In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound

Background: Placement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of...

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Autores principales: Megan L. Settell, Aaron C. Skubal, Rex C. H. Chen, Maïsha Kasole, Bruce E. Knudsen, Evan N. Nicolai, Chengwu Huang, Chenyun Zhou, James K. Trevathan, Aniruddha Upadhye, Chaitanya Kolluru, Andrew J. Shoffstall, Justin C. Williams, Aaron J. Suminski, Warren M. Grill, Nicole A. Pelot, Shigao Chen, Kip A. Ludwig
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/4411a1b983b442e0b0fb7d939fb91530
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id oai:doaj.org-article:4411a1b983b442e0b0fb7d939fb91530
record_format dspace
institution DOAJ
collection DOAJ
language EN
topic vagotopy
histology
vagus nerve
vagus nerve stimulation
bioelectronic medicine
electroceutical
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
spellingShingle vagotopy
histology
vagus nerve
vagus nerve stimulation
bioelectronic medicine
electroceutical
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Megan L. Settell
Megan L. Settell
Aaron C. Skubal
Aaron C. Skubal
Rex C. H. Chen
Rex C. H. Chen
Maïsha Kasole
Maïsha Kasole
Bruce E. Knudsen
Bruce E. Knudsen
Evan N. Nicolai
Evan N. Nicolai
Evan N. Nicolai
Chengwu Huang
Chenyun Zhou
Chenyun Zhou
James K. Trevathan
James K. Trevathan
Aniruddha Upadhye
Aniruddha Upadhye
Chaitanya Kolluru
Chaitanya Kolluru
Andrew J. Shoffstall
Andrew J. Shoffstall
Justin C. Williams
Justin C. Williams
Justin C. Williams
Aaron J. Suminski
Aaron J. Suminski
Aaron J. Suminski
Warren M. Grill
Warren M. Grill
Warren M. Grill
Warren M. Grill
Nicole A. Pelot
Shigao Chen
Kip A. Ludwig
Kip A. Ludwig
Kip A. Ludwig
In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
description Background: Placement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of neck muscle contractions, demonstrated by previous studies to result from stimulation of (1) motor fibers near the cuff in the superior laryngeal and (2) motor fibers within the cuff projecting to the recurrent laryngeal.Objective: Conventional non-invasive ultrasound, where the transducer is placed on the surface of the skin, has been previously used to visualize the vagus with respect to other landmarks such as the carotid and internal jugular vein. However, it lacks sufficient resolution to provide details about the vagus fascicular organization, or detail about smaller neural structures such as the recurrent and superior laryngeal branch responsible for therapy limiting side effects. Here, we characterize the use of ultrasound with the transducer placed in the surgical pocket to improve resolution without adding significant additional risk to the surgical procedure in the pig model.Methods: Ultrasound images were obtained from a point of known functional organization at the nodose ganglia to the point of placement of stimulating electrodes within the surgical window. Naïve volunteers with minimal training were then asked to use these ultrasound videos to trace afferent groupings of fascicles from the nodose to their location within the surgical window where a stimulating cuff would normally be placed. Volunteers were asked to select a location for epineural electrode placement away from the fascicles containing efferent motor nerves responsible for therapy limiting side effects. 2-D and 3-D reconstructions of the ultrasound were directly compared to post-mortem histology in the same animals.Results: High-resolution ultrasound from the surgical pocket enabled 2-D and 3-D reconstruction of the cervical vagus and surrounding structures that accurately depicted the functional vagotopy of the pig vagus nerve as confirmed via histology. Although resolution was not sufficient to match specific fascicles between ultrasound and histology 1 to 1, it was sufficient to trace fascicle groupings from a point of known functional organization at the nodose ganglia to their locations within the surgical window at stimulating electrode placement. Naïve volunteers were able place an electrode proximal to the sensory afferent grouping of fascicles and away from the motor nerve efferent grouping of fascicles in each subject (n = 3).Conclusion: The surgical pocket itself provides a unique opportunity to obtain higher resolution ultrasound images of neural targets responsible for intended therapeutic effect and limiting off-target effects. We demonstrate the increase in resolution is sufficient to aid patient-specific electrode placement to optimize outcomes. This simple technique could be easily adopted for multiple neuromodulation targets to better understand how patient specific anatomy impacts functional outcomes.
