Microstructure-informed brain tissue classification using clustering of quantitative MRI measures.

Traditional tissue classification approaches in vivo use voxel intensities from conventional clinical magnetic resonance (MR) images for segmentation, which does not incorporate information about specific aspects of microstructure. With the Clustering for Anatomical Quantification and Evaluation (CAQE) framework, quantitative MRI measures can be used to classify tissue based only on microstructural features with no spatial enforcement, and pathological changes in disease can be evaluated. In this study, maps of whole-brain myelin water fraction, microscopic fractional anisotropy, and tissue heterogeneity were used to classify brain tissue in 25 healthy participants.

A broad range of antiphospholipid IgM are elevated across different multiple sclerosis clinical phenotypes.

Demyelination releases structural components that trigger immune responses and autoantibodies, indicating central nervous system damage and potential for further injury. Elevated antiphospholipid antibodies (aPL) are reported in multiple sclerosis (MS), but comparisons of their reactivities beyond those included in current antiphospholipid syndrome (APS) criteria across MS types are limited. This exploratory cross-sectional study evaluated serum from 35 healthy controls (HC), 20 clinically isolated syndrome (CIS) and 83 clinically confirmed MS participants (33 relapsing remitting [RRMS], 30 secondary progressive [SPMS], 20 primary progressive [PPMS]).

Myelin water and tensor-valued diffusion imaging: (How) are they related?

Purpose: Conventional MRI offers limited insight into specific characteristics of central nervous system tissue, whereas quantitative MRI measures can provide more detailed information about different aspects of microstructure. A multi-metric approach involving multiple quantitative measures may improve our understanding of healthy tissue and pathology. Previous work shows myelin water fraction (MWF) is related to fractional anisotropy (FA), but this relationship is complicated by confounding factors that may be resolved using tensor-valued diffusion imaging, which yields measurements of microscopic FA (μFA) and tissue heterogeneity (C).

Cervical Spinal Cord Magnetization Transfer Ratio and Its Relationship With Clinical Outcomes in Multiple Sclerosis.

Objective: The cervical spinal cord (cSC) is highly relevant to clinical dysfunction in multiple sclerosis (MS) but remains understudied using quantitative magnetic resonance imaging (MRI). We assessed magnetization transfer ratio (MTR), a semi-quantitative MRI measure sensitive to MS-related tissue microstructural changes, in the cSC and its relationship with clinical outcomes in radiologically isolated syndrome (RIS) and MS.

Methods: MTR data were acquired from 52 RIS, 201 relapsing-remitting MS (RRMS), 47 primary progressive MS (PPMS), and 43 control (CON) participants across four sites in the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) using 3.

Short- and long-term effects of early versus delayed treatment with ocrelizumab on cerebellar volume loss in patients with RMS and PPMS.

Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model.

Serum glial fibrillary acidic protein as a marker of brain MRI metrics in multiple sclerosis: A scoping review.

Background And Purpose: Magnetic resonance imaging (MRI) is heavily relied upon for the diagnosis and monitoring of multiple sclerosis (MS), a chronic, demyelinating disease of the central nervous system. Serum biomarkers may serve as an accessible tool for increasing sensitivity, improving accessibility, corroborating symptoms, and providing additional data to guide clinical management. This scoping review investigates the current understanding of how the serum biomarker glial fibrillary acidic protein (sGFAP) relates to brain MRI metrics.

Evaluation of microglia activation related markers following a clinical course of TBS: A non-human primate study.

While the applicability and popularity of theta burst stimulation (TBS) paradigms remain, current knowledge of their neurobiological effects is still limited, especially with respect to their impact on glial cells and neuroinflammatory processes. We used a multimodal imaging approach to assess the effects of a clinical course of TBS on markers for microglia activation and tissue injury as an indirect assessment of neuroinflammatory processes. Healthy non-human primates received continuous TBS (cTBS), intermittent TBS (iTBS), or sham stimulation over the motor cortex at 90% of resting motor threshold.

Nonaqueous magnetization following adiabatic and selective pulses in brain: T1 and cross-relaxation dynamics.

