Abstract
PurposeTo perform magnetic resonance microscopy (MRM) on human cortex and a cortical lesion as well as the adjacent normal appearing white matter. To shed light on the origins of MRI contrast by comparison with histochemical and immunostaining. Methods3D MRM at a nominal isotropic resolution of 15 and 18 µm was performed on 2 blocks of tissue from the brain of a 77-year-old man who had MS for 47 years. One block contained normal appearing cortical gray matter (CN block) and adjacent normal appearing white matter (NAWM), and the other also included a cortical lesion (CL block). Postmortem ex-vivo MRI was performed at 11.7T using a custom solenoid coil and T2*-weighted 3D GRE sequence. Histochemical and immunostaining were done after paraffin embedding for iron, myelin, oligodendrocytes, neurons, blood vessels, macrophages and microglia, and astrocytes. ResultsMRM could identify individual iron-laden oligodendrocytes with high sensitivity (70% decrease in signal compared to surrounding) in CN and CL blocks, as well as some iron-laden activated macrophages and microglia. Iron-deficient oligodendrocytes seemed to cause relative increase in MRI signal within the cortical lesion. High concentration of myelin in the white matter was primarily responsible for its hypointense appearance relative to the cortex, however, signal variations within NAWM could be attributed to changes in density of iron-laden oligodendrocytes. ConclusionChanges in iron accumulation within cells gave rise to imaging contrast seen between cortical lesions and normal cortex, as well as the patchy signal in NAWM. Densely packed myelin and collagen deposition also contributed to MRM signal changes. Even though we studied only one block each from normal appearing and cortical lesions, such studies can help better understand the origins of histopathological and microstructural correlates of MRI signal changes in multiple sclerosis and contextualize the interpretation of lower-resolution in vivo MRI scans.
Highlights
magnetic resonance imaging (MRI) has long been used to infer microstructural changes seen in neurological diseases, such as multiple sclerosis (MS), with high sensitivity
Changes to T1, T2, and T2* relaxation times, magnetization transfer (MT), apparent diffusion coefficient and diffusion anisotropy of water, as well as susceptibility and phase imaging, all provide a window into the microenvironment of the tissue, and many of these are used extensively in clinic for patient management. (Petracca et al, 2018) signal from MRI sequences typically used in clinical settings are not intrinsically tied to biological processes, and it is sometimes difficult to draw inferences to the specific pathological changes that cause these changes. (Petiet et al, 2018)
MRI signal changes typically seen in the brain and spinal cord of patients with MS are often assumed to be a combination of gliosis, edema, loss of neurons and myelin, and axonal transection. (Filippi and Rocca, 2011) In addition, imbalance of metals associated with oligodendrocyte damage and inflammation in MS (Todorich et al, 2009; Hametner et al, 2013; Popescu et al, 2017) can lead to MRI signal changes
Summary
MRI has long been used to infer microstructural changes seen in neurological diseases, such as multiple sclerosis (MS), with high sensitivity. (Absinta et al, 2014; Luciano et al, 2016; Absinta et al, 2015) Postmortem whole hemisphere MRI at isotropic resolutions on the order of 150–450 μm has led to identification of MRI signal changes in GM and WM Such studies still do not offer clarity about the specific origin of MRI signal changes in affected tissue. The purpose of this study was to perform high resolution MRM of human cortex, adjacent NAWM, and a cortical lesion in postmortem human tissue, with corresponding histopathology, to establish an MRM protocol relevant for MS, better understand the sources of MRI signal, and facilitate proper in vivo interpretation
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