Petra J. W. Pouwels

Background and purpose Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole‐brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi‐compartment relaxometry diffusion‐informed MWI: MCR‐DIMWI, and multi‐echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI). Methods For 9 patients with different leukodystrophies (age range 0.4‐62.4 years) and 15 control subjects (2.3‐61.3 years), T1‐weighted MRI, fluid‐attenuated inversion recovery, multi‐echo gradient echo with variable flip angles, METRICS, and multi‐shell diffusion‐weighted imaging were acquired on 3 Tesla. MCR‐DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi‐level analyses were performed. Results MCR‐DIMWI and METRICS‐derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR‐DIMWI‐MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS‐MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR‐DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other. Conclusion This proof‐of‐concept study shows that MCR‐DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.