Clinical Relevance of Brain Volume Measures in Multiple Sclerosis (original) (raw)
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Assessing Biological and Methodological Aspects of Brain Volume Loss in Multiple Sclerosis
JAMA neurology, 2018
Before using brain volume loss (BVL) as a marker of therapeutic response in multiple sclerosis (MS), certain biological and methodological issues must be clarified. To assess the dynamics of BVL as MS progresses and to evaluate the repeatability and exchangeability of BVL estimates with Jacobian Integration (JI) and Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) (specifically, the Structural Image Evaluation, Using Normalisation, of Atrophy-Cross-Sectional [SIENA-X] tool or FMRIB's Integrated Registration and Segmentation Tool [FIRST]). A cohort of patients who had either clinically isolated syndrome or MS was enrolled from February 2011 through October 2015. All underwent a series of annual magnetic resonance imaging (MRI) scans. Images from 2 cohorts of healthy volunteers were used to evaluate short-term repeatability of the MRI measurements (n = 34) and annual BVL (n = 20). Data analysis occurred from January to May 2017. The goodness of fit...
Correlation of clinical findings and brain volume data in multiple sclerosis
, on behalf of theBrazilian Brain Volume Studies (B-BRAVOS) group a b s t r a c t Brain volume measurements are becoming an important tool for assessing success in controlling multiple sclerosis (MS) activity. MSmetrix (icometrix) is an easy-to-use platform, specific for MS magnetic resonance imaging (MRI) of the brain. It provides data on total brain volume, grey matter volume and lesion load volume. The objective of the present study was to assess whether disability and the number of relapses during the previous year correlated with brain volume measurements from MSmetrix. Data on 185 icometrix reports from patients with MS were used to evaluate the potential correlation between brain volume measurements and clinical parameters. There was a significant correlation between higher disability and decreased brain volume (total and grey matter). Increased lesion load in the brain and higher number of relapses in the previous year were also independently correlated with decreased brain tissue volume and with increased disability. This is the first study with real-world data to show that icometrix is a relevant tool for the study of brain volume loss in MS.
Pathological cut-offs of global and regional brain volume loss in multiple sclerosis
Multiple sclerosis (Houndmills, Basingstoke, England), 2017
Volumetric MRI surrogate markers of disease progression are lacking. To establish cut-off values of brain volume loss able to discriminate between healthy controls and MS patients. In total, 386 patients after first demyelinating event suggestive of MS (CIS), 964 relapsing-remitting MS (RRMS) patients, 63 secondary-progressive MS (SPMS) patients and 58 healthy controls were included in this longitudinal study. A total of 11,438 MRI scans performed on the same MRI scanner with the same protocol were analysed. Annualised percentage changes of whole brain, grey matter, thalamus and corpus callosum volumes were estimated. We investigated cut-offs able to discriminate between healthy controls and MS patients. At a predefined specificity of 90%, the annualised percentage change cut-off of corpus callosum volume (-0.57%) was able to distinguish between healthy controls and patients with the highest sensitivity (51% in CIS, 48% in RRMS and 42% in SPMS patients). Lower sensitivities (22%-49%...
Evaluation of Brain Volume Loss in Different Clinical Types of Multiple Sclerosis Patients
The Medical Journal of Cairo University, 2018
Background: Brain atrophy is an important imaging biomarker in predicting future disability and progression of disease in multiple sclerosis. Aim of Study: We need to evaluate brain volume loss in different clinical types of MS and correlates it with physical disability using NeuroQuaqnt 2.0 automated volumetric measurement of brain atrophy in MS. Material and Methods: We conducted the following study on 40 MS patients (4 CIS, 8 PPMS, 22 RRMS and 6 SPMS) for clinical evaluation, assessment their physical disability by (EDSS) and automated volumetric measurement of 3 parameters (whole brain, lateral ventricles and thalami volumes) by obtain 3D T1 non contrast, saggital MRI scan by using new software (NeuroQuant®2.0 automated volumetric measurement of brain atrophy) of MS patients. Results: Thalami atrophy was predominant atrophy in 24 patients. Also, it was predominant atrophy in different clinical types (2 CIS, 4 PPMS, 12 RRMS and 6 SPMS) patients. Morphometry results were correlated with physical disability (whole brain volume r=-0.400, p=0.026), (thalami volume r=-0.379, p=0.016), and (lateral ventricles volume r=0.365, p=0.044). MS patients with (disease duration >1 year) had significant lower whole brain volume (p=0.037), lower thalami volume (p=0.019) and higher lateral ventricles volumes (p=0.044). Conclusion: Thalami atrophy is a predominant atrophy in different clinical types of MS patients. Thalami atrophy may be used a sole indices in brain atrophy measuring. Brain atrophy correlates with physical disability and progress with duration of illness.
Critical analysis on the present methods for brain volume measurements in multiple sclerosis
Arquivos de Neuro-Psiquiatria, 2017
Objective The treatment of multiple sclerosis (MS) has quickly evolved from a time when controlling clinical relapses would suffice, to the present day, when complete disease control is expected. Measurement of brain volume is still at an early stage to be indicative of therapeutic decisions in MS. Methods This paper provides a critical review of potential biases and artifacts in brain measurement in the follow-up of patients with MS. Results Clinical conditions (such as hydration or ovulation), time of the day, type of magnetic resonance machine (manufacturer and potency), brain volume artifacts and different platforms for volumetric assessment of the brain can induce variations that exceed the acceptable physiological rate of annual loss of brain volume. Conclusion Although potentially extremely valuable, brain volume measurement still has to be regarded with caution in MS.
