Design and Development of a Surgical Robot for Needle-Based Medical Interventions

Lung cancer is the leading cause of cancer related deaths. If diagnosed in a timely manner, the treatment of choice is surgical resection of the cancerous lesions followed by radiotherapy. However, surgical resection may be too invasive for some patients due to old age or weakness. An alternative is minimally invasive needle-based interventions for cancer diagnosis and treatment. This project describes the design, analysis, development and experimental evaluation of a modular, compact, patient-mounted robotic manipulator for lung cancer diagnosis and treatment. In this regard, a novel parallel Remote Centre of Motion (RCM) mechanism is proposed for minimally invasive delivery of needle-based interventions. The proposed robot provides four degrees of freedom (DOFs) to orient and move a surgical needle within a spherical coordinate system. There is an analytical solution for the kinematics of the proposed parallel mechanism and the end-effectors motion is well-conditioned within the required workspace. The RCM is located beneath the skin surface to minimize the invasiveness of the surgical procedure while providing the required workspace to target the cancerous lesions. In addition, the proposed robot benefits from a design capable of measuring the interaction forces between the needle and the tissue. The experimental evaluation of the robot has proved its capability to accurately orient and move a surgical needle within the required workspace. Although this robotic system has been designed for the treatment of lung cancer, it is capable of performing other procedures in the thoracic or abdominal cavity such as liver cancer diagnosis and treatment

Ultrasound-Guided Mechatronic System for Targeted Delivery of Cell-Based Cancer Vaccine Immunotherapy in Preclinical Models

Injection of dendritic cell (DC) vaccines into lymph nodes (LN) is a promising strategy for eliciting immune responses against cancer, but these injections in mouse cancer models are challenging due to the small target scale (~ 1 mm × 2 mm). Direct manual intranodal injection is difficult and can cause architectural damage to the LN, potentially disrupting crucial interactions between DC and T cells. Therefore, a second-generation ultrasound-guided mechatronic device has been developed to perform this intervention. A targeting accuracy of \u3c 500 μm will enable targeted delivery of the DCs specifically to a LN subcapsular space. The device was redesigned from its original CT-guided edition, which used a remote centre of motion architecture, to be easily integrated onto a commercially available VisualSonics imaging rail system. Subtle modifications were made to ensure simple workflow that allows for live-animal interventions that fall within the knockout periods stated in study protocols. Several calibration and registration techniques were developed in order to achieve an overall targeting accuracy appropriate for the intended application. A variety of methods to quantify the positioning accuracy of the device were investigated. The method chosen involved validating a guided injection into a tissue-mimicking phantom using ultrasound imaging post-operatively to localize the end-point position of the needle tip in the track left behind by the needle. Ultrasound-guided injections into a tissue-mimicking phantom revealed a targeting accuracy of 285 ± 94 μm for the developed robot compared to 508 ± 166 μm for a commercial-available manually-actuated injection device from VisuailSonics. The utility of the robot was also demonstrated by performing in vivo injections into the lymph nodes of mice

Hand-eye calibration, constraints and source synchronisation for robotic-assisted minimally invasive surgery

In robotic-assisted minimally invasive surgery (RMIS), the robotic system allows surgeons to remotely control articulated instruments to perform surgical interventions and introduces a potential to implement computer-assisted interventions (CAI). However, the information in the camera must be correctly transformed into the robot coordinate as its movement is controlled by the robot kinematic. Therefore, determining the rigid transformation connecting the coordinates is necessary. Such process is called hand-eye calibration. One of the challenges in solving the hand-eye problem in the RMIS setup is data asynchronicity, which occurs when tracking equipments are integrated into a robotic system and create temporal misalignment. For the calibration itself, noise in the robot and camera motions can be propagated to the calibrated result and as a result of a limited motion range, the error cannot be fully suppressed. Finally, the calibration procedure must be adaptive and simple so a disruption in a surgical workflow is minimal since any change in the setup may require another calibration procedure. We propose solutions to deal with the asynchronicity, noise sensitivity, and a limited motion range. We also propose a potential to use a surgical instrument as the calibration target to reduce the complexity in the calibration procedure. The proposed algorithms are validated through extensive experiments with synthetic and real data from the da Vinci Research Kit and the KUKA robot arms. The calibration performance is compared with existing hand-eye algorithms and it shows promising results. Although the calibration using a surgical instrument as the calibration target still requires a further development, results indicate that the proposed methods increase the calibration performance, and contribute to finding an optimal solution to the hand-eye problem in robotic surgery

