IEEE transactions on medical robotics and bionics, May 1, 2021
Over the past decade, there has been growing interest in high-fidelity simulation for medical app... more Over the past decade, there has been growing interest in high-fidelity simulation for medical applications leading to huge research efforts towards physical organ simulators with realistic representations of human organs. As this is a relatively young research field, this review aims to provide an insight into the current state of the art in high-fidelity physical organ simulators that are used for training purposes, as educational tools, for biomechanical studies, and for preclinical device testing. Motivated by a paucity of clear definitions and categorization of various simulators, we describe high-fidelity physical organ simulators in terms of their degree of representation of the anatomy, material properties, and physiological behavior of the target organs in the context of their applications. We highlight the traditional approaches for static organ simulators using synthetic materials, and diverse approaches for dynamic organ simulators including soft robotic, ex vivo, and biohybrid strategies to meet the ever-increasing demand for realistic anthropomorphic organ models. Finally, we discuss challenges and potential future avenues in the field of high-fidelity physical organ simulators.
Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmicall... more Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmically compressed in the transverse symmetry plane. Due to the resulting asymmetry between the suction and discharge pipes, a net pumping head is achieved. Asymmetric pumping is regarded as one of the main mechanisms responsible for the Liebau effect in addition to impedance pumping. However, there remains a paucity of research surrounding the governing parameters of asymmetric pumping. Here, we conducted an experimental study of the performance of an asymmetric pump, with an aim to assess its potential for extravascular flow augmentation. A custom flexible latex tube and experimental platform were developed for this purpose. We tested various tube thicknesses and pinching frequencies. Our results demonstrate that the performance is within the range of physiological requirements for pediatric circulatory devices (~ 1 L/min and < 30 mmHg). We conclude that due to the absence of reverse flow and its mechanical simplicity, pure asymmetric pumping is promising for selected cardiovascular applications with less complexity than other valveless techniques. The category of valveless pumping encompasses phenomena which can generate a controlled, unidirectional flow without valves. One of the most widely studied valveless pumping mechanisms is the Liebau effect 1. A Liebau pump is a small device consisting of a straight elastic tube with two differentiated segments: a wider and more distensible segment, and a narrow, stiff segment. Upon cyclical compression of the wider segment, a net flow is achieved towards the narrower segment. The Liebau effect can be explained as the superposition of two different pumping mechanisms: impedance pumping and asymmetric pumping 2. Impedance pumping occurs in a circuit where a compliant tube is connected to rigid pipes creating a sharp difference in impedance. Due to this, the pressure waves are strongly reflected in both compliant tube ends. Additionally, the pincher is not placed at the compliant tube symmetry plane. As a result of the pinching, mechanical energy is added to the fluid, mainly in form of pressure. These pressure waves travel from the pinching region towards both ends of the compliant tube, where they are reflected. As the pincher is not equidistant from both ends, the reflected pressure waves do not cancel each other, generating a pressure field that creates the pumping effect 3. Conversely, in asymmetric pumping the actuator is located at the compliant tube symmetry plane and thus reflected pressure waves cancel each other. The main feature of asymmetric pumping is that an asymmetry in the hydraulic resistance of the rigid pipes is necessary to achieve pumping. In order to illustrate this classification, Fig. 1 considers length as the only asymmetric parameter, and includes an example that would not achieve pumping (Fig. 1d). More broadly, asymmetry could be achieved by varying the diameter, material or design of the compliant tube. In all cases, the pumping effect is generated by pulse pressure waves travelling through the system. Asymmetry results in a net axial pressure gradient 4 .
Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular med... more Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, we describe the development of a highly tunable porcine model of HFpEF hemodynamics using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. We demonstrate the feasibility of the proposed model in preclinical testing by evaluating the hemodynamic resp...
Our understanding of cardiac remodeling processes due to left ventricular pressure overload deriv... more Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to simultaneously enable control over disease progression and reversal, hindering their clinical relevance. Here, we describe a method for controlled, progressive, and reversible aortic banding based on an implantable expandable actuator that can be finely controlled to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our model can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leverage the ability of our model to enable non-invasive aortic debanding to show that these changes can be partly reversed due to cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this model could elucidate fundamental mechanisms...
