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Purpose: Complications related to vascular damage such as intra-operative bleeding may be avoided during neurosurgical procedures such as petroclival meningioma surgery. To address this and improve the patient's safety, we designed a real-time blood vessel avoidance strategy that enables operation on deformable tissue during petroclival meningioma surgery using Micron, a handheld surgical robotic tool., Methods: We integrated real-time intra-operative blood vessel segmentation of brain vasculature using deep learning, with a 3D reconstruction algorithm to obtain the vessel point cloud in real time. We then implemented a virtual-fixture-based strategy that prevented Micron's tooltip from entering a forbidden region around the vessel, thus avoiding damage to it., Results: We achieved a median Dice similarity coefficient of 0.97, 0.86, 0.87 and 0.77 on datasets of phantom blood vessels, petrosal vein, internal carotid artery and superficial vessels, respectively. We conducted trials with deformable clay vessel phantoms, keeping the forbidden region 400 [Formula: see text]m outside and 400 [Formula: see text]m inside the vessel. Micron's tip entered the forbidden region with a median penetration of just 8.84 [Formula: see text]m and 9.63 [Formula: see text]m, compared to 148.74 [Formula: see text]m and 117.17 [Formula: see text]m without our strategy, for the former and latter trials, respectively., Conclusion: Real-time control of Micron was achieved at 33.3 fps. We achieved improvements in real-time segmentation of brain vasculature from intra-operative images and showed that our approach works even on non-stationary vessel phantoms. The results suggest that by enabling precise, real-time control, we are one step closer to using Micron in real neurosurgical procedures., (© 2022. CARS.)

Retinal membrane peeling requires delicate manipulation. The presence of the surgeon's physiological tremor, the high variability and often low quality of the ophthalmic image, and excessive forces make the tasks more challenging. Preventing unintended movement caused by tremor and unintentional forces can reduce membrane injury. With the use of an actively stabilized handheld robot, we employ a monocular camera-based surface reconstruction method to estimate the retinal plane and we propose the use of a virtual fixture with the application of a hard stop and motion scaling to improve control of the tool tip during delaminating in a laboratory simulation of retinal membrane peeling. A hard stop helps to limit downward force exerted on the surface. Motion scaling also improves the user's control of contact force when delaminating. We demonstrate a reduction of maximum force and maximum surface-penetration distance from the estimated retinal plane using the proposed technique., (Copyright © 2021 by ASME.)

Frequency domain multiplexing (FDM) is a useful for making multiple measurements simultaneously, such as in optical and electromagnetic position trackers. Much interference is periodic (e.g., AC power harmonics), and is rejected well by FDM, but impulse disturbances are also common. Impulses corrupt the entire spectrum for a short period, and are better rejected in the time domain. Nonlinear blanking is a simple way to suppress impulses, but cannot be easily realized when the required dynamic range is large, and problematic noise may be far smaller than the signal. The described multi-rate Kalman filter upsamples the prediction to the input rate so that impulse departures from the predicted signal are easily detected and blanked out. Also, noise levels in unused adjacent channels are used to estimate measurement noise so that the Kalman filter adapts more slowly when noise is high, keeping output noise roughly constant even in the presence of longer noise bursts.

In this paper we describe work towards retinal vessel cannulation using an actively stabilized handheld robot, guided by monocular vision. We employ a previously developed monocular camera based surface reconstruction method using automated laser beam scanning over the retina. We use the reconstructed plane to find a coordinate transform between the 2D image plane coordinate system and the global 3D frame. Within a hemispherical region around the target, we use motion scaling for higher precision. The contribution of this work is the homography matrix estimation using monocular vision and application of the previously developed laser surface reconstruction to Micron guided vein cannulation. Experiments are conducted in a wet eye phantom to show the higher accuracy of the surface reconstruction as compared to standard stereo reconstruction. Further, experiments to show the increased surgical accuracy due to motion scaling are also carried out.

We describe the development of the In-Loop Electromagnetic Tracker (ILEMT), designed to meet the demanding latency and resolution requirements for active stabilization of hand motion during precision manipulations such as microsurgery. The prototype surpasses the fastest commercial EM trackers by > 4× in root bandwidth/resolution and 2× in latency. The use of two widely spaced carrier frequencies (e.g., 300 Hz and 10 kHz) enables a particularly simple way of reducing the eddy-current interference caused by nonferrous metals present in the workspace. Previously, metal compatibility has only been achieved at a large cost to measurement speed.

