Minimally invasive catheter-based technologies

A simple incision procedure in a blood vessel makes the entire vascular system accessible. Through contrast injection and X-ray visualization, the vascular tree can be mapped and navigated through manual manipulation of thin tubes and wires. This utilization of the vasculature as internal pathways is commonly referred to as the endovascular technique. This technique can be used to deliver implants and drugs, retrieve problematic lesions or objects from the vasculature, or take tissue samples. Compared to open surgery, the advantage of this technique lies in the reduced invasiveness, ideally only leaving a small incision scar at the point of entry. Some interventions, however, are still associated with certain risks, requiring medication or complicating further interventions. The development of sequencing technologies presents an opportunity to improve and miniaturize devices, reducing invasiveness. This thesis aims to mitigate these risks and capitalize on the potential of next-generation sequencing through microfabrication technologies, producing devices that are less invasive than current methods or that enable a new procedure. Initially, the aspect of endovascular heart biopsy is covered. The first work presents the fabrication and in vivo evaluation of a nitinol-based catheter device designed for extracting myocardial tissue. The device is fabricated through picosecond laser machining of nitinol tubes and wires, producing a device that is substantially smaller than what is currently used. The samples are evaluated and compared to samples extracted with conventional devices through RNA-Sequencing, verifying the proof of concept. The second work further emphasizes the device's functionality by evaluating it in a disease model of endomyocardial infarction. Tissue that is affected by the infarct and surrounding healthy tissue is extracted and compared in terms of its genetic expression. This comparison reveals a genetic discrepancy between the sick and healthy tissue, verifying the potential of using the device with RNA-sequencing for diagnostic purposes. The third work evaluates the safety aspects of the novel device in a head-to-head comparison with a conventional device. The study reveals a clear benefit of using the smaller device in terms of the complication rate during the procedure. The fourth work presents the fabrication and in vivo evaluation of another nitinol-based catheter device designed for endothelial cell sampling. The device is fabricated through two-photon polymerization technologies, producing sub-mm brush structures mounted on a nitinol wire. Currently, there are no devices in clinical use that are capable of exclusively extracting endothelial cells. The novel device presents a solution for selective interaction with the innermost layer of the blood vessel. It represents an important step toward sampling endothelial cells for diagnostic and research purposes. The fifth and sixth works collectively present two different aspects of a third nitinol-based catheter device designed to sample tissue from soft organs anywhere in the body. The device is fabricated using laser micromachining, grinding, and two-photon polymerization. The work is separated in terms of the in vivo evaluation and the technical solution. The technical aspects of the device are examined in terms of force generation in miniaturized catheter systems and the problems that arise in terms of mechanical scaling. These problems are solved by attaching pistons along the wire surface coupled with applied pressure to increase the force generated. The sampling with this device is realized, similar to the fourth work, with sub-mm brushes mounted on the wire. In vivo evaluation of this device reveals successful sampling of minute tissue quantities from the liver and kidney, in the size range of 10-100 cells per sample. The seventh work presents the in vivo and in vitro performance of a nanostructure coating on nitinol-based stents. Patients with a stent implant are prescribed an extensive medication regimen to counteract the metal implant's effects on the blood and surrounding tissue. This issue is being continuously targeted by new stent platforms, either with a drug-eluting polymer layer or by being resorbable by the body or through various other means. These implants all have a transient behavior, resulting in different issues over time. Paper VII presents an alternative approach to this problem by instead applying a nanostructure coating that is designed to interact with the blood to a much lesser degree, as demonstrated by CT-angiography and the measurement of multiple biomarkers

