Development and Validation of a Graph Theory Based Computational Analysis Tool for Investigating Neuronal Network Integrity in 3D Cortical Microtissue Models Under Vincristine Treatment and Ischemic and Ischemia-Reperfusion Conditions

Burgess, Amina Zohor

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Year:: 2024
Contributor:: Burgess, Amina Zohor (creator); Hoffman-Kim, Diane (Advisor); Gray, Marissa (Reader); González-Cruz, Rafael (Reader); Kesari, Haneesh (Reader); Brown University. Biology and Medicine: Biomedical Engineering (sponsor)
Genre:: theses
Subject:: tissue engineering; Algorithms; engineered tissue; computational analysis; Graph theory; Toxicity testing--In vitro; 3D Cell Culture; Neuroscience; Hypoxic-ischemic brain injury; Image analysis--Data processing; Vincristine
Extent:: III, 189 p.

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Abstract:: The thesis introduces a novel computational tool developed using graph theory and implemented in Wolfram Mathematica to analyze neuronal network integrity within three-dimensional cortical microtissues. This tool is designed to map network topology and extract key connectivity metrics, facilitating the quantitative assessment of dense neuronal networks in 3D microtissues, a task that has been challenging with previous methodologies. The computational tool was rigorously tested on large z-stacks of over 50 slices, demonstrating its effectiveness and efficiency. It was applied to pre-existing datasets where microtissues were subjected to pathological conditions including exposure to the chemotherapeutic agent vincristine and ischemic conditions followed by reperfusion. The tool's performance was validated through statistical analysis of these conditions. For the vincristine-treated microtissues, the tool identified significant dose-dependent differences between control and treated groups, highlighting its capability to detect and quantify the extent of neuronal injury. In the ischemic models, significant differences were observed between healthy controls and those subjected to ischemic conditions. Notably, tissues that underwent reperfusion exhibited a heterogeneous response, aligning with existing literature and qualitative assessments, thus confirming the tool's accuracy and reliability. Previously, quantitative evaluation of neuronal networks was limited to less dense monolayer cultures. The development of this tool overcomes such limitations by enabling detailed analysis of complex, dense neuronal networks in 3D microtissues. Furthermore, the tool's versatility suggests potential applications beyond neuronal studies, such as in assessing other cell types like astrocytes or conducting vascularization studies. This computational tool not only advances the field of neuronal network analysis in 3D microtissues but also opens new avenues for research in neurobiology and drug testing, providing a robust method for assessing the impact of various treatments on neuronal health and connectivity.
Notes:: Thesis (Sc. M.)--Brown University, 2024

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Burgess, Amina Zohor, "Development and Validation of a Graph Theory Based Computational Analysis Tool for Investigating Neuronal Network Integrity in 3D Cortical Microtissue Models Under Vincristine Treatment and Ischemic and Ischemia-Reperfusion Conditions" (2024). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:6tawvmpu/

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Biomedical Engineering Theses and Dissertations

Theses and Dissertations for the Biomedical Engineering department.
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