OCTOPUS: A versatile open-source tool creating realistic numericalbrain cells

Abstract

Brain cell morphology plays a crucial role in function and pathology. Biophysical models of diffusion MRI (dMRI) quantify cell morphology in vivo, enabling the design of novel biomarkers. These models represent cells by simplified geometries, such as spheres and randomly oriented cylinders, for which analytical signal expressions exist. However, dMRI signals are sensitive to morphological features, such as branching, tapering, undulation, beading, and protrusions, unaccounted for in most models, as they often render analytical solutions impossible. Simulations of the dMRI signal in synthetically generated cells offer a powerful tool to explore how microstructural morphology impacts the dMRI signal. Nevertheless, no tool to generate digital replicas of brain cells is available openly. To address this gap, we introduce the OCTOPUS toolbox, which generates cells featuring all geometrical features described above. OCTOPUS, provided via the Python interface OCTOpool, enables accessible, efficient creation of cells with complex geometries. We recreated histologically reconstructed neuronal and glial cells, including pyramidal, GABAergic and glutamatergic neurons, and astro- and microglia. To illustrate the plausibility of OCTOPUS-generated cells, we reproduced established properties of dMRI signals from brain tissue, such as the signatures of short-range disorder, branching and protrusions, and a high-b-value power law. By comparing the geometries and dMRI signals of generated and original cells, we found different growth strategies adequate for more isotropic and more anisotropic cells. We anticipate that realistic cell substrates created by OCTOPUS will help validate biophysical models, design dMRI sequences sensitive to fine-grained cell morphology beyond analytical models, and generate realistic numerical substrates of brain tissue.