Laminar cortical damage in multiple sclerosis

Barkhof, Frederik; Geurts, Jeroen J. G.

doi:10.1093/brain/awv031

Cited by 3 publications

(1 citation statement)

References 10 publications

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“…Concerning detection of different cortical lesion types, type II lesions are usually very small, which tends to obscure these lesions against the (noisy) background grey matter ( Seewann et al , 2011 ). Type III lesions are particularly hard to detect as they are situated in the outer, far less densely myelinated regions of the cortex, therefore providing only very subtle contrast differences upon demyelination ( Bø et al , 2003 ; Bö et al , 2004 ; Pitt et al , 2010 ; Barkhof and Geurts, 2015 ). Meanwhile, type III lesions are known to be the most abundant cortical lesion type; they can become large and are predominantly present in progressive disease forms, stressing the need for better detection of this lesion type by MRI ( Bø et al , 2003 ; Seewann et al , 2011 , 2012 ; Kilsdonk et al , 2016 ; Trampel et al , 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Histopathology-validated recommendations for cortical lesion imaging in multiple sclerosis

Bouman

Steenwijk

Pouwels

et al. 2020

Brain

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Cortical demyelinating lesions are clinically important in multiple sclerosis, but notoriously difficult to visualize with MRI. At clinical field strengths, double inversion recovery MRI is most sensitive, but still only detects 18% of all histopathologically validated cortical lesions. More recently, phase-sensitive inversion recovery was suggested to have a higher sensitivity than double inversion recovery, although this claim was not histopathologically validated. Therefore, this retrospective study aimed to provide clarity on this matter by identifying which MRI sequence best detects histopathologically-validated cortical lesions at clinical field strength, by comparing sensitivity and specificity of the thus far most commonly used MRI sequences, which are T2, fluid-attenuated inversion recovery (FLAIR), double inversion recovery and phase-sensitive inversion recovery. Post-mortem MRI was performed on non-fixed coronal hemispheric brain slices of 23 patients with progressive multiple sclerosis directly after autopsy, at 3 T, using T1 and proton-density/T2-weighted, as well as FLAIR, double inversion recovery and phase-sensitive inversion recovery sequences. A total of 93 cortical tissue blocks were sampled from these slices. Blinded to histopathology, all MRI sequences were consensus scored for cortical lesions. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesion types I–IV (mixed grey matter/white matter, intracortical, subpial and cortex-spanning lesions, respectively). MRI scores were compared to histopathological scores to calculate sensitivity and specificity per sequence. Next, a retrospective (unblinded) scoring was performed to explore maximum scoring potential per sequence. Histopathologically, 224 cortical lesions were detected, of which the majority were subpial. In a mixed model, sensitivity of T1, proton-density/T2, FLAIR, double inversion recovery and phase-sensitive inversion recovery was 8.9%, 5.4%, 5.4%, 22.8% and 23.7%, respectively (20, 12, 12, 51 and 53 cortical lesions). Specificity of the prospective scoring was 80.0%, 75.0%, 80.0%, 91.1% and 88.3%. Sensitivity and specificity did not significantly differ between double inversion recovery and phase-sensitive inversion recovery, while phase-sensitive inversion recovery identified more lesions than double inversion recovery upon retrospective analysis (126 versus 95; P < 0.001). We conclude that, at 3 T, double inversion recovery and phase-sensitive inversion recovery sequences outperform conventional sequences T1, proton-density/T2 and FLAIR. While their overall sensitivity does not exceed 25%, double inversion recovery and phase-sensitive inversion recovery are highly pathologically specific when using existing scoring criteria and their use is recommended for optimal cortical lesion assessment in multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Histopathology-validated recommendations for cortical lesion imaging in multiple sclerosis

Bouman

Steenwijk

Pouwels

et al. 2020

Brain

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Improved Detection of Cortical Gray Matter Involvement in Multiple Sclerosis with Quantitative Susceptibility Mapping

et al. 2015

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Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study

Kilsdonk¹,

Jonkman²,

Klaver³

et al. 2016

Brain

152

148

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The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. So far, a systematic histopathological verification of ultra-high field magnetic resonance imaging pulse sequences has been lacking. The aim of this study was to determine the sensitivity of 7 T versus 3 T magnetic resonance imaging pulse sequences for the detection of cortical multiple sclerosis lesions by directly comparing them to histopathology. We obtained hemispheric coronally cut brain sections of 19 patients with multiple sclerosis and four control subjects after rapid autopsy and formalin fixation, and scanned them using 3 T and 7 T magnetic resonance imaging systems. Pulse sequences included T1-weighted, T2-weighted, fluid attenuated inversion recovery, double inversion recovery and T2*. Cortical lesions (type I-IV) were scored on all sequences by an experienced rater blinded to histopathology and clinical data. Staining was performed with antibodies against proteolipid protein and scored by a second reader blinded to magnetic resonance imaging and clinical data. Subsequently, magnetic resonance imaging images were matched to histopathology and sensitivity of pulse sequences was calculated. Additionally, a second unblinded (retrospective) scoring of magnetic resonance images was performed. Regardless of pulse sequence, 7 T magnetic resonance imaging detected more cortical lesions than 3 T. Fluid attenuated inversion recovery (7 T) detected 225% more cortical lesions than 3 T fluid attenuated inversion recovery (Z = 2.22, P < 0.05) and 7 T T2* detected 200% more cortical lesions than 3 T T2* (Z = 2.05, P < 0.05). Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal.

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Laminar cortical damage in multiple sclerosis

Cited by 3 publications

References 10 publications

Histopathology-validated recommendations for cortical lesion imaging in multiple sclerosis

Histopathology-validated recommendations for cortical lesion imaging in multiple sclerosis

Improved Detection of Cortical Gray Matter Involvement in Multiple Sclerosis with Quantitative Susceptibility Mapping

Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study

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