Tectonic Infarct Analysis: A Computational Tool for Automated Whole-brain Infarct Analysis from TTC-stained Tissue

Background: Infarct volume measured from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain slices is critical to stroke models. In this study, we developed an interactive, tunable, software that automatically computes whole-brain infarct metrics from serial TTC-stained brain sections.

Methods: Three rat ischemic stroke cohorts were used in this study (Total  = 91 rats; Cohort 1  = 21, Cohort 2  = 40, Cohort 3  = 30). For each, brains were serially-sliced, stained with TTC and scanned on both anterior and posterior sides. Ground truth annotation and infarct morphometric analysis (e.g., brain-V, infarct-V, and non-infarct-V volumes) were completed by domain experts. We used Cohort 1 for brain and infarct segmentation model development ( = 3 training cases with 36 slices [18 anterior and posterior faces],  = 18 testing cases with 218 slices [109 anterior and posterior faces]), as well as infarct morphometrics automation. The infarct quantification pipeline and pre-trained model were packaged as a standalone software and applied to Cohort 2, an internal validation dataset. Finally, software and model trainability were tested as a use-case with Cohort 3, a dataset from a separate institute.

Results: Both high segmentation and statistically significant quantification performance (correlation between manual and software) were observed across all datasets. Segmentation performance: Cohort 1 brain accuracy = 0.95/f1-score = 0.90, infarct accuracy = 0.96/f1-score = 0.89; Cohort 2 brain accuracy = 0.97/f1-score = 0.90, infarct accuracy = 0.97/f1-score = 0.80; Cohort 3 brain accuracy = 0.96/f1-score = 0.92, infarct accuracy = 0.95/f1-score = 0.82. Infarct quantification (cohort average): V (ρ = 0.87,  < 0.001), V (0.92,  < 0.001), V (0.80,  < 0.001), %infarct (0.87,  = 0.001), and infarct:non-infact ratio (ρ = 0.92,  < 0.001).

Conclusion: Tectonic Infarct Analysis software offers a robust and adaptable approach for rapid TTC-based stroke assessment.