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Updated: Aug 1, 2026
An Unbiased Approach of Sampling TEM Sections in Neuroscience
Published on: April 13, 2019
Bridging Neuroimaging and Neuropathology: A Comprehensive Workflow for Targeted Sampling of White Matter Lesions
Nadim Farhat1, Jinghang Li1, Jacob Berardinelli1
1University of Pittsburgh, Department of Bioengineering, Pittsburgh, PA, US.
Background And Purpose:
White matter lesions are common imaging biomarkers associated with aging and neurodegenerative diseases, yet their underlying pathology remains unclear due to limitations in imaging-based characterization. We aim to develop and validate a comprehensive workflow enabling precise MRI-guided histological sampling of white matter lesions to bridge neuroimaging and neuropathology.
Methods:
We establish a workflow integrating agarose-saccharose brain embedding, ultra-high field 7T MRI acquisition, reusable 3D-printed cutting guides, and semi-automated MRI-blockface alignment. Postmortem brains are stabilized in the embedding medium and scanned using optimized MRI protocols. Coronal sectioning is guided by standardized 3D-printed cutting guides, and knife traces are digitally matched to MRI planes. White matter lesions are segmented on MRI and aligned for histopathological sampling. This approach is validated in over 100 postmortem human brains.
Results:
The workflow enables reproducible brain sectioning, minimizes imaging artifacts, and achieves precise spatial alignment between MRI and histology. Consistent, high-resolution MRI data facilitated accurate lesion detection and sampling. The use of standardized cutting guides and alignment protocols reduce variability and improve efficiency.
Conclusions:
Our cost-effective, scalable workflow reliably links neuroimaging findings with histological analysis, enhancing the understanding of white matter lesion pathology. This framework holds significant potential for advancing translational research in aging and neurodegenerative diseases.
Insights
This study presents a new workflow for precise MRI-guided brain tissue sampling. It accurately links neuroimaging to histology, improving understanding of white matter lesions in aging and neurodegenerative diseases.
Area of Science:
- Neuroimaging and neuropathology research.
- Biomedical engineering and translational science.
Background:
- White matter lesions are key biomarkers for aging and neurodegenerative diseases.
- Current imaging methods have limitations in characterizing lesion pathology.
- Bridging neuroimaging and neuropathology is crucial for understanding these conditions.
Purpose of the Study:
- To develop and validate a workflow for precise MRI-guided histological sampling of white matter lesions.
- To enhance the characterization of white matter lesion pathology.
- To link neuroimaging findings with histopathological analysis.
Main Methods:
- Integrated workflow: agarose-saccharose embedding, 7T MRI, 3D-printed cutting guides, MRI-blockface alignment.
- Postmortem brain stabilization, optimized MRI acquisition, and guided coronal sectioning.
- Digital matching of knife traces to MRI planes for accurate lesion segmentation and sampling.
Main Results:
- Reproducible brain sectioning with minimized imaging artifacts.
- Precise spatial alignment achieved between MRI and histology.
- High-resolution MRI data enabled accurate lesion detection and efficient, standardized sampling.
Conclusions:
- Cost-effective, scalable workflow reliably links neuroimaging to histology.
- Enhances understanding of white matter lesion pathology.
- Potential to advance translational research in aging and neurodegenerative diseases.
