Masís, Javier ; Mankus, David ; Wolff, Steffen ; Guitchounts, Grigori ; Jösch, Maximilian AIST Austria ; Cox, David
Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro-electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods.
We would like to thank Greg Lin and Arthur McClelland for their expertise with the micro-CT machine, David Richmond and Hunter Elliott at the Image and Data Analysis Core (IDAC) at Harvard Medical School for their image processing advice, and William Liberti at Boston University for graciously providing a zebra finch brain. This work was performed in part at the Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation under NSF award no. 1541959. CNS is part of Harvard University. This work was supported by the Richard and Susan Smith Family Foundation, and IARPA (contract #D16PC00002). S.B.E.W. was supported by fellowships from the Human Frontier Science Program (HFSP; LT000514/2014) and the European Molecular Biology Organization (EMBO; ALTF1561-2013). G.G. was supported by the National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP).
Masís J, Mankus D, Wolff S, Guitchounts G, Jösch MA, Cox D. A micro-CT-based method for quantitative brain lesion characterization and electrode localization. Scientific Reports. 2018;8(1). doi:10.1038/s41598-018-23247-z
Masís, J., Mankus, D., Wolff, S., Guitchounts, G., Jösch, M. A., & Cox, D. (2018). A micro-CT-based method for quantitative brain lesion characterization and electrode localization. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-23247-z
Masís, Javier, David Mankus, Steffen Wolff, Grigori Guitchounts, Maximilian A Jösch, and David Cox. “A Micro-CT-Based Method for Quantitative Brain Lesion Characterization and Electrode Localization.” Scientific Reports 8, no. 1 (2018). https://doi.org/10.1038/s41598-018-23247-z.
J. Masís, D. Mankus, S. Wolff, G. Guitchounts, M. A. Jösch, and D. Cox, “A micro-CT-based method for quantitative brain lesion characterization and electrode localization,” Scientific Reports, vol. 8, no. 1, 2018.
Masís J, Mankus D, Wolff S, Guitchounts G, Jösch MA, Cox D. 2018. A micro-CT-based method for quantitative brain lesion characterization and electrode localization. Scientific Reports. 8(1).
Masís, Javier, et al. “A Micro-CT-Based Method for Quantitative Brain Lesion Characterization and Electrode Localization.” Scientific Reports, vol. 8, no. 1, Nature Publishing Group, 2018, doi:10.1038/s41598-018-23247-z.
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