Characterization of multiple sclerosis neuroinflammation and neurodegeneration with relaxation and diffusion basis spectrum imaging.

BACKGROUND: Advanced magnetic resonance imaging (MRI) methods can provide more specific information about various microstructural tissue changes in multiple sclerosis (MS) brain. Quantitative measurement of T1 and T2 relaxation, and diffusion basis spectrum imaging (DBSI) yield metrics related to the pathology of neuroinflammation and neurodegeneration that occurs across the spectrum of MS. OBJECTIVE: To use relaxation and DBSI MRI metrics to describe measures of neuroinflammation, myelin and axons in different MS subtypes. METHODS: 103 participants (20 clinically isolated syndrome (CIS), 33 relapsing-remitting MS (RRMS), 30 secondary progressive MS and 20 primary progressive MS) underwent quantitative T1, T2, DBSI and conventional 3T MRI. Whole brain, normal-appearing white matter, lesion and corpus callosum MRI metrics were compared across MS subtypes. RESULTS: A gradation of MRI metric values was seen from CIS to RRMS to progressive MS. RRMS demonstrated large oedema-related differences, while progressive MS had the most extensive abnormalities in myelin and axonal measures. CONCLUSION: Relaxation and DBSI-derived MRI measures show differences between MS subtypes related to the severity and composition of underlying tissue damage. RRMS showed oedema, demyelination and axonal loss compared with CIS. Progressive MS had even more evidence of increased oedema, demyelination and axonal loss compared with CIS and RRMS.

Global loss of myelin water over 5 years in multiple sclerosis normal-appearing white matter.

BACKGROUND: Reduced myelin water fraction (MWF, a marker for myelin), increased geometric mean T2 (ieGMT2, reflecting intra/extracellular water properties), and increased T1 (related to total water content) have been observed in cross-sectional studies of multiple sclerosis (MS) normal-appearing white matter (NAWM). OBJECTIVE: To assess longitudinal changes of magnetic resonance (MR) measures in relapsing-remitting MS (RRMS) brain NAWM. METHODS: A total of 11 subjects with RRMS and 4 controls were scanned on a 3T MRI at baseline and long-term follow-up (LTFU; 3.2-5.8 years) with a 32-echo T2 relaxation and an inversion recovery T1 sequence. For every voxel, MWF, ieGMT2, and T1 were obtained. Mean, peak height, and peak location from NAWM mask-based histograms were determined. RESULTS: In MS subjects, NAWM MWF mean decreased by 8% ( p = 0.0016). No longitudinal changes were measured in T1 or ieGMT2. There was no relationship between change in any MR metric and change in EDSS. Control white matter showed no differences over time in any metric. CONCLUSION: The decreases we observed in MWF suggest that changes in myelin integrity and loss of myelin may be occurring diffusely and over long time periods in the MS brain. The timescale of these changes indicates that chronic, progressive myelin damage is an evolving process occurring over many years.

High-resolution myelin water imaging in post-mortem multiple sclerosis spinal cord: A case report.

BACKGROUND: Loss of myelin in the spinal cord in multiple sclerosis (MS) is likely an important, and early, contributor to atrophy and associated disability. In vivo measurement of myelin is possible using myelin water fraction (MWF) imaging, but MWF has never been assessed in MS along the entire length of the spinal cord in vivo or in post-mortem tissue. OBJECTIVE: To assess the feasibility of measuring the distribution of MWF along the entire length of the spinal cord in post-mortem MS tissue using high-field MRI. METHODS: One formalin-fixed spinal cord from a female with secondary progressive MS (age: 78 years, disease duration: 25 years) was cut into 104 5-mm-thick cross sections along the entire length of the spinal cord from the cervico-medullary junction to the conus medullaris and imaged using a 64 echo T2 relaxation experiment at 7T. RESULTS: Myelin water maps showed cord anatomy in superb detail, white matter demonstrating a higher MWF than the grey matter. Anatomical variation in myelin distribution along cervical, thoracic and lumbar regions was observed. Lesions demonstrated myelin loss. CONCLUSION: Post-mortem myelin water imaging of formalin-fixed MS spinal cord is feasible.