Custom fit 3D-printed brain holders for comparison of histology with MRI in marmosets

• MRI and histopathology are complementary techniques, and data from each can inform the interpretation of the other..
• A method is described to facilitate comparison between MRI and histopathology in individual animals.
• Ex vivo MRI was used to generate 3D models of brains and 3D-printed brain holders.
• The 3D-printed brain holders maintained brain positioning between ultra-high resolution MRI and pathologic cutting.
• The preservation of brain position enabled high precision comparisons of ex vivo MRI to histology and of both to in vivo MRI.

BackgroundMRI 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 method3D-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.ResultsThe 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 methodsExisting 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.ConclusionsThe 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.