Variable-stiffness prosthesis improves biomechanics of walking across speeds compared to a passive device.

Ankle push-off power plays an important role in healthy walking, contributing to center-of-mass acceleration, swing leg dynamics, and accounting for 45% of total leg power. The majority of existing passive energy storage and return prostheses for people with below-knee (transtibial) amputation are stiffer than the biological ankle, particularly at slower walking speeds. Additionally, passive devices provide insufficient levels of energy return and push-off power, negatively impacting biomechanics of gait. Here, we present a clinical study evaluating the kinematics and kinetics of walking with a microprocessor-controlled, variable-stiffness ankle-foot prosthesis (945 g) compared to a standard low-mass passive prosthesis (Ottobock Taleo, 463 g) with 7 study participants having unilateral transtibial amputation. By modulating prosthesis stiffness under computer control across walking speeds, we demonstrate that there exists a stiffness that increases prosthetic-side energy return, peak power, and center-of-mass push-off work, and decreases contralateral limb peak ground reaction force compared to the standard passive prosthesis across all evaluated walking speeds. We demonstrate a significant increase in center-of-mass push-off work of 26.1%, 26.2%, 29.6% and 29.9% at 0.75 m/s, 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively, and a significant decrease in contralateral limb ground reaction force of 3.1%, 3.9%, and 3.2% at 1.0 m/s, 1.25 m/s, and 1.5 m/s, respectively. This study demonstrates the potential for a quasi-passive microprocessor-controlled variable-stiffness prosthesis to increase push-off power and energy return during gait at a range of walking speeds compared to a passive device of a fixed stiffness.

Continuous neural control of a bionic limb restores biomimetic gait after amputation.

For centuries scientists and technologists have sought artificial leg replacements that fully capture the versatility of their intact biological counterparts. However, biological gait requires coordinated volitional and reflexive motor control by complex afferent and efferent neural interplay, making its neuroprosthetic emulation challenging after limb amputation. Here we hypothesize that continuous neural control of a bionic limb can restore biomimetic gait after below-knee amputation when residual muscle afferents are augmented. To test this hypothesis, we present a neuroprosthetic interface consisting of surgically connected, agonist-antagonist muscles including muscle-sensing electrodes. In a cohort of seven leg amputees, the interface is shown to augment residual muscle afferents by 18% of biologically intact values. Compared with a matched amputee cohort without the afferent augmentation, the maximum neuroprosthetic walking speed is increased by 41%, enabling equivalent peak speeds to persons without leg amputation. Further, this level of afferent augmentation enables biomimetic adaptation to various walking speeds and real-world environments, including slopes, stairs and obstructed pathways. Our results suggest that even a small augmentation of residual muscle afferents restores biomimetic gait under continuous neuromodulation in individuals with leg amputation.

Resting state neurophysiology of agonist-antagonist myoneural interface in persons with transtibial amputation.

The agonist-antagonist myoneural interface (AMI) is an amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects conducted by Srinivasan et al. (2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this study on resting state functional magnetic resonance imaging in AMI subjects, we compared functional connectivity in patients with transtibial AMI (n = 12) and traditional (n = 7) amputations (TA). To test our hypothesis that we would find significant neurophysiological differences between AMI and TA subjects, we performed a whole-brain exploratory analysis to identify a seed region; namely, we conducted ANOVA, followed by t-test statistics to locate a seed in the salience network. Then, we implemented a seed-based connectivity analysis to gather cluster-level inferences contrasting our subject groups. We show evidence supporting our hypothesis that the AMI surgery induces functional network reorganization resulting in a neural configuration that significantly differs from the neural configuration after TA surgery. AMI subjects show significantly less coupling with regions functionally dedicated to selecting where to focus attention when it comes to salient stimuli. Our findings provide researchers and clinicians with a critical mechanistic understanding of the effect of AMI amputation on brain networks at rest, which has promising implications for improved neurorehabilitation and prosthetic control.

Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control.

