An open-source stereotaxic container with an integrated cutting guide for human brain fixation during magnetic resonance imaging and sectioning for histology

Berardinelli, J.; Liou, J.-J.; Farhat, N.; Li, J.; Stauffer, M.; Miller, K. L.; Tendler, B. C.; Wu, W.; Ikonomovic, M. D.; Mettenburg, J. M.; Aizenstein, H. J.; Santini, T.; Kofler, J. K.; Ibrahim, T. S.

doi:10.64898/2026.06.01.729391

bioRxiv · 10.64898/2026.06.01.729391

An open-source stereotaxic container with an integrated cutting guide for human brain fixation during magnetic resonance imaging and sectioning for histology

Berardinelli, J.·Liou, J.-J.·Farhat, N.·Li, J.·Stauffer, M.·Miller, K. L.·Tendler, B. C.·Wu, W.·Ikonomovic, M. D.·Mettenburg, J. M.·Aizenstein, H. J.·Santini, T.·Kofler, J. K.·Ibrahim, T. S.

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Abstract

IntroductionPostmortem imaging at ultrahigh field strengths, such as 7 Tesla (7T) magnetic resonance imaging (MRI), enables unprecedented visualization of fine brain structures and pathology. However, precise registration between MRI and histology is often compromised by tissue deformation and lack of standardized tools for preserving anatomical orientation. A reliable, high-resolution MRI-to-histology workflow is essential for MRI-guided sampling to investigate neurodegenerative diseases. MethodsWe developed a human postmortem brain container composed of stereotaxic enclosure and cutting guide system using iterative 3D printing. The final design is constructed from Victrex AM 200, a polyaryletherketone material engineered with MRI compatibility, high mechanical strength, and high resistance to fixatives. Human brains were embedded in an agar/sucrose mixture within the container and scanned at 7T using high-contrast and high-resolution imaging sequences. The cutting guide enables reproducible sectioning at defined tissue coronal slab thicknesses (9.2 {+/-} 0.6 mm). Block face photographs of each coronal slab were then co-registered with MRI for targeted tissue sampling. ResultsTo date, 215 human postmortem brains have been imaged ex vivo using this container. The container maintains consistent spatial orientation from imaging through sectioning, supporting correlation between MR-visible features and histological findings. Imaging-visible abnormalities, such as white matter hyperintensities and cerebral microbleeds, were localized and sampled with minimal deformation. The container enables single-scan workflows, avoiding custom cutting templates or repeat imaging. It supports deep learning-based lesion segmentation and MRI-guided histology registration, facilitating large-scale neuropathological investigations. ConclusionThe stereotaxic cutting guide system addresses a critical gap in postmortem imaging by integrating MRI-compatible materials, precision-guided sectioning, and high-throughput imaging. It has enabled multimodal studies of aging and neurodegeneration and is being adopted in neuropathological workflows. This platform provides a reproducible, scalable, and anatomically precise solution for aligning ultrahigh field MRI with histology, enhancing both clinical research and digital pathology efforts.

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Berardinelli, J., Liou, J.-J., Farhat, N., Li, J., Stauffer, M., Miller, K. L., Tendler, B. C., Wu, W., Ikonomovic, M. D., Mettenburg, J. M., Aizenstein, H. J., Santini, T., Kofler, J. K., Ibrahim, T. S.. 2026-06-04. An open-source stereotaxic container with an integrated cutting guide for human brain fixation during magnetic resonance imaging and sectioning for histology. https://doi.org/10.64898/2026.06.01.729391

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