Force-Sensing-Based Multi-Platform Robotic Assistance for Vitreoretinal Surgery

Vitreoretinal surgery aims to treat disorders of the retina, vitreous body, and macula, such as retinal detachment, diabetic retinopathy, macular hole, epiretinal membrane and retinal vein occlusion. Challenged by several technical and human limitations, vitreoretinal practice currently ranks amongst the most demanding fields in ophthalmic surgery. Of vitreoretinal procedures, membrane peeling is the most common to be performed, over 0.5 million times annually, and among the most prone to complications. It requires an extremely delicate tissue manipulation by various micron scale maneuvers near the retina despite the physiological hand tremor of the operator. In addition, to avoid injuries, the applied forces on the retina need to be kept at a very fine level, which is often well below the tactile sensory threshold of the surgeon. Retinal vein cannulation is another demanding procedure where therapeutic agents are injected into occluded retinal veins. The feasibility of this treatment is limited due to challenges in identifying the moment of venous puncture, achieving cannulation and maintaining it throughout the drug delivery period. Recent advancements in medical robotics have significant potential to address most of the challenges in vitreoretinal practice, and therefore to prevent traumas, lessen complications, minimize intra-operative surgeon effort, maximize surgeon comfort, and promote patient safety. This dissertation presents the development of novel force-sensing tools that can easily be used on various robotic platforms, and robot control methods to produce integrated assistive surgical systems that work in partnership with surgeons against the current limitations in vitreoretinal surgery, specifically focusing on membrane peeling and vein cannulation procedures. Integrating high sensitivity force sensing into the ophthalmic instruments enables precise quantitative monitoring of applied forces. Auditory feedback based upon the measured forces can inform (and warn) the surgeon quickly during the surgery and help prevent injury due to excessive forces. Using these tools on a robotic platform can attenuate hand tremor of the surgeon, which effectively promotes tool manipulation accuracy. In addition, based upon certain force signatures, the robotic system can precisely identify critical instants, such as the venous puncture in retinal vein cannulation, and actively guide the tool towards clinical targets, compensate any involuntary motion of the surgeon, or generate additional motion that will make the surgical task easier. The experimental results using two distinct robotic platforms, the Steady-Hand Eye Robot and Micron, in combination with the force-sensing ophthalmic instruments, show significant performance improvement in artificial dry phantoms and ex vivo biological tissues

Control and Estimation Methods Towards Safe Robot-assisted Eye Surgery

Vitreoretinal surgery is among the most delicate surgical tasks in which physiological hand tremor may severely diminish surgeon performance and put the eye at high risk of injury. Unerring targeting accuracy is required to perform precise operations on micro-scale tissues. Tool tip to tissue interaction forces are usually below human tactile perception, which may result in exertion of excessive forces to the retinal tissue leading to irreversible damages. Notable challenges during retinal surgery lend themselves to robotic assistance which has proven beneficial in providing a safe steady-hand manipulation. Efficient assistance from the robots heavily relies on accurate sensing and intelligent control algorithms of important surgery states and situations (e.g. instrument tip position measurements and control of interaction forces). This dissertation provides novel control and state estimation methods to improve safety during robot-assisted eye surgery. The integration of robotics into retinal microsurgery leads to a reduction in surgeon perception of tool-to-tissue forces at sclera. This blunting of human tactile sensory input, which is due to the inflexible inertia of the robot, is a potential iatrogenic risk during robotic eye surgery. To address this issue, a sensorized surgical instrument equipped with Fiber Bragg Grating (FBG) sensors, which is capable of measuring the sclera forces and instrument insertion depth into the eye, is integrated to the Steady-Hand Eye Robot (SHER). An adaptive control scheme is then customized and implemented on the robot that is intended to autonomously mitigate the risk of unsafe scleral forces and excessive insertion of the instrument. Various preliminary and multi-user clinician studies are then conducted to evaluate the effectiveness of the control method during mock retinal surgery procedures. In addition, due to inherent flexibility and the resulting deflection of eye surgical instruments as well as the need for targeting accuracy, we have developed a method to enhance deflected instrument tip position estimation. Using an iterative method and microscope data, we develop a calibration- and registration-independent (RI) framework to provide online estimates of the instrument stiffness (least squares and adaptive). The estimations are then combined with a state-space model for tip position evolution obtained based on the forward kinematics (FWK) of the robot and FBG sensor measurements. This is accomplished using a Kalman Filtering (KF) approach to improve the instrument tip position estimation during robotic surgery. The entire framework is independent of camera-to-robot coordinate frame registration and is evaluated during various phantom experiments to demonstrate its effectiveness