Background: Peeling procedures in retinal surgery require micron-scale manipulation and control of sub-tactile forces., Methods: Hybrid position/force control of an actuated handheld microsurgical instrument is presented as a means for simultaneously improving positioning accuracy and reducing forces to prevent avoidable trauma to tissue. The system response was evaluated, and membrane-peeling trials were performed by four test subjects in both artificial and animal models., Results: Maximum force was reduced by 56% in both models compared with position control. No statistically significant effect on procedure duration was observed., Conclusions: A hybrid position/force control system has been implemented that successfully attenuates forces and minimizes unwanted excursions during microsurgical procedures such as membrane peeling. Results also suggest that improvements in safety using this technique may be attained without increasing the duration of the procedure., (Copyright © 2015 John Wiley & Sons, Ltd.)

This paper presents robot-aided intraocular laser surgery using a handheld robot known as Micron. The micromanipulator incorporated in Micron enables visual servoing of a laser probe, while maintaining a constant distance of the tool tip from the retinal surface. The comparative study was conducted with various control methods for evaluation of robot-aided intraocular laser surgery.

This paper presents the design and actuation of a six-degree-of-freedom (6-DOF) manipulator for a handheld instrument, known as "Micron," which performs active tremor compensation during microsurgery. The design incorporates a Gough-Stewart platform based on piezoelectric linear motor, with a specified minimum workspace of a cylinder 4 mm long and 4 mm in diameter at the end-effector. Given the stall force of the motors and the loading typically encountered in vitreoretinal microsurgery, the dimensions of the manipulator are optimized to tolerate a transverse load of 0.2 N on a remote center of motion near the midpoint of the tool shaft. The optimization yields a base diameter of 23 mm and a height of 37 mm. The fully handheld instrument includes a custom-built optical tracking system for control feedback, and an ergonomic housing to serve as a handle. The manipulation performance was investigated in both clamped and handheld conditions. In positioning experiments with varying side loads, the manipulator tolerates side load up to 0.25 N while tracking a sinusoidal target trajectory with less than 20 μm error. Physiological hand tremor is reduced by about 90% in a pointing task, and error less than 25 μm is achieved in handheld circle-tracing.

This paper presents a technique for automated intraocular laser surgery using a handheld micromanipulator known as Micron. The novel handheld manipulator enables the automated scanning of a laser probe within a cylinder of 4 mm long and 4 mm in diameter. For the automation, the surface of the retina is reconstructed using a stereomicroscope, and then preplanned targets are placed on the surface. The laser probe is precisely located on the target via visual servoing of the aiming beam, while maintaining a specific distance above the surface. In addition, the system is capable of tracking the surface of the eye in order to compensate for any eye movement introduced during the operation. We compared the performance of the automated scanning using various control thresholds, in order to find the most effective threshold in terms of accuracy and speed. Given the selected threshold, we conducted the handheld operation above a fixed target surface. The average error and execution time are reduced by 63.6% and 28.5%, respectively, compared to the unaided trials. Finally, the automated laser photocoagulation was demonstrated also in an eye phantom, including compensation for the eye movement.

Vitreoretinal microsurgery requires precise hand-eye coordination to manipulate delicate structures within the eye on the order of tens of microns. To achieve these tasks, surgeons use tools of diameter 0.9 mm or less to access the eye's interior structures. The level of force required during these manipulations is often below the human tactile threshold, requiring the surgeon to rely on subtle visual cues or to apply larger forces above the tactile threshold for feedback. However, both of these methods can lead to tissue damage. Excursions can be made into tissues which are not felt by the surgeon, while larger forces have a higher chance of damaging tissue within the eye. To prevent damage to the retina and other anatomy, we present the implementation of hybrid position/force control operating in the sub-tactile force range for a handheld robotic system. This approach resulted in a 42% reduction in the mean force and 52% reduction in maximum force during peeling tasks.

