Postmortem Magnetic Resonance Imaging to Guide the Pathologic Cut

Journal of Neuropathology and Experimental Neurology (Impact Factor: 3.8). 07/2014; 73(8). DOI: 10.1097/NEN.0000000000000096
Source: PubMed


Interfacing magnetic resonance imaging (MRI) with pathology is critically important for understanding the pathologic basis of MRI signal changes in vivo and for clinicopathologic correlations. Postmortem MRI is an intermediate step in this process; unfortunately, however, relating the data to standard pathologic sections, which are relatively thick and often nonparallel, 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 pathologic analysis through precise localization of the target and coordinates of cut. Compared with standard pathologic sectioning, the use of an individualized, 3-dimensionally printed cutting box-designed based on postmortem MRI of formalin-fixed whole brains-improved the speed, quality, and accuracy of radiologic-pathologic correlations and, specifically, the histopathologic 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 diseases.

31 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ocular motor system provides several advantages for studying the brain, including well-defined populations of neurons that contribute to specific eye movements. Generation of rapid eye movements (saccades) depends on excitatory burst neurons (EBN) and omnipause neurons (OPN) within the brainstem, both types of cells are highly active. Experimental lesions of EBN and OPN cause slowing or complete loss of saccades. We report a patient who developed a permanent, selective saccadic palsy following cardiac surgery. When she died several years later, surprisingly, autopsy showed preservation of EBN and OPN. We therefore considered other mechanisms that could explain her saccadic palsy. Recent work has shown that both EBN and OPN are ensheathed by perineuronal nets (PN), which are specialized extracellular matrix structures that may help stabilize synaptic contacts, promote local ion homeostasis, or play a protective role in certain highly active neurons. Here, we review the possibility that damage to PN, rather than to the neurons they support, could lead to neuronal dysfunction-such as saccadic palsy. We also suggest how future studies could test this hypothesis, which may provide insights into the vulnerability of other active neurons in the nervous system that depend on PN. © 2015 New York Academy of Sciences.
    Annals of the New York Academy of Sciences 02/2015; 1343(1). DOI:10.1111/nyas.12666 · 4.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the frequency and nature of leptomeningeal contrast enhancement in multiple sclerosis (MS) via in vivo 3-tesla postcontrast T2-weighted, fluid-attenuated inversion recovery (FLAIR) MRI and 7-tesla postmortem MRI-pathology correlation. Brain MRI, using the postcontrast T2-weighted, FLAIR technique, was prospectively collected in 299 MS cases and 37 age-matched neurologically healthy controls. Expert raters evaluated focal gadolinium enhancement in the leptomeningeal compartment. Two progressive MS cases came to autopsy after in vivo MRI characterization. Pathologic and immunohistochemical examination assessed the association of enhancement with leptomeningeal inflammation and adjacent cortical demyelination. Focal contrast enhancement was detected in the leptomeningeal compartment in 74 of 299 MS cases (25%) vs 1 of 37 neurologically healthy controls (2.7%; p = 0.001). Enhancement was nearly twice as frequent (p = 0.009) in progressive MS (39/118 cases, 33%) as in relapsing-remitting MS (35/181, 19%). Enhancing foci generally remained stable throughout the evaluation period (up to 5.5 years). Pathology showed perivascular lymphocytic and mononuclear infiltration in the enhancing areas in association with flanking subpial cortical demyelination. Leptomeningeal contrast enhancement occurs frequently in MS and is a noninvasive, in vivo marker of inflammation and associated subpial demyelination. It might therefore enable testing of new treatments aimed at eliminating this inflammation and potentially arresting progressive MS. © 2015 American Academy of Neurology.
    Neurology 04/2015; 85(1). DOI:10.1212/WNL.0000000000001587 · 8.29 Impact Factor