Cable-driven parallel mechanisms for minimally invasive robotic surgery

Minimally invasive surgery (MIS) has revolutionised surgery by providing faster recovery times, less post-operative complications, improved cosmesis and reduced pain for the patient. Surgical robotics are used to further decrease the invasiveness of procedures, by using yet smaller and fewer incisions or using natural orifices as entry point. However, many robotic systems still suffer from technical challenges such as sufficient instrument dexterity and payloads, leading to limited adoption in clinical practice. Cable-driven parallel mechanisms (CDPMs) have unique properties, which can be used to overcome existing challenges in surgical robotics. These beneficial properties include high end-effector payloads, efficient force transmission and a large configurable instrument workspace. However, the use of CDPMs in MIS is largely unexplored. This research presents the first structured exploration of CDPMs for MIS and demonstrates the potential of this type of mechanism through the development of multiple prototypes: the ESD CYCLOPS, CDAQS, SIMPLE, neuroCYCLOPS and microCYCLOPS. One key challenge for MIS is the access method used to introduce CDPMs into the body. Three different access methods are presented by the prototypes. By focusing on the minimally invasive access method in which CDPMs are introduced into the body, the thesis provides a framework, which can be used by researchers, engineers and clinicians to identify future opportunities of CDPMs in MIS. Additionally, through user studies and pre-clinical studies, these prototypes demonstrate that this type of mechanism has several key advantages for surgical applications in which haptic feedback, safe automation or a high payload are required. These advantages, combined with the different access methods, demonstrate that CDPMs can have a key role in the advancement of MIS technology.Open Acces

Dynamic Discriminant Analysis with Applications in Computational Surgery

University of Minnesota Ph.D. dissertation. May 2017. Major: Mechanical Engineering. Advisor: Timothy Kowalewski. 1 computer file (PDF); x, 185 pages.Background: The field of computational surgery involves the use of new technologies to improve surgical safety and patient outcomes. Two open problems in this field include smart surgical tools for identifying tissues via backend sensing, and classifying surgical skill level using laparoscopic tool motion. Prior work in these fields has been impeded by the lack of a dynamic discriminant analysis technique capable of classifying data given systems with overwhelming similarity. Methods: Four new machine learning algorithms were developed (DLS, DPP, RELIEF-RBF, and Intent Vectors). These algorithms were then applied to the open problems within computational surgery. These algorithms are designed with the specific goal of finding regions of data with maximum discriminating information while ignoring regions of similarity or data scarcity. The results of these techniques are contrasted with current machine learning algorithms found in the literature. Results: For the tissue identification problem, results indicate that the proposed DLS algorithm provides better classification than existing methods. For the surgical skill evaluation problem, results indicate that the Intent Vectors approach provides equivalent or better classification accuracy when compared to prior art. Interpretation: The algorithms presented in this work provide a novel approach to the classification of time-series data for systems with overwhelming similarity by focusing on separability maximization while maintaining a tractable training routine and real-time classification for unseen data

Bilateral Macro-Micro Teleoperation Using A Magnetic Actuation Mechanism

In recent years, there has been increasing interest in the advancement of microrobotic systems in micro-engineering, micro-fabrication, biological research and biomedical applications. Untethered magnetic-based microrobotic systems are one of the most widely developing groups of microrobotic systems that have been extensively explored for biological and biomedical micro-manipulations. These systems show promise in resolving problems related to on-board power supply limitations as well as mechanical contact sealing and lubrication. In this thesis, a high precision magnetic untethered microrobotic system is demonstrated for micro-handling tasks. A key aspect of the proposed platform concerns the integration of magnetic levitation technology and bilateral macro-micro teleoperation for human intervention to avoid imperceptible failures in poorly observed micro-domain environments. The developed platform has three basic subsystems: a magnetic untethered microrobotic system (MUMS), a haptic device, and a scaled bilateral teleoperation system. The MUMS produces and regulates a magnetic field for non-contact propelling of a microrobot. In order to achieve a controlled motion of the magnetically levitated microrobot, a mathematical force model of the magnetic propulsion mechanism is developed and used to design various control systems. In the workspace of 30 × 32 × 32 mm 3, both PID and LQG\LTR controllers perform similarly the position accuracy of 10 µ m in a vertical direction and 2 µ m in a horizontal motion. The MUMS is equipped with an eddy-current damper to enhance its inherent damping factor in the microrobot's horizontal motions. This paper deals with the modeling and analysis of an eddy-current damper that is formed by a conductive plate placed below the levitated microrobot to overcome inherent dynamical vibrations and improve motion precision. The modeling of eddy-current distribution in the conductive plate is investigated by solving the diffusion equation for vector magnetic potential, and an analytical expression for the horizontal damping force is presented and experimentally validated. It is demonstrated that eddy-current damping is a crucial technique for increasing the damping coefficient in a non-contact way and for improving levitation performance. The damping can be widely used in applications of magnetic actuation systems in micro-manipulation and micro-fabrication. To determine the position of the microrobot in a workspace, the MUMS uses high-accuracy laser sensors. However, laser positioning techniques can only be used in highly transparent environments. A novel technique based on real-time magnetic flux measurement has been proposed for the position estimation of the microrobot in case of laser beam blockage, whereby a combination of Hall-effect sensors is employed to find the microrobot's position in free motion by using the produced magnetic flux. In free motion, the microrobot tends to move toward the horizontally zero magnetic field gradient, Bmax location. As another key feature of the magnetic flux measurement, it was realized that the applied force from the environment to the microrobot can be estimated as linearly proportional to the distance of the microrobot from the Bmax location. The developed micro-domain force estimation method is verified experimentally with an accuracy of 1.27 µ N. A bilateral macro-micro teleoperation technique is employed in the MUMS for the telepresence of a human operator in the task environment. A gain-switching position-position teleoperation scheme is employed and a human operator controls the motion of the microrobot via a master manipulator for dexterous micro-manipulation tasks. The operator can sense a strong force during micro-domain tasks if the microrobot encounters a stiff environment, and the effect of hard contact is fed back to the operator's hand. The position-position method works for both free motion and hard contact. However, to enhance the feeling of a micro-domain environment in the human operator, the scaled force must be transferred to a human, thereby realizing a direct-force-reflection bilateral teleoperation. Additionally, a human-assisted virtual reality interface is developed to improve a human operator's skills in using the haptic-enabled platform, before carrying out an actual dexterous task.1 yea

