Homology analysis detects topological changes of Iba1 localization accompanied by microglial activation
Toshinori Sawano1, Ryo Tsuchihashi1, Eiichi Morii2
1Group of Neurobiology, Division of Health Sciences, Graduate School of Medicine, Osaka University, Osaka, Japan.
Insights
A new index, the Homology Value (HV), quantifies microglial activation by analyzing Iba1 protein distribution in tissue. This method accurately reflects microglial states in brain injury and tumors.
Area of Science:
- Neuroscience
- Immunology
- Computational Biology
Background:
- Microglial activation is crucial for understanding central nervous system conditions.
- A reliable histological index for microglial activation is currently lacking.
Purpose of the Study:
- To develop and validate a novel index for quantifying microglial activation using homology theory.
- To assess the utility of this index in models of brain injury and tumors.
Main Methods:
- Applied homology analysis to Iba1-stained tissue sections to calculate Betti numbers (b0 and b1).
- Defined the Homology Value (HV) as the ratio b1/b0.
- Validated the HV in mouse models of cerebral ischemia and in human brain tumor tissues.
Main Results:
- Microglial activation altered Iba1 localization and morphology, impacting b0 and b1 values.
- The HV increased with microglial activation, correlating with proximity to ischemic lesions and tumor margins.
- HV showed high concordance with established microglial activation markers.
Conclusions:
- The Homology Value (HV) serves as a valid and reliable index for evaluating microglial activation.
- This homology theory-based approach is applicable to diverse tissue imaging contexts.
- The HV offers a quantitative tool for assessing neuroinflammation and related pathological conditions.
Abstract:
The state of microglial activation provides important information about the central nervous system. However, a reliable index of microglial activation in histological samples has yet to be established. Here, we show that microglial activation induces topological changes of Iba1 localization that can be detected by analysis based on homology theory. Analysis of homology was applied to images of Iba1-stained tissue sections, and the 0-dimentional Betti number (b0: the number of solid components) and the 1-dimentional Betti number (b1: the number of windows surrounded by solid components) were obtained. We defined b1/b0 as the Homology Value (HV), and investigated its validity as an index of microglial activation using cerebral ischemia model mice. Microglial activation was accompanied by changes to Iba1 localization and morphology of microglial processes. In single microglial cells, the change of Iba1 localization increased b1. Conversely, thickening or retraction of microglial processes decreased b0. Consequently, microglial activation increased the HV. The HV of a tissue area increased with proximity to the ischemic core and showed a high degree of concordance with the number of microglia expressing activation makers. Furthermore, the HV of human metastatic brain tumor tissue also increased with proximity to the tumor. These results suggest that our index, based on homology theory, can be used to correctly evaluate microglial activation in various tissue images.