Inversion pulses are commonly employed in MRI for -weighted contrast and relaxation measurements. In the brain, it is often assumed that adiabatic pulses saturate the nonaqueous magnetization. We investigated this assumption using solid-state NMR to monitor the nonaqueous signal directly following adiabatic inversion and compared this with signals following hard and soft inversion pulses.

Myelin biomarkers in the healthy adult brain: Correlation, reproducibility, and the effect of fiber orientation.

Purpose: We investigated the correlation, reproducibility, and effect of white matter fiber orientation for three myelin-sensitive MRI techniques: magnetization transfer ratio (MTR), inhomogeneous magnetization transfer ratio (ihMTR), and gradient and spin echo-derived myelin water fraction (MWF).

Methods: We measured the three metrics in 17 white and three deep grey matter regions in 17 healthy adults at 3 T.

Results: We found a strong correlation between ihMTR and MTR (r = 0.

Myelin heterogeneity for assessing normal appearing white matter myelin damage in multiple sclerosis.

Background And Purpose: Conventional MRI measures of multiple sclerosis (MS) disease severity, such as lesion volume and brain atrophy, do not provide information about microstructural tissue changes, which may be driving physical and cognitive progression. Myelin damage in normal-appearing white matter (NAWM) is likely an important contributor to MS disability. Myelin water fraction (MWF) provides quantitative measurements of myelin.

A pilot study comparing myelin measurements from myelin water imaging and C-PIB PET in multiple sclerosis.

MRI-based myelin water fraction (MWF) and PET-based Pittsburgh compound B (PiB) imaging both have potential to measure myelin in multiple sclerosis (MS). We characterised the differences in MWF and PiB binding in MS lesions relative to normal-appearing white matter and assessed the correlation between MWF and PiB binding in 11 MS participants and 3 healthy controls within 14 white matter regions of interest. Both PiB binding and MWF were reduced in MS lesions relative to NAWM, and a modest within subject correlation between MWF and PiB binding was found.

Myelin Content and Gait Impairment in Older Adults with Cerebral Small Vessel Disease and Mild Cognitive Impairment.

We investigated whether myelin is associated with gait parameters in older adults with cerebral small vessel disease (cSVD). Cross-sectional data from sixty-four participants with cSVD and mild cognitive impairment were analyzed. Myelin was assessed via MRI multi-echo gradient and spin echo T relaxation sequence, indexed as myelin water fraction (MWF).

Myelin and Physical Activity in Older Adults With Cerebral Small Vessel Disease and Mild Cognitive Impairment.

Background: Myelin loss is a feature of cerebral small vessel disease (cSVD). Although physical activity levels may exert protective effects over cSVD pathology, its specific relationship with myelin content in people living with the cSVD is unknown. Thus, we investigated whether physical activity levels are associated with myelin in community-dwelling older adults with cSVD and mild cognitive impairment.

In vivo myelin imaging and tissue microstructure in white matter hyperintensities and perilesional white matter.

White matter hyperintensities negatively impact white matter structure and relate to cognitive decline in aging. Diffusion tensor imaging detects changes to white matter microstructure, both within the white matter hyperintensity and extending into surrounding (perilesional) normal-appearing white matter. However, diffusion tensor imaging markers are not specific to tissue components, complicating the interpretation of previous microstructural findings.

Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis.

Background: Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magnetic resonance imaging (MRI) measures related to myelin and axons. We assessed the relationship between serum NfL and brain MRI measures in a diverse group of MS participants.

Diffusely abnormal white matter in multiple sclerosis.

MRI enables detailed in vivo depiction of multiple sclerosis (MS) pathology. Localized areas of MS damage, commonly referred to as lesions, or plaques, have been a focus of clinical and research MRI studies for over four decades. A nonplaque MRI abnormality which is present in at least 25% of MS patients but has received far less attention is diffusely abnormal white matter (DAWM).

Elevated levels of serum CD5 antigen-like protein distinguish secondary progressive multiple sclerosis from other disease subtypes.

