Biology subjects

Pelot, N. A.

Publications and source records attributed to Pelot, N. A..

7 recordsLinked to original sources

bioRxiv2025

Mapping the Fascicular Morphology and Organization of the Human Sciatic Nerve via High-Resolution MicroCT Imaging

ObjectiveImplanted neuroprostheses can restore standing and walking after spinal cord injury and somatosensation after limb loss. Yet current approaches often fail to reliably activate hamstring muscles crucial for upright stability and mobility or to target afferent fibers for sensory restoration. We developed a novel methodology using high-resolution micro-computed tomography (microCT) to visualize and track fascicle groups innervating distinct hamstring muscles along the human sciatic nerve. This approach provides a framework for mapping fascicular topography in complex neural pathways to optimize standing neuroprostheses. MethodsBilateral sciatic nerves were dissected and excised from an embalmed human cadaver, annotated with branch names, and stained with phosphotungstic acid before undergoing microCT scanning at 11.4 m isotropic resolution. Images were segmented with a 3D U-Net convolutional neural network. Segmentation results were used to quantify morphological metrics and track fascicular organization along [~]25 cm of the nerve. MicroCT reconstructions were validated against histological cross sections. ResultsGross dissection revealed matched proximal-to-distal branching between left and right sciatic nerves: branch to long head of the biceps femoris (lhBF), branch to hamstring part of the adductor magnus and semimembranosus (HAM/SM), and branch to semitendinosus (ST). All branches originated medially and followed an inferomedial trajectory. Branch-free lengths of the sciatic exhibited asymmetry, especially between the lumbosacral roots to the first branch (5.5 cm left vs. 1.5 cm right) and lhBF to the HAM/SM branch (9.0 cm left vs. 16.5 cm right). MicroCT analysis revealed bilateral symmetry in fascicle diameters ([~]0.4 mm) and total fascicle counts ([~]84) but asymmetry in hamstring-innervating fascicle counts (left [~]7, right: [~]9). The 3D fascicular maps revealed that hamstring fascicles were located in the anteromedial portion of the sciatic nerve cross section and remained separate for distances up to 15.9 cm proximal to their branching points. SignificanceOur microCT-based approach enables efficient, high-resolution 3D mapping of fascicular organization within large, complex peripheral nerves like the sciatic nerve, overcoming previous technical limitations. This methodology informs development of neuroprostheses with improved hamstring muscle activation for enhanced standing function.

bioengineering↗

bioRxiv2025

Automated 3D Segmentation of Human Vagus Nerve Fascicles and Epineurium from Micro-Computed Tomography Images Using Anatomy-Aware Neural Networks

ObjectivePrecise segmentation and quantification of nerve morphology from imaging data are critical for designing effective and selective peripheral nerve stimulation (PNS) therapies. However, prior studies on nerve morphology segmentation suffer from important limitations in both accuracy and efficiency. This study introduces a deep learning approach for robust and automated 3D segmentation of human vagus nerve fascicles and epineurium from high-resolution micro-computed tomography (microCT) images. MethodsWe developed a multi-class 3D U-Net to segment fascicles and epineurium that incorporates a novel anatomy-aware loss function to ensure that predictions respect nerve topology. We trained and tested the network using subject-level five-fold cross-validation with 100 microCT sub-volumes (11.4 m isotropic resolution) from cervical and thoracic vagus nerves stained with phosphotungstic acid from five subjects. We benchmarked the 3D U-Nets performance against a 2D U-Net using both standard and anatomy-specific segmentation metrics. ResultsOur 3D U-Net generated high-quality segmentations (average Dice similarity coefficient: 0.93). Compared to the 2D U-Net, our 3D U-Net yielded significantly better volumetric overlap, boundary delineation, and fascicle-level accuracy. The 3D approach reduced anatomical errors by 2.5-fold, provided more consistent inter-slice boundaries, and improved detection of fascicle splits/merges by nearly 6-fold. SignificanceOur automated 3D segmentation pipeline provides anatomically accurate 3D maps of peripheral neural morphology from microCT data. The automation allows for high throughput, and the substantial improvement in segmentation quality and anatomical fidelity enhances the reliability of morphological analysis, vagal pathway mapping, and the implementation of realistic computational models. These advancements provide a foundation for understanding the functional organization of the vagus and other peripheral nerves and optimizing PNS therapies.

neuroscience↗

bioRxiv2022

Spatially selective stimulation of the pig vagus nerve to modulate target effect versus side effect

Electrical stimulation of the cervical vagus nerve using implanted electrodes (VNS) is FDA-approved for the treatment of drug-resistant epilepsy, treatment-resistant depression, and most recently, chronic ischemic stroke rehabilitation. However, VNS is critically limited by the unwanted stimulation of nearby neck muscles - a result of non-specific stimulation activating motor nerve fibers within the vagus. Prior studies suggested that precise placement of small epineural electrodes can modify VNS therapeutic effects, such as cardiac responses. However, it remains unclear if placement can alter the balance between intended effect and limiting side effect. We used an FDA investigational device exemption approved six-contact epineural cuff to deliver VNS in pigs and quantified how epineural electrode location impacts on- and off-target VNS activation. Detailed post-mortem histology was conducted to understand how the underlying neuroanatomy impacts observed functional responses. Here we report the discovery and characterization of clear neuroanatomy-dependent differences in threshold and saturation for responses related to both effect (change in heart rate) and side effect (neck muscle contractions). The histological and electrophysiological data were used to develop and validate subject-specific computation models of VNS, creating a well-grounded quantitative framework to optimize electrode location-specific activation of nerve fibers governing intended effect versus unwanted side effect.

