In the nodose ganglia (NG), pseudo-unipolar cell bodies (predominately sensory afferents) are grouped into a large fascicle, distinct from a separate, smaller grouping of nerve fibers.
Previous work in a pig model of VNS demonstrated a bimodal functional organization in the VN. The vagus nerve (VN) contains a topographical organization ( Settell et al., 2020), or vagotopy, that has the potential to be visualized using ultrasound. The SLN and RLN innervate neck muscles involved in many of the therapy-limiting side effects and therefore avoiding stimulation of these nerve fibers is paramount. These nerve branches are either activated through stimulation of fascicles within the stimulating cuff (RLN), or by current escaping the cuff (SLN) ( Boon et al., 2009 Castoro et al., 2011 Nicolai et al., 2020). The inadvertent stimulation of somatic nerve branches extending from the vagus, such as the superior and recurrent laryngeal nerve (SLN and RLN, respectively), has been implicated as the cause of these side effects ( Tosato et al., 2007 Yoo et al., 2013 Nicolai et al., 2020).
The therapeutic effects of vagus nerve stimulation (VNS) for epilepsy and heart failure, while significant in some patients, are often limited by intolerable side effects including throat tightening or pain, voice changes, hoarseness, cough, and dyspnea ( Morris and Mueller, 1999 Howland, 2014). This simple technique could be easily adopted for multiple neuromodulation targets to better understand how patient specific anatomy impacts functional outcomes. We demonstrate the increase in resolution is sufficient to aid patient-specific electrode placement to optimize outcomes.
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).Ĭonclusion: 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. 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. 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. 2-D and 3-D reconstructions of the ultrasound were directly compared to post-mortem histology in the same animals. 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. 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. 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. 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. 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. 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. 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. 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.
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