|
1
|
Yan T, Fortune BC, Liu L, Liu Y, Kaiju T, Suzuki T, Hirata M. Epineural stimulation on distal brachial plexus for functional restoration of the upper limb in a primate study. Front Neurol 2025; 16:1515986. [PMID: 40170903 PMCID: PMC11958176 DOI: 10.3389/fneur.2025.1515986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 02/26/2025] [Indexed: 04/03/2025] Open
Abstract
Restoring upper limb function is critical in individuals with central paralysis, and hand control is a priority in patients with neurological impairments. Functional electrical stimulation with implantable electrodes targeting the peripheral nervous system has the potential to selectively recruit hand muscles and generate multiple functional hand movements. However, the implantation of electrodes in the forearm or elbow areas requires multiple incisions for surgery, and elbow joint movements cannot be performed. In this study, we designed and implanted two epineural cuffs on the median and radial nerves in the distal brachial plexus of a single Japanese macaque (Macaca fuscata) monkey. The cuffs were successfully placed via an axillary approach using a single incision. Electrical stimuli were applied to innervate the contraction patterns of the hand, forearm, and triceps muscles relevant to the median and radial nerves. The evoked potentials of the target muscles electrically stimulated the distal brachial plexus to reliably and selectively innervate the upper limb muscles at the functional group level. Our results demonstrated that the distal brachial plexus can be a useful stimulation site for upper limb muscle contraction and that the axillary approach enables electrode placement to peripheral nerves required for upper limb control.
Collapse
Affiliation(s)
- Tianfang Yan
- Department of Neurological Diagnosis and Restoration, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Benjamin C. Fortune
- Department of Neurological Diagnosis and Restoration, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Lingjun Liu
- Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, and Osaka University, Osaka, Japan
| | - Yan Liu
- Department of Neurological Diagnosis and Restoration, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Taro Kaiju
- Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, and Osaka University, Osaka, Japan
| | - Takafumi Suzuki
- Center for Information and Neural Networks (CiNet), National Institute of Information and Communications Technology, and Osaka University, Osaka, Japan
| | - Masayuki Hirata
- Department of Neurological Diagnosis and Restoration, Graduate School of Medicine, Osaka University, Suita, Japan
| |
Collapse
|
|
2
|
Pušnik L, Radochová B, Janáček J, Saudek F, Serša I, Cvetko E, Umek N, Snoj Ž. Fascicle differentiation of upper extremity nerves on high-resolution ultrasound with multimodal microscopic verification. Sci Rep 2025; 15:557. [PMID: 39747626 PMCID: PMC11696863 DOI: 10.1038/s41598-024-84396-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 12/23/2024] [Indexed: 01/04/2025] Open
Abstract
This study aimed to compare the fascicular anatomy of upper limb nerves visualized using in situ high-resolution ultrasound (HRUS) with ex vivo imaging modalities, namely, magnetic resonance microscopy (MRM), histological cross-sections (HCS), and optical projection tomography (OPT). The median, ulnar, and superficial branch of radial nerve (n = 41) were visualized in 14 cadaveric upper limbs using 22-MHz HRUS. Subsequently, the nerves were excised, imaged with different microscopic techniques, and their morphometric properties were compared. HRUS accurately differentiated 51-74% of fascicles, while MRM detected 87-92% of fascicles when compared to the referential HCS. Among the compared modalities, HRUS demonstrated the smallest fascicular ratios and fascicular cross-sectional areas, but the largest nerve cross-sectional areas. The probability of a fascicle depicted on HRUS representing a cluster of multiple fascicles on the referential HCS increased with the fascicular size, with some differences observed between the larger median and ulnar nerves and the smaller radial nerves. Accordingly, HRUS fascicle differentiation necessitates cautious interpretation, as larger fascicles are more likely to represent clusters. Although HCS is considered the reference modality, alterations in nerve cross-sectional areas or roundness during sample processing should be acknowledged.
Collapse
Affiliation(s)
- Luka Pušnik
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia.
| | - Barbora Radochová
- Laboratory of Biomathematics, Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic
| | - Jiří Janáček
- Laboratory of Biomathematics, Institute of Physiology, The Czech Academy of Sciences, Prague, Czech Republic
| | - František Saudek
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Igor Serša
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
- Department of Condensed Matter Physics, Jožef Stefan Institute, Ljubljana, Slovenia
| | - Erika Cvetko
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Nejc Umek
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia
| | - Žiga Snoj
- Department of Radiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
3
|
Toni L, Pierantoni L, Verardo C, Romeni S, Micera S. Characterization of Machine Learning-Based Surrogate Models of Neural Activation Under Electrical Stimulation. Bioelectromagnetics 2025; 46:e22535. [PMID: 39739852 DOI: 10.1002/bem.22535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Revised: 11/18/2024] [Accepted: 12/06/2024] [Indexed: 01/02/2025]
Abstract
Electrical stimulation of peripheral nerves via implanted electrodes has been shown to be a promising approach to restore sensation, movement, and autonomic functions across a wide range of illnesses and injuries. While in principle computational models of neuromodulation can allow the exploration of large parameter spaces and the automatic optimization of stimulation devices and strategies, their high time complexity hinders their use on a large scale. We recently proposed the use of machine learning-based surrogate models to estimate the activation of nerve fibers under electrical stimulation, producing a considerable speed-up with respect to biophysically accurate models of fiber excitation while retaining good predictivity. Here, we characterize the performance of four frequently employed machine learning algorithms and provide an illustrative example of their ability to generalize to unseen stimulation protocols, stimulating sites, and nerve sections. We then discuss how the ability to generalize to such scenarios is relevant to different optimization protocols, paving the way for the automatic optimization of neuromodulation applications.
Collapse
Affiliation(s)
- Laura Toni
- Modular Implantable Neurotechnologies (MINE) Laboratory, Università Vita-Salute San Raffaele & Scuola Superiore Sant'Anna, Milan, Italy
- The Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Luca Pierantoni
- The Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy
- Brain Connectivity Laboratory, Department of Neuroscience and Neurorehabilitation, IRCCS San Raffaele Roma, Rome, Italy
| | - Claudio Verardo
- The Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy
| | - Simone Romeni
- Modular Implantable Neurotechnologies (MINE) Laboratory, Università Vita-Salute San Raffaele & Scuola Superiore Sant'Anna, Milan, Italy
- Bertarelli Foundation Chair in Translational Neural Engineering, Center for Neuroprosthetics and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
| | - Silvestro Micera
- Modular Implantable Neurotechnologies (MINE) Laboratory, Università Vita-Salute San Raffaele & Scuola Superiore Sant'Anna, Milan, Italy
- The Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy
- Bertarelli Foundation Chair in Translational Neural Engineering, Center for Neuroprosthetics and Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland
| |
Collapse
|
|
4
|
Schädlich IS, Buschbaum S, Magnus T, Reinshagen K, Wintges K, Gelderblom M. Median nerve lesions in pediatric displaced supracondylar humerus fracture: A prospective neurological, electrodiagnostic and ultrasound characterization. Eur J Neurol 2024; 31:e16459. [PMID: 39230443 PMCID: PMC11555132 DOI: 10.1111/ene.16459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 08/12/2024] [Accepted: 08/18/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND AND PURPOSE Supracondylar humerus fractures (SCHFs) are the most common elbow fractures in children. Traumatic median nerve injury and isolated lesions of its pure forearm motor branch, anterior interosseus nerve (AIN), have both been independently reported as complications of displaced SCHFs. Our main objectives were to characterize the neurological syndrome to distinguish median nerve from AIN lesions and to determine the prognosis of median nerve lesions after displaced SCHFs. METHODS Ten children were prospectively followed for an average of 11.6 months. Patients received a standardized clinical examination and high-resolution ultrasound of the median nerve every 1-3 months starting 1-2 months after trauma. Electrodiagnostic studies were performed within the first 4 months and after complete clinical recovery. RESULTS All children shared a clinical syndrome with predominant but not exclusive affection of AIN innervated muscles. High-resolution ultrasound uniformly excluded persistent nerve entrapment and neurotmesis requiring revision surgery but visualized post-traumatic median nerve neuroma at the fracture site in all patients. Electrodiagnostic studies showed axonal motor and sensory median nerve neuropathy. All children achieved complete functional recovery under conservative management. Motor recovery required up to 11 months and differed between involved muscles. CONCLUSIONS It was shown that neurological deficits of the median nerve in displaced SCHFs exceeded an isolated AIN lesion. Notably, detailed neurological follow-up examinations and sonographic exclusion of persistent nerve compression were able to guide conservative therapy in affected children. Under these conditions the prognosis of median nerve lesions was excellent despite severe initial deficits, development of neuroma and axonal injury.
Collapse
Affiliation(s)
| | - Sabriena Buschbaum
- Department of NeurologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Tim Magnus
- Department of NeurologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Konrad Reinshagen
- Department of Pediatric SurgeryUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Kristofer Wintges
- Department of Pediatric SurgeryUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Mathias Gelderblom
- Department of NeurologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| |
Collapse
|
|
5
|
Pušnik L, Lechner L, Serša I, Cvetko E, Haas P, Jengojan SA, Snoj Ž. 3D fascicular reconstruction of median and ulnar nerve: initial experience and comparison between high-resolution ultrasound and MR microscopy. Eur Radiol Exp 2024; 8:100. [PMID: 39196445 PMCID: PMC11358559 DOI: 10.1186/s41747-024-00495-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 07/04/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND The complex anatomy of peripheral nerves has been traditionally investigated through histological microsections, with inherent limitations. We aimed to compare three-dimensional (3D) reconstructions of median and ulnar nerves acquired with tomographic high-resolution ultrasound (HRUS) and magnetic resonance microscopy (MRM) and assess their capacity to depict intraneural anatomy. METHODS Three fresh-frozen human upper extremity specimens were prepared for HRUS imaging by submersion in a water medium. The median and ulnar nerves were pierced with sutures to improve orientation during imaging. Peripheral nerve 3D HRUS scanning was performed on the mid-upper arm using a broadband linear probe (10-22 MHz) equipped with a tomographic 3D HRUS system. Following excision, nerves were cut into 16-mm segments and loaded into the MRM probe of a 9.4-T system (scanning time 27 h). Fascicle and nerve counting was performed to estimate the nerve volume, fascicle volume, fascicle count, and number of interfascicular connections. HRUS reconstructions employed artificial intelligence-based algorithms, while MRM reconstructions were generated using an open-source imaging software 3D slicer. RESULTS Compared to MRM, 3D HRUS underestimated nerve volume by up to 22% and volume of all fascicles by up to 11%. Additionally, 3D HRUS depicted 6-60% fewer fascicles compared to MRM and visualized approximately half as many interfascicular connections. CONCLUSION MRM demonstrated a more detailed fascicular depiction compared to 3D HRUS, with a greater capacity for visualizing smaller fascicles. While 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, their limitations in depicting interfascicular connections and small fascicles within clusters necessitate cautious interpretation. CLINICAL RELEVANCE STATEMENT Although 3D HRUS reconstructions can offer supplementary data in peripheral nerve assessment, even in intraoperative settings, their limitations in depicting interfascicular branches and small fascicles within clusters require cautious interpretation. KEY POINTS 3D HRUS was limited in visualizing nerve interfascicular connections. MRM demonstrated better nerve fascicle depiction than 3D HRUS. MRM depicted more nerve interfascicular connections than 3D HRUS.
