Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York

Author Of 1 Presentation

Imaging Oral Presentation

PS07.05 - Leptomeningeal, dura mater and meningeal vessel wall enhancements in multiple sclerosis

Speakers
Presentation Number
PS07.05
Presentation Topic
Imaging
Lecture Time
13:39 - 13:51

Abstract

Background

Leptomeningeal inflammation (LMI) in multiple sclerosis (MS) can be putatively identified by leptomeningeal contrast enhancement (LMCE) on gadolinium-enhanced 3D T2-fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Dura mater (DME), inclusive falx cerebri (FCE) enhancement and meningeal vessel wall enhancement (VWE) represent two other meningeal enhancement patterns in MS that have not been extensively studied.

Objectives

To investigate the frequency of LMCE, DME/FCE and VWE in patients with MS and their associations with demographic, clinical and MRI characteristics in a longitudinal retrospective study.

Methods

217 MS patients (193 relapsing-remitting MS, 24 progressive MS) were assessed at baseline and over 18 months follow-up using 3T 3D FLAIR pre- and post-contrast and subtraction images. Lesion and brain volume outcomes were additionally calculated. Analysis of covariance (ANCOVA) and regression models were used to assess the relationship between MRI variables and clinical variables, controlling for age.

Results

24% of MS patients revealed LMCE, and 47% and 24% revealed DME/FCE and VWE, respectively. LMCE presence correlated with age and higher ventricular cerebrospinal fluid (vCSF) volume. More LMCE positive subjects (38%) showed additional VWE, compared to LMCE negative subjects (20%, p=0.055). DME/FCE presence was associated with higher T1/T2 lesion load, higher vCSF volume and decreased total deep gray matter (GM) and hippocampus volumes. All three meningeal enhancement patterns showed a high persistence in shape and size at follow-up.

Conclusions

Different patterns of meningeal enhancement, i.e. LMCE, DME/FCE and VWE can be identified by gadolinium-enhanced 3D FLAIR MR imaging. LMCE positive patients show a trend for higher frequency of VWE than LMCE negative patients. DME/FCE is the most frequent meningeal enhancement pattern in MS, which correlates with imaging markers of lesion burden and brain atrophy and may indicate abnormal lymphatic drainage in these patients.

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Author Of 7 Presentations

Biomarkers and Bioinformatics Late Breaking Abstracts

LB1178 - Monitoring of blood neurofilaments improves stratification of disease activity in multiple sclerosis (ID 1322)

Speakers
Presentation Number
LB1178
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

The concept of no evidence of disease activity-3 (absence of brain MRI and clinical disease activity; NEDA-3) in multiple sclerosis (MS) reflects disease activity with limited sensitivity. The added value of neurofilament light chain levels in serum (sNfL) to NEDA-3 has not yet been investigated.

Objectives

To assess whether sNfL allows to identify among patients with and without NEDA-3 status those at higher risk of future disease activity and accelerated brain volume loss.

Methods

We analyzed 369 samples from 155 early relapsing-remitting MS patients (SET study). sNfL levels and brain MRI scans were evaluated annually. The comparison of subgroups defined by high or low sNfL (>90th or <90th percentile of healthy controls of the same age) and NEDA-3 status was performed by generalized estimating equation models. Changes in global and regional brain volumes were calculated on three-dimensional T1-weighted scans.

Results

Patients with disease activity (EDA-3) in the preceding year and high sNfL, compared to those with low sNfL, had: a) higher odds of EDA-3 in the following year (87% versus 58%; OR 4.39, 95%-CI:2.18, 8.94; p<0.001), b) greater whole brain volume loss during the following year (0.39%, 95%-CI:-0.63, -0.16; p<0.001) and c) greater whole brain volume loss (0.61%, 95%-CI:-0.66, -0.17; p<0.001) during the preceding year. Accordingly, NEDA-3 patients with high sNfL showed a trend for a return of disease activity (EDA-3) in the following year compared with those with low sNfL (57% versus 31%).

Conclusions

High sNfL levels are associated with increased future risk of disease activity and accelerated brain volume loss. Adding of sNfL improves the prognostic value of the NEDA-3 concept.

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Biomarkers and Bioinformatics Poster Presentation

P0175 - Towards optimized monitoring of serum neurofilament light chain in MS (ID 1329)

Abstract

Background

Serum neurofilament light chain (sNfL) levels reflect only neuro-axonal injury that took place within 3-6 months prior to the date of sampling. Therefore, the frequency of assessment of sNfL levels for monitoring of disease activity warrants further investigation.

