Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping.

Seongjin Choi,Margaret Spini,Jun Hua,Daniel M Harrison,Niels Bergsland

doi:10.1371/journal.pone.0249973

Abstract

Although the blood-brain barrier (BBB) is altered in most multiple sclerosis (MS) lesions, gadolinium enhancement is seen only in acute lesions. In this study, we aimed to investigate gadolinium-induced changes in T1 relaxation time in MS lesions on 7-tesla (7T) MRI as a means to quantify BBB breakdown in non-enhancing MS lesions. Forty-seven participants with MS underwent 7T MRI of the brain with a magnitude-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) sequence before and after contrast. Subtraction of pre- and post-contrast T1 maps was used to measure T1 relaxation time change (ΔT1) from gadolinium. ΔT1 values were interrogated in enhancing white matter lesions (ELs), non-enhancing white matter lesions (NELs), and normal appearing white matter (NAWM) and metrics were compared to clinical data. ΔT1 was measurable in NELs (median: -0.139 (-0.304, 0.174) seconds; p < 0.001) and was negligible in NAWM (median: -0.001 (-0.036, 0.155) seconds; p = 0.516). Median ΔT1 in NELs correlated with disability as measured by Expanded Disability Status Scale (EDSS) (rho = -0.331, p = 0.026). Multiple measures of NEL ΔT1 variability also correlated with EDSS. NEL ΔT1 values were greater and more variable in patients with progressive forms of MS and greater in those not on MS treatment. Measurement of the changes in T1 relaxation time caused by contrast on 7T MP2RAGE reveals clinically relevant evidence of BBB breakdown in NELs in MS. This data suggests that NEL ΔT1 should be evaluated further as a biomarker for disease severity and treatment effect in MS.

Highlights

Gadolinium enhancement of white matter lesions (WMLs) has long been used as a surrogate marker of active inflammation and blood-brain barrier (BBB) breakdown in multiple sclerosis (MS) [1]
We looked to evaluate this at 7T, where images can be acquired at fine resolution and the absolute T1 relaxation time difference between tissues are greater [13], further enhancing the potential accuracy of measurement over prior, similar studies
Volunteers aged 18 to 65 with diagnoses of relapsing-remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) according to revised 2010 McDonald Criteria [2] were recruited from the Johns Hopkins Multiple Sclerosis Center and the University of Maryland Center for Multiple Sclerosis Treatment and Research

Summary

Introduction

Gadolinium enhancement of white matter lesions (WMLs) has long been used as a surrogate marker of active inflammation and blood-brain barrier (BBB) breakdown in multiple sclerosis (MS) [1]. Previous work using gadolinium-enhanced MRI techniques for measurement of BBB permeability has led to interesting findings, these have not translated to clinically useful tools. The magnetization-prepared rapid acquisition of 2 gradient echoes (MP2RAGE) technique has been used for T1 relaxation time measurement [10]. This technique, which produces both a T1-weighted (T1-w) MPRAGE-like image and a quantitative T1 map, provides several advantages over previous methods. We aimed to take advantage of MP2RAGE’s ability to provide robust, high resolution maps of T1 relaxation time to measure gadolinium-induced T1 signal change as a biomarker of BBB leakage in non-enhancing lesions in MS. We looked to evaluate this at 7T, where images can be acquired at fine resolution and the absolute T1 relaxation time difference between tissues are greater [13], further enhancing the potential accuracy of measurement over prior, similar studies

Materials and methods

Participants

Results

Discussion

Conclusion