Neutrophil Interstitial Migration

Purpose: Molecular events regulating neutrophil extravasation have been extensively researched and described. However, relatively little is known about extravascular interstitial migration of neutrophils and then, much of what we do know has come from in vitro 2-D or 3-D matrix models. These models are limited by their ability to duplicate the nuances of the physiological or physical native environment. Neutrophils often migrate a considerable distance from the site of extravasation through the avascular corneal stroma to reach the site of injury. This migration involves contact with extracellular matrix and resident keratocytes. Ultrastructural morphometric data suggest neutrophil contacts with keratocytes are mediated by the leukocyte β2 (CD18) integrins and ICAM-1(a β2 ligand). While β1 (CD29) and β3 (CD61) integrin families are also expressed on extravascular migrating neutrophils, in vitro studies have shown that locomotion of activated neutrophils is dependent on integrin binding on 2-D surfaces, but not in 3-D matrixes. The role of integrin binding during in vivo corneal stroma migration has yet to be clearly defined. A greater understanding of this migration holds the promise of a more effective means for modulating neutrophil activity to control inflammation and improve the outcome of wound healing. Additionally, it may elicit details of motility applicable to other types of cells. The purpose of this dissertation is to provide insights into the mechanisms of neutrophil migration through the corneal stroma. Specifically, it addresses the influence of the keratocyte network on migrating neutrophils and the relative contribution of β1 (CD29), β2 (CD18) and β3 (CD61) integrins to neutrophil locomotion in the inflamed mouse cornea. In vivo data obtained using Heidelberg Retinal Tomographer III with Rostock Corneal Module (HRT-RCM) time lapse sequences provided the means, for the first time, to quantify speed and directionality of cellular movement while observing neutrophil interaction with stromal keratocytes in the living eye. Methods: Corneal inflammation was induced in female wild type C57BL/6 mice by mechanical removal of the epithelium using an Algerbrush. Eight hours after injury the corneas were imaged with the HRT-RCM. Scanning sequences provided the means to track individual cells for extended time periods to determine motility characteristics. The contribution of integrin binding to neutrophil migration was assessed by blocking antibody (anti-β1-, β2-, or β3-integrin) or IgG control antibody applied to the cornea at the time of epithelial injury. Image stabilization, cell tracking and movement analysis were accomplished with a custom MatLab program. Results: Time-lapse imaging showed an unequivocal preference for neutrophils to follow the network of keratocytes. Neutrophils in control eyes moved with an average speed of 7.56±0.20 (SE) µm/minute. The average confinement ratio (CR) of the neutrophil population was 0.55±0.02, where a value of 1.0 indicates confinement to a perfectly straight path. Compared to the results from control eyes, anti- β1-integrin antibody resulted in a 31 % reduction in speed (p<0.05) and a 33% reduction in CR (p<0.05), while anti-β2- or β3- integrin antibodies had no significant effect on cell speed or CR. Conclusions: Results clearly show that the keratocyte network is the preferred route for neutrophil migration within the corneal stroma. Contrary to expectations based on previously published histological and in vitro evidence, blockade of β2-integrin does not affect in vivo motility and the same is true for β3-integrin blockade. However, β1 blockade produced a significant, but not total, reduction in cell speed and resulted in migrating cells being less confined to a straight path. Therefore, neutrophil locomotion within the physically confined environment of the corneal stroma does not require integrin binding, though β1 binding facilitates the process.Optometry, College o

From 3D Models to 3D Prints: an Overview of the Processing Pipeline

Due to the wide diffusion of 3D printing technologies, geometric algorithms for Additive Manufacturing are being invented at an impressive speed. Each single step, in particular along the Process Planning pipeline, can now count on dozens of methods that prepare the 3D model for fabrication, while analysing and optimizing geometry and machine instructions for various objectives. This report provides a classification of this huge state of the art, and elicits the relation between each single algorithm and a list of desirable objectives during Process Planning. The objectives themselves are listed and discussed, along with possible needs for tradeoffs. Additive Manufacturing technologies are broadly categorized to explicitly relate classes of devices and supported features. Finally, this report offers an analysis of the state of the art while discussing open and challenging problems from both an academic and an industrial perspective.Comment: European Union (EU); Horizon 2020; H2020-FoF-2015; RIA - Research and Innovation action; Grant agreement N. 68044

