SignificanceInflammatory processes drive the autoimmune disease multiple sclerosis (MS). However, what triggers this inflammation remains unknown. Several herpesviruses (HHVs), such as HHV-6 typically acquired during childhood, are associated with MS. The temporal separation between HHV-6 acquisition and MS development complicates its study as a disease trigger. Because rodents are not susceptible to HHV-6 infection, we utilized nonhuman primates to examine the impact of HHV-6 infection on an experimental MS-like disease. The viral infections were asymptomatic; however, the MS-like disease was significantly accelerated in all virally inoculated animals. Our data support the hypothesis that viruses may act as triggers to lower the threshold for autoimmunity, and warrant trials of antiviral interventions in early disease stages.

Magnetic resonance imaging (MRI) allows for the delineation between normal and abnormal tissue on a macroscopic scale, sampling an entire tissue volume three-dimensionally. While MRI is an extremely sensitive tool for detecting tissue abnormalities, association of signal changes with an underlying pathological process is usually not straightforward. In the central nervous system, for example, inflammation, demyelination, axonal damage, gliosis, and neuronal death may all induce similar findings on MRI. As such, interpretation of MRI scans depends on the context, and radiological-histopathological correlation is therefore of the utmost importance. Unfortunately, traditional pathological sectioning of brain tissue is often imprecise and inconsistent, thus complicating the comparison between histology sections and MRI. This article presents novel methodology for accurately sectioning primate brain tissues and thus allowing precise matching between histology and MRI. The detailed protocol described in this article will assist investigators in applying this method, which relies on the creation of 3D printed brain slicers. Slightly modified, it can be easily implemented for brains of other species, including humans.

Background MRI has the advantage of sampling large areas of tissue and locating areas of interest in 3D space in both living and ex vivo systems, whereas histology has the ability to examine thin slices of ex vivo tissue with high detail and specificity. Although both are valuable tools, it is currently difficult to make high-precision comparisons between MRI and histology due to large differences inherent to the techniques. A method combining the advantages would be an asset to understanding the pathological correlates of MRI. New Method 3D-printed brain holders were used to maintain marmoset brains in the same orientation during acquisition of ex vivo MRI and pathologic cutting of the tissue. Results The results of maintaining this same orientation show that sub-millimeter, discrete neuropathological features in marmoset brain consistently share size, shape, and location between histology and ex vivo MRI, which facilitates comparison with serial imaging acquired in vivo. Comparison with Existing Methods Existing methods use computational approaches sensitive to data input in order to warp histologic images to match large-scale features on MRI, but the new method requires no warping of images, due to a preregistration accomplished in the technique, and is insensitive to data formatting and artifacts in both MRI and histology. Conclusions The simple method of using 3D-printed brain holders to match brain orientation during pathologic sectioning and MRI acquisition enables rapid and precise comparison of small features seen on MRI to their underlying histology.

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