Collapse
Affiliation(s)
- Luka Pušnik
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Lisa Lechner
- Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Igor Serša
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Department of Condensed Matter Physics, Jožef Stefan Institute, Ljubljana, Slovenia
| | - Erika Cvetko
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Philipp Haas
- Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Suren Armeni Jengojan
- Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
| | - Žiga Snoj
- Department of Radiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
6
|
Iwanaga R, Mihara A, Sakai T, Muramatsu K, Hashimoto T. Radial Nerve Palsy Caused by Desmoid-Type Fibromatosis: A Case Report and Review of the Literature. Cureus 2024; 16:e65008. [PMID: 39161522 PMCID: PMC11333107 DOI: 10.7759/cureus.65008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2024] [Indexed: 08/21/2024] Open
Abstract
Radial nerve palsy (RNP) is classified as traumatic, non-traumatic, or iatrogenic. The most frequent etiologic agent is the fracture of the humerus of the shaftand distal. We experienced a case of RNP caused by desmoid-type fibromatosis around the radial nerve. The RNP caused by desmoid-type fibromatosis has not been reported in the literature. We present this case here with a review of the RNP literature. The patient is a 16-year-old female, right-hand dominant, who became aware of the difficulty in extending her right little finger without any triggers five months ago. She was also aware of the difficulty in extending the ring finger, and her symptoms gradually worsened. She was referred to our hospital after consulting a home doctor. MRI of the elbow showed a high-intensity occupying lesion on T2-weighted images (T2WI) slightly proximal to the elbow joint. Ultrasonography (US) showed a partial nerve constriction and radial nerve enlargement on the distal side of the constriction. The approach was made from the posterior lateral side of the distal upper arm, and the radial nerve was exposed. There was a 1 cm white tissue strongly adherent on the radial nerve, which was compressing the radial nerve, and it was resected piece by piece. After the resection, the radial nerve was indented. The pathological diagnosis of the resected tissue was fibromatosis. Gradually, she was able to extend her fingers after the surgery and recovered completely in six months.
Collapse
Affiliation(s)
- Ryuta Iwanaga
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, JPN
| | - Atsushi Mihara
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, JPN
| | - Takashi Sakai
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Ube, JPN
| | - Keiichi Muramatsu
- Department of Hand and Microsurgery, Nagato General Hospital, Nagato, JPN
| | | |
Collapse
|
|
7
|
Wang X, Zhang Y, Guo T, Wu S, Zhong J, Cheng C, Sui X. Selective intrafascicular stimulation of myelinated and unmyelinated nerve fibers through a longitudinal electrode: A computational study. Comput Biol Med 2024; 176:108556. [PMID: 38733726 DOI: 10.1016/j.compbiomed.2024.108556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 05/05/2024] [Indexed: 05/13/2024]
Abstract
Carbon nanotube (CNT) fiber electrodes have demonstrated exceptional spatial selectivity and sustained reliability in the context of intrafascicular electrical stimulation, as evidenced through rigorous animal experimentation. A significant presence of unmyelinated C fibers, known to induce uncomfortable somatosensory experiences, exists within peripheral nerves. This presence poses a considerable challenge to the excitation of myelinated Aβ fibers, which are crucial for tactile sensation. To achieve nuanced tactile sensory feedback utilizing CNT fiber electrodes, the selective stimulation of Aβ sensory afferents emerges as a critical factor. In confronting this challenge, the present investigation sought to refine and apply a rat sciatic-nerve model leveraging the capabilities of the COMSOL-NEURON framework. This approach enables a systematic evaluation of the influence exerted by stimulation parameters and electrode geometry on the activation dynamics of both myelinated Aβ and unmyelinated C fibers. The findings advocate for the utilization of current pulses featuring a pulse width of 600 μs, alongside the deployment of CNT fibers characterized by a diminutive diameter of 10 μm, with an exclusively exposed cross-sectional area, to facilitate reduced activation current thresholds. Comparative analysis under monopolar and bipolar electrical stimulation conditions revealed proximate activation thresholds, albeit with bipolar stimulation exhibiting superior fiber selectivity relative to its monopolar counterpart. Concerning pulse waveform characteristics, the adoption of an anodic-first biphasic stimulation modality is favored, taking into account the dual criteria of activation threshold and fiber selectivity optimization. Consequently, this investigation furnishes an efficacious stimulation paradigm for the selective activation of touch-related nerve fibers, alongside provisioning a comprehensive theoretical foundation for the realization of natural tactile feedback within the domain of prosthetic hand applications.
Collapse
Affiliation(s)
- Xintong Wang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Yapeng Zhang
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Tianruo Guo
- Graduate School of Biomedical Engineering, The University of New South Wales, Sydney, NSW, 2052, Australia
| | - Shuhui Wu
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China
| | - Junwen Zhong
- Department of Electromechanical Engineering, University of Macau, Macau SAR, 999078, China
| | - Chengkung Cheng
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China; Med-X Research Institute, Shanghai Jiao Tong University, Engineering Research Center of Digital Medicine, Ministry of Education, Shanghai, China
| | - Xiaohong Sui
- School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
| |
Collapse
|
|
8
|
Kawazoe T, Morishima R, Nakata Y, Sugaya K, Shimizu T, Takahashi K. [MR neurography reveals fascicular constriction of the median nerve in a patient with neuralgic amyotrophy]. Rinsho Shinkeigaku 2024; 64:39-44. [PMID: 38072441 DOI: 10.5692/clinicalneurol.cn-001926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
Diagnosing neuralgic amyotrophy can be challenging in clinical practice. Here, we report the case of a 37-years old Japanese woman who suddenly developed neuropathic pain in the right upper limb after influenza vaccination. The pain, especially at night, was severe and unrelenting, which disturbed her sleep. However, X-ray and MRI did not reveal any fractures or muscle injuries, and brain MRI did not reveal any abnormalities. During neurological consultation, she was in a posture of flexion at the elbow and adduction at the shoulder. Manual muscle testing suggested weakness of the flexor pollicis longus, pronator quadratus, flexor carpi radialis (FCR), and pronator teres (PT), while the flexor digitorum profundus was intact. Medical history and neurological examination suggested neuralgic amyotrophy, particularly anterior interosseous nerve syndrome (AINS) with PT/FCR involvement. Innervation patterns on muscle MRI were compatible with the clinical findings. Conservative treatment with pain medication and oral corticosteroids relieved the pain to minimum discomfort, whereas weakness remained for approximately 3 months. For surgical exploration, lesions above the elbow and fascicles of the median nerve before branching to the PT/FCR were indicated on neurological examinations; thus, we performed high-resolution imaging to detect possible pathognomonic fascicular constrictions. While fascicular constrictions were not evident on ultrasonography, MR neurography indicated fascicular constriction proximal to the elbow joint line, of which the medial topographical regions of the median nerve were abnormally enlarged and showed marked hyperintensity on short-tau inversion recovery. In patients with AINS, when spontaneous regeneration cannot be expected, timely surgical exploration should be considered for a good outcome. In our case, MR neurography was a useful modality for assessing fascicular constrictions when the imaging protocols were appropriately optimized based on clinical assessment.
Collapse
Affiliation(s)
- Tomoya Kawazoe
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH)
| | - Ryo Morishima
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH)
| | - Yasuhiro Nakata
- Department of Neuroradiology, Tokyo Metropolitan Neurological Hospital (TMNH)
| | - Keizo Sugaya
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH)
| | - Toshio Shimizu
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH)
| | - Kazushi Takahashi
- Department of Neurology, Tokyo Metropolitan Neurological Hospital (TMNH)
| |
Collapse
|
|
9
|
Suzuki T, Matsui Y, Momma D, Endo T, Iwasaki N. Median neuropathy after multiple punctures of the forearm for catheterization: A case report. World J Clin Cases 2023; 11:5941-5946. [PMID: 37727486 PMCID: PMC10506017 DOI: 10.12998/wjcc.v11.i25.5941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 07/14/2023] [Accepted: 08/09/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND Neuropathy may occur at some sites after catheterization for close examination of cardiac disease. Although the radial artery is considered a relatively uncom-plicated site for catheterization, the radial artery and median nerve are in relatively close proximity, with the risk of median nerve injury depending on the angle of puncture. The purpose of this study was to report the outcomes of surgery performed for conservative therapy-resistant median neuropathy following forearm catheterization. CASE SUMMARY A 50-year-old woman experienced palsy from the right thumb to the radial side of the ring finger after catheterization from the radial artery of the right forearm. Paresthesia developed at the same site and a positive tinel-like sign was seen for the median nerve area at the high level of the puncture site. Nerve conduction study showed reduced compound muscle action potentials and loss of sensory nerve action potentials. Symptoms did not improve despite pharmacotherapy and the patient gradually developed flexion restrictions of the index and middle fingers. Median nerve injury and associated flexor tendon adhesion was diagnosed, and the patient was referred for surgery at 3 mo after injury. When the same area was opened, no injury to the median nerve epithelium was obvious, but the area of the positive tinel-like sign was highly adherent to surrounding tissue and to the flexor digitorum superficialis of the index and middle fingers. The surgery was terminated with adequate adhesion release. Rehabilitation was initiated postoperatively, improving neurological symptoms and range of motion of the fingers. Six months after surgery, the patient returned to daily activities without discomfort. CONCLUSION This case provides the appropriate diagnosis and treatment for a suspected peripheral nerve injury.
Collapse
Affiliation(s)
- Tomoaki Suzuki
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Yuichiro Matsui
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
- Section for Clinical Education, Faculty of Dental Medicine, Hokkaido University, Sapporo 060-8586, Japan
| | - Daisuke Momma
- Center for Sports Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Takeshi Endo
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| | - Norimasa Iwasaki
- Department of Orthopaedic Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
| |
Collapse
|
|
10
|
Pušnik L, Serša I, Umek N, Cvetko E, Snoj Ž. Correlation between diffusion tensor indices and fascicular morphometric parameters of peripheral nerve. Front Physiol 2023; 14:1070227. [PMID: 36909220 PMCID: PMC9995878 DOI: 10.3389/fphys.2023.1070227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 02/03/2023] [Indexed: 02/25/2023] Open
Abstract
Introduction: Diffusion tensor imaging (DTI) is a magnetic resonance imaging (MRI) technique that measures the anisotropy of water diffusion. Clinical magnetic resonance imaging scanners enable visualization of the structural integrity of larger axonal bundles in the central nervous system and smaller structures like peripheral nerves; however, their resolution for the depiction of nerve fascicular morphology is limited. Accordingly, high-field strength MRI and strong magnetic field gradients are needed to depict the fascicular pattern. The study aimed to quantify diffusion tensor indices with high-field strength MRI within different anatomical compartments of the median nerve and determine if they correlate with nerve structure at the fascicular level. Methods: Three-dimensional pulsed gradient spin-echo (PGSE) imaging sequence in 19 different gradient directions and b value 1,150 s/mm2 was performed on a 9.4T wide-bore vertical superconducting magnet. Nine-millimeter-long segments of five median nerve samples were obtained from fresh cadavers and acquired in sixteen 0.625 mm thick slices. Each nerve sample had the fascicles, perineurium, and interfascicular epineurium segmented. The diffusion tensor was calculated from the region-average diffusion-weighted signals for all diffusion gradient directions. Subsequently, correlations between diffusion tensor indices of segmentations and nerve structure at the fascicular level (number of fascicles, fascicular ratio, and cross-sectional area of fascicles or nerve) were assessed. The acquired diffusion tensor imaging data was employed for display with trajectories and diffusion ellipsoids. Results: The nerve fascicles proved to be the most anisotropic nerve compartment with fractional anisotropy 0.44 ± 0.05. In the interfascicular epineurium, the diffusion was more prominent in orthogonal directions with fractional anisotropy 0.13 ± 0.02. Diffusion tensor indices within the fascicles and perineurium differed significantly between the subjects (p < 0.0001); however, there were no differences within the interfascicular epineurium (p ≥ 0.37). There were no correlations between diffusion tensor indices and nerve structure at the fascicular level (p ≥ 0.29). Conclusion: High-field strength MRI enabled the depiction of the anisotropic diffusion within the fascicles and perineurium. Diffusion tensor indices of the peripheral nerve did not correlate with nerve structure at the fascicular level. Future studies should investigate the relationship between diffusion tensor indices at the fascicular level and axon- and myelin-related parameters.
