Translating pathology in multiple sclerosis: the combination of postmortem imaging, histopathology and clinical findings

Seewann, Alexandra; Kooi, E.J.; Roosendaal, Stefan D.; Barkhof, Frederik; Valk, Paul van der; Geurts, Jeroen J. G.

doi:10.1111/j.1600-0404.2008.01137.x

Cited by 41 publications

(35 citation statements)

References 77 publications

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“…This report confirmed histopathologically the suspicion of demyelination based on MRI lesion morphology and CSF findings. As MRI became accepted as a biomarker of MS [18,19], the nonpathologically confirmed incidental MRI findings suggestive of MS in asymptomatic patients were readily interpreted as a preclinical stage of MS [20]. Prevalence estimates from two large MRI series of incidental lesions suggestive of MS (as defined by the consensus MRI criteria of the time) include 0.7% (6 of 864 consecutive MRIs) [21] and 0.83% (23 of 2783 MRIs) [8].…”

Section: Unexpected Msmentioning

confidence: 99%

The Radiologically Isolated Syndrome: Look (Again) Before You Treat

Spain

Bourdette

2011

Curr Neurol Neurosci Rep

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The advent and wide use of magnetic resonance brain imaging has led to in the unexpected detection of lesions that appear typical of multiple sclerosis (MS) in otherwise asymptomatic patients. Several cohorts of patients with the "radiologically isolated syndrome (RIS)" have been studied mainly retrospectively, and a proportion of them do go on to have clinical symptoms of MS. This has led to the not infrequent clinical conundrum of whether or not to treat patients with MRI lesions suggestive of MS, given the knowledge that MS disease-modifying therapies work best when given early in the disease course. However, the decision to proactively treat patients with RIS is countered by the increasing risks associated with MS disease-modifying therapies as well as the uncertain prognostic outcome of RIS. This review will highlight what is and is not known about the long-term outcomes of RIS and present recommendations for clinicians when faced with this challenging situation.

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Section: Unexpected Msmentioning

confidence: 99%

The Radiologically Isolated Syndrome: Look (Again) Before You Treat

Spain

Bourdette

2011

Curr Neurol Neurosci Rep

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“…As part of the MS Center Amsterdam autopsy protocol, areas of interest are generally sampled from a maximum of 5 coronally cut brain slices, under guidance of postmortem T2-weighted MRI. 25 As T2-weighted scans are usually not helpful in detecting GM lesions, 7 GM areas of interest were selected randomly from the slices for the current study. A total of 60 cortical areas and 8 deep GM areas were selected and used for further histopathologic examination.…”

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confidence: 99%

Postmortem verification of MS cortical lesion detection with 3D DIR

Seewann¹,

et al. 2012

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Objective: 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.Methods: 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. Results: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 Ͼ3-fold upon retrospective scoring). The specificity of 3D DIR to MS CLs was found to be 90%. Conclusions: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. Neurology ® 2012;78:302-308 GLOSSARY BSA ϭ bovine serum albumin; CL ϭ cortical lesion; DIR ϭ double inversion recovery; FLAIR ϭ fluid-attenuated inversion recovery; GM ϭ gray matter; MS ϭ multiple sclerosis; NEX ϭ number of excitations; PBS ϭ phosphate-buffered saline; PLP ϭ proteolipid protein; TE ϭ echo time; TI ϭ inversion time; TR ϭ repetition time; WM ϭ white matter.

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“…There is a growing need for interfacing brain morpho-pathology with magnetic resonance imaging (MRI) to improve understanding of the pathological basis of MRI signal changes and thereby validate the in vivo surrogates of physiological and pathological processes (1–5). Postmortem MRI is a valuable intermediate step to this end.…”

Section: Introductionmentioning

confidence: 99%

Postmortem Magnetic Resonance Imaging to Guide the Pathologic Cut

Absinta

Nair

Filippi

et al. 2014

J Neuropathol Exp Neurol

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Interfacing magnetic resonance imaging (MRI) and pathology is critically important for understanding the pathological basis of MRI signal changes in vivo and for clinicopathological correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathological sections, which are relatively thick and often non-parallel, is both time consuming and insufficiently accurate. The aim of this project was to develop technology to integrate postmortem, high-resolution, whole-brain MRI into the planning and execution of the pathological analysis through precise localization of the target and coordinates of cut. Compared to standard pathological sectioning, the use of an individualized 3D-printed cutting-box, designed based on postmortem MRI of formalin-fixed whole brains, improved the speed, quality, and accuracy of radiological-pathological correlation and, specifically, the histopathological localization of imaging findings. The technology described herein is easily implemented, applicable to any brain disorder, and potentially extendable to other organs. From the point of view of the pathologist this technique can improve localization of small or subtle abnormalities, whereas from the point of view of the radiologist it has the potential to improve understanding of MRI signal changes observed in disease.

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Translating pathology in multiple sclerosis: the combination of postmortem imaging, histopathology and clinical findings

Cited by 41 publications

References 77 publications

The Radiologically Isolated Syndrome: Look (Again) Before You Treat

The Radiologically Isolated Syndrome: Look (Again) Before You Treat

Postmortem verification of MS cortical lesion detection with 3D DIR

Postmortem Magnetic Resonance Imaging to Guide the Pathologic Cut

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