human Brain Mapping, 42(4), 967-977.

3- Torso, M., Ridgway, G. R., Hardingham, I., Schwarz, A. J., Chance, S. A., & Alzheimer’s Disease Neuroimaging Initiative. (2022). In vivo detection of changes related to cortical columnar organization and neuroinflammation across the AD continuum. The Journal of Prevention of Alzheimer’s Disease, 9(4), 769-779.

4- Torso, M., Ridgway, G. R., Jenkinson, M., Chance, S., & Frontotemporal Lobar Degeneration Neuroimaging Initiative and the 4-Repeat Tau Neuroimaging Initiative (4RTNI). (2021). Intracortical diffusion tensor imaging signature of microstructural changes in frontotemporal lobar degeneration. Alzheimer’s Research & Therapy, 13, 1-15.

5- Koga, S., Josephs, K. A., Aiba, I., Yoshida, M., & Dickson, D. W. (2022). Neuropathology and emerging biomarkers in corticobasal syndrome. Journal of Neurology, Neurosurgery & Psychiatry, 93(9), 919-929.

6- Boxer, A. L., Geschwind, M. D., Belfor, N., Gorno-Tempini, M. L., Schauer, G. F., Miller, B. L., … & Rosen, H. J. (2006). Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy. Archives of neurology, 63(1), 81-86.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/differentiating-progressive-supranuclear-palsy-from-corticobasal-syndrome-using-cortical-diffusion-mri/