A homological approach to a mathematical definition of pulmonary fibrosis and emphysema on computed tomography.

Three-dimensional imaging is essential to evaluate local abnormalities and understand structure-function relationships in an organ. However, quantifiable and interpretable methods to localize abnormalities remain unestablished. Visual assessments are prone to bias, machine learning methods depend on training images, and the underlying decision principle is usually difficult to interpret. Here, we developed a homological approach to mathematically define emphysema and fibrosis in the lungs on computed tomography (CT). With the use of persistent homology, the density of homological features, including connected components, tunnels, and voids, was extracted from the volumetric CT scans of lung diseases. A pair of CT values at which each homological feature appeared (birth) and disappeared (death) was computed by sweeping the threshold levels from higher to lower CT values. Consequently, fibrosis and emphysema were defined as voxels with dense voids having a longer lifetime (birth-death difference) and voxels with dense connected components having a lower birth, respectively. In an independent dataset including subjects with idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and combined pulmonary fibrosis and emphysema (CPFE), the proposed definition enabled accurate segmentation with comparable quality to deep learning in terms of Dice coefficients. Persistent homology-defined fibrosis was closely associated with physiological abnormalities such as impaired diffusion capacity and long-term mortality in subjects with IPF and CPFE, and persistent homology-defined emphysema was associated with impaired diffusion capacity in subjects with COPD. The present persistent homology-based evaluation of structural abnormalities could help explore the clinical and physiological impacts of structural changes and morphological mechanisms of disease progression. This study proposes a homological approach to mathematically define a three-dimensional texture feature of emphysema and fibrosis on chest computed tomography using persistent homology. The proposed definition enabled accurate segmentation with comparable quality to deep learning while offering higher interpretability than deep learning-based methods.