Johns Hopkins University School of Medicine
Department of Radiology

Author Of 1 Presentation

Biomarkers and Bioinformatics Poster Presentation

P0036 - Cerebral hypometabolism is a marker of disease severity in multiple sclerosis: a non-invasive imaging study using T2-Relaxation-Under-Spin-Tagging MRI (ID 1856)

Speakers
Presentation Number
P0036
Presentation Topic
Biomarkers and Bioinformatics

Abstract

Background

Metabolic dysfunction at a cellular level is a crucial element of progressive neuronal dysfunction, and ultimately neurodegeneration in multiple sclerosis (MS). Changes in retinal superficial vascular plexus (SVP) density, which is known to be reduced in MS, may in part reflect metabolic demand in the neuronal layers of the retina, and could accordingly provide insight regarding concurrent metabolic alterations in the brain.

Objectives

To compare cerebral metabolism in people with MS (PwMS) to healthy controls (HCs) using T2-Relaxation-Under-Spin-Tagging (TRUST) and phase-contrast (PC) MRI, and assess whether cerebral hypometabolism is related to reduced SVP density measured using optical coherence tomography angiography (OCTA).

Methods

In this cross-sectional study, PwMS and HC underwent TRUST and PC MRI to derive the oxygen extraction fraction (OEF; a measure of the efficiency of cerebral tissue in extracting oxygen from circulating blood) and cerebral metabolic rate of oxygen consumption (CMRO2; a volume-adjusted measure of cerebral tissue metabolism). A subset of PwMS underwent OCTA, with quantification of retinal SVP density using a deep neural network based-algorithm. Statistical analyses were adjusted for age and intra-subject inter-eye correlations, where relevant.

Results

We included 49 PwMS and 80 HCs. Overall, OEF was lower, and CMRO2 trended towards being lower, in PwMS as compared to HCs (OEF: 35.9% [SD 5.1] vs. 40.9%, [SD 5.1], p=0.04; CMRO2: 156.3 umol/mL/min [SD 23.9] vs. 158.7 umol/mL/min [SD 19.9], p=0.08). Lower CMRO2 was associated with longer MS disease duration (p=0.02), higher expanded disability status scale score (p=0.01) and lower subcortical gray matter volume fraction (p=0.04). Additionally, lower CMRO2 was associated with higher age in PwMS (p=0.02), but not in HCs (p=0.19), in whom effective neurovascular coupling is expected to maintain a fairly constant rate with aging. Lower OEF correlated with lower retinal SVP density in PwMS (r=0.32, p=0.02).

Conclusions

Cerebral hypometabolism is evident in PwMS compared to HCs, and is associated with longer disease duration and greater disability. Furthermore, alterations in cerebral metabolism are mirrored by alterations in retinal SVP density, supporting the utility of these non-invasive imaging techniques to measure inter-linked pathobiological processes. The ability to detect metabolic dysfunction in-vivo in PwMS may help facilitate the identification of new therapeutic targets and outcome measures for clinical trials.

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