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

[This corrects the article DOI: 10.1371/journal.pone.0249973.].

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

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 potential biomarker of persistently disrupted BBB in MS.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 potential biomarker of persistently disrupted BBB in MS.

7T MPFLAIR versus MP2RAGE for Quantifying Lesion Volume in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Use of fluid-attenuated inversion recovery (FLAIR) scans to quantify multiple sclerosis (MS) lesion volume on 7 Tesla (7T) magnetic resonance imaging (MRI) has many downsides, including poor image homogeneity. There are little data about the relative benefit of alternative modalities. The purpose of this paper is to investigate if magnetization-prepared 2 rapid acquisition gradient echo (MP2RAGE) is a viable alternative to FLAIR for robust lesion volume measurement and disability correlations. METHODS: Forty-seven participants with MS underwent annual brain 7T MRIs. Magnetization-prepared FLAIR (MPFLAIR) and MP2RAGE (both at .7 mm3 isotropic resolution) sequences from a total of 80 MRI scans from 47 subjects were reviewed. White matter lesion (WML) masks were manually constructed from MPFLAIR and T1 maps (from MP2RAGE). Lesion volumes (normalized to intracranial volume) were compared to clinical characteristics and disability scales scores by Pearson or Spearman correlation, as appropriate. Relative correlation strength was compared by Fisher r- to z-transformation. RESULTS: Normalized lesion volume was greater in MPFLAIR masks (median .005 [range, .001-.030]) than from T1 maps (median .003 [range, .000-.015]). However, lesion volumes between MPFLAIR and T1 maps were highly correlated (rho = .87, P < .001). WML masks from both modalities correlated with most disability measures with no significant difference in the strength of correlation. CONCLUSIONS: 7T MPFLAIR and MP2RAGE T1 map-based WML volumes are highly intercorrelated and both correlate with disability. Thus, MP2RAGE may be a viable alternative to FLAIR-based methods for WML measurement on 7T MRI in MS research.