Has your patient's multiple sclerosis lesion burden or brain atrophy actually changed?

2004 ◽  
Vol 10 (4) ◽  
pp. 402-406 ◽  
Author(s):  
Xingchang Wei ◽  
Charles RG Guttmann ◽  
Simon K Warfield ◽  
Michael Eliasziw ◽  
J Ross Mitchell
Keyword(s):  
Multiple Sclerosis ◽  
Measurement Error ◽  
Brain Tissue ◽  
Brain Atrophy ◽  
Multiple Sclerosis Lesion ◽  
Lesion Volume ◽  
Measurement Variability ◽  
Brain Parenchymal Fraction ◽  
Significant Change ◽  
Brain Parenchymal

Changes in mean magnetic resonance imaging (MRI)-derived measurements between patient groups are often used to determine outcomes in therapeutic trials and other longitudinal studies of multiple sclerosis (MS). However, in day-to-day clinical practice the changes withinindividual patients may also be of interest. In this paper, we estimated the measurement error of an automated brain tissue quantification algorithm and determined the thresholds for statistically significant change of MRI-derived T2 lesion volume and brain atrophy in individual patients. Twenty patients with MS were scanned twice within 30 min. Brain tissue volumes were measured using the computer algorithm. Brain atrophy was estimated by calculation of brain parenchymal fraction. The threshold of change between repeated scans that represented statistically significant change beyond measurement error with 95% certainty was 0.65 mL for T2 lesion burden and 0.0056 for brain parenchymal fraction. Changes in lesion burden and brain atrophy below these thresholds can be safely (with 95% certainty) explained by measurement variability alone. These values provide clinical neurologists with a useful reference to interpret MRI-derived measures in individual patients.

Frontal parenchymal atrophy measures in multiple sclerosis

2004 ◽  
Vol 10 (5) ◽  
pp. 562-568 ◽  
Author(s):  
Laura Locatelli ◽  
Robert Zivadinov ◽  
Attilio Grop ◽  
Marino Zorzon
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Functions ◽  
Brain Atrophy ◽  
Neuropsychological Functioning ◽  
Intraclass Correlation ◽  
Quantitative Mri ◽  
Cross Sectional ◽  
Regional Brain ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal

The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: P=0.001 for Stroop Color Word Interference test, P=0.001 for Paced Auditory Serial Addition Test, P=0.04 for Standard Raven Progressive Matrices, P=0.049 for Expanded Disability Status Scale, P=0.01 for T2-LL of FLs and P< 0.001 for T1-LL of FLs. BPF demonstrated significant correlations with tests assessing cognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures in patients with MS.

Brain atrophy in relapsing multiple sclerosis: relationship to relapses, EDSS, and treatment with interferon β-1a

2000 ◽  
Vol 6 (6) ◽  
pp. 365-372 ◽  
Author(s):  
Richard A Rudick ◽  
Elizabeth Fisher ◽  
Jar-Chi Lee ◽  
Jeffrey T Duda ◽  
Jack Simon
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Brain Atrophy ◽  
Surrogate Marker ◽  
Phase Iii ◽  
Therapeutic Effects ◽  
Lesion Volume ◽  
Interferon Β ◽  
Brain Parenchymal ◽  
The Brain

