Postmortem verification of MS cortical lesion detection with 3D DIR

Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Neurology (Impact Factor: 8.3). 01/2012; 78(5):302-8. DOI: 10.1212/WNL.0b013e31824528a0
Source: PubMed

ABSTRACT To assess the sensitivity and specificity of 3D double inversion recovery (DIR) MRI for detecting multiple sclerosis (MS) cortical lesions (CLs) using a direct postmortem MRI to histopathology comparison.
Single-slab 3D DIR and 3D fluid-attenuated inversion recovery (FLAIR) images of 56 matched fresh brain samples from 14 patients with chronic MS were acquired at 1.5 T. The images of both sequences were prospectively scored for CLs in consensus by 3 experienced raters who were blinded to histopathology and clinical data. Next, CLs were identified histopathologically and were scored again on 3D DIR and 3D FLAIR (retrospective scoring). CLs were classified as intracortical or mixed gray matter (GM)-white matter lesions. Deep GM lesions were also scored. False-positive scores were noted and, from this, specificity was calculated.
We found a sensitivity for 3D DIR to detect MS CLs of 18%, which is 1.6-fold higher than 3D FLAIR (improves to 37% with retrospective scoring; 2.0-fold higher than 3D FLAIR). We detected mixed GM-white matter lesions with a sensitivity of 83% using 3D DIR (65% sensitivity for 3D FLAIR), which improved to 96% upon retrospective scoring (91% for 3D FLAIR). For purely intracortical lesions, 3D DIR detected more than 2-fold more than 3D FLAIR (improved to >3-fold upon retrospective scoring). The specificity of 3D DIR to MS CLs was found to be 90%.
In this postmortem verification study, we have shown that 3D DIR is highly pathologically specific, and more sensitive to CLs than 3D FLAIR in MS.

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    • "Kutzelnigg and Lassmann (2006) report cortical band-like subpial demyelination and destruction, especially in patients with the progressive form of the disease. A new neuroimaging technique, double inversion recovery (DIR) magnetic resonance sequence and high-field magnetic resonance, recently revealed cortical and hippocampal inflammatory lesions that are undetectable using routine MRI (Rinaldi et al., 2010; Seewann et al., 2012). Grey matter lesions have been shown to correlate with cognitive decline, particularly, visuospatial memory disturbances correlated with hippocampal injury detected by DIR (Schmierer et al., 2010). "
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    ABSTRACT: Cognitive dysfunction is relatively frequent in multiple sclerosis (MS) and it happens from the early stages of the disease. There is increasing evidence that the grey matter may be involved in autoimmune inflammation during relapses of MS. The purpose of this study was to evaluate if a single transfer of encephalitogenic T cells, mimicking a relapse of MS, may cause hippocampal damage and memory disturbances in rats. Lewis rats were injected with anti-MBP CD4+ T cells, that induced one-phase autoimmune encephalomyelitis (EAE) with full recovery from motor impairments at 10-15 days. The spatial learning and memory were tested by Morris water maze test in control and EAE animals, 30 and 90 days post-induction (dpi). The neural injury and inflammation was investigated in the hippocampus by immunohistochemistry and quantitative analyses. There was a marked decrease in the number of CA1 and CA4 pyramidal neurons 5 dpi. The loss of neurons then aggravated till 90(th) day. An increase in microglial and astroglial activation and in pro-inflammatory cytokines mRNA expression in the hippocampus, were present 30 and 90 dpi. NGF and BDNF mRNA levels were also significantly elevated. The water maze test, however, did not reveal memory deficits. The present data indicate that a single transfer of autoimmune T cells results in preserved inflammation and probable on-going neuronal injury in the hippocampus, long after recovery from motor disturbances. These findings suggest that any relapse of the MS may start neurodegenerative process in the hippocampus, which isn't necessarily connected with memory deficits.
    Neuroscience 06/2013; 248. DOI:10.1016/j.neuroscience.2013.06.025 · 3.33 Impact Factor
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    • "Because imaging techniques are still unable to adequately detect GM lesions, especially in the cortex [5] [6] [7] [8] [9], measurement of cortical atrophy is gaining increasing attention in the literature [1], in order to assess the real extent of cortical pathology in vivo in patients with MS [2]. "
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    ABSTRACT: We investigated the evolution of cortical atrophy in patients with early relapsing-remitting (RR) multiple sclerosis (MS) and its association with lesion volume (LV) accumulation and disability progression. 136 of 181 RRMS patients who participated in the Avonex-Steroids-Azathioprine study were assessed bimonthly for clinical and MRI outcomes over 2 years. MS patients with disease duration (DD) at baseline of ≤24 months were classified in the early group (DD of 1.2 years, n = 37), while patients with DD > 24 months were classified in the late group (DD of 7.1 years, n = 99). Mixed effect model analysis was used to investigate the associations. Significant changes in whole brain volume (WBV) (P < 0.001), cortical volume (CV) (P < 0.001), and in T2-LV (P < 0.001) were detected. No significant MRI percent change differences were detected between early and late DD groups over 2 years, except for increased T2-LV accumulation between baseline and year 2 in the early DD group (P < 0.01). No significant associations were found between changes in T2-LV and CV over the followup. Change in CV was related to the disability progression over the 2 years, after adjusting for DD (P = 0.01). Significant cortical atrophy, independent of T2-LV accumulation, occurs in early RRMS over 2 years, and it is associated with the disability progression.
    01/2013; 2013:231345. DOI:10.1155/2013/231345
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    • "CGM lesions are more difficult to directly identify using conventional MRI than white matter (WM) lesions (Geurts et al., 2005; Seewann et al., 2011). Only about 10% of histopathologically verified intracortical lesions are detected prospectively using double inversion recovery (DIR), the current standard MRI method (Seewann et al., 2012), and of these the type most frequently seen post-mortem (subpial ) is least readily detected (about 7% prospectively). An alternative is to use a quantifiable MRI measure that is sensitive to pathology seen in cortical lesions. "
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    ABSTRACT: Abstract Background: Histopathology has demonstrated extensive cortical grey matter (GM) demyeli- nation in multiple sclerosis (MS), and suggests that sulcal folds may be preferentially affected, particularly in progressive MS. This has not been confirmed in vivo, and it is not known if it is relevant to clinical status. Objectives: To determine sulcal and gyral crown magnetisation transfer ratio (MTR) in MS cortical GM, and the MTR associations with clinical status. Methods: We measured sulcal and gyral crown cortical GM MTR values in 61 MS patients and 32 healthy controls. Disability was measured using Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores. Results: MTR values were reduced in sulcal and gyral crown regions in all MS subtypes, more so in secondary progressive (SP) MS than relapsing remitting (RR) MS, and similarly in primary progressive (PP) MS and RRMS. Sulcal MTR was lower than gyral crown MTR in controls, PPMS and RRMS patients, but not in SPMS. MTR correlated with clinical status in RRMS and SPMS, but not PPMS. Conclusions: Cortical pathology, as reflected by MTR, is present in all MS subtypes and most pronounced in SPMS. A preferential disease effect on sulcal cortical regions was not observed. Cortical MTR abnormalities appear to be more clinically relevant in relapse-onset rather than progressive-onset MS. & 2013 Elsevier B.V. All rights reserved.
    01/2013; 2(3). DOI:10.1016/j.msard.2013.01.001
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