A System for 3D Ultrasound-Guided Robotic Retrieval of Foreign Bodies from a Beating Heart

Abstract²By way of the venous system or direct penetration, particles such as thrombi, bullet fragments, and shrapnel can become trapped in the heart and disrupt cardiac function. The severity of disruption can range from asymptomatic to fatal. Injuries of this nature are common in both civilian and military populations. For symptomatic cases, the conventional approach is removal of the foreign body through open heart surgery, which comes with high perioperative risks and a long recovery period. To circumvent these disadvantages, we propose a minimally invasive surgical approach for retrieving foreign bodies from a beating heart. This paper describes the first use of 3D transesophageal echocardiography (TEE) for steering a robot. Experiments demonstrate the feasibility of using 3D ultrasound to both guide and track a robot as it pursues a foreign body, with an RMS error of 1.6 mm in a laboratory setup. Results also support the hypothesis that direct pursuit of the foreign body may exceed the capabilities of conventional surgical robots, necessitating alternate retrieval strategies

A minimally invasive surgical system for 3D ultrasound guided robotic retrieval of foreign bodies from a beating heart

The result of various medical conditions and trauma, foreign bodies in the heart pose a serious health risk as they may interfere with cardiovascular function. Particles such as thrombi, bullet fragments, and shrapnel can become trapped in a person's heart after migrating through the venous system, or by direct penetration. The severity of disruption can range from benign to fatal, with associated symptoms including anxiety, fever, cardiac tamponade, hemorrhage, infection, embolism, arrhythmia, and valve dysfunction. Injuries of this nature are common in both civilian and military populations. For symptomatic cases, conventional treatment is removal of the foreign body through open surgery via a median sternotomy, the use of cardiopulmonary bypass, and a wide incision in the heart muscle; these methods incur pronounced perioperative risks and long recovery periods. In order to improve upon the standard of care, we propose an image guided robotic system and a corresponding minimally invasive surgical approach. The system employs a dexterous robotic capture device that can maneuver inside the heart through a small incision. Visualization and guidance within the otherwise occluded internal regions are provided by 3D transesophageal echocardiography (TEE), an emerging form of intraoperative medical imaging used in interventions such as mitral valve repair and device implantation. A robotic approach, as opposed to a manual procedure using rigid instruments, is motivated by the various challenges inherent in minimally invasive surgery, which arise from attempts to perform skilled surgical tasks through small incisions without direct vision. Challenges include reduced dexterity, constrained workspace, limited visualization, and difficult hand-eye coordination, which ultimately lead to poor manipulability. A dexterous robotic end effector with real-time image guidance can help overcome these challenges and potentially improve surgical performance. However promising, such a system and approach require that several technical hurdles be resolved. The foreign body must be automatically tracked as it travels about the dynamic environment of the heart. The erratically moving particle must then be captured using a dexterous robot that moves much more slowly in comparison. Furthermore, retrieval must be performed under 3D ultrasound guidance, amidst the uncertainties presented by both the turbulent flow and by the imaging modality itself. In addressing such barriers, this thesis explores the development of a prototype system capable of retrieving a foreign body from a beating heart, culminating in a set of demonstrative in vitro experiments