Closed-loop neuroprostheses show promise in restoring motion in individuals with neurological conditions. However, conventional activation strategies based on functional electrical stimulation (FES) fail to accurately modulate muscle force and exhibit rapid fatigue because of their unphysiological recruitment mechanism. Here, we present a closed-loop control framework that leverages physiological force modulation under functional optogenetic stimulation (FOS) to enable high-fidelity muscle control for extended periods of time (>60 minutes) in vivo. We first uncovered the force modulation characteristic of FOS, showing more physiological recruitment and significantly higher modulation ranges (>320%) compared with FES. Second, we developed a neuromuscular model that accurately describes the highly nonlinear dynamics of optogenetically stimulated muscle. Third, on the basis of the optogenetic model, we demonstrated real-time control of muscle force with improved performance and fatigue resistance compared with FES. This work lays the foundation for fatigue-resistant neuroprostheses and optogenetically controlled biohybrid robots with high-fidelity force modulation.

3D Ultrasound Shear Wave Elastography for Musculoskeletal Tissue Assessment Under Compressive Load: A Feasibility Study.

Given its real-time capability to quantify mechanical tissue properties, ultrasound shear wave elastography holds significant promise in clinical musculoskeletal imaging. However, existing shear wave elastography methods fall short in enabling full-limb analysis of 3D anatomical structures under diverse loading conditions, and may introduce measurement bias due to sonographer-applied force on the transducer. These limitations pose numerous challenges, particularly for 3D computational biomechanical tissue modeling in areas like prosthetic socket design. In this feasibility study, a clinical linear ultrasound transducer system with integrated shear wave elastography capabilities was utilized to scan both a calibrated phantom and human limbs in a water tank imaging setup. By conducting 2D and 3D scans under varying compressive loads, this study demonstrates the feasibility of volumetric ultrasound shear wave elastography of human limbs. Our preliminary results showcase a potential method for evaluating 3D spatially varying tissue properties, offering future extensions to computational biomechanical modeling of tissue for various clinical scenarios.

Non-pyrogenicity and biocompatibility of parylene-coated magnetic bead implants.

Clinical grade magnetic bead implants have important applications in interfacing with the human body, providing contactless mechanical attachment or wireless communication through human tissue. We recently developed a new strategy, magnetomicrometry, that uses magnetic bead implants as passive communication devices to wirelessly sense muscle tissue lengths. We manufactured clinical-grade magnetic bead implants and verified their biocompatibility via intramuscular implantation, cytotoxicity, sensitization, and intracutaneous irritation testing. In this work, we test the pyrogenicity of the magnetic bead implants via a lagomorph model, and we test the biocompatibility of the magnetic bead implants via a full chemical characterization and toxicological risk assessment. Further, we test the cleaning, sterilization, and dry time of the devices that are used to deploy these magnetic bead implants. We find that the magnetic bead implants are non-pyrogenic and biocompatible, with the insertion device determined to be safe to clean, sterilize, and dry in a healthcare setting. These results provide confidence for the safe use of these magnetic bead implants in humans.

Design, Characterization, and Preliminary Assessment of a Two-Degree-of-Freedom Powered Ankle-Foot Prosthesis.

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle-foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle-subtalar-foot complex beyond the existing powered ankles.

Resting state neurophysiology of agonist-antagonist myoneural interface in persons with transtibial amputation.

The agonist-antagonist myoneural interface (AMI) is a novel amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects (Srinivasan et al., Sci. Transl. Med. 2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this first study on resting state fMRI in AMI subjects, we compared resting state functional connectivity in patients with transtibial AMI (n=12) and traditional (n=7) amputations, as well as biologically intact control subjects (n=10). We hypothesized that the AMI surgery will induce functional network reorganization that significantly differs from the traditional amputation surgery and also more closely resembles the neural configuration of controls. We found AMI subjects to have lower connectivity with salience and motor seed regions compared to traditional amputees. Additionally, with connections affected in traditional amputees, AMI subjects exhibited a connectivity pattern more closely resembling controls. Lastly, sensorimotor connectivity in amputee cohorts was significantly associated with phantom sensation (R2=0.7, p=0.0008). These findings provide researchers and clinicians with a critical mechanistic understanding of the effects of the AMI surgery on the brain at rest, spearheading future research towards improved prosthetic control and embodiment.