Performing micromanipulation and delicate operations in submillimeter workspaces is difficult because of destabilizing tremor and imprecise targeting. Accurate micromanipulation is especially important for microsurgical procedures, such as vitreoretinal surgery, to maximize successful outcomes and minimize collateral damage. Robotic aid combined with filtering techniques that suppress tremor frequency bands increases performance; however, if knowledge of the operator's goals is available, virtual fixtures have been shown to further improve performance. In this paper, we derive a virtual fixture framework for active handheld micromanipulators that is based on high-bandwidth position measurements rather than forces applied to a robot handle. For applicability in surgical environments, the fixtures are generated in real-time from microscope video during the procedure. Additionally, we develop motion scaling behavior around virtual fixtures as a simple and direct extension to the proposed framework. We demonstrate that virtual fixtures significantly outperform tremor cancellation algorithms on a set of synthetic tracing tasks (p < 0.05). In more medically relevant experiments of vein tracing and membrane peeling in eye phantoms, virtual fixtures can significantly reduce both positioning error and forces applied to tissue (p < 0.05).

This paper presents the first experimental results from human users of a new 6-degree-of-freedom handheld micromanipulator. This is the latest prototype of a fully-handheld system, known as "Micron," which performs active compensation of hand tremor for microsurgery. The manipulator is a miniature Gough-Stewart platform incorporating linear ultrasonic motors that provide a cylindrical workspace 4 mm long and 4 mm wide. In addition, the platform allows the possibility of imposing a remote center of motion for controlling motion not only at the tip but also at the entry point in the sclera of the eye. We demonstrate hand tremor reduction in both static and dynamic micromanipulation tasks on a rubber pad. The handheld performance is also evaluated in an artificial eye model while imposing a remote center of motion. In all cases, hand tremor is significantly reduced.

An active handheld micromanipulator has been developed to cancel hand tremor during microsurgery. The micromanipulator is also applicable in optical coherence tomography to improve the quality of scanning and minimize surgical risks during the scans. The manipulator can maneuver the tool tip with six degrees of freedom within a cylindrical workspace 4 mm in diameter and 4 mm high. The imaging system is equipped with a 25-gauge Fourier-domain common-path OCT probe. This paper introduces the handheld OCT imaging system and techniques involved and presents stabilized OCT images of A-mode and M-mode scans in air and live rabbit eyes. We show the first demonstration of OCT imaging using the active handheld micromanipulator in vivo.

This paper presents the characterization and comparison of physiological tremor for pointing tasks in multiple environments, as a baseline for performance evaluation of microsurgical robotics. Previous studies have examined the characteristics of physiological tremor under laboratory settings as well as different operating conditions. However, different test methods make the comparison of results across trials and conditions difficult. Two vitroretinal microsurgeons were evaluated while performing a pointing task with no entry-point constraint, constrained by an artificial eye model, and constrained by a rabbit eye in vivo. For the three respective conditions the 3D RMS positioning error was 144 μm, 258 μm, and 285 μm, and maximum 3D error was 349 μm, 647 μm, and 696 μm. A spectral analysis was also performed, confirming a distinct peak near in the 6-12 Hz frequency range, characteristic of hand tremor during tasks in all three environments.

This paper presents the design and analysis of a handheld manipulator for vitreoretinal microsurgery and other biomedical applications. The design involves a parallel micromanipulator utilizing six piezoelectric linear actuators, combining compactness with a large range of motion and relatively high stiffness. Given the available force of the actuators, the overall dimension of the micromanipulator was optimized considering realistic external loads on a remote center of motion representing the point of expected contact with the sclera of the eye during microsurgery. Based on optimization and workspace analysis, a benchtop version of the micromanipulator was built with a base diameter of 25 mm and a height of 50 mm. It provides a hemispherical workspace of 4.0 mm diameter at the tool tip. The manipulation performance of the constructed manipulator was measured under a lateral load applied at the remote center of motion. The micromanipulator tolerated side loads up to 200 mN.