Vitreo-retinal eye surgery robot : sustainable precision

Vitreo-retinal eye surgery encompasses the surgical procedures performed on the vitreous humor and the retina. A procedure typically consists of the removal of the vitreous humor, the peeling of a membrane and/or the repair of a retinal detachment. Vitreo-retinal surgery is performed minimal invasively. Small needle shaped instruments are inserted into the eye. Instruments are manipulated by hand in four degrees of freedom about the insertion point. Two rotations move the instrument tip laterally, in addition to a translation in axial instrument direction and a rotation about its longitudinal axis. The manipulation of the instrument tip, e.g. a gripping motion can be considered as a fifth degree of freedom. While performing vitreo-retinal surgery manually, the surgeon faces various challenges. Typically, delicate micrometer range thick tissue is operated, for which steady hand movements and high accuracy instrument manipulation are required. Lateral instrument movements are inverted by the pivoting insertion point and scaled depending on the instrument insertion depth. A maximum of two instruments can be used simultaneously. There is nearly no perception of surgical forces, since most forces are below the human detection limit. Therefore, the surgeon relies only on visual feedback, obtained via a microscope or endoscope. Both vision systems force the surgeon to work in a static and non ergonomic body posture. Although the surgeon’s proficiency improves throughout his career, hand tremor will become a problem at higher age. Robotically assisted surgery with a master-slave system can assist the surgeon in these challenges. The slave system performs the actual surgery, by means of instrument manipulators which handle the instruments. The surgeon remains in control of the instruments by operating haptic interfaces via a master. Using electronic hardware and control software, the master and slave are connected. Amongst others, advantages as tremor filtering, up-scaled force feedback, down-scaled motions and stabilized instrument positioning will enhance dexterity on surgical tasks. Furthermore, providing the surgeon an ergonomic body posture will prolong the surgeon’s career. This thesis focuses on the design and realization of a high precision slave system for eye surgery. The master-slave system uses a table mounted design, where the system is compact, lightweight, easy to setup and equipped to perform a complete intervention. The slave system consists of two main parts: the instrument manipulators and their passive support system. Requirements are derived from manual eye surgery, conversations with medical specialists and analysis of the human anatomy and vitreo-retinal interventions. The passive support system provides a stiff connection between the instrument manipulator, patient and surgical table. Given the human anatomical diversity, presurgical adjustments can be made to allow the instrument manipulators to be positioned over each eye. Most of the support system is integrated within the patient’s headrest. On either the left or right side, two exchangeable manipulator-support arms can be installed onto the support system, depending on the eye being operated upon. The compact, lightweight and easy to install design, allows for a short setup time and quick removal in case of a complication. The slave system’s surgical reach is optimized to emulate manually performed surgery. For bimanual instrument operation, two instrument manipulators are used. Additional instrument manipulators can be used for non-active tools e.g. an illumination probe or an endoscope. An instrument manipulator allows the same degrees of freedom and a similar reach as manually performed surgery. Instrument forces are measured to supply force feedback to the surgeon via haptic interfaces. The instrument manipulator is designed for high stiffness, is play free and has low friction to allow tissue manipulation with high accuracy. Each instrument manipulator is equipped with an on board instrument change system, by which instruments can be changed in a fast and secure way. A compact design near the instrument allows easy access to the surgical area, leaving room for the microscope and peripheral equipment. The acceptance of a surgical robot for eye surgery mostly relies on equipment safety and reliability. The design of the slave system features various safety measures, e.g. a quick release mechanism for the instrument manipulator and additional locks on the pre-surgical adjustment fixation clamp. Additional safety measures are proposed, like a hard cover over the instrument manipulator and redundant control loops in the controlling FPGA. A method to fixate the patient’s head to the headrest by use of a custom shaped polymer mask is proposed. Two instrument manipulators and their passive support system have been realized so far, and the first experimental results confirm the designed low actuation torque and high precision performance

Augmentation Of Human Skill In Microsurgery

Surgeons performing highly skilled microsurgery tasks can benefit from information and manual assistance to overcome technological and physiological limitations to make surgery safer, efficient, and more successful. Vitreoretinal surgery is particularly difficult due to inherent micro-scale and fragility of human eye anatomy. Additionally, surgeons are challenged by physiological hand tremor, poor visualization, lack of force sensing, and significant cognitive load while executing high-risk procedures inside the eye, such as epiretinal membrane peeling. This dissertation presents the architecture and the design principles for a surgical augmentation environment which is used to develop innovative functionality to address the fundamental limitations in vitreoretinal surgery. It is an inherently information driven modular system incorporating robotics, sensors, and multimedia components. The integrated nature of the system is leveraged to create intuitive and relevant human-machine interfaces and generate a particular system behavior to provide active physical assistance and present relevant sensory information to the surgeon. These include basic manipulation assistance, audio-visual and haptic feedback, intraoperative imaging and force sensing. The resulting functionality, and the proposed architecture and design methods generalize to other microsurgical procedures. The system's performance is demonstrated and evaluated using phantoms and in vivo experiments

