Guidelines for using quantitative measures of brain magnetic resonance imaging abnormalities in monitoring the treatment of multiple sclerosis (original) (raw)
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Quantitative assessment of magnetic resonance imaging lesion load in multiple sclerosis
PubMed, 1998
Changes of lesion load on yearly conventional spin echo (CSE) T2-weighted scans of the brain from patients with multiple sclerosis, measured using computer assisted techniques, are used to monitor long term disease evolution, either natural or modified by treatment. Although lesion load measurements have several advantages over clinical measures of outcome (they provide a more objective and sensitive measure of disease evolution, which has a linear distribution and a more strict relation with the underlying pathology), the poor correlation between changes of lesion load and changes of disability is of concern when using such an approach for monitoring multiple sclerosis trials. In this review, the main sources of variation in T2 lesion load from brain MRI of patients with multiple sclerosis will be considered, along with possible strategies to, at least partially, overcome them. Also, some of the newer fully automated techniques to segment multiple sclerosis lesions, which have been validated against manual outlining, and a recently developed coregistration technique are presented. It is hoped that a more reliable and standardised approach to lesion load measurements in multiple sclerosis will lead to better correlation with clinical disease course, to a higher confidence in the results of trials, and to reduced numbers of scans needed to conduct the trials, thus improving cost efficiency and reducing discomfort of the patients.
Diagnostics, 2021
Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue propertie...
Magnetic Resonance Imaging as a Major Milestone in Multiple Sclerosis Diagnosis and Treatment
Noro Psikiyatri Arsivi, 2016
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Magnetic resonance imaging (MRI) has played a unique role in the diagnosis and management of patients with MS. In recent years, there have been considerable changes in the diagnostic criteria for MS as MRI-based studies have demonstrated their power in the earlier and more accurate diagnosis of the disease. Moreover, MRI metrics have become key supportive outcome measures for evaluating the efficacy of experimental treatments in randomized controlled trials. MRI can also be used as a prognostic tool in patients with clinically isolated syndrome (CIS). Conventional MR techniques including proton density, T1/T2-weighted images, and FLAIR sequences are now accepted in standard protocols for diagnostic and treatment outcome measures in clinical trials for MS. Radiological features may show a similarity between radiologically isolated syndrome and MS. Approximately two-thirds of individuals with RIS exhibit radiological progression and one-third develop neurological symptoms during mean follow-up times of up to five years. However, a current challenge in the global application of established criteria for RIS involves the accurate classification of subjects with incidentally identified anomalies that are highly characteristic of MS, in comparison to those categorized in medical parlance as possessing "unidentified bright objects" or nonspecific T2-hyperintensities, which are commonly identified in patients with migraine headache who fulfill the spatial dissemination requirements for MS. The need for systematically acquired data for improvements in the classification of radiologically isolated syndrome (RIS) and the generation of risk algorithms are critically important, providing a basis for scientifically supported management and most importantly, minimizing the number of improperly classified subjects exposed to unnecessary medical testing, MS treatments, and psychological harm. In addition, brain atrophy is a common finding that can now be quantitatively assessed by MR volumetric measures. Further, integrated strategies that combine MRI and clinical markers in scoring systems have provided a potentially useful approach for the management of patients with MS.
Quantitative follow‐up of patients with multiple sclerosis using MRI: Technical aspects
Journal of Magnetic Resonance Imaging, 1999
The reproducibility of an automated method for estimating the volume of white matter abnormalities on brain magnetic resonance (MR) images of multiple sclerosis (MS) patients was evaluated. Twenty MS patients underwent MR imaging twice within 30 minutes. Measurement variability is introduced mainly by MRI acquisition and image registration procedures, which demonstrate significantly worse reproducibility than the image segmentation. The correction of partial volume artifacts is essential for sensitive measurements of overall lesion burden. The average lesion volume difference (bias) between two MR exams of the same MS patient (N ؍ 20) was 0.05 cm 3 , with a 95% confidence interval between ؊0.17 and ؉0.28 cm 3 , suggesting that the proposed measurement system is suitable for clinical follow-up trials, even in relatively small patient cohorts. The limits of agreement for lesion volume were between ؊1.3 and ؉1.5 cm 3 , implying that in individual patients changes in lesion load need to be at least this large to be detected reliably. This automated method for estimating lesion burden is a reliable tool for the evaluation of MS progression and exacerbation in patient cohorts and potentially also in individual patients. J. Magn. Reson. Imaging 1999; 9:509-518.
Annals of Neurology, 1996
Because of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRI) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing-remitting and secondary progressive MS, monthly T2-weighted and gadoliniumenhanced brain MRI is an excellent tool for short-term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6to 12-month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N-acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1-weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2017
Magnetic resonance imaging (MRI) is an important paraclinical tool to diagnose and monitor multiple sclerosis (MS). Conventional MRI measures lack of pathological specificity and are weakly correlated with MS clinical manifestations. Advanced MRI techniques are improving the understanding of the mechanisms underlying tissue injury, repair, and functional adaptation in MS; however, they require careful standardization. The definition of standardized methods for the collection and analysis of advanced MRI techniques is central not only to improve the understanding of disease pathophysiology and evolution, but also to generate research hypotheses, monitor treatment, increase cost-effectiveness and power of clinical trials. We promoted the Italian Neuroimaging Network Initiative (INNI), involving centers and investigators with an International recognized expertise, with the major goal to determine and validate novel MRI biomarkers to be utilized as predictors and/or outcomes in future M...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, 2016
To describe methodology, interim baseline, and longitudinal magnetic resonance imaging (MRI) acquisition parameter characteristics of the multiple sclerosis clinical outcome and MRI in the United States (MS-MRIUS). The MS-MRIUS is an ongoing longitudinal and retrospective study of MS patients on fingolimod. Clinical and brain MRI image scan data were collected from 600 patients across 33 MS centers in the United States. MRI brain outcomes included change in whole-brain volume, lateral ventricle volume, T2- and T1-lesion volumes, and new/enlarging T2 and gadolinium-enhancing lesions. Interim baseline and longitudinal MRI acquisition parameters results are presented for 252 patients. Mean age was 44 years and 81% were female. Forty percent of scans had 3-dimensional (3D) T1 sequence in the preindex period, increasing to 50% in the postindex period. Use of 2-dimensional (2D) T1 sequence decreased over time from 85% in the preindex period to 65% in the postindex. About 95% of the scans ...
Sample sizes for brain atrophy outcomes in trials for secondary progressive multiple sclerosis
Neurology, 2009
Background: Progressive brain atrophy in multiple sclerosis (MS) may reflect neuroaxonal and myelin loss and MRI measures of brain tissue loss are used as outcome measures in MS treatment trials. This study investigated sample sizes required to demonstrate reduction of brain atrophy using three outcome measures in a parallel group, placebo-controlled trial for secondary progressive MS (SPMS).