Objectives

To determine differences in accuracy of sNfL levels to detect radiological disease activity during the preceding 6 versus 12 months of follow-up.

Methods

This observational study included 148 patients with early relapsing-remitting multiple sclerosis (MS) from the SET cohort. Based on brain MRI performed at 0, 6 and 12 months, we assessed the ability of categorized sNfL measured at 12 months to reflect the presence of combined unique active lesions, defined as new/enlarging lesion compared with MRI performed in the previous 6 versus 12 months or contrast-enhancing lesion (e.g., active lesions).

Results

Together, 91% (95% CI=85-98%) of patients with ≥1 active lesion during the last 6 months and 84% (95% CI=77-92%) of patients with ≥1 active lesion during the last 12 months had sNfL≥30th percentile. Among the patients with sNfL<30th percentile, 14 (33.3%) developed ≥1 active lesion during the last 12 months, but only 6 (14.3%) developed ≥1 active lesion during the last 6 months. Among patients with sNfL<30th percentile, 6 (14.3%) developed ≥2 active lesions during the last 12 months, but only 2 (4.8%) developed ≥2 active lesions during the last 6 months.

Conclusions

Low levels of sNfL better identified MS patients with the absence of recent radiological disease activity during the previous 6 than the previous 12 months. In the future, assessment of sNfL at least every 6 months may substitute the need for annual brain MRI monitoring to exclude brain lesion activity in clinically stable patients with low sNfL levels.

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Imaging Poster Presentation

P0566 - Diffusion tensor imaging of the nucleus basalis of Meynert reveals associations with cognitive state in patients with multiple sclerosis (ID 1427)

Speakers
Presentation Number
P0566
Presentation Topic
Imaging

Abstract

Background

Previous studies have shown that the nucleus basalis of Meynert (NBM), a group of neurons in the basal forebrain representing the major source of cholinergic innervations for the cerebral and subcortical cortex, is particularly vulnerable to neurodegeneration in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Microstructural NBM damage, as reflected by increased diffusion tensor imaging (DTI)-derived measures of diffusivity, has been shown to be related to cognitive impairment in these diseases. As of now, the NBM has been scarcely investigated in multiple sclerosis (MS).

Objectives

To determine associations between microstructural properties of the NBM and cognitive outcomes in patients with MS (PwMS).

Methods

84 PwMS (54 relapsing-remitting MS, 30 secondary progressive MS) underwent 3T MRI with a protocol that included a diffusion-weighted imaging acquisition. All PwMS underwent cognitive assessment with the Brief International Cognitive Assessment for MS (BICAMS), which includes the Symbol Digit Modalities Test (SDMT), Brief Visuospatial Memory Test-Revised (BVMT-R) and California Verbal Learning Test-2nd edition (CVLT-2). Standard DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were calculated. A probabilistic map of the NBM was utilized to calculate DTI-derived measures. Partial correlations were used to assess the relationship between BICAMS cognitive outcomes and DTI assessments of the NBM, controlling for age and education.

Results

Neuropsychological outcomes correlated with altered diffusivity within the NBM in PwMS. SDMT scores were associated with NBM measures of MD (r=-0.38, p<0.001), AD (r=-0.26, p=0.017), and RD (r=-0.40, p<0.001). BVMT-R was associated with MD (r=-0.33, p=0.002) and RD (r=-0.37, p=0.001), while CVLT-2 was associated with MD (r=-0.27, p=0.015), AD (r=-0.22, p=0.050) and RD (r=-0.27, p=0.016). After accounting for normalized NBM volume, NBM RD explained additional variance for SDMT (R2=0.24, p<0.001) and BVMT-R (R2=0.18, p=0.001), while NBM MD was retained for CVLT-2 (R2=0.17, p=0.015).

Conclusions

Our results show an association between cognitive impairment and microstructural NBM damage in PwMS, highlighting the potential role of NBM damage in determining the cognitive state in PwMS.

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Imaging Poster Presentation

P0577 - Feasibility of thalamic atrophy measurement in clinical routine using artificial intelligence: Results from multi-center study in RRMS patients (ID 1058)

Abstract

Background

The thalamus is a key gray matter structure, and a sensitive marker of neurodegeneration in multiple sclerosis (MS). Previous reports have indicated that thalamic volumetry on clinical-quality T2-FLAIR images alone is fast and reliable, using artificial intelligence (AI).

Objectives

To investigate the feasibility of thalamic atrophy measurement using AI in patients with MS, in a large multi-center, clinical routine study.