Collapse
Affiliation(s)
- Luka Pušnik
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Igor Serša
- Jožef Stefan Institute, Ljubljana, Slovenia
| | - Nejc Umek
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Erika Cvetko
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Žiga Snoj
- Department of Radiology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.,Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
11
|
Activating effective functional hand movements in individuals with complete tetraplegia through neural stimulation. Sci Rep 2022; 12:16189. [PMID: 36202865 PMCID: PMC9537317 DOI: 10.1038/s41598-022-19906-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 09/06/2022] [Indexed: 11/08/2022] Open
Abstract
Individuals with complete cervical spinal cord injury suffer from a permanent paralysis of upper limbs which prevents them from achieving most of the activities of daily living. We developed a neuroprosthetic solution to restore hand motor function. Electrical stimulation of the radial and median nerves by means of two epineural electrodes enabled functional movements of paralyzed hands. We demonstrated in two participants with complete tetraplegia that selective stimulation of nerve fascicles by means of optimized spreading of the current over the active contacts of the multicontact epineural electrodes induced functional and powerful grasping movements which remained stable over the 28 days of implantation. We also showed that participants were able to trigger the activation of movements of their paralyzed limb using an intuitive interface controlled by voluntary actions and that they were able to perform useful functional movements such as holding a can and drinking through a straw.
Collapse
|
|
12
|
Amin KR, Fildes JE. Bionic Prostheses: The Emerging Alternative to Vascularised Composite Allotransplantation of the Limb. Front Surg 2022; 9:873507. [PMID: 35599802 PMCID: PMC9122218 DOI: 10.3389/fsurg.2022.873507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/19/2022] [Indexed: 11/15/2022] Open
Abstract
Twenty years have surpassed since the first vascularised composite allotransplantation (VCA) of the upper limb. This is an opportunity to reflect on the position of VCA as the gold standard in limb reconstruction. The paucity of recipients, tentative clinical outcomes, and insufficient scientific progress question whether VCA will remain a viable treatment option for the growing numbers of amputees. Bionic technology is advancing at a rapid pace. The prospect of widely available, affordable, safely applied prostheses with long-standing functional benefit is appealing. Progress in the field stems from the contributions made by engineering, electronic, computing and material science research groups. This review will address the ongoing reservations surrounding VCA whilst acknowledging the future impact of bionic technology as a realistic alternative for limb reconstruction.
Collapse
Affiliation(s)
- Kavit R. Amin
- Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
- Department of Plastic Surgery & Burns, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom
- Correspondence: Kavit R. Amin ;
| | - James E. Fildes
- The Ex-Vivo Research Centre CIC, Alderley Park, Macclesfield, United Kingdom
- The Healthcare Technologies Institute, School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom
| |
Collapse
|
|
13
|
Karczewski AM, Zeng W, Stratchko LM, Bachus KN, Poore SO, Dingle AM. Clinical Basis for Creating an Osseointegrated Neural Interface. Front Neurosci 2022; 16:828593. [PMID: 35495044 PMCID: PMC9039253 DOI: 10.3389/fnins.2022.828593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 03/16/2022] [Indexed: 11/13/2022] Open
Abstract
As technology continues to improve within the neuroprosthetic landscape, there has been a paradigm shift in the approach to amputation and surgical implementation of haptic neural prosthesis for limb restoration. The Osseointegrated Neural Interface (ONI) is a proposed solution involving the transposition of terminal nerves into the medullary canal of long bones. This design combines concepts of neuroma formation and prevention with osseointegration to provide a stable environment for conduction of neural signals for sophisticated prosthetic control. While this concept has previously been explored in animal models, it has yet to be explored in humans. This anatomic study used three upper limb and three lower limb cadavers to assess the clinical feasibility of creating an ONI in humans. Anatomical measurement of the major peripheral nerves- circumference, length, and depth- were performed as they are critical for electrode design and rerouting of the nerves into the long bones. CT imaging was used for morphologic bone evaluation and virtual implantation of two osseointegrated implants were performed to assess the amount of residual medullary space available for housing the neural interfacing hardware. Use of a small stem osseointegrated implant was found to reduce bone removal and provide more intramedullary space than a traditional implant; however, the higher the amputation site, the less medullary space was available regardless of implant type. Thus the stability of the endoprosthesis must be maximized while still maintaining enough residual space for the interface components. The results from this study provide an anatomic basis required for establishing a clinically applicable ONI in humans. They may serve as a guide for surgical implementation of an osseointegrated endoprosthesis with intramedullary electrodes for prosthetic control.
Collapse
Affiliation(s)
- Alison M. Karczewski
- Division of Plastic Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Weifeng Zeng
- Division of Plastic Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Lindsay M. Stratchko
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Kent N. Bachus
- George E. Wahlen Department of Veterans Affairs Medical Center and the Department of Orthopaedics, University of Utah Orthopaedic Center, Salt Lake City, UT, United States
| | - Samuel O. Poore
- Division of Plastic Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Aaron M. Dingle
- Division of Plastic Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| |
Collapse
|
|
14
|
Žiga S, Igor S, Urša M, Plut D, Erika C, Gregor O. Median and ulnar nerve fascicle imaging using MR microscopy and high-resolution ultrasound. J Neuroimaging 2022; 32:420-429. [PMID: 35229399 DOI: 10.1111/jon.12982] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 02/10/2022] [Accepted: 02/14/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND AND PURPOSE Understanding nerve microanatomy is important as different neuropathies and some nerve neoplasms present with fascicle enlargement. The aim of our study was to gain clinically oriented knowledge on nerve fascicular anatomy using imaging modalities. METHODS On a cadaveric upper extremity, high-resolution ultrasound (HRUS) scan with 22 MHz probe was performed. Sections of the median and ulnar nerves were excised at the level of the distal arm and after magnetic resonance microscopy (MRM), histological cross-sections (HCS) were prepared. Cross-referencing of the MRM and HRUS images with HCS was performed. Fascicle and nerve contouring was performed with morphometric software in order to assess nerve and fascicular cross-sectional area (CSA), fascicle count, and interfascicular distances. Based on fascicle differentiation, factual fascicle (FF) group and fascicular cluster (FC) group were defined. RESULTS On the cross-referenced imaging material, fascicles were differentiated in 92.7% on MRM and in 57.3% on HRUS. High to very high positive correlation among imaging material was observed for the fascicle CSA. FF depiction was 30.1% on HRUS. In comparison to the FF group, the FC group had significantly larger fascicle CSA and shorter interfascicular distances. DISCUSSION The findings of our study contribute to understanding of fascicle depiction on imaging modalities. HRUS offers good visualization of fascicles. The capability of differentiating fascicles is modality specific and depends on the fascicle CSA and the amount of interfascicular epineurium.
Collapse
Affiliation(s)
- Snoj Žiga
- Radiology Institute, University Medical Centre Ljubljana, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Serša Igor
- Department of Condensed Matter Physics, Jožef Stefan Institute, 1000 Ljubljana, Slovenia
| | - Matičič Urša
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Domen Plut
- Radiology Institute, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Cvetko Erika
- Institute of Anatomy, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Omejec Gregor
- Institute of Clinical Neurophysiology, Division of Neurology, University Medical Center Ljubljana, Ljubljana, Slovenia
| |
Collapse
|
|
15
|
Losanno E, Badi M, Wurth S, Borgognon S, Courtine G, Capogrosso M, Rouiller EM, Micera S. Bayesian optimization of peripheral intraneural stimulation protocols to evoke distal limb movements. J Neural Eng 2021; 18. [PMID: 34874320 DOI: 10.1088/1741-2552/ac3f6c] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 12/02/2021] [Indexed: 11/12/2022]
Abstract
Objective.Motor neuroprostheses require the identification of stimulation protocols that effectively produce desired movements. Manual search for these protocols can be very time-consuming and often leads to suboptimal solutions, as several stimulation parameters must be personalized for each subject for a variety of target motor functions. Here, we present an algorithm that efficiently tunes peripheral intraneural stimulation protocols to elicit functionally relevant distal limb movements.Approach.We developed the algorithm using Bayesian optimization (BO) with multi-output Gaussian Processes (GPs) and defined objective functions based on coordinated muscle recruitment. We applied the algorithm offline to data acquired in rats for walking control and in monkeys for hand grasping control and compared different GP models for these two systems. We then performed a preliminary online test in a monkey to experimentally validate the functionality of our method.Main results.Offline, optimal intraneural stimulation protocols for various target motor functions were rapidly identified in both experimental scenarios. Using the model that performed best, the algorithm converged to stimuli that evoked functionally consistent movements with an average number of actions equal to 20% of the search space size in both the rat and monkey animal models. Online, the algorithm quickly guided the observations to stimuli that elicited functional hand gestures, although more selective motor outputs could have been achieved by refining the objective function used.Significance.These results demonstrate that BO can reliably and efficiently automate the tuning of peripheral neurostimulation protocols, establishing a translational framework to configure peripheral motor neuroprostheses in clinical applications. The proposed method can also potentially be applied to optimize motor functions using other stimulation modalities.
Collapse
Affiliation(s)
- E Losanno
- The Biorobotics Institute and Department of Excellent in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy
| | - M Badi
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - S Wurth
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| | - S Borgognon
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland.,Center for Neuroprosthetics and BrainMind Institute, School of Life Sciences, Eécole Polytechnique Feédeérale de Lausanne (EPFL), Lausanne, Switzerland
| | - G Courtine
- Center for Neuroprosthetics and BrainMind Institute, School of Life Sciences, Eécole Polytechnique Feédeérale de Lausanne (EPFL), Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL, University Hospital of Lausanne (CHUV) and University of Lausanne (UNIL), Lausanne, Switzerland
| | - M Capogrosso
- Department of Neurological Surgery, Rehabilitation and Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA, United States of America
| | - E M Rouiller
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, Fribourg, Switzerland
| | - S Micera
- The Biorobotics Institute and Department of Excellent in Robotics and AI, Scuola Superiore Sant'Anna, Pisa, Italy.,Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
| |
Collapse
|
|
16
|
New Stimulation Device to Drive Multiple Transverse Intrafascicular Electrodes and Achieve Highly Selective and Rich Neural Responses. SENSORS 2021; 21:s21217219. [PMID: 34770527 PMCID: PMC8587292 DOI: 10.3390/s21217219] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 10/24/2021] [Accepted: 10/26/2021] [Indexed: 11/25/2022]
Abstract
Peripheral Nerve Stimulation (PNS) is a promising approach in functional restoration following neural impairments. Although it proves to be advantageous in the number of implantation sites provided compared with intramuscular or epimysial stimulation and the fact that it does not require daily placement, as is the case with surface electrodes, the further advancement of PNS paradigms is hampered by the limitation of spatial selectivity due to the current spread and variations of nerve physiology. New electrode designs such as the Transverse Intrafascicular Multichannel Electrode (TIME) were proposed to resolve this issue, but their use was limited by a lack of innovative multichannel stimulation devices. In this study, we introduce a new portable multichannel stimulator—called STIMEP—and implement different stimulation protocols in rats to test its versatility and unveil the potential of its combined use with TIME electrodes in rehabilitation protocols. We developed and tested various stimulation paradigms in a single fascicle and thereafter implanted two TIMEs. We also tested its stimulation using two different waveforms. The results highlighted the versatility of this new stimulation device and advocated for the parameterizing of a hyperpolarizing phase before depolarization as well as the use of small pulse widths when stimulating with multiple electrodes.
