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PurposeNeurite orientation dispersion and density imaging (NODDI) provides measures of neurite density and dispersion through computation of the neurite density index (NDI) and the orientation dispersion index (ODI). However, NODDI overestimates the cerebrospinal fluid water fraction in white matter (WM) and provides physiologically unrealistic high NDI values. Furthermore, derived NDI values are echo time (TE)-dependent. In this work, we propose a modification of NODDI, named constrained NODDI (C-NODDI), for NDI and ODI mapping in WM.MethodsUsing NODDI and C-NODDI, we investigated age-related alterations in WM in a cohort of 58 cognitively unimpaired adults. Further, NDI values derived using NODDI or C-NODDI were correlated with the neurofilament light chain (NfL) concentration levels, a plasma biomarker of axonal degeneration.ResultsODI derived values using both approaches were virtually identical. We confirm the previous finding that NDI estimation using NODDI is TE-dependent. In contrast, C-NODDI-NDI exhibit lower susceptibility to TE. Further, C-NODDI-NDI values were lower than NODDI-NDI. Further, our results indicate a quadratic relationship between NDI and age suggesting that axonal maturation continues until middle age followed by a decrease. This quadratic association was notably significant in several WM regions using C-NODDI, while limited to a few regions using NODDI. ODI exhibited overall constant trends with age. Finally, C-NODDI-NDI values exhibited a stronger correlation with NfL concentration levels as compared NODDI-NDI, with lower NDI values correspond to higher levels of NfL.ConclusionsC-NODDI provides a complementary method to NODDI for determination of NDI in white matter in normative aging.

Mounting evidence indicates that abnormal gait speed predicts the progression of neurodegenerative diseases, including Alzheimer’s disease. Understanding the relationship between white matter integrity, especially myelination, and motor function is crucial to the diagnosis and treatment of neurodegenerative diseases. We recruited 118 cognitively unimpaired adults across an extended age range of 22–94 years to examine associations between rapid or usual gait speeds and cerebral myelin content. Using our advanced multicomponent magnetic resonance relaxometry method, we measured myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R1 and R2), sensitive but nonspecific magnetic resonance imaging measures of myelin content. After adjusting for covariates and excluding 22 data sets due to cognitive impairments or artifacts, our results indicate that participants with higher rapid gait speed exhibited higher MWF, R1, and R2 values, that is, higher myelin content. These associations were statistically significant within several white matter brain regions, particularly the frontal and parietal lobes, splenium, anterior corona radiata, and superior fronto-occipital and longitudinal fasciculus. In contrast, we did not find any significant associations between usual gait speed and MWF, R1, or R2, which suggests that rapid gait speed may be a more sensitive marker of demyelination than usual gait speed. These findings advance our understanding on the implication of myelination in gait impairment among cognitively unimpaired adults, providing further evidence of the interconnection between white matter integrity and motor function.

It is unknown whether hypertension plays any role in cerebral myelination. To fill this knowledge gap, we studied ninety cognitively unimpaired adults, age range 40 to 94 years, that are participants in the Baltimore Longitudinal Study of Aging (BLSA) and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) to look for potential associations between hypertension and cerebral myelin content across fourteen white matter brain regions. Myelin content was probed using our advanced multicomponent magnetic resonance (MR) relaxometry method of myelin water fraction (MWF), a direct and specific MR imaging (MRI) measure of myelin content, and longitudinal and transverse relaxation rates (R1andR2), two highly sensitive MRI metrics of myelin content. We also applied diffusion tensor imaging (DTI) MRI to measure fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) values, which are metrics of cerebral microstructural tissue integrity, to provide contact with previous MRI findings. After adjustment of age, sex, systolic blood pressure, smoking status, diabetes status and cholesterol level, our results indicated that participants with hypertension exhibited lower MWF, FA,R1andR2values and higher MD, RD and AxD values, indicating lower myelin content and higher impairment to the brain microstructure. These associations were significant across several white matter regions, particularly in the corpus callosum, fronto-occipital fasciculus, temporal lobes, internal capsules, and corona radiata. These original findings suggest a direct association between myelin content and hypertension, and form the basis for further investigations including longitudinal assessments of this relationship.

Cerebral tissue integrity decline and cerebral blood flow (CBF) alteration are major aspects of motor and cognitive dysfunctions and neurodegeneration. However, little is known about the association between blood flow and brain microstructural integrity, especially in normal aging.To assess the association between CBF and cerebral microstructural integrity.Cross sectional.A total of 94 cognitively unimpaired adults (mean age 50.7 years, age range between 22 and 88 years, 56 Men).A 3 T; pseudo-continuous arterial spin labeling (pCASL), diffusion tensor imaging (DTI), Bayesian Monte Carlo analysis of multicomponent driven equilibrium steady-state observation of TLobar associations between CBF derived from pCASL, and longitudinal relaxation rate (RMultiple linear regression models were used using the mean region of interest (ROI) values for MWF, RRThese findings suggest that cerebral tissue microstructure may be impacted by global brain perfusion, adding further evidence to the intimate relationship between cerebral blood supply and cerebral tissue integrity.4 TECHNICAL EFFICACY: Stage 4.