Correction: Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping.
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ABSTRACT:
SUBMITTER: Choi S
PROVIDER: S-EPMC8863243 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
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Correction: Blood-brain barrier breakdown in non-enhancing multiple sclerosis lesions detected by 7-Tesla MP2RAGE ΔT1 mapping.
Choi Seongjin S Spini Margaret M Hua Jun J Harrison Daniel M DM
PloS one 20220222 2
[This corrects the article DOI: 10.1371/journal.pone.0249973.]. ...[more]
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Project description: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.
| S-EPMC8075220 | biostudies-literature
Project description:ObjectivesThe disruption of the blood-brain barrier (BBB) is a key and early feature in the pathogenesis of demyelinating multiple sclerosis (MS) lesions and has been neuropathologically demonstrated in both active and chronic plaques. The local overt BBB disruption in acute demyelinating lesions is captured as signal hyperintensity in post-contrast T1-weighted images because of the contrast-related shortening of the T1 relaxation time. On the contrary, the subtle BBB disruption in chronic lesions is not visible at conventional radiological evaluation but it might be of clinical relevance. Indeed, persistent, subtle BBB leakage might be linked to low-grade inflammation and plaque evolution. Here we hypothesised that 3D Quantitative Transient-state Imaging (QTI) was able to reveal and measure T1 shortening (ΔT1) reflecting small amounts of contrast media leakage in apparently non-enhancing lesions (ANELs).Materials and methodsThirty-four patients with relapsing remitting MS were included in the study. All patients underwent a 3 T MRI exam of the brain including conventional sequences and QTI acquisitions (1.1 mm isotropic voxel) performed both before and after contrast media administration. For each patient, a ΔT1 map was obtained via voxel-wise subtraction of pre- and post- contrast QTI-derived T1 maps. ΔT1 values measured in ANELs were compared with those recorded in enhancing lesions and in the normal appearing white matter. A reference distribution of ΔT1 in the white matter was obtained from datasets acquired in 10 non-MS patients with unrevealing MR imaging.ResultsMean ΔT1 in ANELs (57.45 ± 48.27 ms) was significantly lower than in enhancing lesions (297.71 ± 177.52 ms; p < 0. 0001) and higher than in the normal appearing white matter (36.57 ± 10.53 ms; p < 0.005). Fifty-two percent of ANELs exhibited ΔT1 higher than those observed in the white matter of non-MS patients.ConclusionsQTI-derived quantitative ΔT1 mapping enabled to measure contrast-related T1 shortening in ANELs. ANELs exhibiting ΔT1 values that deviate from the reference distribution in non-MS patients may indicate persistent, subtle, BBB disruption. Access to this information may be proved useful to better characterise pathology and objectively monitor disease activity and response to therapy.
| S-EPMC10514220 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Cortical lesions are common and often extensive in multiple sclerosis but are difficult to visualize by MRI, leaving important questions about their clinical implications and response to therapy unanswered. Our aim was to determine whether cortical lesions are better visualized using magnetization prepared 2 rapid acquisition gradient echoes (MP2RAGE) than T2*-weighted imaging on 7T MR imaging. MATERIALS AND METHODS:Brain MR imaging using T1-weighted MP2RAGE at 500-μm isotropic resolution, T2*-weighted gradient-echo, and T2*-weighted segmented echo-planar imaging sequences were collected for 13 patients with MS and 5 age-matched neurologically healthy controls on a 7T research system. One MS case underwent postmortem MR imaging including gradient-echo and MP2RAGE sequences, after which cortical lesions seen on MR imaging were assessed with immunohistochemistry. RESULTS:MP2RAGE detected 203 cortical lesions (median, 16 lesions/case; interquartile range, 15), compared to 92 with T2*gradient-echo (median, 7; interquartile range, 8; P < .001) and 81 with T2*EPI (median, 7; interquartile range, 5; P < .001). This increase in lesion number detected on MP2RAGE versus T2* was observed for juxtacortical, leukocortical, and intracortical lesions. Forty-three percent of all cortical lesions were identified only on MP2RAGE. White matter lesion volume correlated with total juxtacortical (r = 0.86, P < .001) and leukocortical lesion volume (r = 0.70, P < .01) but not intracortical lesion volume, suggesting that pathophysiology may differ by lesion type. Of 4 suspected lesions seen on postmortem imaging, 3 were found to be true cortical lesions while 1 represented postmortem tissue damage. CONCLUSIONS:A combination of MP2RAGE and T2*-weighted imaging at 7T improved detection of cortical lesions and should enable longitudinal studies to elucidate their spatiotemporal dynamics and clinical implications.
