Naveen Jayaprakash,PhD
Stavros Zanos, MD, PhD
The Feinstein Institutes for Medical Research
Mary Barbe, PhD
Professor, Aging + Cardiovascular Discovery Center
Lewis Katz School of Medicine, Temple University
The vagus nerve has thousands of sensory and motor fibers that convey information between the brain and peripheral organs to maintain physiological stability. The fibers travel in fascicles and form branches to innervate organs and regulate organ functions, but it is essentially unknown how vagal fibers are arranged. Existing vagus nerve stimulation (VNS) therapies often activate vagal fibers non-selectively and can result in reduced efficacy and side effects from non-targeted organs. This study is part of an effort to characterize the nerve’s microscopic structure to better understand its function and improve treatments with bioelectronic devices through VNS. Micro-CT plays a key role, providing detailed, high-definition 3D images to contribute towards an anatomical map of the human vagus nerve.
Despite the importance of the vagus nerve and wide interest in VNS, the basic anatomy of this nerve is largely unknown. Characterizing the vagus nerve will help researchers to understand what part of the nerve is being stimulated and the effect on the body, all with the goal of advancing the field of bioelectronic medicine and VNS therapies. For the work referenced here, the research team used advanced methods for surgical dissection, imaging, and microscopic anatomy to study how vagal fibers are organized inside the vagus nerve in animal and human models. The results “indicate that fibers in the trunk of the vagus nerve are anatomically organized according to functions they mediate and organs they innervate and can be asymmetrically activated by fascicular cervical VNS”1.
The micro-CT imaging was performed on Bruker SkyScan 1172 and SkyScan 1272 micro-CT systems.
Gallery: X-ray microscopic imaging of the vagus nerve
Below are selected images from the research article and supplementary data, with links at the end of the article for access to the full material.
Figure 2: Sensory and motor fascicles form clusters along the trunk of the swine vagus nerve. (A) Schematic showing a segment of the vagal trunk with several fascicles along its path. At rostral levels, sensory fascicles (green) converge into the nodose ganglion, while motor fascicles (red) bypass the nodose. At more caudal levels, sensory and motor fascicles merge to form mixed fascicles (yellow). (B) Micro-computed tomography imaging of an intact right vagus nerve trunk, from just above the nodose ganglion to the upper thoracic level.
Figure 3: (Supplementary Fig S2) Micro-CT image of the Bronchopulmonary branch. A) Representative section of the nerve showing bronchopulmonary branch of the pig right vagus nerve. B) Micro-CT image of the vagus nerve showing bronchopulmonary branch of the main vagal trunk. C) Fascicles in the bronchopulmonary branch was manually annotated in the segmented micro-CT images with yellow color and was traced back to the caudal part of the main trunk. D) Micro-CT image of the bronchopulmonary branch of a Yucatan pig, showing 15 fascicles at distance of 24 cm from the nodose ganglion.
Figure 4: Supplementary Fig S4. Nodose ganglion and the Superior Laryngeal branch. A) Representative image of the right vagus that includes the nodose ganglion and the cervical region of the nerve. B) Micro-CT image of the corresponding section of the nerve shown in (A). Plane of the cut shows the region of the nerve where segmented micro-CT images was analyzed. C) Superior Laryngeal nerve extending from the nodose ganglion showing 8 fascicles was annotated in pink, motor fascicles in red color and the nodose ganglion containing the pseudo unipolar cells in green color.
Figure 5: (Supplementary Fig S29): Left: Reconstructed micro-CT image of a nerve segment (about 6 cm in length), comprised of 8830 image slices. Right: A “raw” single micro-CT image slice taken at the horizontal plane indicated by the yellow plane on the left.
Figure 6: Supplementary Fig S32: Aspects of 3D-reconstructed fascicular tracks in a pig vagus nerve resolved in micro-CT data. (A) A “rostral” segment of the nerve, at a level rostral to the cardiac branch emergence, where most RLN and bronchopulmonary fascicles have merged, whereas cardiac fascicles are still independent. For clarity, shown are fascicle centroids of all mixed RLN and bronchopulmonary fascicles (orange traces), and of cardiac fascicles (blue). Several actual micro-CT images are shown at regular intervals. Vertical scale bar: 900 µm. (B) The same nerve segment as in A, shown with an approximately 15-degree rostral tilt. (C) A more “caudal” segment of the same nerve, from the level of RLN emergence at the bottom all the way to the level of cardiac branch emergence at the top, and the vagal trunk in between. Bronchopulmonary fascicle centroids are traced in yellow, RLN fascicle centroids are traced in red and cardiac fascicle centroids are traced in blue. Merged bronchopulmonary and RLN fascicle centroids are traced in orange. Vertical scale bar is 2250 µm. (D) The same nerve segment as in C, shown with an approximate 15-degree rostral. Note that some fascicle centroid tracks that end/emerge abruptly are due to fascicular splitting/merging events: two centroids become one and the new centroid moves abruptly to a nearby location.
Full research article and supplementary data:
© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND License