Adapted clustering method for generic analysis of histological fibrosis staining as an open source tool

Pathological remodeling of the extracellular matrix is a hallmark of cardiovascular disease. Abnormal fibrosis causes cardiac dysfunction by reducing ejection fraction and impairing electrical conductance, leading to arrhythmias. Hence, accurate quantification of fibrosis deposition in histological sections is of extreme importance for preclinical and clinical studies. Current automatic tools do not perform well under variant conditions. Moreover, users do not have the option to evaluate data from staining methods of their choice according to their purpose. To overcome these challenges, we underline a novel machine learning-based tool (FibroSoft) and we show its feasibility in a model of cardiac hypertrophy and heart failure in mice. Our results demonstrate that FibroSoft can identify fibrosis in diseased myocardium and the obtained results are user-independent. In addition, the results acquired using our software strongly correlate to those obtained by Western blot analysis of collagen 1 expression. Additionally, we could show that this method can be used for Masson's Trichrome and Picosirius Red stained histological images. The evaluation of our method also indicates that it can be used for any particular histology segmentation and quantification. In conclusion, our approach provides a powerful example of the feasibility of machine learning strategies to enable automatic analysis of histological images.

Automated summary

Pathological remodeling of the extracellular matrix is a key feature of cardiovascular disease. Accurately quantifying fibrosis deposition in histological sections is essential for research, but currently available automatic tools are limited by their performance under different conditions and lack of flexibility in evaluating staining methods. Our novel machine learning-based tool, FibroSoft, demonstrated its feasibility in assessing fibrosis in a mouse model of cardiac hypertrophy and heart failure. The results were consistent and correlated well with Western blot analysis. This tool can also be applied to different staining methods, making it suitable for various histology segmentation and quantification studies.