Advances in Clinical and Experimental Medicine
We review the current role of magnetic resonance (MR) volumetry as a meaningful indicator of neurodegeneration and clinical disease progression in multiple sclerosis (MS) patients. Based on a review of the current literature we summarize the mechanisms that contribute to brain atrophy. We present the newest magnetic resonance imaging (MRI)-based methods used in atrophy quantification. We also analyze important biological factors which can influence the accuracy of brain atrophy evaluation. Evidence shows that measures of brain volume (BV) have the potential to be an important determinant of disease progression to a greater extent than conventional lesion assessment. Finally, scientific reports concerning limitations of MRI-based volumetry that affect its implementation into routine clinical practice are also reviewed. The technical challenges that need to be overcome include creating a standardized protocol for image acquisition − a fully automated, accurate and reproducible method that allows comparison in either single-center or multicenter settings. In the near future, quantitative MR research will probably be the basic method used in neurology to monitor the rate of atrophic processes and clinical deterioration in MS patients, and to evaluate the results of treatment.
Journal of the Neurological Sciences, 1998
We compared the volumes of the brain as a whole and of different cerebral structures from patients with multiple sclerosis (MS) and normal subjects. In the patients, we also correlated brain volumes with T2 and T1 lesion loads and disability. A magnetization-prepared rapid acquisition gradient echo (MP RAGE) sequence with subsequent reconstruction of axial 1-mm thick slices and a dual-echo sequence were obtained in 15 patients with relapsing-remitting or secondary progressive MS and 15 sex-, age-, height-and weight-matched normal subjects. The brains and the different cerebral structures studied (cerebral hemispheres, cerebellum and brainstem) were segmented manually by a single observer on the 1-mm MP RAGE scans. The hyperintense lesion volumes seen on dual-echo scans and the hypointense lesion volumes seen on the 1-mm MP RAGE scans were measured using a semi-automated segmentation technique based on local thresholding. Compared to the normal volunteers, patients had significantly lower cerebral (P50.008), hemispheric (P50.01) and brainstem (P50.03) volumes. Cerebral atrophy was detected in seven (47%) MS patients. Patients with brainstem signs had significantly lower mean brainstem volume than the others (P50.04). No significant correlations were found between the cerebral volumes and the EDSS scores, the hyperintense lesion volumes and the hypointense lesion volumes. We conclude that cerebral atrophy is a relatively frequent finding in MS, but its relationship with physical disability is modest.
Correlation between brain volume loss and clinical and MRI outcomes in multiple sclerosis
Neurology, 2015
We investigated the determinants and clinical correlations of MRI-detected brain volume loss (BVL) among patients with relapsing-remitting multiple sclerosis from the phase 3 trials of fingolimod: FREEDOMS, FREEDOMS II, and TRANSFORMS. Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 patients from the trials and their extensions. The relationship between brain volume changes and demographic, clinical, and MRI parameters was studied in pairwise correlations (Pearson) and in multiple regression models. The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years. Increasing age, disease duration, T2 lesion volume, T1-hypointense lesion volume, and disability were associated with reduced brain volume (p < 0.001, all). The strongest individual baseline predictors of on-study BVL were T2 lesion volume, gadolinium-enhancing lesion count,...
Journal of Clinical Medicine
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and degenerative disorder of the central nervous system. Accelerated brain volume loss (BVL) has emerged as a promising magnetic resonance imaging marker (MRI) of neurodegeneration, correlating with present and future clinical disability. We have systematically selected MS patients fulfilling ‘no evidence of disease activity-3′ (NEDA-3) criteria under high-efficacy disease-modifying treatment (DMT) from the database of two Belgian MS centers. BVL between both MRI scans demarcating the NEDA-3 period was assessed and compared with a group of prospectively recruited healthy volunteers who were matched for age and gender. Annualized whole brain volume percentage change was similar between 29 MS patients achieving NEDA-3 and 24 healthy controls (−0.25 ± 0.49 versus −0.24 ± 0.20, p = 0.9992; median follow-up 21 versus 33 months; respectively). In contrast, we found a mean BVL increase of 72%, as compared with the former, in a...
Neuroimage, 2005
We used SPM99 to obtain normalized whole brain volumes of gray matter, white matter, and total parenchyma in patients with multiple sclerosis (MS) (n = 41) and age-/sex-matched normal controls (n = 18). As SPM99's automated gray/white matter volumes were significantly influenced by tissue compartment misclassification due to the effect of MS-related brain lesions, we corrected these automated volumes for misclassification before performing our primary analyses. For MS patients (disease duration = 9.5 T 6.3 years; EDSS score = 3.2 T 1.8; 25FTW = 6.6 T 3.1 s), we also measured lesion load total T1 hypointense [T1LV] and FLAIR hyperintense lesion volume [FLLV]), central brain atrophy (third ventricular width [TVW] and bicaudate ratio [BCR]), and clinical status (Expanded Disability Status Scale [EDSS] and 25-ft timed walk [25FTW]