The human vagal complex: from gross anatomy to single neurons, from brainstem to abdomen

The vagus nerve (VN) connects the brainstem to the viscera to regulate many physiological functions. Mapping the VN with state-of-the-art high-resolution imaging modalities has tremendous potential to improve the safety and efficacy of existing autonomic neuromodulation therapies and to inform design of new therapies. We developed the most comprehensive mapping pipeline of the VN to date, from the perspectives of sample size, lengths of nerve, and range of imaging modalities. Our pipeline maps cadaveric human vagal anatomy with complementary imaging modalities applied serially to the same tissue: pre-dissection MRI, pre-dissection CT, 3D tracing of the dissected nerve in situ, CT of the excised nerve, microCT, histology, and a novel serial block-face imaging technique, "3D-MUSE". The resulting co-registered data enable quantification of gross anatomy, fascicular morphology, and fiber organization in three dimensions. We demonstrated the utility of the data by implementing anatomically realistic computational models of vagus nerve stimulation. These approaches and resulting anatomical data will seed and accelerate the development of novel neuromodulation therapies to treat diseases.