The combined action of a passive exoskeleton and an EMG-controlled neuroprosthesis for upper limb stroke rehabilitation: First results of the RETRAINER project.

The combined use of Functional Electrical Stimulation (FES) and robotic technologies is advocated to improve rehabilitation outcomes after stroke. This work describes an arm rehabilitation system developed within the European project RETRAINER. The system consists of a passive 4-degrees-of-freedom exoskeleton equipped with springs to provide gravity compensation and electromagnetic brakes to hold target positions. FES is integrated in the system to provide additional support to the most impaired muscles. FES is triggered based on the volitional EMG signal of the same stimulated muscle; in order to encourage the active involvement of the patient the volitional EMG is also monitored throughout the task execution and based on it a happy or sad emoji is visualized at the end of each task. The control interface control of the system provides a GUI and multiple software tools to organize rehabilitation exercises and monitor rehabilitation progress. The functionality and the usability of the system was evaluated on four stroke patients. All patients were able to use the system and judged positively its wearability and the provided support. They were able to trigger the stimulation based on their residual muscle activity and provided different levels of active involvement in the exercise, in agreement with their level of impairment. A randomized controlled trial aimed at evaluating the effectiveness of the RETRAINER system to improve arm function after stroke is currently ongoing.

Enhanced torque-based impedance control to assist brain targeting during open-skull neurosurgery: a feasibility study.

BACKGROUND: Cooperatively-controlled robotic assistance could provide increased positional accuracy and stable and safe tissue targeting tasks during open-skull neurosurgical procedures, which are currently performed free-hand. METHODS: Two enhanced torque-based impedance control approaches, i.e. a variable damping criterion and a force-feedback enhancement control, were proposed in combination with an image-based navigation system. Control systems were evaluated on brain-mimicking phantoms by 13 naive users and 8 neurosurgeons (4 novices and 4 experts). RESULTS: In addition to a 60% reduction of user effort, the combination of the proposed strategies showed comparable performances with respect to state-of-the-art admittance controller, thus satisfying the clinical accuracy requirements (below 1 mm), reducing the hand tremor (by a factor of 10) and the tissue's indentation overshooting (by 80%). CONCLUSION: Although the perceived reliability of the system should be improved, the proposed control was suitable to assist targeting procedures, such as brain cortex stimulation, allowing for accurate, stable and safe contact with soft tissues. Copyright © 2015 John Wiley & Sons, Ltd.

A method for the assessment of time-varying brain shift during navigated epilepsy surgery.

PURPOSE: Image guidance is widely used in neurosurgery. Tracking systems (neuronavigators) allow registering the preoperative image space to the surgical space. The localization accuracy is influenced by technical and clinical factors, such as brain shift. This paper aims at providing quantitative measure of the time-varying brain shift during open epilepsy surgery, and at measuring the pattern of brain deformation with respect to three potentially meaningful parameters: craniotomy area, craniotomy orientation and gravity vector direction in the images reference frame. METHODS: We integrated an image-guided surgery system with 3D Slicer, an open-source package freely available in the Internet. We identified the preoperative position of several cortical features in the image space of 12 patients, inspecting both the multiplanar and the 3D reconstructions. We subsequently repeatedly tracked their position in the surgical space. Therefore, we measured the cortical shift, following its time-related changes and estimating its correlation with gravity and craniotomy normal directions. RESULTS: The mean of the median brain shift amount is 9.64 mm ([Formula: see text] mm). The brain shift amount resulted not correlated with respect to the gravity direction, the craniotomy normal, the angle between the gravity and the craniotomy normal and the craniotomy area. CONCLUSIONS: Our method, which relies on cortex surface 3D measurements, gave results, which are consistent with literature. Our measurements are useful for the neurosurgeon, since they provide a continuous monitoring of the intra-operative sinking or bulking of the brain, giving an estimate of the preoperative images validity versus time.

Neuro-mechanics of muscle coordination during recumbent pedaling in post-acute stroke patients.

Motor impairment after stroke has been hypothesized to be related, among others, to impairments in the modular control of movement. In this study we analyzed muscle coordination and pedal forces during a recumbent pedaling exercise from a sample of post-acute stroke patients (n=5) and a population of age-matched healthy individuals (n=4). Healthy subjects and the less impaired patients showed a shared modular organization of pedaling based on 4 similar muscle synergies. The most impaired patient, characterized by a Motricity Index of 52/100, showed a reduced complexity (only 2 muscle synergies for the affected side). Differences between healthy subjects and post-stroke patients in the execution of the task were identified in terms of unbalance in mechanical work production, which well corresponded to the level of impairment. This pedaling unbalance could be traced back to different activation strategies of the 4 identified modules. Investigation on a more representative sample will provide a full characterization of the neuro-mechanics of pedaling after stroke, helping our understandings of the disruption of motor coordination at central level after stroke and of the most effective solutions for functional recovery.

Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG).

PURPOSE: StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ([Formula: see text]1%). In order to increase the intervention safety, we developed and tested planning tools to assist neurosurgeons in choosing the best trajectory configuration. METHODS: An automated planning method was developed that maximizes the distance of the electrode from the vessels and avoids the sulci as entry points. The angle of the guiding screws is optimized to reduce positioning error. The planner was quantitatively and qualitatively compared with manually computed trajectories on 26 electrodes planned for three patients undergoing SEEG by four neurosurgeons. Quantitative comparison was performed computing for each trajectory using (a) the Euclidean distance from the closest vessel and (b) the incidence angle. RESULTS: Quantitative evaluation shows that automatic planned trajectories are safer in terms of distance from the closest vessel with respect to manually planned trajectories. Qualitative evaluation performed by four neurosurgeons showed that the automatically computed trajectories would have been preferred to manually computed ones in 30% of the cases and were judged good or acceptable in about 86% of the cases. A significant reduction in time required for planning was observed with the automated system (approximately 1/10). CONCLUSION: The automatic SEEG electrode planner satisfied the essential clinical requirements, by providing safe trajectories in an efficient timeframe.

A novel environmental chamber for neuronal network multisite recordings.

Environmental stability is a critical issue for neuronal networks in vitro. Hence, the ability to control the physical and chemical environment of cell cultures during electrophysiological measurements is an important requirement in the experimental design. In this work, we describe the development and the experimental verification of a closed chamber for multisite electrophysiology and optical monitoring. The chamber provides stable temperature, pH and humidity and guarantees cell viability comparable to standard incubators. Besides, it integrates the electronics for long-term neuronal activity recording. The system is portable and adaptable for multiple network housings, which allows performing parallel experiments in the same environment. Our results show that this device can be a solution for long-term electrophysiology, for dual network experiments and for coupled optical and electrical measurements.

Biomimetic NMES controller for arm movements supported by a passive exoskeleton.

The European Project MUltimodal Neuroprosthesis for Daily Upper limb Support (MUNDUS) aims at the development of an assistive platform for recovering direct interaction capability during daily life activities based on arm reaching and hand functions. Within this project the present study is focused on the design of a biomimetic controller able to modulate the neuromuscular electrical stimulation needed to perform reaching movements supported by a commercial passive exoskeleton for weight relief. Once defined the activities of daily life to be supported by the MUNDUS system, an experimental campaign on healthy subjects was carried out to identify the repeatable kinematics and muscular solution adopted during the target movements. The kinematics resulted to be highly stereotyped, a root mean squared error lower than 5° was found between all the trajectories obtained by healthy subjects in the same movement. A principal component analysis was performed on the EMG signals: less than 5 components explained more than the 85% of the signal variance. This result suggested that the muscular strategy adopted by healthy subjects was stereotyped and can be replicated by a biomimetic NMES controller. The controller was based on a time-delay artificial neural network which mapped the dynamic and non-linear relationship between kinematics and EMG activations to determine the stimulation timing. The stimulation levels reproduced the same scaling factors found between muscles in the stereotyped strategy. The controller was tested on 2 healthy subjects and though it was a feedforward controller, it showed good accuracy in reaching the desired target positions. The integration of a feedback controller is foreseen to ensure the complete accomplishment of the task and to compensate for unpredictable conditions such as muscular fatigue.

Functional evaluation and rehabilitation engineering.

Life is complex and all about movement, which allows us to interact with the environment and communicate with each other. The human nervous system is capable of performing a simultaneous and integrated control of 100-150 mechanical degrees of freedom of movement in the body via tensions generated by about 700 muscles. In its widest context, movement is carried out by a sensory motor system comprising multiple sensors (visual,auditory, and proprioceptive),multiple actuators (muscles acting on the skeletal system),and an intermediary processor that can be summarized as a multiple-input­multiple-output nonlinear dynamic time-varying control system. This grand control system is capable of responding with remarkable accuracy,speed, appropriateness,versatility, and adaptability to a wide spectrum of continuous and discrete stimuli and conditions and is certainly orders of magnitude more complex and sophisticated than the most advanced robotic systems currently available. In the last decades,a great deal of research has been carried out in the fields of functional evaluation of human performance and rehabilitation engineering. These fields combine knowledge, concepts, and methods from across many disciplines (e.g., biomechanics,neuroscience, and physiology), with the aim of developing apparatuses and methods fort he measurement and analysis of complex sensory motor performance and the ultimate goal of enhancing the execution of different tasks in both healthy people and persons with reduced capabilities from different causes (injury, disease, amputation,and neural degeneration).

A new cross-correlation algorithm for the analysis of "in vitro" neuronal network activity aimed at pharmacological studies.

Modern drug discovery for Central Nervous System pathologies has recently focused its attention to in vitro neuronal networks as models for the study of neuronal activities. Micro Electrode Arrays (MEAs), a widely recognized tool for pharmacological investigations, enable the simultaneous study of the spiking activity of discrete regions of a neuronal culture, providing an insight into the dynamics of networks. Taking advantage of MEAs features and making the most of the cross-correlation analysis to assess internal parameters of a neuronal system, we provide an efficient method for the evaluation of comprehensive neuronal network activity. We developed an intra network burst correlation algorithm, we evaluated its sensitivity and we explored its potential use in pharmacological studies. Our results demonstrate the high sensitivity of this algorithm and the efficacy of this methodology in pharmacological dose-response studies, with the advantage of analyzing the effect of drugs on the comprehensive correlative properties of integrated neuronal networks.

Assessment of long-term radon concentration measurement precision in field conditions (Serbian Schools) for a survey carried out by an international collaboration.

In an international collaboration, a long-term radon concentration survey was carried out in schools of Southern Serbia with radon detectors prepared, etched and read-out in Italy. In such surveys it is necessary to evaluate measurement precision in field conditions, and to check whether quality assurance protocols were effective in keeping uncertainties under control, despite the complex organisation of measurements. In the first stage of the survey, which involves only some of the total number of municipalities, paired detectors were exposed in each monitored room in order to experimentally assess measurement precision. Paired passive devices (containing CR-39 detectors) were exposed for two consecutive 6-month periods. Two different measurement systems were used to read out CR-39s of the first and second period, respectively. The median of the coefficient of variation (CV) of the measured exposures was 8 % for 232 paired devices of the first 6-month period and 4 % for 242 paired devices of the second 6-month period, respectively. This difference was mainly due to a different track count repeatability of the two read-out systems, which was 4 and 1 %, respectively, as the median value of CV of repeated countings. The in-field measured precision results are very similar to the precision assessed in calibration conditions and are much lower than the room-to-room variation of radon concentration in the monitored schools. Moreover, a quality assurance protocol was followed to reduce extra-exposures during detector transport from Rome to schools measured and back.

Robotic and artificial intelligence for keyhole neurosurgery: the ROBOCAST project, a multi-modal autonomous path planner.

The robot and sensors integration for computer-assisted surgery and therapy (ROBOCAST) project (FP7-ICT-2007-215190) is co-funded by the European Union within the Seventh Framework Programme in the field of information and communication technologies. The ROBOCAST project focuses on robot- and artificial-intelligence-assisted keyhole neurosurgery (tumour biopsy and local drug delivery along straight or turning paths). The goal of this project is to assist surgeons with a robotic system controlled by an intelligent high-level controller (HLC) able to gather and integrate information from the surgeon, from diagnostic images, and from an array of on-field sensors. The HLC integrates pre-operative and intra-operative diagnostics data and measurements, intelligence augmentation, multiple-robot dexterity, and multiple sensory inputs in a closed-loop cooperating scheme including a smart interface for improved haptic immersion and integration. This paper, after the overall architecture description, focuses on the intelligent trajectory planner based on risk estimation and human criticism. The current status of development is reported, and first tests on the planner are shown by using a real image stack and risk descriptor phantom. The advantages of using a fuzzy risk description are given by the possibility of upgrading the knowledge on-field without the intervention of a knowledge engineer.

Development and validation of a spike detection and classification algorithm aimed at implementation on hardware devices.

Neurons cultured in vitro on MicroElectrode Array (MEA) devices connect to each other, forming a network. To study electrophysiological activity and long term plasticity effects, long period recording and spike sorter methods are needed. Therefore, on-line and real time analysis, optimization of memory use and data transmission rate improvement become necessary. We developed an algorithm for amplitude-threshold spikes detection, whose performances were verified with (a) statistical analysis on both simulated and real signal and (b) Big O Notation. Moreover, we developed a PCA-hierarchical classifier, evaluated on simulated and real signal. Finally we proposed a spike detection hardware design on FPGA, whose feasibility was verified in terms of CLBs number, memory occupation and temporal requirements; once realized, it will be able to execute on-line detection and real time waveform analysis, reducing data storage problems.

Method for the estimation of a double hinge kinematic model for the trapeziometacarpal joint using MR imaging.

In this paper, we propose a method to estimate the parameters of a double hinge model of the trapeziometacarpal joint (TMC) by MRI-based motion analysis. The model includes two non-orthogonal and non-intersecting rotation axes accounting for flexion-extension (F-E) and adduction-abduction (A-A). We evaluated the quality of the estimated model parameters in the prediction of the relative motion of the first metacarpal bone with respect to the trapezium. As a result, we obtained that: (a) the estimated location and orientation of the F-E and A-A axes were in agreement with previous in vitro studies, (b) the motion of the first metacarpal predicted by the 2 degrees of freedom (2DoF) model exhibits a maximum surface distance error in the range of about 2 mm and (c) four thumb postures at the boundary of the TMC range of motion are sufficient to provide a good estimation of the 2DoF TMC kinematic model and good reproducibility (~1.7 mm) of the real thumb motion at TMC level.

Effects of Parkinson's disease on proprioceptive control of posture and reaching while standing.

Although previous studies have shown pointing errors and abnormal multijoint coordination in seated subjects with Parkinson's disease (PD) who cannot view their arm, the extent to which subjects with PD have problems using proprioception to coordinate equilibrium maintenance and goal-oriented task execution has not been adequately investigated. If a common motor program controls voluntary arm pointing movements and the accompanying postural adjustments, then impairments of proprioceptive integration in subjects with PD should have similar effects on pointing and body center of mass (CoM) control with eyes closed. Ten standing subjects with PD (OFF-medication) and 10 age-matched control (CTR) subjects pointed to a target with their eyes closed and open. Although pointing accuracy was not significantly different between groups, body CoM displacements were reduced in subjects with PD, but not in CTR, when eyes were closed. In addition, with eyes closed, PD subjects showed reduced temporal coupling between pointing and CoM velocity profiles and reduced spatial coupling between pointing and CoM endpoints. This poor coupling with eyes closed could be related to the PD subjects' increased jerkiness of CoM displacements. The different effects of eye closure between CTR and PD subjects on the CoM displacements, but not pointing accuracy, are consistent with separate motor programs for the pointing and postural components of this task. Furthermore, the decoupling between the two movement components in subjects with PD when they could not use vision, suggests that the basal ganglia are involved in the integration of proprioceptive information for posture-movement coordination.

Cycling induced by functional electrical stimulation improves the muscular strength and the motor control of individuals with post-acute stroke. Europa Medicophysica-SIMFER 2007 Award Winner.

AIM: The aim of this study was to investigate the effectiveness of cycling induced by functional electrical stimulation (FES) in patients with postacute stroke. METHODS: Twenty postacute inpatients were recruited and were randomly shared in a control group (56+/-9.2 years old, 50.8+/-24.5 days post-stroke) performing the standard rehabilitation (SR) and a FES group (51+/-12 years old, 56.1+/-22.8 days post-stroke) performing FES cycling in addition to SR. Both the groups performed 3 hours of rehabilitation per day for 4 weeks. The FES cycling was applied daily for 35 minutes and quadriceps, hamstring, gluteus maximus and tibialis anterior of both the legs were stimulated. The two groups were compared by the following outcome measurements before and after treatment: maximum isometric voluntary contraction (MVC) of quadriceps, walking and sit-to-stand ability, motricity index, upright motor control test and trunk control test. RESULTS: After the treatment, the U-Mann-Whitney test demonstrated that the FES group produced a significantly higher increase of the muscular force produced by both the quadriceps during MVC with respect to the control group (P<0.05). Seventy percent of FES patients learned how to perform the sit to stand movement with three different rising speeds while no control patients develop the ability to perform the task properly. CONCLUSION: Rehabilitation including FES cycling was more effective in promoting muscle strength and motor recovery of the lower extremity than therapist-assisted SR alone. Tests on an enlarged number of patients are necessary for generalization before proposing FES cycling in the clinical rehabilitation of post-acute stroke patients.

In vivo validation of a realistic kinematic model for the trapezio-metacarpal joint using an optoelectronic system.

This article analyzes a realistic kinematic model of the trapezio-metacarpal (TM) joint in the human thumb that involves two non-orthogonal and non-intersecting rotation axes. The estimation of the model parameters, i.e. the position and orientation of the two axes with respect to an anatomical coordinate system, was carried out by processing the motion of nine retroreflective markers, externally attached to the hand surface, surveyed by a video motion capture system. In order to compute the model parameters, prototypical circumduction movements were processed within an evolutionary optimization approach. Quality and reproducibility in assessing the parameters were demonstrated across multiple testing sessions on 10 healthy subjects (both left and right thumbs), involving the complete removal of all markers and then retesting. Maximum errors of less than 5 mm in the axis position and less than 6 degrees in the orientation were found, respectively. The inter-subject mean distance between the two axes was 4.16 and 4.71 mm for right and left TM joints, respectively. The inter-subject mean relative orientation between the two axes was about 106 and 113 degrees for right and left TM joints, respectively. Generalization properties of the model were evaluated quantitatively on opposition movements in terms of distance between measured and predicted marker positions (maximum error less than 5 mm). The performance of the proposed model compared favorably with the one (maximum error in the range of 7-8 mm) obtained by applying a universal joint model (orthogonal and intersecting axes). The ability of in vivo estimating the parameters of the proposed kinematic model represents a significant improvement for the biomechanical analysis of the hand motion.

Finger kinematic modeling and real-time hand motion estimation.

This paper describes methods and experimental studies concerned with quantitative reconstruction of finger movements in real-time, by means of multi-camera system and 24 surface markers. The approach utilizes a kinematic model of the articulated hand which consists in a hierarchical chain of rigid body segments characterized by 22 functional degrees of freedom and the global roto-translation. This work is focused on the experimental evaluation of a kinematical hand model for biomechanical analysis purposes. From a static posture, a completely automatic calibration procedure, based on anthropometric measures and geometric constraints, computes axes, and centers of rotations which are then utilized as the base of an interactive real-time animation of the hand model. The motion tracking, based on automatic marker labeling and predictive filter, is empowered by introducing constraints from functional finger postures. The validation is performed on four normal subjects through different right-handed motor tasks involving voluntary flexion-extension of the thumb, voluntary abduction-adduction of the thumb, grasping, and finger pointing. Performances are tested in terms of repeatability of angular profiles, model-based ability to predict marker trajectories and tracking success during real-time motion estimation. Results show intra-subject repeatability of the model calibration both to different postures and to re-marking in the range of 0.5 and 2 mm, respectively. Kinematic estimation proves satisfactory in terms of prediction capability (index finger: maximum RMSE 2.02 mm; thumb: maximum RMSE 3.25 mm) and motion reproducibility (R (2) coefficients--index finger: 0.96, thumb: 0.94). During fast grasping sequence (60 Hz), the percentage of residual marker occlusions is less than 1% and processing and visualization frequency of 50 Hz confirms the real-time capability of the motion estimation system.

How does microgravity affect the muscular and kinematic synergies in a complex movement?

The planning and the execution of voluntary movement relies on sensorimotor transformations in which representations of the external environment are integrated into motor programs. We studied executions of Whole Body Pointing movements, in normal and in transient microgravity (parabolic flights) conditions. Three processes could lead to adaptation to the new environmental condition: a radical change of terrestrial synergies, their partial modification or preservation. By applying a multivariate analysis on kinematic and electromyographic (EMG) data and by comparing the 1g and 0g conditions, our findings hint the hypothesis the descending information from vestibular system may be directed to change the synergies' modulation. An analogous analysis was performed on the kinematics: the invariance of intersegmental coordination among the segments' elevation angles suggests that these kinematic waveforms are used as reference signals to determine the appropriate muscle synergies in a subordinate and flexible manner in order to adapt to the novel mechanical constraints.

Automatic extraction of the mid-facial plane for cranio-maxillofacial surgery planning.

Recently developed computer applications provide tools for planning cranio-maxillofacial interventions based on 3-dimensional (3D) virtual models of the patient's skull obtained from computed-tomography (CT) scans. Precise knowledge of the location of the mid-facial plane is important for the assessment of deformities and for planning reconstructive procedures. In this work, a new method is presented to automatically compute the mid-facial plane on the basis of a surface model of the facial skeleton obtained from CT. The method matches homologous surface areas selected by the user on the left and right facial side using an iterative closest point optimization. The symmetry plane which best approximates this matching transformation is then computed. This new automatic method was evaluated in an experimental study. The study included experienced and inexperienced clinicians defining the symmetry plane by a selection of landmarks. This manual definition was systematically compared with the definition resulting from the new automatic method: Quality of the symmetry planes was evaluated by their ability to match homologous areas of the face. Results show that the new automatic method is reliable and leads to significantly higher accuracy than the manual method when performed by inexperienced clinicians. In addition, the method performs equally well in difficult trauma situations, where key landmarks are unreliable or absent.

A neural network based method for optical patient set-up registration in breast radiotherapy.

Patient set-up optimization is required in breast-cancer radiotherapy to fill the accuracy gap between personalized treatment planning and uncertainties in the irradiation set-up. Opto-electronic systems allow implementing automatic procedures to minimize the positional mismatches of light-reflecting markers located on the patient surface with respect to a corresponding reference configuration. The same systems are used to detect the position of the irradiated body surface by means of laser spots; patient set-up is then corrected by matching the control points onto a CT based reference model through surface registration algorithms. In this paper, a non-deterministic approach based on Artificial Neural Networks is proposed for the automatic, real-time verification of geometrical set-up of breast irradiation. Unlike iterative surface registration methods, no passive fiducials are used and true real-time performance is obtained. Moreover, the non-deterministic modeling performed by the neural algorithm minimizes sensitivity to intra-fractional and inter-fractional non-rigid motion of the breast. The technique was validated through simulated activities by using reference CT data acquired on four subjects. Results show that the procedure is able to detect and reduce simulated set-up errors and revealed high reliability in patient position correction, even when the surface deformation is included in testing conditions.