Multisite harmonization of diffusion tensor image analysis along the perivascular space using the COMBined Association Test.

PURPOSE: This multisite study aimed to use the COMBined Association Test (COMBAT), a harmonization technique that uses regression of covariates with an empirical Bayesian framework, to harmonize diffusion tensor image analysis along the perivascular space (DTI-ALPS) variations caused by scanner, site, and protocol differences. MATERIALS AND METHODS: This study included multisite diffusion magnetic resonance imaging (dMRI) data of 45 patients with Alzheimer's disease (AD) and 82 cognitively normal (CN) participants from the AD neuroimaging initiative database. The dMRI data were obtained with two b values (0 and 1000 s/mm2) from 27 institutions and three different 3-Tesla MRI scanners (two vendors). The ALPS index was calculated from multisite dMRI data, and COMBAT was used to harmonize the factors causing site variations. Welch's t test was used, Cohen's d was calculated to compare the difference in the ALPS index between AD and CN before and after harmonization, and Pearson's correlation coefficient was calculated to assess the relationships between the ALPS index and the cognitive score, [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET), and [18F] florbetapir (AV45)-PET standardized uptake value ratios (SUVRs). RESULTS: COMBAT harmonized scanner differences and increased Cohen's d of the left and right ALPS indexes between AD and CN from 0.288 to 0.438 and 0.328 to 0.480, respectively. The ALPS indexes were significantly different between AD and CN after harmonization (P < 0.05) but not before it. Moreover, Pearson's correlation coefficients between the ALPS index and cognitive score, FDG-PET, and AV45-PET SUVRs were higher after harmonization than before it. CONCLUSION: This study demonstrates the application of COMBAT harmonization to eliminate between-scanner, site, and protocol variations in the ALPS index calculated from DTI-ALPS using dMRI and possibly facilitate the use of the ALPS index in multi-center studies.

Fiber-specific micro- and macroscopic white matter alterations in progressive supranuclear palsy and corticobasal syndrome.

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are characterized by progressive white matter (WM) alterations associated with the prion-like spreading of four-repeat tau, which has been pathologically confirmed. It has been challenging to monitor the WM degeneration patterns underlying the clinical deficits in vivo. Here, a fiber-specific fiber density and fiber cross-section, and their combined measure estimated using fixel-based analysis (FBA), were cross-sectionally and longitudinally assessed in PSP (n = 20), CBS (n = 17), and healthy controls (n = 20). FBA indicated disease-specific progression patterns of fiber density loss and subsequent bundle atrophy consistent with the tau propagation patterns previously suggested in a histopathological study. This consistency suggests the new insight that FBA can monitor the progressive tau-related WM changes in vivo. Furthermore, fixel-wise metrics indicated strong correlations with motor and cognitive dysfunction and the classifiability of highly overlapping diseases. Our findings might also provide a tool to monitor clinical decline and classify both diseases.