Design and Development of a Tele-operated Surgical Simulation Environment

With the introduction of robots into laparoscopic surgery, surgeons have difficulties in selecting the placement of the incisions required to insert the robots instruments into the body and also determine which patients are suitable for robotically assisted surgery. Poor selection of these two items mentioned above can result in a conversion to a more invasive form of surgery during the procedure. This work introduces the design and development of a surgical simulation environment to assist in the research for optimal incision placement and patient selection. The simulator allows importing any serial link robot that was designed in a computer aided modelling package. With minimal added information, the imported robot can be controlled using a multi-degree of freedom user input device. The simulator allows for importing patient geometries along with the robot to allow for the simulation of surgical procedures. A Jacobian transpose algorithm was added onto the simulator in a modular format to control the simulated robots, as well as to allow for other control systems to be created and implemented. Experiments were performed to determine the effects of patient geometry models on rendering speeds. The control system could control the tested robots with a maximum lag time of 15 ms between moving the input device and the simulated robot moving to the correct desired position. The simulator makes importing and controlling robots a simple and intuitive matter, without putting a large restriction on the type of robots to be simulated. The simulator also allows for importing models of a patient, to make real world analysis of a patient possible. Further improvements on the presented simulator include the addition of collision detection and more testing on the control system for stability and response over a larger range of robots

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

Wetland mapping and monitoring using polarimetric and interferometric synthetic aperture radar (SAR) data and tools

Wetlands are home to a great variety of flora and fauna species and provide several unique environmental functions, such as controlling floods, improving water-quality, supporting wildlife habitat, and shoreline stabilization. Detailed information on spatial distribution of wetland classes is crucial for sustainable management and resource assessment. Furthermore, hydrological monitoring of wetlands is also important for maintaining and preserving the habitat of various plant and animal species. This thesis investigates the existing knowledge and technological challenges associated with wetland mapping and monitoring and evaluates the limitations of the methodologies that have been developed to date. The study also proposes new methods to improve the characterization of these productive ecosystems using advanced remote sensing (RS) tools and data. Specifically, a comprehensive literature review on wetland monitoring using Synthetic Aperture Radar (SAR) and Interferometric SAR (InSAR) techniques is provided. The application of the InSAR technique for wetland mapping provides the following advantages: (i) the high sensitivity of interferometric coherence to land cover changes is taken into account and (ii) the exploitation of interferometric coherence for wetland classification further enhances the discrimination between similar wetland classes. A statistical analysis of the interferometric coherence and SAR backscattering variation of Canadian wetlands, which are ignored in the literature, is carried out using multi-temporal, multi-frequency, and multi-polarization SAR data. The study also examines the capability of compact polarimetry (CP) SAR data, which will be collected by the upcoming RADARSAT Constellation Mission (RCM) and will constitute the main source of SAR observation in Canada, for wetland mapping. The research in this dissertation proposes a methodology for wetland classification using the synergistic use of intensity, polarimetry, and interferometry features using a novel classification framework. Finally, this work introduces a novel model based on the deep convolutional neural network (CNN) for wetland classification that can be trained in an end-to-end scheme and is specifically designed for the classification of wetland complexes using polarimetric SAR (PolSAR) imagery. The results of the proposed methods are promising and will significantly contribute to the ongoing efforts of conservation strategies for wetlands and monitoring changes. The approaches presented in this thesis serve as frameworks, progressing towards an operational methodology for mapping wetland complexes in Canada, as well as other wetlands worldwide with similar ecological characteristics

Clinical Reflectance Confocal Microscope for Imaging of Oral Cancer

Biopsy and histopathology remain the standard method for diagnosis of oral cancer in the clinic today. Early detection of oral cancer is fundamental to a higher survival rate, and a non-invasive method is preferred. This is possible through optical imaging techniques. This dissertation describes the design, development and testing of a clinical reflectance confocal microscope for imaging of oral cancer in combination with macroscopic fluorescence lifetime imaging (FLIM). A compact bench top reflectance confocal microscope was designed and constructed for use in combination with a bench top FLIM system. The system was evaluated by imaging porcine oral tissue ex vivo and normal and dysplastic hamster cheek pouch tissue in vivo. To facilitate in vivo imaging of the human oral cavity, an electrically tunable lens was integrated in the system for axial scanning and a miniature objective lens was designed and fabricated for access into the oral cavity. Performance of the system was characterized over the full range of axial scanning with the electrically tunable lens. The reflectance confocal microscopy system was tested in combination with macroscopic FLIM by imaging normal and pre-cancerous human oral tissue ex vivo and in vivo in the clinic