Collapse
|
|
17
|
Badi M, Wurth S, Scarpato I, Roussinova E, Losanno E, Bogaard A, Delacombaz M, Borgognon S, C Vanc Ara P, Fallegger F, Su DK, Schmidlin E, Courtine G, Bloch J, Lacour SP, Stieglitz T, Rouiller EM, Capogrosso M, Micera S. Intrafascicular peripheral nerve stimulation produces fine functional hand movements in primates. Sci Transl Med 2021; 13:eabg6463. [PMID: 34705521 DOI: 10.1126/scitranslmed.abg6463] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
[Figure: see text].
Collapse
Affiliation(s)
- Marion Badi
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics, and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
| | - Sophie Wurth
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics, and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
| | - Ilaria Scarpato
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics, and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
| | - Evgenia Roussinova
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics, and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland
| | - Elena Losanno
- Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, 56025 Pisa, Italy
| | - Andrew Bogaard
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
| | - Maude Delacombaz
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
| | - Simon Borgognon
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.,Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland
| | - Paul C Vanc Ara
- Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center Freiburg, and BrainLinks-BrainTools Center, University of Freiburg, 79110 Freiburg, Germany
| | - Florian Fallegger
- Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, 1202 Geneva, Switzerland
| | - David K Su
- Neurological Surgery, Harborview Medical Center, Seattle, WA 98104, USA
| | - Eric Schmidlin
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
| | - Grégoire Courtine
- Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, EPFL, 1015 Lausanne, Switzerland.,Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL, University Hospital of Lausanne (CHUV), and University of Lausanne (UNIL), 1015 Lausanne, Switzerland
| | - Jocelyne Bloch
- Defitech Center for Interventional Neurotherapies (NeuroRestore), EPFL, University Hospital of Lausanne (CHUV), and University of Lausanne (UNIL), 1015 Lausanne, Switzerland
| | - Stéphanie P Lacour
- Bertarelli Foundation Chair in Neuroprosthetic Technology, Laboratory for Soft Bioelectronics Interface, Institute of Microengineering, Institute of Bioengineering, Centre for Neuroprosthetics, 1202 Geneva, Switzerland
| | - Thomas Stieglitz
- Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center Freiburg, and BrainLinks-BrainTools Center, University of Freiburg, 79110 Freiburg, Germany
| | - Eric M Rouiller
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland
| | - Marco Capogrosso
- Department of Neuroscience and Movement Sciences, Platform of Translational Neurosciences, Section of Medicine, Faculty of Sciences and Medicine, University of Fribourg, 1700 Fribourg, Switzerland.,Department of Neurological Surgery, Rehabilitation and Neural Engineering Laboratories, University of Pittsburgh, Pittsburgh, PA 15213, USA
| | - Silvestro Micera
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics, and Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.,Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant'Anna, 56025 Pisa, Italy
| |
Collapse
|
|
18
|
Zhou X, Du J, Qing L, Mee T, Xu X, Wang Z, Xu C, Jia X. Identification of sensory and motor nerve fascicles by immunofluorescence staining after peripheral nerve injury. J Transl Med 2021; 19:207. [PMID: 33985539 PMCID: PMC8117274 DOI: 10.1186/s12967-021-02871-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 05/03/2021] [Indexed: 11/25/2022] Open
Abstract
Background Inappropriate matching of motor and sensory fibers after nerve repair or nerve grafting can lead to failure of nerve recovery. Identification of motor and sensory fibers is important for the development of new approaches that facilitate neural regeneration and the next generation of nerve signal-controlled neuro-prosthetic limbs with sensory feedback technology. Only a few methods have been reported to differentiate sensory and motor nerve fascicles, and the reliability of these techniques is unknown. Immunofluorescence staining is one of the most commonly used methods to distinguish sensory and motor nerve fibers, however, its accuracy remains unknown. Methods In this study, we aim to determine the efficacy of popular immunofluorescence markers for motor and sensory nerve fibers. We harvested the facial (primarily motor fascicles) and sural (primarily sensory fascicles) nerves in rats, and examined the immunofluorescent staining expressions of motor markers (choline acetyltransferase (ChAT), tyrosine kinase (TrkA)), and sensory markers [neurofilament protein 200 kDa (NF-200), calcitonin gene-related peptide (CGRP) and Transient receptor potential vanillic acid subtype 1 (TRPV1)]. Three methods, including the average area percentage, the mean gray value, and the axon count, were used to quantify the positive expression of nerve markers in the immunofluorescence images. Results Our results suggest the mean gray value method is the most reliable method. The mean gray value of immunofluorescence in ChAT (63.0 ± 0.76%) and TRKA (47.6 ± 0.43%) on the motor fascicles was significantly higher than that on the sensory fascicles (ChAT: 49.2 ± 0.72%, P < 0.001; and TRKA: 29.1 ± 0.85%, P < 0.001). Additionally, the mean gray values of TRPV1 (51.5 ± 0.83%), NF-200 (61.5 ± 0.62%) and CGRP (37.7 ± 1.22%) on the motor fascicles were significantly lower than that on the sensory fascicles respectively (71.9 ± 2.32%, 69.3 ± 0.46%, and 54.3 ± 1.04%) (P < 0.001). The most accurate cutpoint occurred using CHAT/CRCP ratio, where a value of 0.855 had 100% sensitivity and 100% specificity to identify motor and sensory nerve with an area under the ROC curve of 1.000 (P < 0.001). Conclusions A combination of ChAT and CGRP is suggested to distinguish motor and sensory nerve fibers.
Collapse
Affiliation(s)
- Xijie Zhou
- Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children'S Hospital of Wenzhou Medical University, Wenzhou, 325027, China.,Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Jian Du
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Liming Qing
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Thomas Mee
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Xiang Xu
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Zhuoran Wang
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Cynthia Xu
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA
| | - Xiaofeng Jia
- Department of Neurosurgery, University of Maryland School of Medicine, 10 South Pine Street, MSTF Building 823, Baltimore, MD, 21201, USA. .,Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. .,Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. .,Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. .,Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
| |
Collapse
|
|
19
|
Niu Y, Stadler FJ, Fu M. Biomimetic electrospun tubular PLLA/gelatin nanofiber scaffold promoting regeneration of sciatic nerve transection in SD rat. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 121:111858. [PMID: 33579490 DOI: 10.1016/j.msec.2020.111858] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 12/07/2020] [Accepted: 12/27/2020] [Indexed: 01/08/2023]
Abstract
The micro- or nanoscale surface morphology of the tissue engineering nerve guidance scaffold (NGS) will affect different cell behaviors, such as their growth rate, migration, and matrix secretion. Although different technologies for manufacturing scaffolds with biomimetic topography have been established, most of them tend to be high cost and long preparation time. Here we have prepared a biomimetic NGS with physical properties to simulate native nerve tissue more accurately. We used poly(l-lactic acid) (PLLA) nanofibers doped with gelatin to prepare a biomimetic NGS whose structure mimics the native epineurium layer. By adjusting the doping ratio of gelatin and PLLA in the tubular scaffold, the bionic scaffold's surface morphology and mechanical properties are closer to native tissues. In vitro cell scaffold interaction experiments demonstrated that the PLLA/gelatin nanofibers could significantly promote the elongation, proliferation, and the secretion of glial cell-derived neurotrophic factor (GDNF) of RSC96 Schwann cells (SCs), as well as the diffusion of GDNF. In vivo scaffold replacement of SD rat, sciatic nerves showed that the nerve guide scaffold composed of PLLA/gelatin nanofibers was helpful to the myelination of SCs and the remolding of epineurium in the injured area, which could effectively rehabilitate the motor and sensory functions of the injured nerve and prevent the atrophy of the target muscle tissue. This study showed that the synergistic impact of nano topographical and biochemical clues on designing biomimetic scaffolds could efficiently promote regenerating nerve tissue.
Collapse
Affiliation(s)
- Yuqing Niu
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
| | - Florian J Stadler
- Nanshan District Key Lab for Biopolymers and Safety Evaluation, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen 518055, China
| | - Ming Fu
- Department of Pediatric Surgery, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| |
Collapse
|
|
20
|
George JA, Page DM, Davis TS, Duncan CC, Hutchinson DT, Rieth LW, Clark GA. Long-term performance of Utah slanted electrode arrays and intramuscular electromyographic leads implanted chronically in human arm nerves and muscles. J Neural Eng 2020; 17:056042. [PMID: 33045689 DOI: 10.1088/1741-2552/abc025] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
OBJECTIVE We explore the long-term performance and stability of seven percutaneous Utah Slanted Electrode Arrays (USEAs) and intramuscular recording leads (iEMGs) implanted chronically in the residual arm nerves and muscles of three human participants as a means to permanently restore sensorimotor function after transradial amputations. APPROACH We quantify the number of functional recording and functional stimulating electrodes over time. We also calculate the signal-to-noise ratio (SNR) of USEA and iEMG recordings and quantify the stimulation current necessary to evoke detectable sensory percepts. Furthermore, we quantify the consistency of the sensory modality, receptive field location, and receptive field size of USEA-evoked percepts. MAIN RESULTS In the most recent subject, involving USEAs with technical improvements, neural recordings persisted for 502 d (entire implant duration) and the number of functional recording electrodes for one USEA increased over time. However, for six out of seven USEAs across the three participants, the number of functional recording electrodes decreased within the first 2 months after implantation. The SNR of neural recordings and electromyographic recordings stayed relatively consistent over time. Sensory percepts were consistently evoked over the span of 14 months, were not significantly different in size, and highlighted the nerves' fascicular organization. The percentage of percepts with consistent modality or consistent receptive field location between sessions (∼1 month apart) varied between 0%-86.2% and 9.1%-100%, respectively. Stimulation thresholds and electrode impedances increased initially but then remained relatively stable over time. SIGNIFICANCE This work demonstrates improved performance of USEAs, and provides a basis for comparing the longevity and stability of USEAs to that of other neural interfaces. USEAs provide a rich repertoire of neural recordings and sensory percepts. Although their performance still generally declines over time, functionality can persist long-term. Future work should leverage the results presented here to further improve USEA design or to develop adaptive algorithms that can maintain a high level of performance.
Collapse
Affiliation(s)
- Jacob A George
- Physical Medicine & Rehabilitation, University of Utah, Salt Lake City, United States of America
| | | | | | | | | | | | | |
Collapse
|
|
21
|
Tutorial: a computational framework for the design and optimization of peripheral neural interfaces. Nat Protoc 2020; 15:3129-3153. [DOI: 10.1038/s41596-020-0377-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 06/15/2020] [Indexed: 01/05/2023]
|
|
22
|
Vu PP, Chestek CA, Nason SR, Kung TA, Kemp SW, Cederna PS. The future of upper extremity rehabilitation robotics: research and practice. Muscle Nerve 2020; 61:708-718. [PMID: 32413247 PMCID: PMC7868083 DOI: 10.1002/mus.26860] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 03/03/2020] [Accepted: 03/03/2020] [Indexed: 01/14/2023]
Abstract
The loss of upper limb motor function can have a devastating effect on people's lives. To restore upper limb control and functionality, researchers and clinicians have developed interfaces to interact directly with the human body's motor system. In this invited review, we aim to provide details on the peripheral nerve interfaces and brain-machine interfaces that have been developed in the past 30 years for upper extremity control, and we highlight the challenges that still remain to transition the technology into the clinical market. The findings show that peripheral nerve interfaces and brain-machine interfaces have many similar characteristics that enable them to be concurrently developed. Decoding neural information from both interfaces may lead to novel physiological models that may one day fully restore upper limb motor function for a growing patient population.
