ECTRIMS eLearning

Gadolinium-induced changes in T1 relaxation time on 7-Tesla MRI in non-enhancing MS lesions may reveal chronic inflammation linked with disability and progressive phenotypes
Author(s): ,
S. Choi
Affiliations:
Neurology, University of Maryland, School of Medicine
,
S. Bojedla
Affiliations:
University of Maryland
,
M. Spini
Affiliations:
University of Maryland
,
J. Hua
Affiliations:
Radiology and Radiological Science, Johns Hopkins University School of Medicine; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute
D. Harrison
Affiliations:
Neurology, University of Maryland, School of Medicine; Johns Hopkins University School of Medicine, Baltimore, MD, United States
ECTRIMS Learn. Harrison D. 10/10/18; 228316; P472
Dr. Daniel Harrison
Dr. Daniel Harrison
Contributions Biography
Abstract

Abstract: P472

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: Gadolinium contrast reveals blood brain barrier (BBB) breakdown in newly developed multiple sclerosis (MS) white matter lesions (WMLs), resulting in visually apparent T1 shortening. Previous attempts at quantification of gadolinium-induced T1 shortening in non-enhancing WMLs, suggestive of sub-visual BBB breakdown, have had mixed results.
Objectives: Our goals were to find associations of contrast-induced T1 shortening in non-enhancing WMLs at 7-Tesla (7T) with clinical measures and demonstrate its potential as a biomarker of MS disease progression.
Aims: We aimed to evaluate the ability of quantitative T1 maps acquired at 7T to reveal subtle inflammatory changes in non-enhancing WMLs in MS.
Methods: Forty-seven participants with MS underwent brain MRI on a 7T MRI scanner (Philips, Achieva) with a volume transmit/32-channel receive coil. Magnetization prepared 2 rapid gradient echo (MP2RAGE) images were acquired before and after contrast and processed for T1-weighted images and T1 maps. T1 difference (delta T1) maps were generated by subtracting post-contrast T1 maps from pre-contrast T1 maps. WML masks were delineated manually on the pre-contrast T1 maps for all WMLs and enhancing WMLs separately and a non-enhanced WML mask was created by subtraction. T1 values in these masks were then compared to clinical and demographic data. Group differences were assessed by Mann-Whitney U-test and correlations were assessed by Spearman or Pearson correlations, as appropriate.
Results: Only 5(10.6%) participants had enhancing lesions. Delta T1 in non-enhanced WMLs correlated with Expanded Disability Status Scale (EDSS; rho=0.314, p=0.032) scores. Delta T1 was greater (p=0.022) in participants with EDSS ≥5.0 (median: 0.192, range: -0.003 to 0.386) than those with EDSS< 5.0 (median: 0.127, range: -0.079 to 0.574). Delta T1 in non-enhanced WMLs was greater (p=0.001) in participants with progressive MS phenotypes (median: 0.198, range: 0.132 to 0.386) than those with relapsing-remitting MS (median: 0.121, range: -0.079 to 0.574).
Conclusions: Greater changes in T1 relaxation time due to gadolinium in non-enhancing WMLs were seen in participants with higher levels of disability and progressive phenotypes. This suggests that clinically-significant, sub-visual BBB breakdown, potentially due to chronically inflamed WMLs, can be measured by T1 mapping on 7T MRI. This data supports further exploration of this technique as a novel treatment outcome measure in MS.
Disclosure: Dr. Harrison has received research support from EMD-Serono and consulting fees from EMD-Serono, Sanofi-Genzyme, Genentech, and Biogen. Drs. Choi, Bojedla, and Hua and Ms. Spini have no financial disclosures. The study was funded in part by grants from EMD-Serono and the National Institutes of Health (NINDS 1K23NS072366-01A1).

Abstract: P472

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Introduction: Gadolinium contrast reveals blood brain barrier (BBB) breakdown in newly developed multiple sclerosis (MS) white matter lesions (WMLs), resulting in visually apparent T1 shortening. Previous attempts at quantification of gadolinium-induced T1 shortening in non-enhancing WMLs, suggestive of sub-visual BBB breakdown, have had mixed results.
Objectives: Our goals were to find associations of contrast-induced T1 shortening in non-enhancing WMLs at 7-Tesla (7T) with clinical measures and demonstrate its potential as a biomarker of MS disease progression.
Aims: We aimed to evaluate the ability of quantitative T1 maps acquired at 7T to reveal subtle inflammatory changes in non-enhancing WMLs in MS.
Methods: Forty-seven participants with MS underwent brain MRI on a 7T MRI scanner (Philips, Achieva) with a volume transmit/32-channel receive coil. Magnetization prepared 2 rapid gradient echo (MP2RAGE) images were acquired before and after contrast and processed for T1-weighted images and T1 maps. T1 difference (delta T1) maps were generated by subtracting post-contrast T1 maps from pre-contrast T1 maps. WML masks were delineated manually on the pre-contrast T1 maps for all WMLs and enhancing WMLs separately and a non-enhanced WML mask was created by subtraction. T1 values in these masks were then compared to clinical and demographic data. Group differences were assessed by Mann-Whitney U-test and correlations were assessed by Spearman or Pearson correlations, as appropriate.
Results: Only 5(10.6%) participants had enhancing lesions. Delta T1 in non-enhanced WMLs correlated with Expanded Disability Status Scale (EDSS; rho=0.314, p=0.032) scores. Delta T1 was greater (p=0.022) in participants with EDSS ≥5.0 (median: 0.192, range: -0.003 to 0.386) than those with EDSS< 5.0 (median: 0.127, range: -0.079 to 0.574). Delta T1 in non-enhanced WMLs was greater (p=0.001) in participants with progressive MS phenotypes (median: 0.198, range: 0.132 to 0.386) than those with relapsing-remitting MS (median: 0.121, range: -0.079 to 0.574).
Conclusions: Greater changes in T1 relaxation time due to gadolinium in non-enhancing WMLs were seen in participants with higher levels of disability and progressive phenotypes. This suggests that clinically-significant, sub-visual BBB breakdown, potentially due to chronically inflamed WMLs, can be measured by T1 mapping on 7T MRI. This data supports further exploration of this technique as a novel treatment outcome measure in MS.
Disclosure: Dr. Harrison has received research support from EMD-Serono and consulting fees from EMD-Serono, Sanofi-Genzyme, Genentech, and Biogen. Drs. Choi, Bojedla, and Hua and Ms. Spini have no financial disclosures. The study was funded in part by grants from EMD-Serono and the National Institutes of Health (NINDS 1K23NS072366-01A1).

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