Microscopy-informed structural connectivity mapping in the in vivo human brain via domain adaptation

Characterising human brain connectivity remains a major challenge in neuroscience. Multimodal datasets combining diffusion MRI with high-resolution microscopy in the same brain offer a unique link between macroscopic imaging and microstructural detail, but we lack tools to leverage these data to improve connectivity estimates for in vivo human imaging. We present a deep learning model that predicts high-resolution microscopy-informed fibre orientations from diffusion MRI. The model uses microscopy-derived three-dimensional fibre orientation maps as biologically grounded training targets. It is trained on a bespoke macaque dataset integrating in vivo MRI, postmortem MRI, and whole-brain microscopy, and then translated to in vivo human imaging. We use domain adaptation to predict fibre orientations from diverse MRI datasets: first to bridge differences in tissue state in the macaque (postmortem to in vivo), and then to generalise across species (macaque to human). Our method derives microscale-informed fibre architecture from diffusion MRI without requiring microscopy at inference. It leverages data that can easily be acquired only in animal models whilst generalising to in vivo human diffusion MRI with minimal acquisition requirements. The microscopy-informed fibre orientation distributions support biologically meaningful tractography, enhancing superficial white matter and cortical-subcortical pathway delineation for in vivo human data. More broadly, this work establishes a general framework for transferring microstructural information from microscopy to non-invasive imaging, enabling biologically informed mapping of brain connectivity.