Constitutive parameter identification of transtibial residual limb soft tissue using ultrasound indentation and shear wave elastography.

Finite element analysis (FEA) can be used to evaluate applied interface pressures and internal tissue strains for computational prosthetic socket design. This type of framework requires realistic patient-specific limb geometry and constitutive properties. In recent studies, indentations and inverse FEA with MRI-derived 3D patient geometries were used for constitutive parameter identification. However, long computational times and use of specialized equipment presents challenges for clinical, deployment. In this study, we present a novel approach for constitutive parameter identification using a combination of FEA, ultrasound indentation, and shear wave elastography. Local shear modulus measurement using elastography during an ultrasound indentation experiment has particular significance for biomechanical modeling of the residual limb since there are known regional dependencies of soft tissue properties such as varying levels of scarring and atrophy. Beyond prosthesis design, this work has broader implications to the fields of muscle health and monitoring of disease progression.

Untethered muscle tracking using magnetomicrometry.

Muscle tissue drives nearly all movement in the animal kingdom, providing power, mobility, and dexterity. Technologies for measuring muscle tissue motion, such as sonomicrometry, fluoromicrometry, and ultrasound, have significantly advanced our understanding of biomechanics. Yet, the field lacks the ability to monitor muscle tissue motion for animal behavior outside the lab. Towards addressing this issue, we previously introduced magnetomicrometry, a method that uses magnetic beads to wirelessly monitor muscle tissue length changes, and we validated magnetomicrometry via tightly-controlled in situ testing. In this study we validate the accuracy of magnetomicrometry against fluoromicrometry during untethered running in an in vivo turkey model. We demonstrate real-time muscle tissue length tracking of the freely-moving turkeys executing various motor activities, including ramp ascent and descent, vertical ascent and descent, and free roaming movement. Given the demonstrated capacity of magnetomicrometry to track muscle movement in untethered animals, we feel that this technique will enable new scientific explorations and an improved understanding of muscle function.

Clinical viability of magnetic bead implants in muscle.

Human movement is accomplished through muscle contraction, yet there does not exist a portable system capable of monitoring muscle length changes in real time. To address this limitation, we previously introduced magnetomicrometry, a minimally-invasive tracking technique comprising two implanted magnetic beads in muscle and a magnetic field sensor array positioned on the body's surface adjacent the implanted beads. The implant system comprises a pair of spherical magnetic beads, each with a first coating of nickel-copper-nickel and an outer coating of Parylene C. In parallel work, we demonstrate submillimeter accuracy of magnetic bead tracking for muscle contractions in an untethered freely-roaming avian model. Here, we address the clinical viability of magnetomicrometry. Using a specialized device to insert magnetic beads into muscle in avian and lagomorph models, we collect data to assess gait metrics, bead migration, and bead biocompatibility. For these animal models, we find no gait differences post-versus pre-implantation, and bead migration towards one another within muscle does not occur for initial bead separation distances greater than 3 cm. Further, using extensive biocompatibility testing, the implants are shown to be non-irritant, non-cytotoxic, non-allergenic, and non-irritating. Our cumulative results lend support for the viability of these magnetic bead implants for implantation in human muscle. We thus anticipate their imminent use in human-machine interfaces, such as in control of prostheses and exoskeletons and in closed-loop neuroprosthetics to aid recovery from neurological disorders.

Erratum: Publisher Correction: Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation.

[This corrects the article DOI: 10.1038/s43856-022-00162-z.].

Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation.