The Hand-Held Force Magnifier: Surgical Tools to Augment the Sense of Touch

Modern surgeons routinely perform procedures with noisy, sub-threshold, or obscured visual and haptic feedback,either due to the necessary approach, or because the systems on which they are operating are exceeding delicate. For example, in cataract extraction, ophthalmic surgeons must peel away thin membranes in order to access and replace the lens of the eye. Elsewhere, dissection is now commonly performed with energy-delivering tools – rather than sharp blades – and damage to deep structures is possible if tissue contact is not well controlled. Surgeons compensate for their lack of tactile sensibility by relying solely on visual feedback, observing tissue deformation and other visual cues through surgical microscopes or cameras. Using visual information alone can make a procedure more difficult, because cognitive mediation is required to convert visual feedback into motor action. We call this the “haptic problem” in surgery because the human sensorimotor loop is deprived of critical tactile afferent information, increasing the chance for intraoperative injury and requiring extensive training before clinicians reach independent proficiency. Tools that enhance the surgeon’s direct perception of tool-tissue forces can therefore potentially reduce the risk of iatrogenic complications and improve patient outcomes. Towards this end, we have developed and characterized a new robotic surgical tool, the Hand-Held Force Magnifier (HHFM), which amplifies forces at the tool tip so they may be readily perceived by the user, a paradigm we call “in-situ” force feedback. In this dissertation, we describe the development of successive generations of HHFM prototypes, and the evaluation of a proposed human-in-the-loop control framework using the methods of psychophysics. Using these techniques, we have verified that our tool can reduce sensory perception thresholds, augmenting the user’s abilities beyond what is normally possible. Further, we have created models of human motor control in surgically relevant tasks such as membrane puncture, which have shown to be sensitive to push-pull direction and handedness effects. Force augmentation has also demonstrated improvements to force control in isometric force generation tasks. Finally, in support of future psychophysics work, we have developed an inexpensive, high-bandwidth, single axis haptic renderer using a commercial audio speaker

Image-Guided Interventions Using Cone-Beam CT: Improving Image Quality with Motion Compensation and Task-Based Modeling