bioengineering↗

bioRxiv2021

Fascicles split or merge every ~560 microns within the human cervical vagus nerve

1Vagus nerve stimulation (VNS) is FDA approved for stroke rehabilitation, epilepsy, and depression; however, the vagus functional anatomy underlying the implant is poorly understood. We used microCT to quantify fascicular structure and neuroanatomy within human cervical vagus nerves. Fascicles split or merged every ~560 m (17.8 {+/-} 6.1 events/cm). The high degree of fascicular splitting and merging in humans may explain the clinical heterogeneity in patient responses.

neuroscience↗

bioRxiv2020

In vivo visualization of pig vagus nerve 'vagotopy' using ultrasound

BackgroundPlacement 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. ObjectiveThe use of patient-specific visualization of vagus nerve fascicular organization could better inform clinical cuff placement and improve clinical outcomes. MethodsThe viability of ultrasound, with the transducer in the surgical pocket, to visualize vagus nerve fascicular organization (i.e. vagotopy) was characterized in a pig model. Ultrasound images were matched to post-mortem histology to confirm the utility of ultrasound in identifying fascicular organization. ResultsHigh-resolution ultrasound accurately depicted the vagotopy of the pig vagus nerve intra-operatively, as confirmed via histology. The stereotypical pseudo-unipolar cell body aggregation at the nodose ganglion was identifiable, and these sensory afferent fascicular bundles were traced down the length of the vagus nerve. Additionally, the superior and recurrent laryngeal nerves were identified via ultrasound. ConclusionsIntraoperative visualization of vagotopy and surrounding nerves using ultrasound is a novel approach to optimize stimulating cuff placement, avoid unwanted activation of motor nerve fibers implicated in off-target effects, and seed patient-specific models of vagal fiber activation to improve patient outcomes.

neuroscience↗

bioRxiv2020

Sources of Off-Target Effects of Vagus Nerve Stimulation Using the Helical Clinical Lead in Domestic Pigs

Clinical data suggest that efficacious vagus nerve stimulation (VNS) is limited by side effects such as cough and dyspnea that have stimulation thresholds lower than those for therapeutic outcomes. VNS side effects are putatively caused by activation of nearby muscles within the neck, via direct muscle activation or activation of nerve fibers innervating those muscles. Our goal was to determine the thresholds at which various VNS-evoked effects occur in the domestic pig--an animal model with vagus anatomy similar to human--using the bipolar helical lead deployed clinically. Intrafascicular electrodes were placed within the vagus nerve to record electroneurographic (ENG) responses, and needle electrodes were placed in the vagal-innervated neck muscles to record electromyographic (EMG) responses. Contraction of the cricoarytenoid muscle occurred at low amplitudes ([~]0.3 mA) and resulted from activation of motor nerve fibers in the cervical vagus trunk within the electrode cuff which bifurcate into the recurrent laryngeal branch of the vagus. At higher amplitudes ([~]1.4 mA), contraction of the cricoarytenoid and cricothyroid muscles was generated by current leakage outside the cuff to activate motor nerve fibers running within the nearby superior laryngeal branch of the vagus. Activation of these muscles generated artifacts in the ENG recordings that may be mistaken for compound action potentials representing slowly conducting A{delta}-, B-, and C-fibers. Our data resolve conflicting reports of the stimulation amplitudes required for C-fiber activation in large animal studies (>10 mA) and human studies (<250 {micro}A). After removing muscle-generated artifacts, ENG signals with post-stimulus latencies consistent with A{delta}- and B-fibers occurred in only a small subset of animals, and these signals had similar thresholds to those that caused bradycardia. By identifying specific neuroanatomical pathways that cause off-target effects and characterizing the stimulation dose-response curves for on- and off-target effects, we hope to guide interpretation and optimization of clinical VNS.

neuroscience↗

bioRxiv2019

Functional Vagotopy in the Cervical Vagus Nerve of the Domestic Pig: Implications for Vagus Nerve Stimulation

Given current clinical interest in vagus nerve stimulation, there are surprisingly few studies characterizing the anatomy of the vagus nerve in large animal models as it pertains to on-and off-target engagement of local fibers. We sought to address this gap by evaluating vagal anatomy in the domestic pig, whose vagus nerve organization and size approximates the human cervical vagus nerve. We provide data on key features across the cervical vagus nerve including diameter, number and diameter of fascicles, and distance of fascicles from the epineural surface where stimulating electrodes are placed. We also characterized the relative locations of the superior and recurrent laryngeal branches of the vagus nerve that have been implicated in therapy limiting side effects with common electrode placement. We identified key variants across the cohort that may be important for vagus nerve stimulation with respect to changing sympathetic/parasympathetic tone, such as cross-connections to the sympathetic trunk. We discovered that cell bodies of pseudo-unipolar cells aggregate together to form a very distinct grouping within the nodose ganglion. This distinct grouping gives rise to a larger number of smaller fascicles as one moves caudally down the cervical vagus nerve. This often leads to a distinct bimodal organization, or vagotopy that may be advantageous to exploit in design of electrodes/stimulation paradigms. Finally, we placed our data in context of historic and recent histology spanning mouse, rat, canine, pig, non-human primate and human models, thus providing a comprehensive resource to understand similarities and differences across species.

neuroscience↗