Collapse
Affiliation(s)
- Philip P. Vu
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
- Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan
| | - Cynthia A. Chestek
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
- Robotics Institute, University of Michigan, Ann Arbor, Michigan
- Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan
- Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan
| | - Samuel R. Nason
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
| | - Theodore A. Kung
- Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan
| | - Stephen W.P. Kemp
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
- Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan
| | - Paul S. Cederna
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan
- Section of Plastic Surgery, University of Michigan, Ann Arbor, Michigan
| |
Collapse
|
|
23
|
Tigra W, Dali M, William L, Fattal C, Gélis A, Divoux JL, Coulet B, Teissier J, Guiraud D, Azevedo Coste C. Selective neural electrical stimulation restores hand and forearm movements in individuals with complete tetraplegia. J Neuroeng Rehabil 2020; 17:66. [PMID: 32429963 PMCID: PMC7236876 DOI: 10.1186/s12984-020-00676-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 04/01/2020] [Indexed: 11/15/2022] Open
Abstract
Background We hypothesized that a selective neural electrical stimulation of radial and median nerves enables the activation of functional movements in the paralyzed hand of individuals with tetraplegia. Compared to previous approaches for which up to 12 muscles were targeted through individual muscular stimulations, we focused on minimizing the number of implanted electrodes however providing almost all the needed and useful hand movements for subjects with complete tetraplegia. Methods We performed acute experiments during scheduled surgeries of the upper limb with eligible subjects. We scanned a set of multicontact neural stimulation cuff electrode configurations, pre-computed through modeling simulations. We reported the obtained isolated and functional movements that were considered useful for the subject (different grasping movements). Results In eight subjects, we demonstrated that selective stimulation based on multicontact cuff electrodes and optimized current spreading over the active contacts provided isolated, compound, functional and strong movements; most importantly 3 out of 4 had isolated fingers or thumb flexion, one patient performed a Key Grip, another one the Power and Hook Grips, and the 2 last all the 3 Grips. Several configurations were needed to target different areas within the nerve to obtain all the envisioned movements. We further confirmed that the upper limb nerves have muscle specific fascicles, which makes it possible to activate isolated movements. Conclusions The future goal is to provide patients with functional restoration of object grasping and releasing with a minimally invasive solution: only two cuff electrodes above the elbow. Ethics Committee / ANSM clearance prior to the beginning of the study (inclusion period 2016–2018): CPP Sud Méditerranée, #ID-RCB:2014-A01752–45, first acceptance 10th of February 2015, amended 12th of January 2016. Trial registration (www.clinicaltrials.gov): #NCT03721861, Retrospectively registered on 26th of October 2018.
Collapse
Affiliation(s)
- Wafa Tigra
- INRIA, University of Montpellier, CNRS, Montpellier, France.,MXM group, Sophia-Antipolis, France
| | - Mélissa Dali
- INRIA, University of Montpellier, CNRS, Montpellier, France
| | - Lucie William
- INRIA, University of Montpellier, CNRS, Montpellier, France
| | - Charles Fattal
- La Châtaigneraie Rehabilitation Center, Menucourt, France
| | | | | | | | | | - David Guiraud
- INRIA, University of Montpellier, CNRS, Montpellier, France. .,NEURINNOV SAS, Montpellier, France.
| | | |
Collapse
|
|
24
|
Tovbis D, Agur A, Mogk JPM, Zariffa J. Automatic three-dimensional reconstruction of fascicles in peripheral nerves from histological images. PLoS One 2020; 15:e0233028. [PMID: 32407341 PMCID: PMC7224505 DOI: 10.1371/journal.pone.0233028] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Accepted: 04/27/2020] [Indexed: 11/24/2022] Open
Abstract
Computational studies can be used to support the development of peripheral nerve interfaces, but currently use simplified models of nerve anatomy, which may impact the applicability of simulation results. To better quantify and model neural anatomy across the population, we have developed an algorithm to automatically reconstruct accurate peripheral nerve models from histological cross-sections. We acquired serial median nerve cross-sections from human cadaveric samples, staining one set with hematoxylin and eosin (H&E) and the other using immunohistochemistry (IHC) with anti-neurofilament antibody. We developed a four-step processing pipeline involving registration, fascicle detection, segmentation, and reconstruction. We compared the output of each step to manual ground truths, and additionally compared the final models to commonly used extrusions, via intersection-over-union (IOU). Fascicle detection and segmentation required the use of a neural network and active contours in H&E-stained images, but only simple image processing methods for IHC-stained images. Reconstruction achieved an IOU of 0.42±0.07 for H&E and 0.37±0.16 for IHC images, with errors partially attributable to global misalignment at the registration step, rather than poor reconstruction. This work provides a quantitative baseline for fully automatic construction of peripheral nerve models. Our models provided fascicular shape and branching information that would be lost via extrusion.
Collapse
Affiliation(s)
- Daniel Tovbis
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- KITE, Toronto Rehab, University Health Network, Toronto, Ontario, Canada
| | - Anne Agur
- Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, Ontario, Canada
| | - Jeremy P. M. Mogk
- Division of Anatomy, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - José Zariffa
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada
- KITE, Toronto Rehab, University Health Network, Toronto, Ontario, Canada
- Rehabilitation Sciences Institute, University of Toronto, Toronto, Ontario, Canada
- Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, Ontario, Canada
| |
Collapse
|
|
25
|
Wei S, Hu Q, Cheng X, Ma J, Liang X, Peng J, Xu W, Sun X, Han G, Ma X, Wang Y. Differences in the Structure and Protein Expression of Femoral Nerve Branches in Rats. Front Neuroanat 2020; 14:16. [PMID: 32322192 PMCID: PMC7156789 DOI: 10.3389/fnana.2020.00016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 03/18/2020] [Indexed: 11/13/2022] Open
Affiliation(s)
- Shuai Wei
- Tianjin Hospital Tianjin University, Tianjin, China
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Qian Hu
- Department of Geriatrics, The Second People’s Hospital of Nantong, Nantong, China
| | - Xiaoqing Cheng
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Jianxiong Ma
- Tianjin Hospital Tianjin University, Tianjin, China
| | - Xuezhen Liang
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Shandong, China
| | - Jiang Peng
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
| | - Wenjing Xu
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Xun Sun
- Tianjin Hospital Tianjin University, Tianjin, China
| | - Gonghai Han
- The First People’s Hospital of Yunnan Province, Kunming, China
| | - Xinlong Ma
- Tianjin Hospital Tianjin University, Tianjin, China
- *Correspondence: Xinlong Ma Yu Wang
| | - Yu Wang
- Institute of Orthopedics, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China
- *Correspondence: Xinlong Ma Yu Wang
| |
Collapse
|
|
26
|
Rugel CL, Franz CK, Lee SSM. Influence of limb position on assessment of nerve mechanical properties by using shear wave ultrasound elastography. Muscle Nerve 2020; 61:616-622. [PMID: 32086830 DOI: 10.1002/mus.26842] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Revised: 02/17/2020] [Accepted: 02/18/2020] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Evaluation of nerve mechanical properties has the potential to improve assessment of nerve impairment. Shear wave velocity, as measured by using shear wave (SW) ultrasound elastography, is a promising indicator of nerve mechanical properties such as stiffness. However, elucidation of external factors that influence SW velocity, particularly nerve tension, is required for accurate interpretations. METHODS Median and ulnar nerve SW velocities were measured at proximal and distal locations with limb positions that indirectly altered nerve tension. RESULTS Shear wave velocity was greater at proximal and distal locations for limb positions that induced greater tension in the median (mean increase proximal 89.3%, distal 64%) and ulnar (mean increase proximal 91.1%, distal 37.4%) nerves. DISCUSSION Due to the influence of nerve tension when SW ultrasound elastography is used, careful consideration must be given to limb positioning.
Collapse
Affiliation(s)
- Chelsea L Rugel
- Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Colin K Franz
- Department of Physical Medicine and Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,The Ken & Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Shirley Ryan AbilityLab, Chicago, Illinois
| | - Sabrina S M Lee
- Department of Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| |
Collapse
|
|
27
|
Raspopovic S, Cimolato A, Panarese A, Vallone F, Del Valle J, Micera S, Navarro X. Neural signal recording and processing in somatic neuroprosthetic applications. A review. J Neurosci Methods 2020; 337:108653. [PMID: 32114143 DOI: 10.1016/j.jneumeth.2020.108653] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 11/30/2019] [Accepted: 02/26/2020] [Indexed: 12/11/2022]
Abstract
Neurointerfaces have acquired major relevance as both rehabilitative and therapeutic tools for patients with spinal cord injury, limb amputations and other neural disorders. Bidirectional neural interfaces are a key component for the functional control of neuroprosthetic devices. The two main neuroprosthetic applications of interfaces with the peripheral nervous system (PNS) are: the refined control of artificial prostheses with sensory neural feedback, and functional electrical stimulation (FES) systems attempting to generate motor or visceral responses in paralyzed organs. The results obtained in experimental and clinical studies with both, extraneural and intraneural electrodes are very promising in terms of the achieved functionality for the neural stimulation mode. However, the results of neural recordings with peripheral nerve interfaces are more limited. In this paper we review the different existing approaches for PNS signals recording, denoising, processing and classification, enabling their use for bidirectional interfaces. PNS recordings can provide three types of signals: i) population activity signals recorded by using extraneural electrodes placed on the outer surface of the nerve, which carry information about cumulative nerve activity; ii) spike activity signals recorded with intraneural electrodes placed inside the nerve, which carry information about the electrical activity of a set of individual nerve fibers; and iii) hybrid signals, which contain both spiking and cumulative signals. Finally, we also point out some of the main limitations, which are hampering clinical translation of neural decoding, and indicate possible solutions for improvement.