| S-EPMC6082739 | biostudies-literature
Project description:BackgroundBaló's concentric sclerosis (BCS) is a rare condition characterized by concentrically layered white matter lesions. While its pathogenesis is unknown, hypoxia-induced tissue injury and chemotactic stimuli have been proposed as potential causes of BCS lesion formation. BCS has been suggested to be a variant of multiple sclerosis (MS). Here, we aimed to elucidate similarities and differences between BCS and MS by describing lesion morphology and localization in high-resolution 7 Tesla (7 T) magnetic resonance imaging (MRI) scans.MethodsTen patients with Baló-type lesions underwent 7 T MRI, and 10 relapsing remitting MS patients served as controls. The 7 T MR imaging protocol included 3D T1-weighted (T1w) magnetization-prepared rapid gradient echo, 2D high spatial resolution T2*-weighted (T2*w) fast low-angle shot and susceptibility-weighted imaging.ResultsIntralesional veins were visible in the center of all but one Baló-type lesion. Four Baló-type lesions displayed inhomogeneous intralesional T2*w signal intensities, which are suggestive of microhemorrhages or small ectatic venules. Eight of 10 BCS patients presented with 97 additional lesions, 36 of which (37%) had a central vein. Lesions involving the cortical gray matter and the U-fibers were not detected in BCS patients.ConclusionOur findings support the hypothesis that BCS and MS share common pathogenetic mechanisms but patients present with different lesion phenotypes.
| S-EPMC6093849 | biostudies-literature
Project description:BackgroundParamagnetic rim lesions (PRLs) are associated with chronic inflammation in multiple sclerosis (MS). 7-Tesla (7T) magnetic resonance imaging (MRI) can evaluate the integrity of the blood-brain barrier (BBB) in addition to the tissue myelination status and cell loss.PurposeTo use MRI metrics to investigate underlying physiology and clinical importance of PRLs.Study typeProspective.SubjectsThirty-six participants (mean-age 47, 23 females, 13 males) of mixed MS subtypes.Field strength/sequence7T, MP2RAGE, MULTI-ECHO 3D-GRE, FLAIR.AssessmentLesion heterogeneity; longitudinal changes in lesion counts; comparison of T1, R2*, and χ; association between baseline lesion types and disease progression (2-3 annual MRI visits with additional years of annual clinical follow-up).Statistical testsTwo-sample t-test, Wilcoxon Rank-Sum test, Pearson's chi-square test, two-group comparison with linear-mixed-effect model, mixed-effect ANOVA, logistic regression. P-values <0.05 were considered significant.ResultsA total of 58.3% of participants had at least one PRL at baseline. Higher male proportion in PRL+ group was found. Average change in PRL count was 0.20 (SD = 2.82) for PRLs and 0.00 (SD = 0.82) for mottled lesions. Mean and median pre-/post-contrast T1 were longer in PRL+ than in PRL-. No differences in mean χ were seen for lesions grouped by PRL (P = 0.310, pre-contrast; 0.086, post-contrast) or PRL/M presence (P = 0.234, pre-contrast; 0.163, post-contrast). Median χ were less negative in PRL+ and PRL/M+ than in PRL- and PRL/M-. Mean and median pre-/post-contrast R2* were slower in PRL+ compared to PRL-. Mean and median pre-/post-contrast R2* were slower in PRL/M+ than in PRL/M-. PRL presence at baseline was associated with confirmed EDSS Plus progression (OR 3.75 [1.22-7.59]) and PRL/M+ at baseline with confirmed EDSS Plus progression (OR 3.63 [1.14-7.43]).Data conclusionEvidence of BBB breakdown in PRLs was not seen. Quantitative metrics confirmed prior results suggesting greater demyelination, cell loss, and possibly disruption of tissue anisotropy in PRLs.Evidence level2 TECHNICAL EFFICACY: Stage 2.