Peeling delicate retinal membranes, which are often less than 5 µm thick, is one of the most challenging retinal surgeries. Preventing rips and tears caused by tremor and excessive force can decrease injury and reduce the need for follow up surgeries. We propose the use of a fully handheld microsurgical robot to suppress tremor while enforcing helpful constraints on the motion of the tool. Using stereo vision and tracking algorithms, the robot activates motion-scaled behavior as the tip reaches the surface, providing finer control during the critical step of engaging the membrane edge. A hard virtual fixture just below the surface limits the total downward force that can be applied. Furthermore, velocity limiting during the peeling helps the surgeon maintain a smooth, constant force while lifting and delaminating the membrane. On a phantom consisting of plastic wrap stretched across a rubber slide, we demonstrate our approach reduces maximum force by 40-70%.

Injecting clot-busting drugs such as t-PA into tiny vessels thinner than a human hair in the eye is a challenging procedure, especially since the vessels lie directly on top of the delicate and easily damaged retina. Various robotic aids have been proposed with the goal of increasing safety by removing tremor and increasing precision with motion scaling. We have developed a fully handheld micromanipulator, Micron, that has demonstrated reduced tremor when cannulating porcine retinal veins in an "open sky" scenario. In this paper, we present work towards handheld robotic cannulation with the goal of vision-based virtual fixtures guiding the tip of the cannula to the vessel. Using a realistic eyeball phantom, we address sclerotomy constraints, eye movement, and non-planar retina. Preliminary results indicate a handheld micromanipulator aided by visual control is a promising solution to retinal vessel occlusion.

We describe the design and performance of a hand-held actively stabilized tool to increase accuracy in micro-surgery or other precision manipulation. It removes involuntary motion such as tremor by actuating the tip to counteract the effect of the undesired handle motion. The key components are a three-degree-of-freedom piezoelectric manipulator that has 400 μm range of motion, 1 N force capability, and bandwidth over 100 Hz, and an optical position measurement subsystem that acquires the tool pose with 4 μm resolution at 2000 samples/s. A control system using these components attenuates hand motion by at least 15 dB (a fivefold reduction). By considering the effect of the frequency response of Micron on the human visual feedback loop, we have developed a filter that reduces unintentional motion, yet preserves intuitive eye-hand coordination. We evaluated the effectiveness of Micron by measuring the accuracy of the human/machine system in three simple manipulation tasks. Handheld testing by three eye surgeons and three non-surgeons showed a reduction in position error of between 32% and 52%, depending on the error metric.

An active handheld micromanipulator has been developed that is capable of automated intraocular acquisition of B-mode and C-mode optical coherence tomography scans that are up to 4 mm wide. The manipulator is a handheld Gough-Stewart platform actuated by ultrasonic linear motors. The manipulator has been equipped with a Fourier-domain common-path intraocular OCT probe that fits within a 25-gauge needle. The paper describes the systems and techniques involved, and presents preliminary results of B-mode and C-mode scans.

A voltage current convertor is described having a quasi complementary class AB architecture that is particularly suited to implementation using discrete power MOSFETs. High-voltage mirror designs are presented, enabling the construction of sources with kilovolt compliance range, tens of watts of output power and greater than 100 kHz bandwidth. GΩ output impedance and distortion below 1% can be obtained with no trimming or transistor matching.

Active compensation of physiological tremor for handheld micromanipulators depends on fast control and actuation responses. Because of real-world latencies, real-time compensation is usually not completely effective at eliminating unwanted hand motion. By modeling tremor, more effective cancellation is possible by anticipating future hand motion. We propose a feedforward control strategy that utilizes tremor velocity from a state-estimating Kalman filter. We demonstrate that estimating hand motion in a feedforward controller overcomes real-world latencies in micromanipulator actuation. In hold-still tasks with a fully handheld micromanipulator, the proposed feedforward approach improves tremor rejection by over 50%.

Precise movement during micromanipulation becomes difficult in submillimeter workspaces, largely due to the destabilizing influence of tremor. Robotic aid combined with filtering techniques that suppress tremor frequency bands increases performance; however, if knowledge of the operator's goals is available, virtual fixtures have been shown to greatly improve micromanipulator precision. In this paper, we derive a control law for position-based virtual fixtures within the framework of an active handheld micromanipulator, where the fixtures are generated in real-time from microscope video. Additionally, we develop motion scaling behavior centered on virtual fixtures as a simple and direct extension to our formulation. We demonstrate that hard and soft (motion-scaled) virtual fixtures outperform state-of-the-art tremor cancellation performance on a set of artificial but medically relevant tasks: holding, move-and-hold, curve tracing, and volume restriction.