Collapse
Affiliation(s)
- Stanisa Raspopovic
- Neuroengineering Lab, Department of Health Sciences and Technology, Institute for Robotics and Intelligent Systems, ETH Zürich, 8092, Zürich, Switzerland
| | - Andrea Cimolato
- Neuroengineering Lab, Department of Health Sciences and Technology, Institute for Robotics and Intelligent Systems, ETH Zürich, 8092, Zürich, Switzerland; NEARLab - Neuroengineering and Medical Robotics Laboratory, DEIB Department of Electronics, Information and Bioengineering, Politecnico Di Milano, 20133, Milano, Italy; IIT Central Research Labs Genova, Istituto Italiano Tecnologia, 16163, Genova, Italy
| | | | - Fabio Vallone
- The BioRobotics Institute, Scuola Superiore Sant'Anna, I-56127, Pisa, Italy
| | - Jaume Del Valle
- Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma De Barcelona, CIBERNED, 08193, Bellaterra, Spain
| | - Silvestro Micera
- The BioRobotics Institute, Scuola Superiore Sant'Anna, I-56127, Pisa, Italy; Translational Neural Engineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, Ecole Polytechnique Federale De Lausanne, Lausanne, CH-1015, Switzerland.
| | - Xavier Navarro
- Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma De Barcelona, CIBERNED, 08193, Bellaterra, Spain; Institut Guttmann De Neurorehabilitació, Badalona, Spain.
| |
Collapse
|
|
28
|
Soubeyrand M, Melhem R, Protais M, Artuso M, Crézé M. Anatomy of the median nerve and its clinical applications. HAND SURGERY & REHABILITATION 2020; 39:2-18. [DOI: 10.1016/j.hansur.2019.10.197] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 09/25/2019] [Accepted: 10/28/2019] [Indexed: 12/11/2022]
|
|
29
|
Customized Scaffold Design Based on Natural Peripheral Nerve Fascicle Characteristics for Biofabrication in Tissue Regeneration. BIOMED RESEARCH INTERNATIONAL 2020; 2019:3845780. [PMID: 31915690 PMCID: PMC6935460 DOI: 10.1155/2019/3845780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 07/21/2019] [Accepted: 08/31/2019] [Indexed: 12/21/2022]
Abstract
Objective The use of a biofabrication nerve scaffold, which mimics the nerve microstructure, as an alternative for autologous nerve transplantation is a promising strategy for treating peripheral nerve defects. This study aimed to design a customized biofabrication scaffold model with the characteristics of human peripheral nerve fascicles. Methods We used Micro-MRI technique to obtain different nerve fascicles. A full-length 28 cm tibial nerve specimen was obtained and was divided into 14 two-centimetre nerve segments. 3D models of the nerve fascicles were obtained by three-dimensional reconstruction after image segmentation. The central line of the nerve fascicles was fitted, and the aggregation of nerve fascicles was analysed quantitatively. The nerve scaffold was designed by simulating the clinical nerve defect and extracting information from the acquired nerve fascicle data; the scaffold design was displayed by 3D printing to verify the accuracy of the model. Result The microstructure of the sciatic nerve, tibial nerve, and common peroneal nerve in the nerve fascicles could be obtained by three-dimensional reconstruction. The number of cross fusions of tibial nerve fascicles from proximal end to distal end decreased gradually. By designing the nerve graft in accordance with the microstructure of the nerve fascicles, the 3D printed model demonstrated that the two ends of the nerve defect can be well matched. Conclusion The microstructure of the nerve fascicles is complicated and changeable, and the spatial position of each nerve fascicle and the long segment of the nerve fascicle aggregation show great changes at different levels. Under the premise of the stability of the existing imaging techniques, a large number of scanning nerve samples can be used to set up a three-dimensional database of the peripheral nerve fascicle microstructure, integrating the gross imaging information, and provide a template for the design of the downstream nerve graft model.
Collapse
|
|
30
|
Overstreet CK, Cheng J, Keefer EW. Fascicle specific targeting for selective peripheral nerve stimulation. J Neural Eng 2019; 16:066040. [PMID: 31509815 DOI: 10.1088/1741-2552/ab4370] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Electrical stimulation is a blunt tool for evoking neural activity. Neurons are naturally activated asynchronously and non-uniformly, whereas stimulation drives simultaneous activity within a population of cells. These differences in activation pattern can result in unintended side effects, including muddled sensory percepts and undesirable muscle contractions. These effects can be mitigated by the placement of electrodes in close approximation to nerve fibers and careful selection of the neural interface's location. This work describes the benefits of placing electrodes within specific fascicles of peripheral nerve to form selective neural interfaces for bidirectional neuroprosthetic devices. APPROACH Chronic electrodes were targeted to individual fascicles of the ulnar and median nerves in the forearm of four human subjects. During the surgical implant procedure, fascicles were dissected from each nerve, and functional testing was used to identify the relative composition of sensory and motor fibers within each. FAST-LIFE arrays, composed of longitudinal intrafascicular arrays and fascicular cuff electrodes, were implanted in each fascicle. The location, quality, and stimulation parameters associated with sensations evoked by electrical stimulation on these electrodes were characterized throughout the 90-180 d implant period. MAIN RESULTS FAST-LIFE arrays enable selective and chronic electrical stimulation of individual peripheral nerve fascicles. The quality of sensations evoked by stimulation in each fascicle is predictable and distinct; subjects reported tactile and cutaneous sensations during stimulation of sensory fascicles and deeper proprioceptive sensations during stimulation of motor fascicles. Stimulation thresholds and strength-duration time constants were typically higher within sensory fascicles. SIGNIFICANCE Highly selective, stable neural interfaces can be created by placing electrodes within and around single fascicles of peripheral nerves. This method enables targeting electrodes to nerve fibers that innervate a specific body region or have specific functions. Fascicle-specific interfacing techniques have broad potential to maximize the therapeutic effects of electrical stimulation in many neuromodulation applications. (Clinical Trial ID NCT02994160.).
Collapse
|
|
31
|
Wang J, Wang H, Lee C. Mechanism and Applications of Electrical Stimulation Disturbance on Motoneuron Excitability Studied Using Flexible Intramuscular Electrode. ACTA ACUST UNITED AC 2019; 3:e1800281. [DOI: 10.1002/adbi.201800281] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 04/17/2019] [Indexed: 12/28/2022]
Affiliation(s)
- Jiahui Wang
- Department of Electrical & Computer EngineeringNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
- Singapore Institute for Neurotechnology (SINAPSE)National University of Singapore 28 Medical Drive, #05‐COR Singapore 117456 Singapore
- Center for Intelligent Sensors and MEMSNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
| | - Hao Wang
- Department of Electrical & Computer EngineeringNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
- Center for Intelligent Sensors and MEMSNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
| | - Chengkuo Lee
- Department of Electrical & Computer EngineeringNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
- Singapore Institute for Neurotechnology (SINAPSE)National University of Singapore 28 Medical Drive, #05‐COR Singapore 117456 Singapore
- Center for Intelligent Sensors and MEMSNational University of Singapore 4 Engineering Drive 3 Singapore 117576 Singapore
| |
Collapse
|
|
32
|
A Quantitative Investigation on the Peripheral Nerve Response within the Small Strain Range. APPLIED SCIENCES-BASEL 2019. [DOI: 10.3390/app9061115] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Peripheral nerves are very complex biological structures crucial to linking the central nervous system to the periphery of the body. However, their real behaviour is partially unknown because of the intrinsic difficulty of studying these structures in vivo. As a consequence, theoretical and computational tools together with in vitro experiments are widely used to approximate the mechanical response of the peripheral nervous tissue to different kind of solicitations. More specifically, particular conditions narrow the mechanical response of peripheral nerves within the small strain regime. Therefore, in this work, the mechanical response of nerves was investigated through the study of the relationships among strain, stress and displacements within the small strain range. Theoretical predictions were quantitatively compared to experimental evidences, while the displacement field was studied for different values of the tissue compressibility. This framework provided a straightforward computational assessment of the nerve response, which was needed to design suitable connections to biomaterials or neural interfaces within the small strain range.
Collapse
|
|
33
|
Clemente F, Valle G, Controzzi M, Strauss I, Iberite F, Stieglitz T, Granata G, Rossini PM, Petrini F, Micera S, Cipriani C. Intraneural sensory feedback restores grip force control and motor coordination while using a prosthetic hand. J Neural Eng 2019; 16:026034. [DOI: 10.1088/1741-2552/ab059b] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
|
|
34
|
Petrini FM, Valle G, Strauss I, Granata G, Di Iorio R, D'Anna E, Čvančara P, Mueller M, Carpaneto J, Clemente F, Controzzi M, Bisoni L, Carboni C, Barbaro M, Iodice F, Andreu D, Hiairrassary A, Divoux JL, Cipriani C, Guiraud D, Raffo L, Fernandez E, Stieglitz T, Raspopovic S, Rossini PM, Micera S. Six-Month Assessment of a Hand Prosthesis with Intraneural Tactile Feedback. Ann Neurol 2018; 85:137-154. [DOI: 10.1002/ana.25384] [Citation(s) in RCA: 101] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2018] [Revised: 11/15/2018] [Accepted: 11/15/2018] [Indexed: 11/12/2022]
Affiliation(s)
- Francesco M. Petrini
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering; Swiss Federal Institute of Technology of Lausanne (EPFL); Lausanne Switzerland
| | - Giacomo Valle
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering; Swiss Federal Institute of Technology of Lausanne (EPFL); Lausanne Switzerland
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - Ivo Strauss
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering; Swiss Federal Institute of Technology of Lausanne (EPFL); Lausanne Switzerland
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - Giuseppe Granata
- Institute of Neurology; Catholic University; Rome Italy
- Department of Geriatrics, Neuroscience, and Orthopedics; Policlinic A. Gemelli Foundation-IRCCS; Rome Italy
| | - Riccardo Di Iorio
- Institute of Neurology; Catholic University; Rome Italy
- Department of Geriatrics, Neuroscience, and Orthopedics; Policlinic A. Gemelli Foundation-IRCCS; Rome Italy
| | - Edoardo D'Anna
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering; Swiss Federal Institute of Technology of Lausanne (EPFL); Lausanne Switzerland
| | - Paul Čvančara
- Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center Freiburg and BrainLinks-BrainTools Center; University of Freiburg; Freiburg Germany
| | - Matthias Mueller
- Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center Freiburg and BrainLinks-BrainTools Center; University of Freiburg; Freiburg Germany
| | - Jacopo Carpaneto
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - Francesco Clemente
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - Marco Controzzi
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - Lorenzo Bisoni
- Department of Electrical and Electronic Engineering; University of Cagliari; Cagliari Italy
| | - Caterina Carboni
- Department of Electrical and Electronic Engineering; University of Cagliari; Cagliari Italy
| | - Massimo Barbaro
- Department of Electrical and Electronic Engineering; University of Cagliari; Cagliari Italy
| | - Francesco Iodice
- Institute of Neurology; Catholic University; Rome Italy
- Department of Geriatrics, Neuroscience, and Orthopedics; Policlinic A. Gemelli Foundation-IRCCS; Rome Italy
| | - David Andreu
- INRIA, CAMIN Team; University of Montpellier; Montpellier France
| | | | | | - Christian Cipriani
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| | - David Guiraud
- INRIA, CAMIN Team; University of Montpellier; Montpellier France
| | - Luigi Raffo
- Department of Electrical and Electronic Engineering; University of Cagliari; Cagliari Italy
| | - Eduardo Fernandez
- Institute of Neurology; Catholic University; Rome Italy
- Department of Geriatrics, Neuroscience, and Orthopedics; Policlinic A. Gemelli Foundation-IRCCS; Rome Italy
| | - Thomas Stieglitz
- Laboratory for Biomedical Microtechnology, Department of Microsystems Engineering-IMTEK, Bernstein Center Freiburg and BrainLinks-BrainTools Center; University of Freiburg; Freiburg Germany
| | - Stanisa Raspopovic
- Laboratory for Neuroengineering, Department of Health Sciences and Technology; Institute for Robotics and Intelligent Systems; ETH Zürich, Zürich Switzerland
| | - Paolo M. Rossini
- Institute of Neurology; Catholic University; Rome Italy
- Department of Geriatrics, Neuroscience, and Orthopedics; Policlinic A. Gemelli Foundation-IRCCS; Rome Italy
| | - Silvestro Micera
- Bertarelli Foundation Chair in Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering; Swiss Federal Institute of Technology of Lausanne (EPFL); Lausanne Switzerland
- Biorobotics Institute; Sant'Anna School of Advanced Studies (SSSA); Pisa Italy
| |
Collapse
|
|
35
|
Hope J, Braeuer B, Amirapu S, McDaid A, Vanholsbeeck F. Extracting morphometric information from rat sciatic nerve using optical coherence tomography. JOURNAL OF BIOMEDICAL OPTICS 2018; 23:1-14. [PMID: 30392195 DOI: 10.1117/1.jbo.23.11.116001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Accepted: 10/15/2018] [Indexed: 06/08/2023]
Abstract
We apply three optical coherence tomography (OCT) image analysis techniques to extract morphometric information from OCT images obtained on peripheral nerves of rat. The accuracy of each technique is evaluated against histological measurements accurate to + / - 1 μm. The three OCT techniques are: (1) average depth-resolved profile (ADRP), (2) autoregressive spectral estimation (AR-SE), and (3) correlation of the derivative spectral estimation (CoD-SE). We introduce a scanning window to the ADRP technique, which provides transverse resolution and improves epineurium thickness estimates-with the number of analyzed images showing agreement with histology increasing from 2 / 10 to 5 / 10 (Kruskal-Wallis test, α = 0.05). A method of estimating epineurium thickness, using the AR-SE technique, showed agreement with histology in 6 / 10 analyzed images (Kruskal-Wallis test, α = 0.05). Using a tissue sample in which histology identified two fascicles with an estimated difference in mean fiber diameter of 4 μm, the AR-SE and CoD-SE techniques both correctly identified the fascicle with larger fiber diameter distribution but incorrectly estimated the magnitude of this difference as 0.5 μm. The ability of the OCT signal analysis techniques to extract accurate morphometric details from peripheral nerves is promising but restricted in depth by scattering in adipose and neural tissues.