| S-EPMC10754232 | biostudies-literature
Project description:ObjectivesIn multiple sclerosis (MS), contrast-enhancing lesions (CELs) in T1-weighted postcontrast MRI are considered markers of blood-brain barrier breakdown. It remains unknown if re-enhancement can be considered a radiologic indicator of different pathology in CELs. We investigated 1) the incidence of re-enhancing lesions (re-CELs) from chronic lesions; 2) differences in size, magnetization transfer ratio (MTR), and likelihood to appear as acute black holes (aBHs) between new lesions (n-CELs) and re-CELs; and 3) associations between re-CELs and features indicating more advanced disease.MethodsIn this retrospective natural history study, we examined 264 monthly MRI scans performed at month 1 (M1), month 2 (M2), and month 3 (M3) for 88 patients with MS. CELs were defined as n-CELs if not present in the M1 T2W MRI and re-CELs if present in the M1 T2W MRI.ResultsA total of 311 (82.7%) n-CELs and 65 (17.3%) re-CELs were identified. Of the 88 patients, 54 presented only n-CELs, 8 presented only re-CELs, and 26 presented both CEL types. Patients with both lesion types presented more CELs than those presenting only one type (p = 0.01). Re-CELs were larger (z = 2.72, p = 0.007) and had lower MTR (z = -2.80, p = 0.005) than n-CELs but the estimated proportion of aBHs from n-CELs was similar (z = -0.09, p = 0.1) from the proportion of aBHs from re-CELs.ConclusionsNearly 20% of CELs represent the reoccurrence of enhancement in chronic plaques. Re-CELs represent larger areas of inflammation, not necessarily associated with larger areas of edema.
| S-EPMC3345616 | biostudies-literature
Project description:In some active multiple sclerosis (MS) lesions, a strong immune reaction at the lesion edge may contain growth and thereby isolate the lesion from the surrounding parenchyma. Our previous studies suggest that this process involves opening of the blood-brain barrier in capillaries at the lesion edge, seen on MRI as centripetal contrast enhancement and a colocalized phase rim. We hypothesized that using these features to characterize early lesion evolution will allow in vivo tracking of tissue degeneration and/or repair, thus improving the evaluation of potential therapies for chronic active lesions.Centripetally and centrifugally enhancing lesions were studied in 17 patients with MS using 7-tesla MRI. High-resolution, susceptibility-weighted, T1-weighted (before/after gadolinium), and dynamic contrast-enhanced scans were acquired at baseline and months 1, 3, 6, and 12. For each lesion, time evolution of the phase rim, lesion volume, and T1 hypointensity were assessed. In autopsies of 3 progressive MS cases, the histopathology of the phase rim was determined.In centripetal lesions, a phase rim colocalized with initial contrast enhancement. In 12 of 22, this phase rim persisted after enhancement resolved. Compared with centripetal lesions with transient rim, those with persistent rim had less volume shrinkage and became more T1 hypointense between months 3 and 12. No centrifugal lesions developed phase rims at any time point. Pathologically, persistent rims corresponded to an iron-laden inflammatory myeloid cell population at the edge of chronic demyelinated lesions.In early lesion evolution, a persistent phase rim in lesions that shrink least and become more T1 hypointense over time suggests that the rim might mark failure of early lesion repair and/or irreversible tissue damage. In later stages of MS, phase rim lesions continue to smolder, exerting detrimental effects on affected brain tissue.NCT00001248.The Intramural Research Program of NINDS supported this study.
