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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Frontiers Media S.A.
2021
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vagotopy histology vagus nerve vagus nerve stimulation bioelectronic medicine electroceutical Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
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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 |
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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. |
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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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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) |