Translational cell based therapies to repair the heart

Cardiovascular disease comprising of Coronary Artery Disease (CAD) and Valvular Heart Disease (VHD) represents the leading disease in western societies accounting for the death of numerous patients. CAD may lead to heart failure (HF) and despite the therapeutic options for HF which evolved over the past years, the incidence of HF is continuously increasing with a higher percentage of aged people. Similarly, an increase of VHD can be observed and although valve replacement represents the most common therapy strategy for VHD, approximately 30% of the treated patients are affected from prosthesis-related problems within 10 years. While mechanical valves require lifelong anticoagulation treatment, bioprosthetic valves present with continuous degeneration without the ability to grow, repair or remodel. The concept of regenerative medicine comprising of cell-based therapies, bio engineering technologies and hybrid solutions has been proposed as a promising next generation approach to address CAD and VHD. While myocardial cell therapy has been suggested to have a beneficial effect on the failing myocardium, heart valve tissue engineering has been demonstrated to be a promising concept to generate living, autologous heart valves with the capability to grow and to remodel which may be particularly beneficial for children. Although these regenerative strategies have shown great potential in experimental studies, the translation into a clinical setting has either been limited or has been too rapid and premature leaving many key questions unanswered. The aim of this thesis was the systematic development of translational, cell-based bio engineering concepts addressing CAD (part A) and VHD (part B) with a particular focus on minimally invasive, transcatheter-based implantation techniques. In the setting of myocardial regeneration, in the second chapter the intrinsic regenerative potential of the heart is investigated. Myocardial samples were harvested from all four chambers of the human heart and were assessed for resident stem/progenitor cell populations. The results demonstrated that BRCP+ cells can be detected within the human heart and that they were more abundant than their c-kit+ counterparts. In the non-ischemic heart they were preferentially located in the atria while following ischemia, their numbers were increased significantly in the left ventricle. There were no c-kit+/BCRP+ co-expressing stem/progenitor cell populations suggesting that these two markers are expressed by two distinct cell populations in the human heart. Although these results provided a valuable snapshot at cardiac progenitor cells after acute ischemia, the data also indicated that the absolute numbers of cells acquiring a myocardial phenotype are rather low and further effort is needed to upscale such cells into clinically relevant numbers. In chapter three, it is demonstrated that human bone marrow and adipose tissue derived mesenchymal stem cells can be efficiently isolated via minimally invasive procedures and expanded to clinically relevant numbers for myocardial cell therapy. Thereafter, these cells were tested in a uniquely developed intrauterine, fetal, preimmune ovine myocardial infarction model for the evaluation of human cell fate in vivo. After the successful intrauterine induction of acute myocardial infarction, the cells were intramyocardially transplanted and tracked using a multimodal imaging approach comprising MRI, Micro CT as well as in vitro analysis tools. The principal feasibility of intra-myocardial stem-cell transplantation following intra-uterine induction of myocardial infarction in the preimmune fetal sheep could be demonstrated suggesting this as a unique platform to evaluate human cell-fate in a relevant large animal-model without the necessity of immunosuppressive therapy. In chapter four, adipose tissue derived mesenchymal stem cells (ATMSCs) were processed to generate three dimensional microtissues (3D-MTs) prior to transplantation to address the important issue of cell retention and survival. Thereafter, the ATMSCs based 3D-MTs were transplanted into the healthy and infarcted porcine myocardium using a catheter-based, 3D electromechanical mapping guided approach. The previously used MRI based tracking concept was successfully translated into this preclinical model allowing for the in vivo monitoring of 3D-MTs. To address Valvular Heart Disease (part B), in chapter five, marrow stromal derived cells were used to develop a unique autologous, cell-based engineered heart valve in situ tissue engineering concept comprising of minimally-invasive techniques for both, cell harvest and valve implantation. Autologous marrow stromal derived cells were harvested, seeded onto biodegradable scaffolds and integrated into self-expanding nitinol stents, before they were transapically delivered into the pulmonary position of non-human primates within the same intervention while avoiding any in vitro bio-reactor period. The results of these experiments demonstrated the principal feasibility of generating marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) and the transapical implantation in a one-step intervention. In chapter six, this concept was then successfully applied to the high-pressure system of the systemic circulation. After detailed adaption of the TEHV and stent design to the anatomic conditions of an orthotopic aortic valve, marrow stromal cell-based TEHV were implanted into the orthotopic aortic position. The implantation was successful and valve functionality was confirmed using fluoroscopy and trans-esophageal echocardiography. While displaying an ideal opening and closing behaviour with a sufficient co-aptation and a low pressure gradient, there were no signs of coronary occlusion or mal-perfusion. In conclusion, the results of this thesis represent a promising portfolio of translational concepts for cardiovascular regenerative medicine addressing CAD and VHD. In particular, it was demonstrated that mesenchymal stem cells / multipotent stromal derived cells represent a clinically relevant cell source for both myocardial regeneration and heart valve tissue engineering. It was shown that the preimmune fetal sheep myocardial infarction model represents a unique platform for the in vivo evaluation of human stem cells without the necessity of immunosuppressive therapy. Moreover, the concept of transcatheter based intramyocardial transplantation of mesenchymal stem cell-based 3D-MTs was introduced to enhance cellular retention and survival. Finally, in the setting of VHD it could be shown that marrow stromal cell based issue engineered heart valves can successfully generated and transapically implanted into the pulmonary and aortic position within a one-step intervention