Cone-beam CT (CBCT) is an increasingly important modality for intraoperative 3D imaging in interventional radiology (IR). However, CBCT exhibits several factors that diminish image quality — notably, the major challenges of patient motion and detectability of low-contrast structures — which motivate the work undertaken in this thesis. A 3D–2D registration method is presented to compensate for rigid patient motion. The method is fiducial-free, works naturally within standard clinical workflow, and is applicable to image-guided interventions in locally rigid anatomy, such as the head and pelvis. A second method is presented to address the challenge of deformable motion, presenting a 3D autofocus concept that is purely image-based and does not require additional fiducials, tracking hardware, or prior images. The proposed method is intended to improve interventional CBCT in scenarios where patient motion may not be sufficiently managed by immobilization and breath-hold, such as the prostate, liver, and lungs. Furthermore, the work aims to improve the detectability of low-contrast structures by computing source–detector trajectories that are optimal to a particular imaging task. The approach is applicable to CBCT systems with the capability for general source–detector positioning, as with a robotic C-arm. A “task-driven” analytical framework is introduced, various objective functions and optimization methods are described, and the method is investigated via simulation and phantom experiments and translated to task-driven source–detector trajectories on a clinical robotic C-arm to demonstrate the potential for improved image quality in intraoperative CBCT. Overall, the work demonstrates how novel optimization-based imaging techniques can address major challenges to CBCT image quality

Physical to Virtual: A Model for Future Virtual Classroom Environments

Virtual reality is a technology that has seen unprecedented growth since the turn of the century with increasing applications within business, entertainment, and educational applications. As virtual reality technologies continue to develops and markets expand, the world may see an increased demand for virtual classrooms: virtual environments (VEs) that students may access through immersive virtual reality technologies to receive guided instruction, conduct simulations, or perform tasks typical in a classroom setting. While many studies document how virtual reality is beneficial to educational processes, there is little discussion on how virtual environments should be architecturally designed. Thus one may hypothesize that physical design strategies translated to virtual environments may have similar results. This thesis investigates virtual environments for education by creating several virtual classrooms embedded within a selective digital twin of the University of Massachusetts Amherst campus. The design of the virtual classrooms was influenced by current architectural trends in classroom design while capturing unique abilities present within a virtual context. A physical teaching module was also designed to create a platform for educators within the university to deliver instruction within the virtual campus

Cytocompatible Functional Polymers: In Situ Synthesis, Novel Triggering, and Multistep Actuation

Shape-memory polymers (SMPs) are a class of smart materials that can respond to stimuli. A one-way SMP can transform from a temporary shape to a permanent one. Taking advantage of their active response and deformation properties, SMPs have been studied for a variety of applications. Despite the extensive study on SMPs, significant challenges to their successful application in biomedical science still need to be addressed. For instance, although many studies have researched diverse shape-memory triggers as well as multi-shape memory (such as triple-shape memory and two-way SMPs), there has been almost no study of cytocompatible, non-thermally triggered, multi-shape change SMP, further limiting their applications in biomedicine. Furthermore, most SMPs used in biomedical research are synthesized at the macroscale, restricting their use in applications such as drug delivery. An additional limitation is the lack of biological coatings capable of enhancing SMP cytocompatibility or bioactivity. Scaling down to the micro/nano scale to address these issues is limited by currently available methods of synthesis. Previously, these topics have been studied independently, in isolation; in this thesis, in the interests of broadening the triggering and shape change mechanisms available to biomedical researchers, these concepts are integrated in a novel way. In the following subsections, each of these building blocks will be addressed independently, and the relationship between each will be systematically enlightened. First, this dissertation describes the development of a cytocompatible SMP that responds directly to cells (Chapter 2). Shape recovery in response to hepatic cells in the presence of heparin was successfully demonstrated. We envision using cell-responsive materials and phenomena in biomedical fields, expanding the range of SMP-triggering mechanisms to include biological cells. Next, this dissertation describes a triple-SMP that, with cells present, can undergo two different shape changes via two distinct cytocompatible triggers during active cell culture (Chapter 3). Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. This development can be anticipated to enable the incorporation of triple-shape memory into biomedical devices and strategies. Then, Chapter 4 of this dissertation describes the in situ fabrication and application of a human body temperature-triggered nanoscale SMP. The SMP NPs at their original shape exhibited reduced toxicity and enhanced cellular uptake towards homotypic cells. This innovative approach revealed a promising potential for cell membrane coating applications, as well as a novel method for targeted drug delivery of nanosized SMPs. Finally, Chapter 5 of this dissertation describes the cell-mediated polymerization of a fluorescent polymer (PNaSS) without the addition of initiator or ultraviolet illumination. Collectively, this dissertation addresses in situ polymerization of nanosized SMPs, a biological triggering mechanism, and a triple-SMP for biomedical applications