Background and Objective: In laser retinal photocoagulation, hundreds of dot-like burns are applied. We introduce a robot-assisted technique to enhance the accuracy and reduce the tedium of the procedure., Materials and Methods: Laser burn locations are overlaid on preoperative retinal images using common patterns such as grids. A stereo camera/monitor setup registers and displays the planned burn locations overlaid on real-time video. Using an active handheld micromanipulator, a 7 x 7 grid of burns spaced 650 microm apart is applied to both paper slides and porcine retina in vitro using 30 milliseconds laser pulses at 532 nm. Two scenarios were tested: unaided, in which the micromanipulator is inert and the laser fires at a fixed frequency, and aided, in which the micromanipulator actively targets burn locations and the laser fires automatically upon target acquisition. Error is defined as the distance from the center of the observed burn mark to the preoperatively selected target location., Results: An experienced retinal surgeon performed trials with and without robotic assistance, on both paper slides and porcine retina in vitro. In the paper slide experiments at an unaided laser repeat rate of 0.5 Hz, error was 125+/-62 microm with robotic assistance and 149+/-76 microm without (P < 0.005), and trial duration was 70+/-8 seconds with robotic assistance and 97+/-7 seconds without (P < 0.005). At a repeat rate of 1.0 Hz, error was 129+/-69 microm with robotic assistance and 166+/-91 microm without (P < 0.005), and trial duration was 26+/-4 seconds with robotic assistance and 47+/-1 seconds without (P < 0.005). At a repeat rate of 2.0 Hz on porcine retinal tissue, error was 123+/-69 microm with robotic assistance and 203+/-104 microm without (P < 0.005)., Conclusion: Robotic assistance can increase the accuracy of laser photocoagulation while reducing the duration of the operation.

The paper describes the use of an active handheld micromanipulator, known as Micron, for micromanipulation of cells. The device enables users to manipulate objects on the order of tens of microns in size, with the natural ease of use of a fully handheld tool. Micron senses its own position using a purpose-built microscale optical tracker, estimates the erroneous or undesired component of hand motion, and actively corrects it by deflecting its own tool tip using piezoelectric actuators. Benchtop experiments in tip positioning show that active compensation can reduce positioning error by up to 51% compared to unaided performance. Preliminary experiments in bisection of sea urchin embryos exhibit an increased success rate when performed with the help of Micron.

Position-sensitive detectors (PSDs), or lateral-effect photodiodes, are commonly used for high-speed, high-resolution optical position measurement. This paper describes the instrument design for multidimensional position and orientation measurement based on the simultaneous position measurement of multiple modulated sources using frequency-domain-multiplexed (FDM) PSDs. The important advantages of this optical configuration in comparison with laser/mirror combinations are that it has a large angular measurement range and allows the use of a probe that is small in comparison with the measurement volume. We review PSD characteristics and quantitative resolution limits, consider the lock-in amplifier measurement system as a communication link, discuss the application of FDM to PSDs, and make comparisons with time-domain techniques. We consider the phase-sensitive detector as a multirate DSP problem, explore parallels with Fourier spectral estimation and filter banks, discuss how to choose the modulation frequencies and sample rates that maximize channel isolation under design constraints, and describe efficient digital implementation. We also discuss hardware design considerations, sensor calibration, probe construction and calibration, and 3-D measurement by triangulation using two sensors. As an example, we characterize the resolution, speed, and accuracy of an instrument that measures the position and orientation of a 10 mm × 5 mm probe in 5 degrees of freedom (DOF) over a 30-mm cube with 4-μm peak-to-peak resolution at 1-kHz sampling.