Development and preliminary results of bimanual smart micro-surgical system using a ball-lens coupled OCT distance sensor

Bimanual surgery enhances surgical effectiveness and is required to successfully accomplish complex microsurgical tasks. The essential advantage is the ability to simultaneously grasp tissue with one hand to provide counter traction or exposure, while dissecting with the other. Towards enhancing the precision and safety of bimanual microsurgery we present a bimanual SMART micro-surgical system for a preliminary ex-vivo study. To the best of our knowledge, this is the first demonstration of a handheld bimanual microsurgical system. The essential components include a ball-lens coupled common-path swept source optical coherence tomography sensor. This system effectively suppresses asynchronous hand tremor using two PZT motors in feedback control loop and efficiently assists ambidextrous tasks. It allows precise bimanual dissection of biological tissues with a reduction in operating time as compared to the same tasks performed with conventional onehanded approaches. © 2016 Optical Society of America.1

A Translational Pathway for Recombinant Adeno-Associated Virus Human Gene Therapy: From Target Identification and Animal Modeling of the Disease to Non-Human Primate and Human Studies

Many steps go into developing a clinical viral gene therapy. The course starts with appropriate disease selection and moves through the many hurdles of in-vitro testing, animal model validation and proof-of-concept studies, all the way through pre-clinical large animal studies. In this thesis, I propose to outline the process of developing a translation pathway for a gene therapy using recombinant adeno-associated virus (rAAV). I will expand on this outline using data that I have generated during the course of my Ph.D. that ranges from animal model validation all the way through pre-clinical vector stability studies. Two disease models will be discussed throughout this thesis, Cockayne Syndrome (CS) and Alpha-1 Antitrypsin Deficiency (AATD). Cockayne Syndrome is a rare autosomal recessive genetic disorder involving mutations in either the CSA or CSB gene, leading to defects in DNA repair. Clinically this presents as progressive degeneration of the central nervous system, retina, cardiovascular system, and cochlea, which leads to mental retardation, post-natal growth defects, ocular abnormalities, and shortened life expectancy. Alpha-1 antitrypsin is a serine protease inhibitor largely produced in the liver that mainly functions to inhibit neutrophil elastase within the lung. AATD leads to an increased risk of emphysema, with shortened life expectancy, and also results in accumulations of mutant AAT polymers in the liver, sometimes leading to liver failure. Using these two disease models I will outline the upstream and downstream pre-clinical work as well as the transition to clinical trials of a rAAV based gene therapy

From Benchtop to Beside: Patient-specific Outcomes Explained by Invitro Experiment

Study: Recent analyses show that females have higher early postoperative (PO) mortality and right ventricular failure (RVF) than males after left ventricular assist device (LVAD) implantation; and that this association is partially mediated by smaller LV size in females. Benchtop experiments allow us to investigate patient-specific (PS) characteristics in a reproducible way given the fact that the PS anatomy and physiology is mimicked accurately. With multiple heart models of varying LV size, we can directly study the individual effects of titrating the LVAD speed and the resulting bi-ventricular volumes, shedding light on the interplay between LV and RV as well as resulting inter-ventricular septum (IVS) positions, which may cause the different outcomes pertaining to sex. Methods: In vitro, we studied the impact of the heart size to IVS position using two smaller and two larger sized PS silicone heart phantoms derived from clinical CT images (Fig. 1A). With ultrasound crystals that were integrated on a placeholder inflow cannula, the IVS position was measured during LV and RV volume changes (dV) mimicking varying ventricular loading states (Fig. 1B). Figure 1 A Two small (blue) and two large PS heart phantoms (orange) on B benchtop. C Median septum curvature results. LVEDD/LVV/RVV: LV enddiastolic diameter/LV and RV volume. Results: Going from small to large dV, at zero curvature, the septum starts to shift towards the left; for smaller hearts at dV = -40 mL and for larger hearts at dV = -50 mL (Fig. 1C). This result indicates that smaller hearts are more prone to an IVS shift to the left than larger hearts. We conclude that smaller LV size may therefore mediate increased early PO LVAD mortality and RVF observed in females compared to males. Novel 3D silicone printing technology enables us to study accurate, PS heart models across a heterogeneous patient population. PS relationships can be studied simultaneously to clinical assessments and support the decision-making prior to LVAD implantation