CD5 antigen-like (CD5L) protein is a macrophage-secreted protein with roles in immunomodulation and lipid homeostasis. We compared serum CD5L levels in healthy controls to individuals diagnosed with clinically isolated syndrome, relapsing remitting (RR), secondary progressive (SP), and primary progressive (PP) multiple sclerosis (MS). CD5L was increased in SPMS relative to controls, RRMS, and PPMS.

Water content changes in new multiple sclerosis lesions have a minimal effect on the determination of myelin water fraction values.

Background And Purpose: Myelin water fraction (MWF) is a histopathologically validated in vivo myelin marker. As MWF is the proportion of water with a short T relative to the total water, increases in water from edema and inflammation may confound MWF determination in multiple sclerosis (MS) lesions. Total water content (TWC) measurement enables calculation of absolute myelin water content (MWC) and can be used to distinguish edema/inflammation from demyelination.

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 T and T 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.

Nonlesional diffusely abnormal appearing white matter in clinically isolated syndrome: Prevalence, association with clinical and MRI features, and risk for conversion to multiple sclerosis.

Background And Purpose: While diffusely abnormal white matter (DAWM) is a nonlesional MRI abnormality identified in ∼25% of patients with multiple sclerosis (MS), it has yet to be investigated in patients at an earlier disease stage, namely clinically isolated syndrome (CIS). The goals of this study were to (1) determine the prevalence of DAWM in patients with a CIS suggestive of MS, (2) evaluate the association between DAWM and demographic, clinical, and MRI features, and (3) evaluate the prognostic significance of DAWM on conversion from CIS to MS.

Methods: One hundred and forty-two CIS participants were categorized into DAWM and non-DAWM groups at baseline and followed for up to 24 months or until MS diagnosis.

Cortical N-acetylaspartate concentrations are impacted in chronic stroke but do not relate to motor impairment: A magnetic resonance spectroscopy study.

Magnetic resonance spectroscopy (MRS) measures cerebral metabolite concentrations, which can inform our understanding of the neurobiological processes associated with stroke recovery. Here, we investigated whether metabolite concentrations in primary motor and somatosensory cortices (sensorimotor cortex) are impacted by stroke and relate to upper-extremity motor impairment in 45 individuals with chronic stroke. Cerebral metabolite estimates were adjusted for cerebrospinal fluid and brain tissue composition in the MRS voxel.

Myelin water fraction decrease in individuals with chronic mild traumatic brain injury and persistent symptoms.

The diffuse and continually evolving secondary changes after mild traumatic brain injury (mTBI) make it challenging to assess alterations in brain-behaviour relationships. In this study we used myelin water imaging to evaluate changes in myelin water fraction (MWF) in individuals with chronic mTBI and persistent symptoms and measured their cognitive status using the NIH Toolbox Cognitive Battery. Fifteen adults with mTBI with persistent symptoms and twelve age, gender and education matched healthy controls took part in this study.

Temperature dependence and histological correlation of inhomogeneous magnetization transfer and myelin water imaging in ex vivo brain.

Purpose: The promise of inhomogeneous magnetization transfer (ihMT) as a new myelin imaging method was studied in ex vivo human brain tissue and in relation to myelin water fraction (MWF). The temperature dependence of both methods was characterized, as well as their correspondence with a histological measure of myelin content. Unfiltered and filtered ihMT protocols were studied by adjusting the saturation scheme to preserve or attenuate signal from tissue with short dipolar relaxation time T.

Cervical cord myelin abnormality is associated with clinical disability in multiple sclerosis.

Background: Myelin water imaging (MWI) was recently optimized to provide quantitative in vivo measurement of spinal cord myelin, which is critically involved in multiple sclerosis (MS) disability.

Objective: To assess cervical cord myelin measurements in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (ProgMS) participants and evaluate the correlation between myelin measures and clinical disability.

Methods: We used MWI data from 35 RRMS, 30 ProgMS, and 28 healthy control (HC) participants collected at cord level C2/C3 on a 3 T magnetic resonance imaging (MRI) scanner.