R_1ρ dispersion in white matter correlates with quantitative metrics of cognitive impairment

Much previous neuroimaging research in Alzheimer^'s disease has focused on the roles of amyloid and tau proteins, but recent studies have implicated microvascular changes in white matter as early indicators of damage related to later dementia. We used MRI to derive novel, non-invasive measurements of R_1ρ dispersion using different locking fields to characterize variations of microvascular structure and integrity in brain tissues. We developed a non-invasive 3D R_1ρ dispersion imaging technique using different locking fields at 3T. We acquired MR images and cognitive assessments of participants with mild cognitive impairment (MCI) and compared them to age-matched healthy controls in a cross-sectional study. After providing informed consent, 40 adults aged 62 to 82 years (n = 17 MCI) were included in this study. White matter ΔR_1ρ-fraction measured by R_1ρ dispersion imaging showed a strong correlation with the cognitive status of older adults (β_std = -0.4, p-value < 0.01) independent of age, in contrast to other conventional MRI markers such as T₂, R_1ρ, and white matter hyperintense lesion volume (WMHs) measured with T₂-FLAIR. The correlation of WMHs with cognitive status was no longer significant after adjusting for age and sex in linear regression analysis, and the size of the regression coefficient was substantially decreased (53% lower). This work establishes a new non-invasive method that potentially characterizes impairment of the microvascular structure of white matter in MCI patients compared to healthy controls. The application of this method in longitudinal studies would improve our fundamental understanding of the pathophysiologic changes that accompany abnormal cognitive decline with aging and help identify potential targets for treatment of Alzheimer's disease.