Collapse
Affiliation(s)
- James Hope
- The Dodd Walls Centre for Photonic and Quantum Technologies, New Zealand
- University of Auckland, Department of Mechanical Engineering, Auckland, New Zealand
| | - Bastian Braeuer
- The Dodd Walls Centre for Photonic and Quantum Technologies, New Zealand
- University of Auckland, Department of Physics, Auckland, New Zealand
| | - Satya Amirapu
- University of Auckland, Anatomy and Medical Imaging, Auckland, New Zealand
| | - Andrew McDaid
- University of Auckland, Department of Mechanical Engineering, Auckland, New Zealand
| | - Frédérique Vanholsbeeck
- The Dodd Walls Centre for Photonic and Quantum Technologies, New Zealand
- University of Auckland, Department of Physics, Auckland, New Zealand
| |
Collapse
|
|
36
|
Valle G, Mazzoni A, Iberite F, D’Anna E, Strauss I, Granata G, Controzzi M, Clemente F, Rognini G, Cipriani C, Stieglitz T, Petrini FM, Rossini PM, Micera S. Biomimetic Intraneural Sensory Feedback Enhances Sensation Naturalness, Tactile Sensitivity, and Manual Dexterity in a Bidirectional Prosthesis. Neuron 2018; 100:37-45.e7. [DOI: 10.1016/j.neuron.2018.08.033] [Citation(s) in RCA: 98] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Revised: 07/05/2018] [Accepted: 08/22/2018] [Indexed: 10/28/2022]
|
|
37
|
Eggers TE, Dweiri YM, McCallum GA, Durand DM. Recovering Motor Activation with Chronic Peripheral Nerve Computer Interface. Sci Rep 2018; 8:14149. [PMID: 30237487 PMCID: PMC6148292 DOI: 10.1038/s41598-018-32357-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Accepted: 08/23/2018] [Indexed: 11/17/2022] Open
Abstract
Interfaces with the peripheral nerve provide the ability to extract motor activation and restore sensation to amputee patients. The ability to chronically extract motor activations from the peripheral nervous system remains an unsolved problem. In this study, chronic recordings with the Flat Interface Nerve Electrode (FINE) are employed to recover the activation levels of innervated muscles. The FINEs were implanted on the sciatic nerves of canines, and neural recordings were obtained as the animal walked on a treadmill. During these trials, electromyograms (EMG) from the surrounding hamstring muscles were simultaneously recorded and the neural recordings are shown to be free of interference or crosstalk from these muscles. Using a novel Bayesian algorithm, the signals from individual fascicles were recovered and then compared to the corresponding target EMG of the lower limb. High correlation coefficients (0.84 ± 0.07 and 0.61 ± 0.12) between the extracted tibial fascicle/medial gastrocnemius and peroneal fascicle/tibialis anterior muscle were obtained. Analysis calculating the information transfer rate (ITR) from the muscle to the motor predictions yielded approximately 5 and 1 bit per second (bps) for the two sources. This method can predict motor signals from neural recordings and could be used to drive a prosthesis by interfacing with residual nerves.
Collapse
Affiliation(s)
- Thomas E Eggers
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University, Cleveland, USA
| | - Yazan M Dweiri
- Department of Biomedical Engineering, Jordan University of Science and Technology, Irbid, Jordan
| | - Grant A McCallum
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University, Cleveland, USA
| | - Dominique M Durand
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University, Cleveland, USA.
| |
Collapse
|
|
38
|
Delgado-Martínez I, Righi M, Santos D, Cutrone A, Bossi S, D'Amico S, Del Valle J, Micera S, Navarro X. Fascicular nerve stimulation and recording using a novel double-aisle regenerative electrode. J Neural Eng 2018; 14:046003. [PMID: 28382924 DOI: 10.1088/1741-2552/aa6bac] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE As artificial prostheses become more refined, they are most often used as a therapeutic option for hand amputation. By contrast to extra- or intraneural interfaces, regenerative nerve electrodes are designed to enable electrical interfaces with regrowing axonal bundles of injured nerves, aiming to achieve high selectivity for recording and stimulation. However, most of the developed designs pose an obstacle to the regrowth mechanisms due to low transparency and cause impairment to the nerve regeneration. APPROACH Here we present the double-aisle electrode, a new type of highly transparent, non-obstructive regenerative electrode. Using a double-side thin-film polyimide planar multi-contact electrode, two nerve fascicles can regenerate without physical impairment through two electrically isolated aisles. MAIN RESULTS We show that this electrode can be used to selectively record and stimulate fascicles, acutely as well as chronically, and allow regeneration in nerve gaps of several millimeters without impairment. SIGNIFICANCE This multi-aisle regenerative electrode may be suitable for neuroprosthetic applications, such as prostheses, for the restoration of hand function after amputation or severe nerve injuries.
Collapse
Affiliation(s)
- I Delgado-Martínez
- Department of Cell Biology, Physiology and Immunology, Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain
| | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Brill N, Naufel SN, Polasek K, Ethier C, Cheesborough J, Agnew S, Miller LE, Tyler DJ. Evaluation of high-density, multi-contact nerve cuffs for activation of grasp muscles in monkeys. J Neural Eng 2018; 15:036003. [PMID: 28825407 PMCID: PMC5910281 DOI: 10.1088/1741-2552/aa8735] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The objective of this work was to evaluate whether nerve cuffs can selectively activate hand muscles for functional electrical stimulation (FES). FES typically involves identifying and implanting electrodes in many individual muscles, but nerve cuffs only require implantation at a single site around the nerve. This method is surgically more attractive. Nerve cuffs may also more effectively stimulate intrinsic hand muscles, which are difficult to implant and stimulate without spillover to adjacent muscles. APPROACH To evaluate its ability to selectively activate muscles, we implanted and tested the flat interface nerve electrode (FINE), which is designed to selectively stimulate peripheral nerves that innervate multiple muscles (Tyler and Durand 2002 IEEE Trans. Neural Syst. Rehabil. Eng. 10 294-303). We implanted FINEs on the nerves and bipolar intramuscular wires for recording compound muscle action potentials (CMAPs) from up to 20 muscles in each arm of six monkeys. We then collected recruitment curves while the animals were anesthetized. MAIN RESULT A single FINE implanted on an upper extremity nerve in the monkey can selectively activate muscles or small groups of muscles to produce multiple, independent hand functions. SIGNIFICANCE FINE cuffs can serve as a viable supplement to intramuscular electrodes in FES systems, where they can better activate intrinsic and extrinsic muscles with lower currents and less extensive surgery.
Collapse
Affiliation(s)
| | - SN Naufel
- Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
| | - K Polasek
- Department of Engineering, Hope College, 27 Graves Pl. Holland MI, 49423
| | - C Ethier
- Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Université Laval, Quebec City, QC, Canada
| | - J Cheesborough
- Clinical Instructor, Surgery, Plastic & Reconstructive Surgery, Stanford University
| | - S Agnew
- Assistant Professor, Division of Plastic Surgery and Department of Orthopaedic Surgery, Loyola University Medical Center
| | - LE Miller
- Department of Biomedical Engineering, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA
- Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Chicago, IL 60611, USA
- Sensory Motor Performance Program (SMPP), Shirley Ryan Ability Lab, 355 Erie Street, Suite 1406, Chicago, IL 60611, USA
- Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, IL, USA
| | - DJ Tyler
- Biomedical Engineering Department, Case Western Reserve University, Cleveland, OH, USA
- Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, USA
| |
Collapse
|
|
40
|
Hope J, Vanholsbeeck F, McDaid A. A model of electrical impedance tomography implemented in nerve-cuff for neural-prosthetics control. Physiol Meas 2018; 39:044002. [DOI: 10.1088/1361-6579/aab73a] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
|
|
41
|
Spearman BS, Desai VH, Mobini S, McDermott MD, Graham JB, Otto KJ, Judy JW, Schmidt CE. Tissue-Engineered Peripheral Nerve Interfaces. ADVANCED FUNCTIONAL MATERIALS 2018; 28:1701713. [PMID: 37829558 PMCID: PMC10569514 DOI: 10.1002/adfm.201701713] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Research on neural interfaces has historically concentrated on development of systems for the brain; however, there is increasing interest in peripheral nerve interfaces (PNIs) that could provide benefit when peripheral nerve function is compromised, such as for amputees. Efforts focus on designing scalable and high-performance sensory and motor peripheral nervous system interfaces. Current PNIs face several design challenges such as undersampling of signals from the thousands of axons, nerve-fiber selectivity, and device-tissue integration. To improve PNIs, several researchers have turned to tissue engineering. Peripheral nerve tissue engineering has focused on designing regeneration scaffolds that mimic normal nerve extracellular matrix composition, provide advanced microarchitecture to stimulate cell migration, and have mechanical properties like the native nerve. By combining PNIs with tissue engineering, the goal is to promote natural axon regeneration into the devices to facilitate close contact with electrodes; in contrast, traditional PNIs rely on insertion or placement of electrodes into or around existing nerves, or do not utilize materials to actively facilitate axon regeneration. This review presents the state-of-the-art of PNIs and nerve tissue engineering, highlights recent approaches to combine neural-interface technology and tissue engineering, and addresses the remaining challenges with foreign-body response.