Background: Elucidating underlying mechanisms in subject-specific motor control and perception after amputation could guide development of advanced surgical and neuroprosthetic technologies. In this study, relationships between preserved agonist-antagonist muscle strain within the residual limb and preserved motor control and perception capacity are investigated. Methods: Fourteen persons with unilateral transtibial amputations spanning a range of ages, etiologies, and surgical procedures underwent evaluations involving free-space mirrored motions of their lower limbs. Research has shown that varied motor control in biologically intact limbs is executed by the activation of muscle synergies. Here, we assess the naturalness of phantom joint motor control postamputation based on extracted muscle synergies and their activation profiles. Muscle synergy extraction, degree of agonist-antagonist muscle strain, and perception capacity are estimated from electromyography, ultrasonography, and goniometry, respectively. Results: Here, we show significant positive correlations (P < 0.005-0.05) between sensorimotor responses and residual limb agonist-antagonist muscle strain. Identified trends indicate that preserving even 20-26% of agonist-antagonist muscle strain within the residuum compared to a biologically intact limb is effective in preserving natural motor control postamputation, though preserving limb perception capacity requires more (61%) agonist-antagonist muscle strain preservation. Conclusions: The results suggest that agonist-antagonist muscle strain is a characteristic, readily ascertainable residual limb structural feature that can help explain variability in amputation outcome, and agonist-antagonist muscle strain preserving surgical amputation strategies are one way to enable more effective and biomimetic sensorimotor control postamputation.

ARACAM: A RGB-D Multi-View Photogrammetry System for Lower Limb 3D Reconstruction Applications.

In the world, there is a growing need for lower limb prostheses due to a rising number of amputations caused primarily, by diabetic foot. Researchers enable functional and comfortable prostheses through prosthetic design by integrating new technologies applied to the traditional handcrafted method for prosthesis fabrication that is still current. That is why computer vision shows to be a promising tool for the integration of 3D reconstruction that may be useful for prosthetic design. This work has the objective to design, prototype, and test a functional system to scan plaster cast molds, which may serve as a platform for future technologies for lower limb reconstruction applications. The image capture system comprises 5 stereoscopic color and depth cameras, each with 4 DOF mountings on an enveloping frame, as well as algorithms for calibration, segmentation, registration, and surface reconstruction. The segmentation metrics of dice coefficient and Hausdorff distance (HD) show strong visual similarity with an average similarity of 87% and average error of 6.40 mm, respectively. Moving forward, the system was tested on a known 3D printed model obtained from a computer tomography scan to which comparison results via HD show an average error of ≤1.93 mm thereby making the system competitive against the systems reviewed from the state-of-the-art.

A cutaneous mechanoneural interface for neuroprosthetic feedback.

Amputation destroys sensory end organs and does not provide an anatomical interface for cutaneous neuroprosthetic feedback. Here, we report the design and a biomechanical and electrophysiological evaluation of the cutaneous mechanoneural interface consisting of an afferent neural system that comprises a muscle actuator coupled to a natively pedicled skin flap in a cuff-like architecture. Muscle is actuated through electrical stimulation to induce strains or oscillatory vibrations on the skin flap that are proportional to a desired contact duration or contact pressure. In rat hindlimbs, the mechanoneural interface elicited native dermal mechanotransducers to generate at least four levels of graded contact and eight distinct vibratory afferents that were not significantly different from analogous mechanical stimulation of intact skin. The application of different patterns of electrical stimulation independently engaged slowly adapting and rapidly adapting mechanotransducers, and recreated an array of cutaneous sensations. The cutaneous mechanoneural interface can be integrated with current prosthetic technologies for tactile feedback.

Rejecting Impulse Artifacts from Surface EMG Signals using Real-time Cumulative Histogram Filtering.

This paper presents a cumulative histogram filtering (CHF) algorithm to filter impulsive artifacts within surface electromyograhy (sEMG) signal for time-domain signal feature extraction. The proposed CHF algorithm filters sEMG signals by extracting a continuous subset of amplitude-sorted values within a real-time window of measured samples using information about the probabilistic distribution of sEMG amplitude. For real-time deployment of the proposed CHF algorithm on an embedded computing platform, we also present an efficient, iterative implementation of the proposed algorithm. The proposed CHF algorithm was evaluated on synthetic impulse artifacts superimposed upon undisturbed sEMG recorded from a subject with transtibial amputation. Results suggest that the CHF algorithm effectively suppresses the simulated impulse artifacts while preserving a minimum signal-to-noise ratio of 95% and an average Pearson correlation of 0.99 compared to the undisturbed sEMG recordings.