Investigating a novel intramyocardial delivery method for induced pluripotent stem cell-derived cardiomyocytes

Cell therapy is a potential novel treatment for cardiac regeneration and numerous studies have attempted to transplant cells to regenerate the myocardium lost during myocardial infarction. To date, only minimal improvements to cardiac function have been reported. This is likely to occur from low cell retention following delivery and high cell death after transplantation. The thesis aimed to improve the delivery and engraftment of viable cells by using an injectable biomaterial which provides an implantable, biodegradable substrate for attachment and growth of cardiomyocytes derived from induced pluripotent stem cells (iPSC). The thesis describes the fabrication and characterisation of Thermally Induced Phase Separation (TIPS) microspheres, and functionalisation of the microspheres to enable cell attachment in xeno-free conditions. The selected formulation resulted in iPSC attachment, expansion, and retention of pluripotent phenotype. Differentiation of iPSC into cardiomyocytes was investigated and characterised, comparing in vitro culture to microsphere culture using flow cytometry, immunocytochemistry and western blotting techniques. Microsphere culture was shown to be protective against anoikis and compatible for injectable delivery. The in vivo compatibility of the microspheres was assessed using pre-clinical murine models. The microspheres were rendered trackable, using the computed tomography contrast agent barium sulphate, to assess the distribution after ultra-sound guided intramyocardial injections for targeted delivery. The findings suggest that barium sulphate-loaded microspheres can be used as a novel tool for optimising delivery techniques and tracking persistence and distribution of implanted products. Once in vivo compatibility was established, a cellularised microsphere formulation was delivered to the myocardium of immunocompromised mice, to compare the efficacy of biomaterial assisted versus suspension cell therapy. This work demonstrates that TIPS microcarriers offer a supporting matrix for culturing iPSC and iPSC derived cardiomyocytes in vitro and when implanted in vivo have the potential to be developed into an injectable biomaterial for cardiac regeneration

Advancements and Breakthroughs in Ultrasound Imaging

Ultrasonic imaging is a powerful diagnostic tool available to medical practitioners, engineers and researchers today. Due to the relative safety, and the non-invasive nature, ultrasonic imaging has become one of the most rapidly advancing technologies. These rapid advances are directly related to the parallel advancements in electronics, computing, and transducer technology together with sophisticated signal processing techniques. This book focuses on state of the art developments in ultrasonic imaging applications and underlying technologies presented by leading practitioners and researchers from many parts of the world

Histotripsy for Pediatric Cardiac Applications.