Brain atrophy is a relevant surrogate marker of the disease process in multiple sclerosis (MS) because it represents the net effect of various pathological processes leading to brain tissue loss. There are various approaches to quantifying central nervous system atrophy in MS. We have focused on a normalized measure of whole brain atrophy, the brain parenchymal fraction (BPF). BPF is defined as the brain parenchymal volume, divided by the volume within the surface of the brain. We applied this method to an MRI data set generated during a phase III clinical trial of interferon β-1a (AVONEX). The purpose of the current study is to further explore clinical and MRI correlates of the BPF, particularly as they relate to relapse rate and Kurtzke's Expanded Disability Status Score (EDSS); and to further explore the therapeutic effects observed in interferon β-1a recipients. Of all demographic and disease measures in the clinical trial data base, T2 lesion volume most closely correlated with BPF in cross sectional studies, and was the baseline factor most closely correlated with progressive brain atrophy in the subsequent 2 years. We also observed that change in T2 lesion volume was the disease measure most closely correlated with change in BPF during 2 years of observation. Of interest, relapse number and EDSS change during 2 years were only weakly correlated with BPF change during the same period. Disability progression, defined as sustained worsening of at least 1.0 EDSS points from baseline, persisting at least 6 months, was associated with significantly greater brain atrophy progression. We observed a therapeutic effect of interferon β-1a in the second year of the clinical trial, and this beneficial effect was not accounted for by change in gadolinium enhanced lesion volume, or by corticosteroid medication within 40 days of the final MRI scan. The BPF is an informative surrogate marker for destructive pathological processes in relaping MS patients, and is useful in demonstrating treatment effects in controlled clinical trials. The significance of progressive brain atrophy during relapsing MS will be assessed by measuring clinical and MRI changes in prospective follow up studies.

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments

2020 ◽  
Vol 26 (6) ◽  
pp. 725-734
Author(s):  
Miklos Palotai ◽  
Michele Cavallari ◽  
Brian C Healy ◽  
Charles RG Guttmann
Keyword(s):  
Multiple Sclerosis ◽  
Statistical Power ◽  
Temporal Dynamics ◽  
Lesion Volume ◽  
Brain Parenchymal Fraction ◽  
Magnetic Resonance Imaging Mri ◽  
Brain Parenchymal ◽  
Time Point

Background: Magnetic resonance imaging (MRI) studies of multiple sclerosis–related fatigue had limited reproducibility. Temporal fatigue fluctuations have not been considered. Objective: To investigate whether a novel group allocation that reflects temporal dynamics of fatigue improves our ability to detect fatigue-associated structural brain abnormalities. Methods: Patient stratification based on biennial fatigue assessments: sustained fatigue (SF, n = 29, fatigued at the latest ⩾2 assessments), one time-point fatigue (1F, n = 15, fatigued at the latest, but non-fatigued at the penultimate assessment), reversible fatigue (RF, n = 31, non-fatigued at the latest assessment, but reported fatigue previously), and never fatigued (NF, n = 54). Brain parenchymal fraction (BPF) and T2 lesion volume (T2LV) were compared between these groups and were derived using a conventional, single time-point fatigued versus non-fatigued stratification. Results: The SF versus NF stratification yielded improved power. SF ( p = 0.005) and RF ( p = 0.043) showed significantly higher T2LV than NF. T2LV showed no significant differences in SF versus 1F, SF versus RF, or 1F versus RF. Fatigued versus non-fatigued patients showed significantly higher T2LV ( p = 0.030). We found no significant differences in BPF between the groups. Conclusion: Taking into account temporal fatigue dynamics increases the statistical power with respect to T2LV and may improve characterization of brain pathological correlates of MS-related fatigue.

Relationship between brain atrophy and disability: an 8-year follow-up study of multiple sclerosis patients

2000 ◽  
Vol 6 (6) ◽  
pp. 373-377 ◽  
Author(s):  
E Fisher ◽  
R A Rudick ◽  
G Cutter ◽  
M Baier ◽  
D Miller ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Brain Atrophy ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Follow Up Study ◽  
Relapsing Remitting ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal

Brain atrophy measurement can provide an estimate of the amount of tissue destruction due to the pathologic processes in multiple sclerosis. The potential usefulness of atrophy as a marker of disease progression depends upon the concurrent and predictive relationships between atrophy and disability. A follow-up study was performed to measure atrophy and disability scores in patients from the Multiple Sclerosis Collaborative Research Group's phase III trial of IFNb-1a (Avonex) in relapsing-remitting multiple sclerosis. New data were obtained on 160 out of 172 eligible patients from the original trial were enrolled in the follow-up study approximately 8 years after randomization. The follow-up visit consisted of several tests and questionnaires including a clinical exam to determine Expanded Disability Status Score (EDSS) and Multiple Sclerosis Functional Composite (MSFC), and a magnetic resonance imaging exam to calculate the brain parenchymal fraction. Brain parenchymal fraction was correlated with both EDSS and MSFC at each of the four time points for which data were available (baseline 1, 2 and 8 years). Furthermore, the change in BPF was correlated with the changes in disability scores from the end of the phase III trial to the follow-up exam. These data suggest that brain atrophy may be a useful and clinically relevant marker of disease progression in relapsing-remitting MS.

Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue

2002 ◽  
Vol 8 (5) ◽  
pp. 410-414 ◽  
Author(s):  
N F Kalkers ◽  
H Vrenken ◽  
B MJ Uitdehaag ◽  
C H Polman ◽  
F Barkhof
Keyword(s):  
Multiple Sclerosis ◽  
Brain Tissue ◽  
Brain Atrophy ◽  
Brain Volume ◽  
Peak Height ◽  
Tissue Loss ◽  
Magnetization Transfer Ratio ◽  
Lesion Volume ◽  
Intracranial Volume ◽  
Whole Brain

Introduction: In multiple sclerosis (MS), brain atrophy measurement on magnetic resonance imaging (MRI) reflects overall tissue loss, especially demyelination and axonal loss. We studied which factor contributes most to the development of brain atrophy: extent and severity of lesions or damage of whole brain tissue (WBT). Methods: Eighty-six patients with MS [32 primary progressive (PP), 32 secondary progressive (SP)] and 22 relapsing-remitting (RR) were studied. MRI included T1- and T2-weighted imaging to obtain hypointense T1 lesion volume (T1LV) and two brain volume measurements: 1) the parenchymal fraction (PF; whole brain parenchymal volume/intracranial volume) as a marker of overall brain volume, and 2) the ventricular fraction (VF; ventricular volume/intracranial volume) as a marker of central atrophy. From magnetization transfer ratio (MTR) histograms, the relative peak height (rHp) was derived as an index of damage of WBT (a lower peak height reflects damage of WBT). Results: Multiple linear regression analysis revealed that damage of WBT explains most of the variance of PF (standardized coefficient b=0.59, p <0.001 for WBT and b= −0.19, p <0.05 for T1LV). These findings are independent of disease phase; even in RR patients, damage of WBT plays a dominant role in explaining the variance in overall brain volume. By contrast, the variance in VF is explained by both T1LV and damage of WBT (standardized coefficient b =0.43, p<0.001 for T1LV and b = −0.38, p <0.001 for WBT). Conclusion: This study shows that overall brain volume (PF) is best explained by damage of WBT, supporting the significance of nonfocal pathology in MS in producing tissue loss. Central atrophy (VF) is determined by both lesion volume and damage of WBT. Our results underline the importance of nonfocal pathology even in the early (RR) phase of the disease.

A 24-month advanced magnetic resonance imaging study of multiple sclerosis patients treated with alemtuzumab

2018 ◽  
Vol 25 (6) ◽  
pp. 811-818 ◽  
Author(s):  
Irene M Vavasour ◽  
Roger Tam ◽  
David KB Li ◽  
Cornelia Laule ◽  
Carolyn Taylor ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Cortical Thickness ◽  
Diffusion Tensor ◽  
Imaging Study ◽  
Water Fraction ◽  
Normal Appearing White Matter ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
Multiple Sclerosis Patients