Spatiotemporally Synchronized Surface EMG and Ultrasonography Measurement Using a Flexible and Low-Profile EMG Electrode.

The temporally synchronized recording of muscle activity and fascicle dynamics is essential in understanding the neurophysiology of human motor control which could promote developments of effective rehabilitation strategies and assistive technologies. Surface electromyography (sEMG) and ultrasonography provide easy-to-use, low-cost, and noninvasive modalities to assess muscle activity and fascicle dynamics, and have been widely used in both clinical and lab settings. However, due to size of these sensors and limited skin surface area, it is extremely challenging to collect data from a muscle of interest in a spatially as well as temporally synchronized manner. Here, we introduce a low-cost, noninvasive flexible electrode that provides high quality sEMG recording, while also enabling spatiotemporally synchronized ultrasonography recordings. The proposed method was verified by comparing ultrasonography of a phantom and a tibialis anterior (TA) muscle during dorsiflexion and plantarflexion with and without the electrode acutely placed under an ultrasound probe. Our results show no significant artifact in ultrasonography from both the phantom and TA fascicle strains due to the presence of the electrode, demonstrating the capability of spatiotemporally synchronized sEMG and ultrasonography recording.

The Agonist-antagonist Myoneural Interface.

Scientist and technologist have long sought to advance limb prostheses that connect directly to the peripheral nervous system, enabling a person with amputation to volitionally control synthetic actuators that move, stiffen and power the prosthesis, as well as to experience natural afferent sensations from the prosthesis. Recently, the agonist-antagonist myoneural interface (AMI) was developed, a mechanoneural transduction architecture and neural interface system designed to provide persons with amputation improved muscle-tendon proprioception and neuroprosthetic control. In this paper, we provide an overview of the AMI, including its conceptual framing and pre-clinical science, surgical techniques for its construction, and clinical efficacy related to pain mitigation, phantom limb range of motion, fascicle dynamics, central brain proprioceptive sensorimotor preservation, and prosthetic controllability. Following this broad overview, we end with a discussion of current limitations of the AMI and potential resolutions to such challenges.

Acquisition of Surface EMG Using Flexible and Low-Profile Electrodes for Lower Extremity Neuroprosthetic Control.

For persons with lower extremity (LE) amputation, acquisition of surface electromyography (sEMG) from within the prosthetic socket remains a significant challenge due to the dynamic loads experienced during the gait cycle. However, these signals are critical for both understanding the clinical effects of LE amputation and determining the desired control trajectories of active LE prostheses. Current solutions for collecting within-socket sEMG are generally (i) incompatible with a subject's prescribed prosthetic socket and liners, (ii) uncomfortable, and (iii) expensive. This study presents an alternative within-socket sEMG acquisition paradigm using a novel flexible and low-profile electrode. First, the practical performance of this Sub-Liner Interface for Prosthetics (SLIP) electrode is compared to that of commercial Ag/AgCl electrodes within a cohort of subjects without amputation. Then, the corresponding SLIP electrode sEMG acquisition paradigm is implemented in a single subject with unilateral transtibial amputation performing unconstrained movements and walking on level ground. Finally, a quantitative questionnaire characterizes subjective comfort for SLIP electrode and commercial Ag/AgCl electrode instrumentation setups. Quantitative analyses suggest comparable signal qualities between SLIP and Ag/AgCl electrodes while qualitative analyses suggest the feasibility of using the SLIP electrode for real-time sEMG data collection from load-bearing, ambulatory subjects with LE amputation.

The Agonist-Antagonist Myoneural Interface.

The agonist-antagonist myoneural interface is a novel surgical construct and neural interfacing approach designed to augment volitional control of adapted prostheses, preserve proprioception, and prevent limb atrophy in the setting of limb amputation.