Collapse
Affiliation(s)
- Benjamin S Spearman
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
| | - Vidhi H Desai
- Department of Electrical and Computer Engineering, The University of Florida, 216 Larsen Hall, 116200, Gainesville, FL 32611-6200
- Nanoscience Institute for Medical and Engineering Technology, The University of Florida, 1041 Center Drive, 116621, Gainesville, FL 32611-6621
| | - Sahba Mobini
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
| | - Matthew D McDermott
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
- Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Dr., West Lafayette, IN 47907-2032
| | - James B Graham
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
| | - Kevin J Otto
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
- Nanoscience Institute for Medical and Engineering Technology, The University of Florida, 1041 Center Drive, 116621, Gainesville, FL 32611-6621
- Department of Neuroscience, The University of Florida, 1149 Newell Dr., Room L1-100, 100244, Gainesville, FL 32610-0244
- Department of Neurology, The University of Florida, 2000 SW Archer Rd., Third Floor, 100383, Gainesville, FL 32610
| | - Jack W Judy
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
- Department of Electrical and Computer Engineering, The University of Florida, 216 Larsen Hall, 116200, Gainesville, FL 32611-6200
- Nanoscience Institute for Medical and Engineering Technology, The University of Florida, 1041 Center Drive, 116621, Gainesville, FL 32611-6621
| | - Christine E Schmidt
- Crayton Pruitt Family Department of Biomedical Engineering, The University of Florida, 1275 Center Dr., BMS Building JG-56, 116131, Gainesville, FL 32611-6131
- Nanoscience Institute for Medical and Engineering Technology, The University of Florida, 1041 Center Drive, 116621, Gainesville, FL 32611-6621
| |
Collapse
|
|
42
|
|
|
43
|
Yao Z, Yan LW, Wang T, Qiu S, Lin T, He FL, Yuan RH, Liu XL, Qi J, Zhu QT. A rapid micro-magnetic resonance imaging scanning for three-dimensional reconstruction of peripheral nerve fascicles. Neural Regen Res 2018; 13:1953-1960. [PMID: 30233069 PMCID: PMC6183031 DOI: 10.4103/1673-5374.238718] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The most common methods for three-dimensional reconstruction of peripheral nerve fascicles include histological and radiology techniques. Histological techniques have many drawbacks including an enormous manual workload and poor image registration. Micro-magnetic resonance imaging (Micro-MRI), an emerging radiology technique, has been used to report results in the brain, liver and tumor tissues. However, micro-MRI usage for obtaining intraneural structures has not been reported. The aim of this study was to present a new imaging method for three-dimensional reconstruction of peripheral nerve fascicles by 1T micro-MRI. Freshly harvested sciatic nerve samples from an amputated limb were divided into four groups. Two different scanning conditions (Mannerist Solution/GD-DTPA contrast agent, distilled water) were selected, and both T1 and T2 phases programmed for each scanning condition. Three clinical surgeons evaluated the quality of the images via a standardized scale. Moreover, to analyze deformation of the two-dimensional image, the nerve diameter and total area of the micro-MRI images were compared after hematoxylin-eosin staining. The results show that rapid micro-MRI imaging method can be used for three-dimensional reconstruction of the fascicle structure. Nerve sample immersed in contrast agent (Mannerist Solution/GD-DTPA) and scanned in the T1 phase was the best. Moreover, the nerve sample was scanned freshly and can be recycled for other procedures. MRI images show better stability and smaller deformation compared with histological images. In conclusion, micro-MRI provides a feasible and rapid method for three-dimensional reconstruction of peripheral nerve fascicles, which can clearly show the internal structure of the peripheral nerve.
Collapse
Affiliation(s)
- Zhi Yao
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Li-Wei Yan
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Tao Wang
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Shuai Qiu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Tao Lin
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Fu-Lin He
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Ru-Heng Yuan
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangzhou, Guangdong Province, China
| | - Xiao-Lin Liu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
| | - Jian Qi
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
| | - Qing-Tang Zhu
- Department of Microsurgery and Orthopedic Trauma, First Affiliated Hospital of Sun Yat-sen University; Center for Peripheral Nerve Tissue Engineering and Technology Research; Guangdong Province Engineering Laboratory for Soft Tissue Biofabrication, Guangzhou, Guangdong Province, China
| |
Collapse
|
|
44
|
Anand S, Desai V, Alsmadi N, Kanneganti A, Nguyen DHT, Tran M, Patil L, Vasudevan S, Xu C, Hong Y, Cheng J, Keefer E, Romero-Ortega MI. Asymmetric Sensory-Motor Regeneration of Transected Peripheral Nerves Using Molecular Guidance Cues. Sci Rep 2017; 7:14323. [PMID: 29085079 PMCID: PMC5662603 DOI: 10.1038/s41598-017-14331-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 10/06/2017] [Indexed: 11/22/2022] Open
Abstract
Neural interfaces are designed to decode motor intent and evoke sensory precepts in amputees. In peripheral nerves, recording movement intent is challenging because motor axons are only a small fraction compared to sensory fibers and are heterogeneously mixed particularly at proximal levels. We previously reported that pain and myelinated axons regenerating through a Y-shaped nerve guide with sealed ends, can be modulated by luminar release of nerve growth factor (NGF) and neurotrophin-3 (NT-3), respectively. Here, we evaluate the differential potency of NGF, glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), pleiotrophin (PTN), and NT-3 in asymmetrically guiding the regeneration of sensory and motor neurons. We report that, in the absence of distal target organs, molecular guidance cues can mediate the growth of electrically conductive fascicles with normal microanatomy. Compared to Y-tube compartments with bovine serum albumin (BSA), GDNF and NGF increased the motor and sensory axon content, respectively. In addition, the sensory to motor ratio was significantly increased by PTN (12.7:1) when compared to a BDNF + GDNF choice. The differential content of motor and sensory axons modulated by selective guidance cues may provide a strategy to better define axon types in peripheral nerve interfaces.
Collapse
Affiliation(s)
- Sanjay Anand
- Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA
| | - Vidhi Desai
- Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, Texas, 76010, USA
| | - Nesreen Alsmadi
- Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA
| | - Aswini Kanneganti
- Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA
| | - Dianna Huyen-Tram Nguyen
- Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, Texas, 76010, USA
| | - Martin Tran
- Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, Texas, 76010, USA
| | - Lokesh Patil
- Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA
| | - Srikanth Vasudevan
- Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Cancan Xu
- Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, Texas, 76010, USA
| | - Yi Hong
- Department of Bioengineering, University of Texas at Arlington, 500 UTA Blvd, Arlington, Texas, 76010, USA
| | - Jonathan Cheng
- Department of Plastic Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390, USA
| | - Edward Keefer
- Nerves Incorporated, P.O. Box 141295, Dallas, TX 75214, USA
| | - Mario I Romero-Ortega
- Department of Bioengineering, University of Texas at Dallas, 800 W. Campbell Road, Richardson, TX, 75080, USA.
| |
Collapse
|
|
45
|
Eggers TE, Dweiri YM, McCallum GA, Durand DM. Model-based Bayesian signal extraction algorithm for peripheral nerves. J Neural Eng 2017; 14:056009. [PMID: 28675376 PMCID: PMC5734869 DOI: 10.1088/1741-2552/aa7d94] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE Multi-channel cuff electrodes have recently been investigated for extracting fascicular-level motor commands from mixed neural recordings. Such signals could provide volitional, intuitive control over a robotic prosthesis for amputee patients. Recent work has demonstrated success in extracting these signals in acute and chronic preparations using spatial filtering techniques. These extracted signals, however, had low signal-to-noise ratios and thus limited their utility to binary classification. In this work a new algorithm is proposed which combines previous source localization approaches to create a model based method which operates in real time. APPROACH To validate this algorithm, a saline benchtop setup was created to allow the precise placement of artificial sources within a cuff and interference sources outside the cuff. The artificial source was taken from five seconds of chronic neural activity to replicate realistic recordings. The proposed algorithm, hybrid Bayesian signal extraction (HBSE), is then compared to previous algorithms, beamforming and a Bayesian spatial filtering method, on this test data. An example chronic neural recording is also analyzed with all three algorithms. MAIN RESULTS The proposed algorithm improved the signal to noise and signal to interference ratio of extracted test signals two to three fold, as well as increased the correlation coefficient between the original and recovered signals by 10-20%. These improvements translated to the chronic recording example and increased the calculated bit rate between the recovered signals and the recorded motor activity. SIGNIFICANCE HBSE significantly outperforms previous algorithms in extracting realistic neural signals, even in the presence of external noise sources. These results demonstrate the feasibility of extracting dynamic motor signals from a multi-fascicled intact nerve trunk, which in turn could extract motor command signals from an amputee for the end goal of controlling a prosthetic limb.
Collapse
Affiliation(s)
- Thomas E. Eggers
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University
| | - Yazan M. Dweiri
- Department of Biomedical Engineering, Jordan University of science and Technology
| | - Grant A. McCallum
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University
| | - Dominique M. Durand
- Neural Engineering Center, Biomedical Engineering, Case Western Reserve University
| |
Collapse
|
|
46
|
Yan L, Guo Y, Qi J, Zhu Q, Gu L, Zheng C, Lin T, Lu Y, Zeng Z, Yu S, Zhu S, Zhou X, Zhang X, Du Y, Yao Z, Lu Y, Liu X. Iodine and freeze-drying enhanced high-resolution MicroCT imaging for reconstructing 3D intraneural topography of human peripheral nerve fascicles. J Neurosci Methods 2017. [PMID: 28634148 DOI: 10.1016/j.jneumeth.2017.06.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND The precise annotation and accurate identification of the topography of fascicles to the end organs are prerequisites for studying human peripheral nerves. NEW METHOD In this study, we present a feasible imaging method that acquires 3D high-resolution (HR) topography of peripheral nerve fascicles using an iodine and freeze-drying (IFD) micro-computed tomography (microCT) method to greatly increase the contrast of fascicle images. RESULTS The enhanced microCT imaging method can facilitate the reconstruction of high-contrast HR fascicle images, fascicle segmentation and extraction, feature analysis, and the tracing of fascicle topography to end organs, which define fascicle functions. COMPARISON WITH EXISTING METHODS The complex intraneural aggregation and distribution of fascicles is typically assessed using histological techniques or MR imaging to acquire coarse axial three-dimensional (3D) maps. However, the disadvantages of histological techniques (static, axial manual registration, and data instability) and MR imaging (low-resolution) limit these applications in reconstructing the topography of nerve fascicles. CONCLUSIONS Thus, enhanced microCT is a new technique for acquiring 3D intraneural topography of the human peripheral nerve fascicles both to improve our understanding of neurobiological principles and to guide accurate repair in the clinic. Additionally, 3D microstructure data can be used as a biofabrication model, which in turn can be used to fabricate scaffolds to repair long nerve gaps.
Collapse
Affiliation(s)
- Liwei Yan
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Yongze Guo
- School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Computational Science, Guangzhou 510080, PR China.
| | - Jian Qi
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Qingtang Zhu
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Liqiang Gu
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Canbin Zheng
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Tao Lin
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Yutong Lu
- National Supercomputer Center in GuangZhou, Sun Yat-sen University, Guangzhou 510080, PR China.
| | - Zitao Zeng
- School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Computational Science, Guangzhou 510080, PR China.
| | - Sha Yu
- School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Computational Science, Guangzhou 510080, PR China.
| | - Shuang Zhu
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Xiang Zhou
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Xi Zhang
- National Supercomputer Center in GuangZhou, Sun Yat-sen University, Guangzhou 510080, PR China.
| | - Yunfei Du
- National Supercomputer Center in GuangZhou, Sun Yat-sen University, Guangzhou 510080, PR China.
| | - Zhi Yao
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| | - Yao Lu
- School of Data and Computer Science, Sun Yat-sen University, Guangzhou 510080, PR China; Guangdong Province Key Laboratory of Computational Science, Guangzhou 510080, PR China.
| | - Xiaolin Liu
- Department of Microsurgery and Orthopedic Trauma, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, PR China; Center for Peripheral Nerve Tissue Engineering and Technology Research, Guangdong, Guangzhou 510080, PR China.
| |
Collapse
|