Background: Tissue damage in both multiple sclerosis (MS) lesions and normal-appearing white matter (NAWM) are important contributors to disability and progression. Specific aspects of MS pathology can be measured using advanced imaging. Alemtuzumab is a humanised monoclonal antibody targeting CD52 developed for MS treatment. Objective: To investigate changes over 2 years of advanced magnetic resonance (MR) metrics in lesions and NAWM of MS patients treated with alemtuzumab. Methods: A total of 42 relapsing–remitting alemtuzumab-treated MS subjects were scanned for 2 years at 3 T. T1 relaxation, T2 relaxation, diffusion tensor, MR spectroscopy and volumetric sequences were performed. Mean T1 and myelin water fraction (MWF) were determined for stable lesions, new lesions and NAWM. Fractional anisotropy was calculated for the corpus callosum (CC) and N-acetylaspartate (NAA) concentration was determined from a large NAWM voxel. Brain parenchymal fraction (BPF), cortical thickness and CC area were also calculated. Results: No change in any MR measurement was found in lesions or NAWM over 24 months. BPF, cortical thickness and CC area all showed decreases in the first year followed by stability in the second year. Conclusion: Advanced MR biomarkers of myelin (MWF) and neuron/axons (NAA) show no change in NAWM over 24 months in alemtuzumab-treated MS participants.

scholarly journals Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS

Neurology ◽  
2011 ◽  
Vol 76 (22) ◽  
pp. 1893-1893
Author(s):  
R. A. Rudick ◽  
E. Fisher ◽  
J.- C. Lee ◽  
J. Simon ◽  
L. Jacobs ◽  
...  
Keyword(s):  
Brain Atrophy ◽  
Whole Brain ◽  
Relapsing Remitting ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
The Brain

Robustness of the brain parenchymal fraction for measuring brain atrophy

2002 ◽  
Author(s):  
M. Stella Atkins ◽  
Jeffery J. Orchard ◽  
Benjamin Law ◽  
Melanie K. Tory
Keyword(s):  
Brain Atrophy ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
The Brain

scholarly journals Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis

2012 ◽  
Vol 34 (3) ◽  
pp. 498-504 ◽  
Author(s):  
M. Vågberg ◽  
T. Lindqvist ◽  
K. Ambarki ◽  
J.B.M. Warntjes ◽  
P. Sundström ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal ◽  
Automated Determination

scholarly journals The link between resting-state functional connectivity and cognition in MS patients

2013 ◽  
Vol 20 (3) ◽  
pp. 338-348 ◽  
Author(s):  
Álvaro J Cruz-Gómez ◽  
Noelia Ventura-Campos ◽  
Antonio Belenguer ◽  
Cesar Ávila ◽  
Cristina Forn
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Cognitive Status ◽  
Control Group ◽  
Cognitively Impaired ◽  
Lesion Volume ◽  
Resting State Functional Connectivity ◽  
Frontoparietal Network ◽  
Brain Parenchymal Fraction ◽  
Brain Parenchymal

Objective: The objective of this paper is to explore differences in resting-state functional connectivity between cognitively impaired and preserved multiple sclerosis (MS) patients. Methods: Sixty MS patients and 18 controls were assessed with the Brief Repeatable Battery of Neuropsychological Tests (BRB-N). A global Z score of the BRB-N was obtained and allowed us to classify MS patients as cognitively impaired and cognitively preserved ( n = 30 per group). Functional connectivity was assessed by independent component analysis of resting-state networks (RSNs) related to cognition: the default mode network, left and right frontoparietal and salience network. Between-group differences were evaluated and a regression analysis was performed to describe relationships among cognitive status, functional connectivity and radiological variables. Results: Compared to cognitively preserved patients and healthy controls, cognitively impaired patients showed a lesser degree of functional connectivity in all RSNs explored. Cognitively preserved patients presented less connectivity than the control group in the left frontoparietal network. Global Z scores were positively and negatively correlated with brain parenchymal fraction and lesion volume, respectively. Conclusion: Decreased cognitive performance is accompanied by reduced resting state functional connectivity and directly related to brain damage. These results support the use of connectivity as a powerful tool to monitor and predict cognitive impairment in MS patients.

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