Medicine continues to move towards less invasive techniques for many cardiac conditions, especially for high-risk patients that may not tolerate the alternative, more invasive approach. For instance, patients born with the congenital heart defect hypoplastic left heart syndrome often require emergent creation of a perforation through the atrial septum for survival prior to palliative surgery. However, most approaches are catheter based, still invasive, and continue to have significant challenges, limitations, and complications. A completely non-invasive technique such as histotripsy may provide the same result in a faster, safer, and more efficient manner. Using high-pressure ultrasound pulses applied outside the body and focused to the targeted tissue, histotripsy generates a cluster of cavitating micro-bubbles that fractionate the target tissue. The goal of this work is to investigate the safety and efficacy of histotripsy for neonatal cardiac applications. To aid in this goal, therapy guidance and monitoring techniques are developed, and an integrated histotripsy therapy system, optimized for the human neonate with congenital heart disease, was designed and constructed. In this dissertation, histotripsy is first demonstrated to be capable of generating targeted intra-cardiac communications when positioned outside the body in an intact neonatal animal model with minimal collateral damage or systemic side-effects. Second, to mitigate the possibility of unintended injury due to heart motion, real-time motion correction using ultrasound imaging is developed and integrated into a histotripsy therapy system. The performance of the motion correction is quantified in vitro and a validated in a single in vivo experiment. Third, to maximize therapy efficacy, novel bubble-induced color Doppler feedback to monitor the degree of tissue damage during histotripsy treatment is developed and validated in vitro. Finally, a histotripsy therapy transducer with appropriate physical dimensions and acoustic parameters to precisely ablate cardiac tissue non-invasively in a human neonate is developed and integrated into an ultrasound guided histotripsy therapy system. The data and the integrated system accomplished from this dissertation form the essential foundation to a pioneering clinical trial for histotripsy cardiac therapy in infants, which will position histotripsy for application on a broad range of cardiac disorders in patients of all ages.PHDBiomedical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/108732/1/millerrm_1.pd

A Framework for Tumor Localization in Robot-Assisted Minimally Invasive Surgery

Manual palpation of tissue is frequently used in open surgery, e.g., for localization of tumors and buried vessels and for tissue characterization. The overall objective of this work is to explore how tissue palpation can be performed in Robot-Assisted Minimally Invasive Surgery (RAMIS) using laparoscopic instruments conventionally used in RAMIS. This thesis presents a framework where a surgical tool is moved teleoperatively in a manner analogous to the repetitive pressing motion of a finger during manual palpation. We interpret the changes in parameters due to this motion such as the applied force and the resulting indentation depth to accurately determine the variation in tissue stiffness. This approach requires the sensorization of the laparoscopic tool for force sensing. In our work, we have used a da Vinci needle driver which has been sensorized in our lab at CSTAR for force sensing using Fiber Bragg Grating (FBG). A computer vision algorithm has been developed for 3D surgical tool-tip tracking using the da Vinci \u27s stereo endoscope. This enables us to measure changes in surface indentation resulting from pressing the needle driver on the tissue. The proposed palpation framework is based on the hypothesis that the indentation depth is inversely proportional to the tissue stiffness when a constant pressing force is applied. This was validated in a telemanipulated setup using the da Vinci surgical system with a phantom in which artificial tumors were embedded to represent areas of different stiffnesses. The region with high stiffness representing tumor and region with low stiffness representing healthy tissue showed an average indentation depth change of 5.19 mm and 10.09 mm respectively while maintaining a maximum force of 8N during robot-assisted palpation. These indentation depth variations were then distinguished using the k-means clustering algorithm to classify groups of low and high stiffnesses. The results were presented in a colour-coded map. The unique feature of this framework is its use of a conventional laparoscopic tool and minimal re-design of the existing da Vinci surgical setup. Additional work includes a vision-based algorithm for tracking the motion of the tissue surface such as that of the lung resulting from respiratory and cardiac motion. The extracted motion information was analyzed to characterize the lung tissue stiffness based on the lateral strain variations as the surface inflates and deflates

Echocardiography

The book "Echocardiography - New Techniques" brings worldwide contributions from highly acclaimed clinical and imaging science investigators, and representatives from academic medical centers. Each chapter is designed and written to be accessible to those with a basic knowledge of echocardiography. Additionally, the chapters are meant to be stimulating and educational to the experts and investigators in the field of echocardiography. This book is aimed primarily at cardiology fellows on their basic echocardiography rotation, fellows in general internal medicine, radiology and emergency medicine, and experts in the arena of echocardiography. Over the last few decades, the rate of technological advancements has developed dramatically, resulting in new techniques and improved echocardiographic imaging. The authors of this book focused on presenting the most advanced techniques useful in today's research and in daily clinical practice. These advanced techniques are utilized in the detection of different cardiac pathologies in patients, in contributing to their clinical decision, as well as follow-up and outcome predictions. In addition to the advanced techniques covered, this book expounds upon several special pathologies with respect to the functions of echocardiography