In microsurgery, a surgeon often deals with anatomical structures of sizes that are close to the limit of the human hand accuracy. Robotic assistants can help to push beyond the current state of practice by integrating imaging and robot-assisted tools. This paper demonstrates control of a handheld tremor reduction micromanipulator with visual servo techniques, aiding the operator by providing three behaviors: snap-to, motion-scaling, and standoff-regulation. A stereo camera setup viewing the workspace under high magnification tracks the tip of the micromanipulator and the desired target object being manipulated. Individual behaviors activate in task-specific situations when the micromanipulator tip is in the vicinity of the target. We show that the snap-to behavior can reach and maintain a position at a target with an accuracy of 17.5 ± 0.4μm Root Mean Squared Error (RMSE) distance between the tip and target. Scaling the operator's motions and preventing unwanted contact with non-target objects also provides a larger margin of safety.

This paper demonstrates tremor compensation for human subjects using an active handheld micromanipulator. This instrument uses optical and inertial sensing to detect its own motion, estimates tremor using linear filtering, and a flexure-based manipulator to actuate the tip. Compensation results while tracing a line with the tool are presented for both novice users and a trained surgeon. Learning effects from repetition of the trials over a ten-day period are described.

Accuracy in manual manipulation in a simulated craniotomy environment has been studied. Eighty-eight neurosurgeons with varying amounts of surgical experience were tested in two tasks: attempting to hold an instrument still, and trying to trace a line. Results for RMS and maximum linear and angular motion were measured in the static task. RMS and maximum error were measured in the dynamic task. Spectral analysis was also performed for both tasks. The median RMS amplitude of the position vector in three dimensions was 526 microm in the stationary task, and the median RMS amplitude of the error vector was 289 microm in the tracing task.

To assess the validity of a single stool or perianal swab specimen when screening for potentially pathogenic parasites, 88 residents of a centre for developmentally handicapped adults were screened by collecting on alternate days three stool samples and pinworm swabs. Both sensitivity and negative predictive values were so low that three samples were required for some parasites. The species being screened for and its underlying prevalence must be considered before collecting only one specimen to reduce laboratory costs.

The prevalence of increased anterior atlanto-odontoid distance (AAOD), a risk factor for spinal cord compression, and degenerative disease of the cervical spine (DDCS) in a population of institutionalized adults with Down's syndrome (DS) was determined and compared with age- and sex-matched 'normals' presenting to a hospital emergency department. Radiographs of the cervical spines of 99 adults with DS and 198 'normals' were compared using a standardized rating scale. The prevalence of an AAOD of 3 mm or greater, the threshold of risk from the literature, was 8% for DS cases and 2% for controls (P < 0.01). The mean AAOD for DS cases was 2.0 +/- 1 mm and for controls 1.5 +/- 0.5 mm (P < 0.01). There was a negative correlation between AAOD and age of DS cases. The prevalence of any degree of DDCS among the DS cases was 64%, the controls 39% (P < 0.001); for moderate or severe DDCS the prevalence among DS cases was 45%, controls 12% (P < 0.001). The prevalence of DDCS increased with age in both groups, but the severity of DDCS was significantly increased with age in both groups, but the severity of DDCS was significantly greater for DS individuals in all age groups. The levels of the cervical spine affected ranged from C2 to C6; the most commonly affected level was C5-C6. While DS adults are at increased theoretical risk for spinal cord compression due to increased AAOD, its clinical significance would appear to be small and to decline with age.(ABSTRACT TRUNCATED AT 250 WORDS)

An intestinal parasite eradication program consisting of antiparasitic drug treatment and hygiene measures was conducted at an Ontario residential facility for developmentally handicapped adults from October, 1989 to August, 1990. The prevalence of intestinal parasites in general was initially over 90% while that of pathogenic species was 59%. Six months later, overall prevalence and that of pathogenic species were reduced to 32.9% and 11%. In one subgroup, the reduction in the prevalence of pathogenic parasites was sustained for at least one year. However, the prevalence of non-pathogenic species was similar to the baseline level. Simultaneous treatment and application of hygiene measures appeared to be effective in reducing pathogenic intestinal parasites.

An 82-year-old white female developed a 36-hour episode of unresponsiveness/drowsiness after a single dose of triazolam 0.5 mg in combination with cimetidine. This case illustrates the need for careful dose-titration of drug therapy in the elderly, particularly when a drug with the potential to impair drug metabolism is coadministered. Cimetidine, when coadministered with triazolam, may increase the intensity and duration of action of single doses of triazolam.