| S-EPMC4922708 | biostudies-literature
Project description:Background and purposeDisruption of the BBB in MS is associated with the development of new lesions and clinical relapses and signifies the presence of active inflammation. It is most commonly detected as enhancement on MR imaging performed with contrast agents that are costly and occasionally toxic. We investigated whether the BBB status in white matter lesions may be indirectly ascertained via examination of features on T1- and T2-weighted images obtained before the injection of a contrast agent.Materials and methodsWe considered 93 brain MR imaging studies on 16 patients that included T1-, T2-, and T2-weighted FLAIR images and predicted voxel wise enhancement after intravenous injection of a gadolinium chelate. We then used these voxel-level predictions to determine the presence or absence of abnormal enhancement anywhere in the brain.ResultsOn a voxel-by-voxel basis, enhancement can be predicted by using contrast-free measures with an AUC of 0.83 (95% CI, 0.80-0.87). At the whole-brain level, enhancement can be predicted with an AUC of 0.72 (95% CI, 0.62-0.82).ConclusionsIn many cases, breakdown of the BBB in acute MS lesions may be inferred without the need to inject an MR imaging contrast agent. The inference relies on intrinsic properties of tissue damage in acute lesions. Although contrast studies are more accurate, they may sometimes be unnecessary.
| S-EPMC3555688 | biostudies-literature
Project description:BackgroundAutopsy data suggest a causative link between meningeal inflammation and cortical lesions (CLs) in multiple sclerosis (MS).ObjectiveTo use leptomeningeal enhancement (LME) and CLs on 7-Tesla (7T) magnetic resonance imaging (MRI) to investigate associations between meningeal inflammation and cortical pathology.MethodsForty-one participants with MS underwent 7T MRI of the brain. CLs and foci of LME were quantified.ResultsAll MS participants had CLs; 27 (65.8%) had >1 focus of LME. Except for hippocampal CL count (ρ = 0.32 with spread/fill-sulcal pattern LME, p = 0.042), no significant correlations were seen between LME and CLs. Mean cortical thickness correlated with the number of LME foci (ρ = -0.43, p = 0.005). Participants with relapsing-remitting multiple sclerosis (RRMS) showed no correlation with neocortical CLs, but significant correlations were seen between LME and hippocampal lesion count (ρ = 0.39, p = 0.030), normalized cortical gray matter (GM) volume (ρ = -0.49, p = 0.005), and mean cortical thickness (ρ = -0.59, p < 0.001).ConclusionThis study supports a relationship between LME and cortical GM atrophy but does not support an association of LME and neocortical CLs. This may indicate that meningeal inflammation is involved with neurodegenerative inflammatory processes, rather than focal lesion development.
| S-EPMC7021560 | biostudies-literature
Project description:ObjectiveThe aim of this study is to assess the performance of deep learning convolutional neural networks (CNNs) in segmenting gadolinium-enhancing lesions using a large cohort of multiple sclerosis (MS) patients.MethodsA three-dimensional (3D) CNN model was trained for segmentation of gadolinium-enhancing lesions using multispectral magnetic resonance imaging data (MRI) from 1006 relapsing-remitting MS patients. The network performance was evaluated for three combinations of multispectral MRI used as input: (U5) fluid-attenuated inversion recovery (FLAIR), T2-weighted, proton density-weighted, and pre- and post-contrast T1-weighted images; (U2) pre- and post-contrast T1-weighted images; and (U1) only post-contrast T1-weighted images. Segmentation performance was evaluated using the Dice similarity coefficient (DSC) and lesion-wise true-positive (TPR) and false-positive (FPR) rates. Performance was also evaluated as a function of enhancing lesion volume.ResultsThe DSC/TPR/FPR values averaged over all the enhancing lesion sizes were 0.77/0.90/0.23 using the U5 model. These values for the largest enhancement volumes (>500 mm3) were 0.81/0.97/0.04. For U2, the average DSC/TPR/FPR values were 0.72/0.86/0.31. Comparable performance was observed with U1. For all types of input, the network performance degraded with decreased enhancement size.ConclusionExcellent segmentation of enhancing lesions was observed for enhancement volume ⩾70 mm3. The best performance was achieved when the input included all five multispectral image sets.
| S-EPMC7680286 | biostudies-literature