Robustness of the brain parenchymal fraction for measuring brain atrophy

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.

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Frontal parenchymal atrophy measures in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/1352458504ms1093oa ◽

2004 ◽

Vol 10 (5) ◽

pp. 562-568 ◽

Cited By ~ 27

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.

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

Multiple Sclerosis Journal ◽

10.1177/135245850000600601 ◽

2000 ◽

Vol 6 (6) ◽

pp. 365-372 ◽

Cited By ~ 73

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.

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A new evaluation of the brain parenchymal fraction: Application in multiple sclerosis longitudinal studies

2008 5th IEEE International Symposium on Biomedical Imaging: From Nano to Macro ◽

10.1109/isbi.2008.4540933 ◽

2008 ◽

Cited By ~ 1

Author(s):

J.C. Souplet ◽

C. Lebrun ◽

N. Ayache ◽

G. Malandain

Keyword(s):

Multiple Sclerosis ◽

Longitudinal Studies ◽

Brain Parenchymal Fraction ◽

Brain Parenchymal ◽

The Brain

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Efficacy of an executive function intervention programme in MS: a placebo-controlled and pseudo-randomized trial

Multiple Sclerosis Journal ◽

10.1177/1352458510375440 ◽

2010 ◽

Vol 16 (9) ◽

pp. 1148-1151 ◽

Cited By ~ 42

Author(s):

Frauke Fink ◽

Eva Rischkau ◽

Martina Butt ◽

Jan Klein ◽

Paul Eling ◽

...

Keyword(s):

Executive Functioning ◽

Brain Atrophy ◽

Verbal Learning ◽

Intervention Group ◽

Cognitive Intervention ◽

Intervention Programme ◽

Brain Parenchymal Fraction ◽

Executive Deficits ◽

Brain Parenchymal ◽

Multiple Sclerosis Patients

We evaluated a rehabilitation programme for executive deficits in multiple sclerosis patients by comparing outcome scores of a cognitive intervention group (CIG; n = 11) with those of a placebo group ( n = 14) and an untreated group ( n = 15). Executive functioning and verbal learning improved significantly more in the CIG. The treatment effect on verbal learning was still present at 1-year follow-up. Baseline brain atrophy, quantified by the brain parenchymal fraction, was associated with treatment effects for one aspect of executive functioning. Consequently, cognitive intervention may be beneficial and baseline brain atrophy has some predictive value in determining treatment outcome for executive functioning.

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Brain atrophy 15 years after CIS: Baseline and follow-up clinico-radiological correlations

Multiple Sclerosis Journal ◽

10.1177/1352458517707070 ◽

2017 ◽

Vol 24 (6) ◽

pp. 721-727 ◽

Cited By ~ 2

Author(s):

Angela Vidal-Jordana ◽

Jaume Sastre-Garriga ◽

Deborah Pareto ◽

Carmen Tur ◽

Georgina Arrambide ◽

...

Keyword(s):

Brain Atrophy ◽

Brain Magnetic Resonance Imaging ◽

Multivariable Logistic Regression Analysis ◽

Increased Risk ◽

Disability Status ◽

Brain Parenchymal Fraction ◽

Multivariable Analyses ◽

Magnetic Resonance Imaging Mri ◽

Brain Parenchymal

Background: Brain atrophy in multiple sclerosis (MS) patients is present since the very early stages of the disease and it has been related to long-term disability. Objective: To estimate brain volume (BV) at 15 years after a clinically isolated syndrome (CIS) and to evaluate its relationship with disease outcomes. Methods: From a prospective cohort including patients presenting with a CIS, 54 patients with a brain magnetic resonance imaging (MRI) performed 15 years after CIS were included. Brain parenchymal fraction (BPF), grey matter fraction (GMF) and white matter fraction (WMF) at 15-year follow-up were obtained. Regression analyses were conducted to predict BV loss and reaching an Expanded Disability Status Scale (EDSS) of 3.0 in that 15-year period. Results: In multivariable analyses, lower values of BPF and WMF were significantly associated with being male, presenting 3–4 Barkhof criteria at baseline, presenting a second relapse, and with a decision to start treatment. In the multivariable logistic regression analysis, only lower GMF was associated with a greater risk of reaching EDSS 3.0 (odds ratio (OR) = 0.24, p = 0.028). Conclusion: Lower BPF and WMF 15 years after CIS are associated with previous markers of inflammatory disease. Lower GMF 15 years after a CIS is associated with an increased risk of reaching an EDSS of 3.0.

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

Multiple Sclerosis Journal ◽

10.1177/135245850000600602 ◽

2000 ◽

Vol 6 (6) ◽

pp. 373-377 ◽

Cited By ~ 107

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.

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