format article
author Megan L. Settell
Megan L. Settell
Aaron C. Skubal
Aaron C. Skubal
Rex C. H. Chen
Rex C. H. Chen
Maïsha Kasole
Maïsha Kasole
Bruce E. Knudsen
Bruce E. Knudsen
Evan N. Nicolai
Evan N. Nicolai
Evan N. Nicolai
Chengwu Huang
Chenyun Zhou
Chenyun Zhou
James K. Trevathan
James K. Trevathan
Aniruddha Upadhye
Aniruddha Upadhye
Chaitanya Kolluru
Chaitanya Kolluru
Andrew J. Shoffstall
Andrew J. Shoffstall
Justin C. Williams
Justin C. Williams
Justin C. Williams
Aaron J. Suminski
Aaron J. Suminski
Aaron J. Suminski
Warren M. Grill
Warren M. Grill
Warren M. Grill
Warren M. Grill
Nicole A. Pelot
Shigao Chen
Kip A. Ludwig
Kip A. Ludwig
Kip A. Ludwig
author_facet Megan L. Settell
Megan L. Settell
Aaron C. Skubal
Aaron C. Skubal
Rex C. H. Chen
Rex C. H. Chen
Maïsha Kasole
Maïsha Kasole
Bruce E. Knudsen
Bruce E. Knudsen
Evan N. Nicolai
Evan N. Nicolai
Evan N. Nicolai
Chengwu Huang
Chenyun Zhou
Chenyun Zhou
James K. Trevathan
James K. Trevathan
Aniruddha Upadhye
Aniruddha Upadhye
Chaitanya Kolluru
Chaitanya Kolluru
Andrew J. Shoffstall
Andrew J. Shoffstall
Justin C. Williams
Justin C. Williams
Justin C. Williams
Aaron J. Suminski
Aaron J. Suminski
Aaron J. Suminski
Warren M. Grill
Warren M. Grill
Warren M. Grill
Warren M. Grill
Nicole A. Pelot
Shigao Chen
Kip A. Ludwig
Kip A. Ludwig
Kip A. Ludwig
author_sort Megan L. Settell
title In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
title_short In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
title_full In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
title_fullStr In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
title_full_unstemmed In vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound
title_sort in vivo visualization of pig vagus nerve “vagotopy” using ultrasound
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/4411a1b983b442e0b0fb7d939fb91530
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spelling oai:doaj.org-article:4411a1b983b442e0b0fb7d939fb915302021-12-01T01:28:44ZIn vivo Visualization of Pig Vagus Nerve “Vagotopy” Using Ultrasound1662-453X10.3389/fnins.2021.676680https://doaj.org/article/4411a1b983b442e0b0fb7d939fb915302021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnins.2021.676680/fullhttps://doaj.org/toc/1662-453XBackground: Placement of the clinical vagus nerve stimulating cuff is a standard surgical procedure based on anatomical landmarks, with limited patient specificity in terms of fascicular organization or vagal anatomy. As such, the therapeutic effects are generally limited by unwanted side effects of neck muscle contractions, demonstrated by previous studies to result from stimulation of (1) motor fibers near the cuff in the superior laryngeal and (2) motor fibers within the cuff projecting to the recurrent laryngeal.Objective: Conventional non-invasive ultrasound, where the transducer is placed on the surface of the skin, has been previously used to visualize the vagus with respect to other landmarks such as the carotid and internal jugular vein. However, it lacks sufficient resolution to provide details about the vagus fascicular organization, or detail about smaller neural structures such as the recurrent and superior laryngeal branch responsible for therapy limiting side effects. Here, we characterize the use of ultrasound with the transducer placed in the surgical pocket to improve resolution without adding significant additional risk to the surgical procedure in the pig model.Methods: Ultrasound images were obtained from a point of known functional organization at the nodose ganglia to the point of placement of stimulating electrodes within the surgical window. Naïve volunteers with minimal training were then asked to use these ultrasound videos to trace afferent groupings of fascicles from the nodose to their location within the surgical window where a stimulating cuff would normally be placed. Volunteers were asked to select a location for epineural electrode placement away from the fascicles containing efferent motor nerves responsible for therapy limiting side effects. 2-D and 3-D reconstructions of the ultrasound were directly compared to post-mortem histology in the same animals.Results: High-resolution ultrasound from the surgical pocket enabled 2-D and 3-D reconstruction of the cervical vagus and surrounding structures that accurately depicted the functional vagotopy of the pig vagus nerve as confirmed via histology. Although resolution was not sufficient to match specific fascicles between ultrasound and histology 1 to 1, it was sufficient to trace fascicle groupings from a point of known functional organization at the nodose ganglia to their locations within the surgical window at stimulating electrode placement. Naïve volunteers were able place an electrode proximal to the sensory afferent grouping of fascicles and away from the motor nerve efferent grouping of fascicles in each subject (n = 3).Conclusion: The surgical pocket itself provides a unique opportunity to obtain higher resolution ultrasound images of neural targets responsible for intended therapeutic effect and limiting off-target effects. We demonstrate the increase in resolution is sufficient to aid patient-specific electrode placement to optimize outcomes. This simple technique could be easily adopted for multiple neuromodulation targets to better understand how patient specific anatomy impacts functional outcomes.Megan L. SettellMegan L. SettellAaron C. SkubalAaron C. SkubalRex C. H. ChenRex C. H. ChenMaïsha KasoleMaïsha KasoleBruce E. KnudsenBruce E. KnudsenEvan N. NicolaiEvan N. NicolaiEvan N. NicolaiChengwu HuangChenyun ZhouChenyun ZhouJames K. TrevathanJames K. TrevathanAniruddha UpadhyeAniruddha UpadhyeChaitanya KolluruChaitanya KolluruAndrew J. ShoffstallAndrew J. ShoffstallJustin C. WilliamsJustin C. WilliamsJustin C. WilliamsAaron J. SuminskiAaron J. SuminskiAaron J. SuminskiWarren M. GrillWarren M. GrillWarren M. GrillWarren M. GrillNicole A. PelotShigao ChenKip A. LudwigKip A. LudwigKip A. LudwigFrontiers Media S.A.articlevagotopyhistologyvagus nervevagus nerve stimulationbioelectronic medicineelectroceuticalNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Neuroscience, Vol 15 (2021)