MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies

Harmonization; MRI; Multiple sclerosisHarmonització; Ressonància magnètica; Esclerosi múltipleArmonización; Resonancia magnética; Esclerosis múltipleThere is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resources

MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies

There is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resource

MRI quantification of multiple sclerosis pathology

Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease and a common cause of neurologic disability. MS pathology is characterized by demyelination, neuroaxonal loss and atrophy. Magnetic Resonance Imaging (MRI) is an essential tool in diagnosing and monitoring MS, but its clinical value could be even further expanded by more advanced and quantitative MRI methods, which may also provide additional pathophysiological insights. Purpose: The overall aim of this thesis was to quantify MS pathology using volumetric brain MRI, ultra-high field brain and cervical spinal cord MRI as well as a newly developed rapid myelin imaging technique in relation to cognitive and physical MS disability. Study I, a prospective 17-year longitudinal study of 37 MS participants with 23 age/sex- matched healthy controls for comparison at the last follow-up. Longitudinal volumetric brain 1.5 Tesla MRI during the second half of the study showed that lesion accumulation and corpus callosum atrophy were the most strongly associated neuroanatomical correlates of cognitive disability, with the lesion fraction being an independent predictor of cognitive performance 8.5 years later. Study II, a prospective cross-sectional study of 35 MS participants and 11 age-matched healthy controls using 3 and 7 Tesla MRI. The study demonstrated involvement of both grey and white matter in MS, not only the brain but also the cervical spinal cord, associated with MS disability. Lesions appeared in proximity to the cerebrospinal fluid (CSF), with special predilection to the periventricular and grey matter surrounding the central canal in secondary progressive MS. Study III, a prospective in vivo (71 MS participants and 21 age/sex-matched healthy controls) and ex vivo (brain tissue from 3 MS donors) study at 3 Tesla, showed that a new clinically approved and feasible rapid myelin imaging technique correlates well with myelin stainings and produces robust in vivo myelin quantification that is related to both current and future cognitive and physical disability in MS. Study IV, an in-depth topographical analysis based on Study III, mapped the distribution of demyelination, both in vivo and ex vivo, in the periventricular and perilesional regions of the brain. A gradient of demyelination with predominance near the CSF spaces was seen. Measures of clinical disability were consistently and more strongly associated with the myelin content in normal-appearing tissue compared to the intralesional myelin content. Conclusions: Lesions and atrophy contribute to cognitive and physical disability in MS but to a varying degree, likely dependent on the relative involvement of white vs. grey matter. Both focal lesions/demyelination as well as diffuse demyelination in normal-appearing white matter shows an apparent gradient from the CSF, which differ between relapsing-remitting and progressive MS subtypes/phases. The growing utility and clinical availability of advanced and quantitative MRI techniques holds promise for improved monitoring of MS pathology and likely represents a vital tool for assessing the efficacy of potential remyelinating/reparative therapies in MS

Quantitative analysis of fiber tractography in cervical spondylotic myelopathy

Background context: Diffusion tensor fiber tractography is an emerging tool for the visualization of spinal cord microstructure. However, there are few quantitative analyses of the damage in the nerve fiber tracts of the myelopathic spinal cord. Purpose: The aim of this study was to develop a quantitative approach for fiber tractography analysis in cervical spondylotic myelopathy (CSM). Study design/setting: Prospective study on a series of patients. Materials and methods: A total of 22 volunteers were recruited with informed consent, including 15 healthy subjects and 7 CSM patients. The clinical severity of CSM was evaluated using modified Japanese Orthopedic Association (JOA) score. The microstructure of myelopathic cervical cord was analyzed using diffusion tensor imaging. Diffusion tensor imaging was performed with a 3.0-T magnetic resonance imaging scanner using pulsed gradient, spin-echo, echo-planar imaging sequence. Fiber tractography was generated via TrackVis with fractional anisotropy threshold set at 0.2 and angle threshold at 40. Region of interest (ROI) was defined to cover C4 level only or the whole-length cervical spinal cord from C1 to C7 for analysis. The length and density of tracked nerve bundles were measured for comparison between healthy subjects and CSM patients. Results: The length of tracked nerve bundles significantly shortened in CSM patients compared with healthy subjects (healthy: 6.85-77.90 mm, CSM: 0.68-62.53 mm). The density of the tracked nerve bundles was also lower in CSM patients (healthy: 086±0.03, CSM: 0.80±0.06, p<.05). Although the definition of ROI covering C4 only or whole cervical cord appeared not to affect the trend of the disparity between healthy and myelopathic cervical cords, the density of the tracked nerve bundle through whole myelopathic cords was in an association with the modified JOA score in CSM cases (r=0.949, p=.015), yet not found with ROI at C4 only (r=0.316, p=.684). Conclusions: The quantitative analysis of fiber tractography is a reliable approach to detect cervical spondylotic myelopathic lesions compared with healthy spinal cords. It could be employed to delineate the severity of CSM. © 2013 Published by Elsevier Inc. All rights reserved.postprin

Emerging magnetic resonance imaging techniques and analysis methods in amyotrophic lateral sclerosis

Objective markers of disease sensitive to the clinical activity, symptomatic progression, and underlying substrates of neurodegeneration are highly coveted in amyotrophic lateral sclerosis in order to more eloquently stratify the highly heterogeneous phenotype and facilitate the discovery of effective disease modifying treatments for patients. Magnetic resonance imaging (MRI) is a promising, non-invasive biomarker candidate whose acquisition techniques and analysis methods are undergoing constant evolution in the pursuit of parameters which more closely represent biologically-applicable tissue changes. Neurite Orientation Dispersion and Density Imaging (NODDI; a form of diffusion imaging), and quantitative Magnetization Transfer Imaging (qMTi) are two such emerging modalities which have each broadened the understanding of other neurological disorders and have the potential to provide new insights into structural alterations initiated by the disease process in ALS. Furthermore, novel neuroimaging data analysis approaches such as Event-Based Modeling (EBM) may be able to circumvent the requirement for longitudinal scanning as a means to comprehend the dynamic stages of neurodegeneration . Combining these and other innovative imaging protocols with more sophisticated techniques to analyse ever-increasing datasets holds the exciting prospect of transforming understanding of the biological processes and temporal evolution of the ALS syndrome, and can only benefit from multicentre collaboration across the entire ALS research community

Diffusion magnetic resonance imaging reveals tract‐specific microstructural correlates of electrophysiological impairments in non‐myelopathic and myelopathic spinal cord compression

ABSTRACT: Background and purpose: Non- myelopathic degenerative cervical spinal cord compres-sion (NMDC) frequently occurs throughout aging and may progress to potentially irre-versible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression sever-ity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract- specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. Methods: High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relation-ships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract-specific mi-crostructural changes in DCM patients was also explored. Results: The study identified diffusion-derived abnormalities in the gray matter, dor-sal and lateral tracts congruent with trans-synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3-6 area as well as above the com-pression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked po-tentials, respectively, whereas electromyography outcomes corresponded with gray mat-ter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. Conclusions: Outcomes imply the necessity of high- resolution tract-specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies