Validating a minipig model of reversible cerebral demyelination using human diagnostic modalities and electron microscopy.

BACKGROUND: Inflammatory demyelinating diseases of the central nervous system, such as multiple sclerosis, are significant sources of morbidity in young adults despite therapeutic advances. Current murine models of remyelination have limited applicability due to the low white matter content of their brains, which restricts the spatial resolution of diagnostic imaging. Large animal models might be more suitable but pose significant technological, ethical and logistical challenges. METHODS: We induced targeted cerebral demyelinating lesions by serially repeated injections of lysophosphatidylcholine in the minipig brain. Lesions were amenable to follow-up using the same clinical imaging modalities (3T magnetic resonance imaging, 11C-PIB positron emission tomography) and standard histopathology protocols as for human diagnostics (myelin, glia and neuronal cell markers), as well as electron microscopy (EM), to compare against biopsy data from two patients. FINDINGS: We demonstrate controlled, clinically unapparent, reversible and multimodally trackable brain white matter demyelination in a large animal model. De-/remyelination dynamics were slower than reported for rodent models and paralleled by a degree of secondary axonal pathology. Regression modelling of ultrastructural parameters (g-ratio, axon thickness) predicted EM features of cerebral de- and remyelination in human data. INTERPRETATION: We validated our minipig model of demyelinating brain diseases by employing human diagnostic tools and comparing it with biopsy data from patients with cerebral demyelination. FUNDING: This work was supported by the DFG under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy, ID 390857198) and TRR 274/1 2020, 408885537 (projects B03 and Z01).

Design of topology optimized compliant legs for bio-inspired quadruped robots.

Robotic legs are an important component of the quadruped robot for achieving different motion gaits. Although the conventional rigid-link-based legs can generally perform robust motions, they still have the issues with poor sealing when operating in complex and liquid terrains. To cope with this problem, fully compliant legs with monolithic structure have been introduced in recent years to improve the system compactness and structural compliance of quadruped robots. In this article, we present a topology-optimization-based method to achieve efficient design of compliant robotic legs. In order to balance the structural stiffness and bending flexibility of the realized leg, a multi-objective optimization algorithm is utilized. A series of design cases are presented to illustrate the design principle and analytical procedure of the proposed method. In addition, experimental evaluation is also performed, and the results have demonstrated that, a quadruped robot with the optimized legs can successfully achieve stable and continuous straight-line walking motions.

Concept and first Implementation of an intracochlearly navigated Electrode Array for Cochlear Implantation.

Cochlear implants (CI) are an established treatment for people with deafness or severe hearing loss. To restore patients' hearing an electrode array (EA) of the CI is inserted into the cochlea to stimulate the auditory nerve. Thereby, the exact positioning and gentle insertion of the EA is crucial for optimal hearing perception outcome. Currently, only microscopic vision is available for entering the cochlea, but the critical intracochlear process during EA insertion is like a "black box" and the surgeon has to rely on haptic feedback. Methods for visualizing the insertion process during surgery are inaccurate or not suitable for routine use due to radiation exposure. To address this problem, we developed a computer-assisted and image-guided cochlear implantation system with an exact real-time visualization of the EA position during the insertion process. The system is based on an electromagnetic tracking system that measures the position and orientation of a sensor integrated into the tip of a EA prototype and visualizes it in presurgical image data. A first experiment with our system showed that a EA prototype could be inserted into a cochlea of a human temporal bone and placed with an accuracy of [Formula: see text]. A maximum insertion angle of 120° was achieved.

Design of Bionic Prosthetic Fingers Using 3D Topology Optimization.

Compliant mechanisms are frequently used in the design of prosthetic fingers since their monolithic structure and flexible movement are quite similar to the biological human fingers. However, the design of compliant prosthetic fingers is not easy, as the conventional rigid-link-based mechanism theory cannot be directly applied. In this paper, we introduce a 3D topology optimization based design framework to simplify the synthesis process of bionic compliant prosthetic fingers. The proposed framework is implemented in the software MATLAB and the realized fingers can be quickly fabricated using selective laser sintering (SLS) technology. To illustrate the design process of the proposed framework, a design example was presented. The bending performance of the realized finger was successfully verified by the FEM-based simulation and the payload test. In future work, the optimized fingers have the potential to be integrated into prosthetic hands to realize sophisticated grasping movements.

Cruciate-Ligament-Inspired Compliant Joints: Application to 3D-Printed Continuum Surgical Robots.

The rapid development of additive manufacturing technology makes it possible to fabricate a patient-specific surgical robot in a short time. To simplify the assembly process of the printed robotic system, compliant-joint-based monolithic structures are often used as substitutes for rigid-link mechanisms to realize flexible bending. In this paper, we introduce a cruciate-ligament-inspired compliant joint (CLCJ) to improve the bending stability of the 3D-printed continuum surgical robots. The basic structure of the tendon-driven CLCJ mechanism and its kinematic model were described in detail. The bending performance of CLCJ was also successfully evaluated by FEM simulation and experimental tests. Besides, a prototype of CLCJ-based surgical robotic system was presented to demonstrate its application in 3D-printed continuum surgical robots.

Design of a novel tendon-driven manipulator structure based on monolithic compliant rolling-contact joint for minimally invasive surgery.

PURPOSE: Compliant mechanisms are commonly used in the design of manipulator and surgical robotic tools for minimally invasive surgery (MIS) thanks to their compactness, ability of miniaturization and lower part count. However, conventional compliant joint has higher internal stiffness, which limits the bending radius. To overcome this problem, a novel tendon-driven manipulator structure based on monolithic compliant rolling-contact joint (CRCJ) is proposed. METHODS: The proposed rolling-contact mechanism is used to prevent cable slack during actuation, which occurs in conventional compliant joint design. By means of selective laser sintering (SLS) technique, the CRCJ can be fabricated in a monolithic structure, thus granting the CRCJ both the advantages of compliant joints and rolling-contact mechanism. Simulations with nonlinear finite element analysis (FEA) and experiments were conducted to evaluate and compare the mechanical properties of the proposed CRCJ with conventional leaf-type compliant joint including the bending and compliant motion. RESULTS: Experimental results showed that the CRCJ has lower bending stiffness, higher maximum bending angle (over [Formula: see text]) and a higher compliance compared to conventional compliant hinges, which allows a larger workspace and reduces the possibility of tissue injury. Agreement was also found between the nonlinear FEA and experiments regarding the relation between actuation force and bending angle. A primary prototype of a 3-DOF handheld laparoscopic manipulator with a diameter of 7 mm was further developed. CONCLUSION: A dexterous tendon-driven monolithic manipulator structure based on CRCJ for MIS is proposed. A preliminary prototype of a handheld laparoscopic manipulator demonstrates the capability of the CRCJ for steerable medical devices. However, design improvements based on FEA and application-orientated prototypes considering anatomical requirements still show room for improvements.

Evaluation of improved bi-manual endoscopic resection using a customizable 3D-printed manipulator system designed for use with standard endoscopes: a feasibility study using a porcine ex-vivo model.

Background and study aims A major drawback of endoscopic en-bloc resection technique is its inability to perform bimanual tasks. Although endoscopic platforms that enable bimanual tasks are commercially available, they are neither approved for various locations nor adaptable to specific patients and indications. Methods Based on evolution of an adaptive 3D-printable platform concept, system variants with different characteristic properties were evaluated for ESD scenarios, ex-vivo in two locations in the stomach and colorectum. Results In total 28 ESDs were performed (7 antrum, 7 corpus in inversion, 7 cecum, 7 rectum) in a porcine ex-vivo setup. ESD was feasible in 21 cases. Investigated manipulator variants are differently well suited for performing ESD within the varying interventions scenarios. Dual-arm manipulators allowed autonomous ESD, while single-arm flexible manipulators could be used more universally due to their compact design, especially for lesions difficult to access. Pediatric scopes were too frail to guide the overtube-manipulators in extremely angled positions. Working in the rectum was impaired using long-sized manipulator arms. Conclusions The presented endoscopic platform based on 3D-printable and customizable manipulator structures might be a promising approach for future improvement of ESD procedure. With regard to localization, especially flexible manipulators attached to standard endoscopes appear to be most promising for further application of specific and individualised manipulator systems.

Patient-Specific Instrument with a Cutting Template for Mitral Valve Repair by Resection.

Mitral valve regurgitation is one of the most common heart valve diseases and mitral valve repair is the favored therapy, in which a part of the mitral valve is resected. To improve preoperative planning of this challenging surgery, patient-specific mitral valve replicas have been developed on which the repair can be simulated. However, there is no possibility yet to transfer the planning from the replica to the surgery of the patient. To solve this problem, we developed a patient-specific instrument with a cutting template, intraoperatively visualizing the part of the mitral valve to be resected as planned on the replica. To realize this instrument, the surgeon first simulates mitral valve repair by resection on a patient-specific mitral valve replica. This postoperative mitral valve replica is then digitalized and from it and a preoperative mitral valve model the instrument with cutting template is automatically designed and then 3D printed. An expert heart surgeon successfully tested the functional principle of the instrument on a pig mitral valve.

Bionic Design of a Disposable Compliant Surgical Forceps With Optimized Clamping Performance.

Disposable forceps are frequently used in different surgical procedures to prevent infections caused by poorly sterilized reusable metal forceps. Compared to traditional rigid-joint mechanisms, compliant mechanisms are much easier to sterilize due to their monolithic structure, hence they are widely used for designing disposable surgical forceps. However, the clamping performance of plastic compliant forceps is generally less robust than metal forceps, which has greatly limited their use in medical applications. To cope with this problem, a novel 3D-printed plastic compliant forceps with optimized clamping performance was developed in this paper for open surgery and physical nursing applications. Bio-inspired topology optimization techniques were employed to synthesize the forceps. The clamping capability of the proposed forceps was evaluated by finite element analysis and loading tests. Results showed that the proposed forceps can generate greater and more stable clamping forces than the previous model of disposable compliant forceps. The proposed bionic optimization method also has potential for synthesizing compliant devices for robotic surgery.

Evaluation of long-term stability of monolithic 3D-printed robotic manipulator structures for minimally invasive surgery.

PURPOSE: In the era of patient-centered medicine, clinical procedures, tools and instruments should be individually adapted to the patient. In this context, the presented 3D-printed Single-Port Overtube Manipulator System follows the aims to provide patient- and task-specific disposable manipulators for minimally invasive surgery. In a first experiment, the robustness of the monolithic flexure hinge structures in use as robotic manipulators will be investigated. METHODS: Customizable monolithic manipulator structures designed by means of an automated design process and manufactured with selective laser sintering were investigated with regard to long-term stability in an endurance test. Therefore, a bare manipulator arm, an arm equipped with a standard instrument and finally loaded with an additional load of 0.5 N were evaluated by continuously following a trajectory within the workspace of the manipulator arms over a period of 90 min. RESULTS: The unloaded manipulator as well as the manipulator arm equipped with a standard instrument showed a sufficient reproducibility (deviation of 1.5 mm and 2.5 mm, respectively, on average) with regard to an application as telemanipulated master-slave surgical robotic system. The 3D-printed manipulators showed no damage and maintained integrity after the experiment. CONCLUSION: It has been shown that 3D-printed manipulators in principle are suitable for use as disposable surgical manipulator systems and offer a long-term stability over at least 90 min. The developed manipulator design shows great potential for the production of patient-, task- and user-specific robot systems. However, the manipulator geometries as well as the control strategies still show room for improvements.

A handheld flexible manipulator system for frontal sinus surgery.

PURPOSE: Draf drainage is the standard treatment procedure for frontal sinus diseases. In this procedure, rigid angled endoscopes and rigid curved instruments are used. However, laterally located pathologies in the frontal sinus cannot be reached with rigid instrumentation. In order to assist surgeons with such complicated cases, we propose a novel handheld flexible manipulator system. METHODS: A cross section of 3 mm × 4.6 mm enables transnasal guiding of a flexible endoscope with 1.4 mm diameter and a standard flexible surgical instrument with up to 1.8 mm diameter into the frontal sinus with increased reachability. The developed system consists of an electrical discharge-machined flexure hinge-based nitinol manipulator arm and a purely mechanical handheld control unit. The corresponding control unit enables upward and left-right bending of the manipulator arm, translation, rolling, actuation and also quick exchange of the surgical instrument. In order to verify the fulfillment of performance requirements, tests regarding reachability and payload capacity were conducted. RESULTS: Reachability tests showed that the manipulator arm can be inserted into the frontal sinus and reach its lateral regions following a Draf IIa procedure. The system can exert forces of at least 2 N in the vertical direction and 1 N in the lateral direction which is sufficient for manipulation of frontal sinus pathologies. CONCLUSION: Considering the fact that the anatomical requirements of the frontal sinus are not addressed satisfactorily in the development of prospective flexible instruments, the proposed system shows great potential in terms of therapeutic use owing to its small cross section and dexterity.

Design and development of the efficient anguilliform swimming robot- MAR.

Propulsion of swimming robots at the surface and underwater is largely dominated by rotary propellers due to high thrust, but at the cost of low efficiency. Due to their inherently high speed turning motion, sharp propeller blades and generated noise, they also present a disturbance to maritime ecosystems. Our work presents a bio-inspired approach to efficient and eco-friendly swimming with moderate to high thrust. This paper describes the concept, development and experimental validation of the novel anguilliform robot MAR. With 15 elements making up the 0.5 m long propulsive section and driven by a single, speed-controlled brushless DC motor (BLDC), the robot creates a smooth continuous traveling wave for propulsion. Steering and autonomy are realized by an actuated head with integrated batteries that serves as a front-rudder. Almost neutral buoyancy paired with individually actuated pectoral fins furthermore enable submerged swimming and diving maneuvers. MAR accomplished high thrusts at a moderate power consumption in first performance tests. The achieved maximum velocity and the speed related efficiency (defined as the achieved speed over the power consumption m Ws-1) did not fulfill the expectations in the first tests (in comparison to commercial rotary thrusters), which can be largely attributed to the spatial limitations and an imperfect test setup. Nevertheless, the potential towards highly efficient and high thrust propulsion is visible and will be further investigated in future efforts.

Mechatronic Support System for NOTES and Monoport Surgery - A New Approach.

To circumvent the drawbacks of currently available platforms for natural orifice transluminal endoscopic surgery (NOTES) and monoport surgery (MPS), we developed a patient-specific, disposable, surgical soft robotic system. The system (Single-Port Overtube; SPOT) is designed as an overtube for standard surgical equipment. The platform body and the manipulators can be quickly adapted to transmural (monoport), NOTES and endoluminal (endoscopic) applications, and 3D-printed overnight as an individualized system. In addition, practical considerations, such as the predicted "ideal" dimensions of the platform, were evaluated. As a result, we found that preoperatively available biometric data currently provide little support for tailored instrument design. Further work is required to provide engineers / developers with more useful preoperative information.

Anatomical Characterization of Frontal Sinus and Development of Representative Models.

This paper presents the methods and the materials towards characterizing frontal sinus anatomy and developing representative anatomical models which reflect the variance of the anatomy with three different sizes: small, medium and large. Anatomical characterization was performed using computer tomography data of up to 50 anonymous patients. Dimensional and volumetric measurements were conducted using the .stl files generated by segmentation and 3-D reconstruction. Three representative data sets were chosen to be realized in the form of models with frontal sinuses of small, medium and large sizes. The models include bone, mucosa and skin structures, whereas bone structures were manufactured by selective laser sintering of polyamide and the soft tissues by casting of gelatin and silicone. To ensure realistic optical and mechanical properties of the mucosa, verification tests were performed and the results were integrated into the manufacturing process.

Patient-specific catheter shaping for the minimally invasive closure of the left atrial appendage.

PURPOSE: The minimally invasive closure of the left atrial appendage is a promising alternative to anticoagulation for stroke prevention in patients suffering from atrial fibrillation. One of the challenges of this procedure is the correct positioning and the coaxial alignment of the tip of the catheter sheath to the implant landing zone. METHOD: In this paper, a novel preoperative planning system is proposed that allows patient-individual shaping of catheters to facilitate the correct positioning of the catheter sheath by offering a patient-specific catheter shape. Based on preoperative three-dimensional image data, anatomical points and the planned implant position are marked interactively and a patient-specific catheter shape is calculated if the standard catheter is not considered as suitable. An approach to calculate a catheter shape with four bends by maximization of the bending radii is presented. Shaping of the catheter is supported by a bending form that is automatically generated in the planning program and can be directly manufactured by using additive manufacturing methods. RESULTS: The feasibility of the planning and shaping of the catheter could be successfully shown using six data sets. The patient-specific catheters were tested in comparison with standard catheters by physicians on heart models. In four of the six tested models, the participating physicians rated the patient-individual catheters better than the standard catheter. CONCLUSION: The novel approach for preoperatively planned and shaped patient-specific catheters designed for the minimally invasive closure of the left atrial appendage could be successfully implemented and a feasibility test showed promising results in anatomies that are difficult to access with the standard catheter.

OR.NET RT: how service-oriented medical device architecture meets real-time communication.

Today's landscape of medical devices is dominated by stand-alone systems and proprietary interfaces lacking cross-vendor interoperability. This complicates or even impedes the innovation of novel, intelligent assistance systems relying on the collaboration of medical devices. Emerging approaches use the service-oriented architecture (SOA) paradigm based on Internet protocol (IP) to enable communication between medical devices. While this works well for scenarios with no or only soft timing constraints, the underlying best-effort communication scheme is insufficient for time critical data. Real-time (RT) networks are able to reliably guarantee fixed latency boundaries, for example, by using time division multiple access (TDMA) communication patterns. However, deterministic RT networks come with their own limitations such as tedious, inflexible configuration and a more restricted bandwidth allocation. In this contribution we overcome the drawbacks of both approaches by describing and implementing mechanisms that allow the two networks to interact. We introduce the first implementation of a medical device network that offers hard RT guarantees for control and sensor data and integrates into SOA networks. Based on two application examples we show how the flexibility of SOA networks and the reliability of RT networks can be combined to achieve an open network infrastructure for medical devices in the operating room (OR).

A 3D-printed functioning anatomical human middle ear model.

The middle ear is a sophisticated and complex structure with a variety of functions, yet a delicate organ prone to injuries due to various reasons. Both, understanding and reconstructing its functions has always been an important topic for researchers from medical and technical background. Currently, human temporal bones are generally used as model for tests, experiments and validation of the numerical results. However, fresh human preparations are not always easily accessible and their mechanical properties vary with time and between individuals. Therefore we have built an anatomically based and functional middle ear model to serve as a reproducible test environment. Our middle ear model was manufactured with the aid of 3D-printing technology. We have segmented the essential functional elements from micro computed tomography data (µCT) of a single temporal bone. The ossicles were 3D-printed by selective laser melting (SLM) and the soft tissues were casted with silicone rubber into 3D-printed molds. The ear canal, the tympanic cavity and the inner ear were artificially designed, but their design ensured the anatomically correct position of the tympanic membrane, ossicular ligaments and the oval window. For the determination of their auditory properties we have conducted two kinds of tests: measurement of the stapes footplate response to sound and tympanometry of the model. Our experiments regarding the sound transmission showed that the model has a similar behavior to a human middle ear. The transfer function has a resonance frequency at around 1 kHz, the stapes' response is almost constant for frequencies below the resonance and a roll-off is observed above the resonance. The tympanometry results show that the compliance of the middle ear model is similar to the compliance of a healthy human middle ear. We also present that we were able to manipulate the transmission behavior, so that healthy or pathological scenarios can be created. For this purpose we have built models with different mechanical properties by varying the hardness of the silicone rubber used for different structures, such as tympanic membrane, oval window and ossicle attachments in the range of Shore 10-40 A. This allowed us to set the transmission amplitudes in the plateau region higher, lower or within the tolerances of normal middle ears (Rosowski et al., 2007). Our results showed that it is possible to build an artificial model of the human middle ear by using 3D-printing technology in combination with silicone rubber molding. We were able to reproduce the anatomical shape of the middle ear's essential elements with high accuracy and also assemble them into a functioning middle ear model. The acoustic behavior of the model can be reproduced and manipulated by the choice of material. If the issues such as resonance of the casing and steep roll-off slope in higher frequencies can be solved, this model creates a reproducible environment for experiments and can be useful for the evaluation of prosthetic devices.

Development of a snake-like dexterous manipulator for skull base surgery.

Petrous apex lesions constitute considerable surgical challenges due to their location in the skull base and close relationship with critical structures such as inner ear, carotid arteries, facial nerves and jugular bulb. These lesions often cannot be treated completely with rigid tools due to the limited accessibility. We are aiming to develop a snake-like manipulator to assist surgeons with the infralabyrinthine treatment of petrous apex lesions with increased dexterity. This snake-like dexterous manipulator (SDM) with 3.3 mm outer diameter and 40 mm working length was designed including a tool channel with a diameter of 1.8 mm and an endoscope channel with a diameter of 0.7 mm. The SDM can be actuated in one plane and two directions enabling the C- and S-shaped bends and rotated around its longitudinal axis. The constant curvature modeling was implemented to predict the deflection in one direction. Experiments were carried out with optical microscope to find out different bending modes. Experimental bending modes were in a good agreement with the theoretical ones in terms of the bending behavior. However tip position prediction showed discrepancies up to 1 mm in X and 2 mm in Z axes.

Quantitative Assessment of Parkinsonian Tremor Based on an Inertial Measurement Unit.

Quantitative assessment of parkinsonian tremor based on inertial sensors can provide reliable feedback on the effect of medication. In this regard, the features of parkinsonian tremor and its unique properties such as motor fluctuations and dyskinesia are taken into account. Least-square-estimation models are used to assess the severities of rest, postural, and action tremors. In addition, a time-frequency signal analysis algorithm for tremor state detection was also included in the tremor assessment method. This inertial sensor-based method was verified through comparison with an electromagnetic motion tracking system. Seven Parkinson's disease (PD) patients were tested using this tremor assessment system. The measured tremor amplitudes correlated well with the judgments of a neurologist (r = 0.98). The systematic analysis of sensor-based tremor quantification and the corresponding experiments could be of great help in monitoring the severity of parkinsonian tremor.

Quantitative assessment of parkinsonian bradykinesia based on an inertial measurement unit.

BACKGROUND: As the most characteristic feature of Parkinson's disease (PD), bradykinesia (slowness of movement) affects all patients with Parkinson's disease and interferes with their daily activities. This study introduces a wearable bradykinesia assessment system whose core component is composed of an inertial measurement unit. METHODS: The system diagram and assessment task were defined in accordance with clinical requirements from neurologists. Based on hand grasping actions, calculations of hand grasping ranges and statistical methods of quantitatively assessing parkinsonian bradykinesia were presented. Seven control subjects and eight patients were tested with this system. RESULTS: Experimental results show that a calculated bradykinesia parameter (modified mean range, instead of mean and standard deviation of the grasp ranges) correlated well with the evaluations of a neurologist (Pearson's correlation coefficient r = -0.83, p < 0.001). CONCLUSIONS: The bradykinesia assessment system was tested on both health subjects and PD patients. The results show that this system has greater correlation with the evaluations by neurologists than other parkinsonian bradykinesia assessment systems. The modified mean range was verified as the major bradykinesia parameter (key indicator). This study is helpful to those who want to use consumer-grade inertial sensors for quantitative assessment of motor symptoms during treatment.