Methods

DeepGRAI (Deep Gray Rating via Artificial Intelligence) is a multi-center (31 USA sites), longitudinal, observational, real-word, registry study that will enroll 1,000 relapsing-remitting MS patients. Brain MRI exams previously acquired at baseline and at follow-up on 1.5T or 3T scanners with no prior standardization are used, in order to resemble real-world situation. Thalamic volume measurement is performed at baseline and follow-up on T2-FLAIR by DeepGRAI tool and on 3D T1-weighted image (WI) and 2D T1-WI by using FIRST software.

Results

In this pre-planned interim analysis, 515 RRMS patients were followed for an average of 2.7 years. There were 487 (94.6%) T2-FLAIR, 342 (66.4%) 2D T1-WI and 176 (34.2%) 3D T1-WI longitudinal pair of MRI exams available for analyses. Estimation of thalamic volume by DeepGRAI on T2-FLAIR correlated significantly with FIRST on 3D-T1-WI (r=0.733 and r=0.816, p<0.001) and with FIRST on 2D-T1-WI (r=0.555 and r=0.704, p<0.001) at baseline and at follow-up. The correlation between thalamic volume estimated by FIRST on 3D T1-WI and 2D T1-WI was r=0.642 and r=0.679, p<0.001, respectively. The thalamic volume % change over the follow-up was similar between DeepGRAI (-0.75) and 3D T1-WI (-0.82), but somewhat higher for 2D T1-WI (-0.92). Similar relationship was found between the Expanded Disability Status Scale (EDSS) and thalamic volume by DeepGRAI on T2-FLAIR and by FIRST on 3D T1-WI at baseline (r=-0.214, p=0.01 and r=-0.287, p=0.001) and at follow-up (r=-0.298, p=0.001 and r=-0.291, p=0.001).

Conclusions

DeepGRAI provides feasible thalamic volume measurement on multi-center clinical-quality T2-FLAIR images. The relationship between thalamic atrophy and physical disability is similar using DeepGRAI T2-FLAIR and standard high-resolution research approaches. This indicates potential for real-world thalamic volume monitoring, as well as quantification on legacy datasets without research-quality MRI.

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Imaging Poster Presentation

P0617 - Predicting Disease Progression in Multiple Sclerosis from Clinical Routine T2-FLAIR MRI (ID 1670)

Speakers
Presentation Number
P0617
Presentation Topic
Imaging

Abstract

Background

Although quantitative measures from research-quality MRI relate well to clinical outcomes in persons with multiple sclerosis (PwMS), these metrics are largely unavailable in clinical settings.

Objectives

To determine how well a quantitative snapshot of brain pathology, measured on routine clinical T2-FLAIR MRI, relates to standard research-quality MRI, clinical disability, and clinical progression over mid-term.

Methods

This retrospective study of prospectively collected data was approved by the local Institutional Review Board. 3T MRI was acquired for 172 PwMS at baseline and neurologic disability was assessed at baseline and five-years later. Five measures (thalamus volume, lateral ventricle volume, medulla oblongata volume, lesion volume, and network efficiency) for quantifying disparate aspects of brain pathology from low-resolution T2-FLAIR were applied to predict similar measures obtained from research-quality MRI and associated with neurologic disability and disease progression over five years.

Results

The combination of the five T2-FLAIR measures explained most of the variance in standard research-quality MRI, including T2-lesion volume (R2=0.97, p<0.001) and thalamus volume (R2=0.90, p<0.001). T2-FLAIR measures (R2=0.279, p<0.001; R2=0.382, p<0.001) were associated with neurologic disability and cognitive function five-years later, similar to standard research-quality MRI (R2=0.279, p<0.001; R2=0.366, p<0.001). They also similarly predicted disability progression over five years (%-correctly-classified=69.8, R2=0.145, p=0.034), compared to standard research-quality MRI (%-correctly-classified=72.4%, R2=0.196, p=0.022) in relapsing-remitting MS.

Conclusions

T2-FLAIR measures explained considerable variance of standard research-quality MRI, correlated with neurologic disability, and predicted progression of disability over five years. Quantifying brain pathology at a single time-point with clinical-quality T2-FLAIR can be useful in clinical settings.

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Imaging Poster Presentation

P0641 - Serum neurofilament light chain levels are associated with poorer thalamic perfusion in multiple sclerosis: cross-sectional DSC-PWI study (ID 1387)

Speakers
Presentation Number
P0641
Presentation Topic
Imaging

Abstract

Background

Both perfusion-based imaging (PWI) measures and serum neurofilament light chain levels (sNfL) have been associated with multiple sclerosis (MS) disability and different pathologies.

Objectives

To determine whether the perfusion and neurofilament biomarkers are correlated to each other or independently describe different MS processes.

Methods

3T MRI dynamic susceptibility contrast (DSC)-PWI and single molecule assay (Simoa)-based sNfL (in pg/mL) were utilized in 86 MS patients. Perfusion measures of mean transit time (MTT), cerebral blood volume (CBV) and cerebral blood flow (CBF) were derived for the regions of normal-appearing whole brain (NAWB), normal-appearing white matter (NAWM), gray matter (GM), deep GM (DGM) and thalamus. Normalized CBV and CBF (nCBV and nCBV) were adjusted with the corresponding NAWM measure. Age and sex-adjusted linear regression models determined associations between DSC-PWI measures and sNfL. False discovery rate (FDR)-adjusted p-values lower than 0.05 were considered statistically significant.

Results

After age and sex adjustment, thalamic MTT significantly and independently was associated with higher sNfL (standardized β=0.648, t-statistics=2.868, adjusted p-value=0.011) and explained additional 4.0% of sNfL variance. NAWM MTT was initially added in the model (adding additional 3.3%) but did not survive FDR correction. Similarly, after adjusting for age and sex effects, lower nCBV of the thalamus was associated with greater sNfL (standardized β=-0.221, t-statistics=-2.529, p=0.013, adjusted p-value=0.022). Correspondingly, lower nCBF of the thalamus was also associated with greater sNfL (standardized β=-0.346, t-statistics=-4.188, p<0.001, adjusted p-value=0.001).

Conclusions

Higher sNfL are associated with poorer PWI-based measures of the thalamus. Future longitudinal studies should determine their temporal relationship.

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Observational Studies Poster Presentation

P0874 - Fingolimod therapy in real world relapsing MS patients: Cognition, quantitative MRI and deep gray matter quantitative susceptibility mapping (ID 1238)

Abstract

Background

Limited data is available regarding the effect of disease modifying therapies on cognitive decline and brain volume change in real world multiple sclerosis (MS) patients. Novel deep gray matter (DGM) quantitative susceptibility mapping (QSM) techniques have not been extensively studied in MS.

Objectives

To assess cognitive performance, magnetic resonance imaging (MRI) brain volumetrics and deep gray matter QSM at baseline, 6 months, 12 months and 24 months in a real world relapsing MS patient cohort treated with fingolimod, referenced to age- and sex-matched healthy controls (HCs).

Methods

Relapsing MS patients from 2 centers (Sydney, Australia and Buffalo, United States of America) were recruited to this observational, prospective study following the decision by their treating neurologist to commence fingolimod therapy. Neurological assessment (Expanded Disability Status Scale (EDSS)), cognitive testing (Minimal Assessment of Cognitive Function (MACFIMS)), and 3 tesla (3T) MRI brain acquisition occurred at baseline, 6 months, 12 months and 24 months. Matched HCs were recruited prospectively from both centers and were followed longitudinally at the same time points.

Results

The relapsing MS (n = 50) and HC (n = 41) cohorts were well matched for age and sex. With fingolimod treatment, clinical relapse rates and MRI lesion activity were significantly reduced, and the EDSS remained stable, in the relapsing MS patient group. Baseline DGM volumes, but not whole brain volumes, were significantly lower in the patient cohort compared to the HC cohort (p < 0.05). Longitudinal DGM volume changes were not significantly different between the groups. Between the baseline and 24 month time points the percentage whole brain atrophy, as measured using Structural Image Evaluation using Normalisation of Atrophy (SIENA), was higher in the patient group (mean: -1.25%) compared with the HC group (mean: -0.44%) (p = 0.006). Baseline thalamus QSM was significantly lower, and the baseline caudate and pallidus QSM were significantly higher, in the MS patient group (p < 0.05). Longitudinal DGM QSM changes were not significantly different between groups. Baseline cognitive performance was worse in the MS group (p < 0.05), but longitudinal cognitive stability/improvement was not significantly different between the two groups.

Conclusions

This real world prospective observational study suggests that fingolimod reduced clinical relapses and MRI lesion activity, and stabilized cognitive performance in the relapsing MS patient cohort. DGM volume and DGM QSM change rates were comparable between the fingolimod treated relapsing MS patients and the age- and sex-matched healthy controls. Whole brain atrophy between baseline and 24 months was greater in the fingolimod treated MS patients compared with HCs, but the differences were not significant for other epochs; further subgroup analysis is underway to explore this finding.

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