A range of congenital heart diseases result in a single functioning ventricle. This is palliative... more A range of congenital heart diseases result in a single functioning ventricle. This is palliatively treated by connecting the systemic and pulmonary vasculature in series, establishing what is known as the Fontan circulation. This physiology allows post-natal survival but causes aberrant haemodynamics that causes high morbidity and mortality. Due to limited clinical data, accurate modelling of single ventricle haemodynamics is critical for improving patient care. Although sophisticated haemodynamic models have been developed, their clinical relevance is hindered by their inability to mimic the biomechanical interactions of breathing pressures with vascular reservoirs as one interdependent unit which governs flow patterns and flow reversal in this physiology. Here, we report the development of a tuneable biomimetic single ventricle simulator platform that re-creates breathing mechanics and recapitulates Fontan venous flow patterns. Benchtop characterization, computational modelling, ...
An Abdominal Aortic Aneurysm (AAA) is a dilation of the aorta at the level of the abdomen. To red... more An Abdominal Aortic Aneurysm (AAA) is a dilation of the aorta at the level of the abdomen. To reduce the risk of rupture, an endograft is often implanted inside the aneurysm to decrease pressure on the aneurysm sac. To maintain blood flow to major abdominal vessels, a fenestrated endograft can be used, whereby physicians modify commercial endografts by creating fenestrations based on preoperative computed tomography imaging. The manual process of aligning patient-specific visceral anatomy onto endografts can be tedious and subject to human error. Here we developed a computational program, ‘FenFit’, for automated fitting of fenestrations onto commercially available endografts. A pilot clinical study was conducted to evaluate the efficiency of FenFit compared to physician manual planning, showing FenFit can reduce planning time by 62-fold on average. Our program has potential to improve clinical outcomes by providing a user interface that is expeditious and far less susceptible to hum...
Blood clots originating in the left atrial appendage (LAA) are the leading cause of ischemic stro... more Blood clots originating in the left atrial appendage (LAA) are the leading cause of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Complications from and contraindications to oral anticoagulants (OACs), in addition to the recent successes of endocardial LAA closure devices, have driven increased interest in mechanical LAA occlusion. However, current devices are limited in their abilities to accommodate diverse LAA anatomies, motivating the development of a novel endocardial LAA occluder that supports more anatomical variability. We present the design of an in-situ expandable plug as well as an accompanying pacifier module for LAA occlusion. The final design accommodates LAA diameter ranges of 14 millimeters for each device size (10-24mm and 24-38mm), double that of any approved device. This adaptability can help to overcome imperfect pre-procedural imaging and suboptimal device fit. Benchtop tug and leak tests demonstrate the stability and sealing capacities ...
Broad adoption of magnetic soft robotics is hampered by the sophisticated field paradigms for the... more Broad adoption of magnetic soft robotics is hampered by the sophisticated field paradigms for their manipulation and the complexities in controlling multiple devices. Furthermore, high‐throughput fabrication of such devices across spatial scales remains challenging. Here, advances in fiber‐based actuators and magnetic elastomer composites are leveraged to create 3D magnetic soft robots controlled by unidirectional fields. Thermally drawn elastomeric fibers are instrumented with a magnetic composite synthesized to withstand strains exceeding 600%. A combination of strain and magnetization engineering in these fibers enables programming of 3D robots capable of crawling or walking in magnetic fields orthogonal to the plane of motion. Magnetic robots act as cargo carriers, and multiple robots can be controlled simultaneously and in opposing directions using a single stationary electromagnet. The scalable approach to fabrication and control of magnetic soft robots invites their future ap...
Soft pneumatic artificial muscles are increasingly popular in the field of soft robotics due to t... more Soft pneumatic artificial muscles are increasingly popular in the field of soft robotics due to their light-weight, complex motions, and safe interfacing with humans. In this paper, we present a Vacuum-Powered Artificial Muscle (VPAM) with an adjustable operating length that offers adaptability throughout its use, particularly in settings with variable workspaces. To achieve the adjustable operating length, we designed the VPAM with a modular structure consisting of cells that can be clipped in a collapsed state and unclipped as desired. We then conducted a case study in infant physical therapy to demonstrate the capabilities of our actuator. We developed a dynamic model of the device and a model-informed open-loop control system, and validated their accuracy in a simulated patient setup. Our results showed that the VPAM maintains its performance as it grows. This is crucial in applications such as infant physical therapy where the device must adapt to the growth of the patient duri...
Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with... more Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient’s cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients’ hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD)...
Aortic stenosis (AS) affects approximately 1.5 million people in the US and is associated with a ... more Aortic stenosis (AS) affects approximately 1.5 million people in the US and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need of high-fidelity testing platforms for these devices. We propose a soft robotic model of AS capable of recapitulating patient-specific hemodynamics of AS and secondary ventricular remodeling, validated against clinical data. The model leverages 3D printed replicas of each patient’s cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients’ hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, while a left ventricular sleeve recapitulates loss of ventricular compliance, and impaired filling associate...
IEEE transactions on medical robotics and bionics, May 1, 2021
Over the past decade, there has been growing interest in high-fidelity simulation for medical app... more Over the past decade, there has been growing interest in high-fidelity simulation for medical applications leading to huge research efforts towards physical organ simulators with realistic representations of human organs. As this is a relatively young research field, this review aims to provide an insight into the current state of the art in high-fidelity physical organ simulators that are used for training purposes, as educational tools, for biomechanical studies, and for preclinical device testing. Motivated by a paucity of clear definitions and categorization of various simulators, we describe high-fidelity physical organ simulators in terms of their degree of representation of the anatomy, material properties, and physiological behavior of the target organs in the context of their applications. We highlight the traditional approaches for static organ simulators using synthetic materials, and diverse approaches for dynamic organ simulators including soft robotic, ex vivo, and biohybrid strategies to meet the ever-increasing demand for realistic anthropomorphic organ models. Finally, we discuss challenges and potential future avenues in the field of high-fidelity physical organ simulators.
Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmicall... more Asymmetric pumping is a sub-category of valveless pumping in which a flexible tube is rhythmically compressed in the transverse symmetry plane. Due to the resulting asymmetry between the suction and discharge pipes, a net pumping head is achieved. Asymmetric pumping is regarded as one of the main mechanisms responsible for the Liebau effect in addition to impedance pumping. However, there remains a paucity of research surrounding the governing parameters of asymmetric pumping. Here, we conducted an experimental study of the performance of an asymmetric pump, with an aim to assess its potential for extravascular flow augmentation. A custom flexible latex tube and experimental platform were developed for this purpose. We tested various tube thicknesses and pinching frequencies. Our results demonstrate that the performance is within the range of physiological requirements for pediatric circulatory devices (~ 1 L/min and < 30 mmHg). We conclude that due to the absence of reverse flow and its mechanical simplicity, pure asymmetric pumping is promising for selected cardiovascular applications with less complexity than other valveless techniques. The category of valveless pumping encompasses phenomena which can generate a controlled, unidirectional flow without valves. One of the most widely studied valveless pumping mechanisms is the Liebau effect 1. A Liebau pump is a small device consisting of a straight elastic tube with two differentiated segments: a wider and more distensible segment, and a narrow, stiff segment. Upon cyclical compression of the wider segment, a net flow is achieved towards the narrower segment. The Liebau effect can be explained as the superposition of two different pumping mechanisms: impedance pumping and asymmetric pumping 2. Impedance pumping occurs in a circuit where a compliant tube is connected to rigid pipes creating a sharp difference in impedance. Due to this, the pressure waves are strongly reflected in both compliant tube ends. Additionally, the pincher is not placed at the compliant tube symmetry plane. As a result of the pinching, mechanical energy is added to the fluid, mainly in form of pressure. These pressure waves travel from the pinching region towards both ends of the compliant tube, where they are reflected. As the pincher is not equidistant from both ends, the reflected pressure waves do not cancel each other, generating a pressure field that creates the pumping effect 3. Conversely, in asymmetric pumping the actuator is located at the compliant tube symmetry plane and thus reflected pressure waves cancel each other. The main feature of asymmetric pumping is that an asymmetry in the hydraulic resistance of the rigid pipes is necessary to achieve pumping. In order to illustrate this classification, Fig. 1 considers length as the only asymmetric parameter, and includes an example that would not achieve pumping (Fig. 1d). More broadly, asymmetry could be achieved by varying the diameter, material or design of the compliant tube. In all cases, the pumping effect is generated by pulse pressure waves travelling through the system. Asymmetry results in a net axial pressure gradient 4 .
Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular med... more Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, we describe the development of a highly tunable porcine model of HFpEF hemodynamics using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. We demonstrate the feasibility of the proposed model in preclinical testing by evaluating the hemodynamic resp...
Our understanding of cardiac remodeling processes due to left ventricular pressure overload deriv... more Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to simultaneously enable control over disease progression and reversal, hindering their clinical relevance. Here, we describe a method for controlled, progressive, and reversible aortic banding based on an implantable expandable actuator that can be finely controlled to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our model can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leverage the ability of our model to enable non-invasive aortic debanding to show that these changes can be partly reversed due to cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this model could elucidate fundamental mechanisms...
A range of congenital heart diseases result in a single functioning ventricle. This is palliative... more A range of congenital heart diseases result in a single functioning ventricle. This is palliatively treated by connecting the systemic and pulmonary vasculature in series, establishing what is known as the Fontan circulation. This physiology allows post-natal survival but causes aberrant haemodynamics that causes high morbidity and mortality. Due to limited clinical data, accurate modelling of single ventricle haemodynamics is critical for improving patient care. Although sophisticated haemodynamic models have been developed, their clinical relevance is hindered by their inability to mimic the biomechanical interactions of breathing pressures with vascular reservoirs as one interdependent unit which governs flow patterns and flow reversal in this physiology. Here, we report the development of a tuneable biomimetic single ventricle simulator platform that re-creates breathing mechanics and recapitulates Fontan venous flow patterns. Benchtop characterization, computational modelling, ...
An Abdominal Aortic Aneurysm (AAA) is a dilation of the aorta at the level of the abdomen. To red... more An Abdominal Aortic Aneurysm (AAA) is a dilation of the aorta at the level of the abdomen. To reduce the risk of rupture, an endograft is often implanted inside the aneurysm to decrease pressure on the aneurysm sac. To maintain blood flow to major abdominal vessels, a fenestrated endograft can be used, whereby physicians modify commercial endografts by creating fenestrations based on preoperative computed tomography imaging. The manual process of aligning patient-specific visceral anatomy onto endografts can be tedious and subject to human error. Here we developed a computational program, ‘FenFit’, for automated fitting of fenestrations onto commercially available endografts. A pilot clinical study was conducted to evaluate the efficiency of FenFit compared to physician manual planning, showing FenFit can reduce planning time by 62-fold on average. Our program has potential to improve clinical outcomes by providing a user interface that is expeditious and far less susceptible to hum...
Blood clots originating in the left atrial appendage (LAA) are the leading cause of ischemic stro... more Blood clots originating in the left atrial appendage (LAA) are the leading cause of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Complications from and contraindications to oral anticoagulants (OACs), in addition to the recent successes of endocardial LAA closure devices, have driven increased interest in mechanical LAA occlusion. However, current devices are limited in their abilities to accommodate diverse LAA anatomies, motivating the development of a novel endocardial LAA occluder that supports more anatomical variability. We present the design of an in-situ expandable plug as well as an accompanying pacifier module for LAA occlusion. The final design accommodates LAA diameter ranges of 14 millimeters for each device size (10-24mm and 24-38mm), double that of any approved device. This adaptability can help to overcome imperfect pre-procedural imaging and suboptimal device fit. Benchtop tug and leak tests demonstrate the stability and sealing capacities ...
Broad adoption of magnetic soft robotics is hampered by the sophisticated field paradigms for the... more Broad adoption of magnetic soft robotics is hampered by the sophisticated field paradigms for their manipulation and the complexities in controlling multiple devices. Furthermore, high‐throughput fabrication of such devices across spatial scales remains challenging. Here, advances in fiber‐based actuators and magnetic elastomer composites are leveraged to create 3D magnetic soft robots controlled by unidirectional fields. Thermally drawn elastomeric fibers are instrumented with a magnetic composite synthesized to withstand strains exceeding 600%. A combination of strain and magnetization engineering in these fibers enables programming of 3D robots capable of crawling or walking in magnetic fields orthogonal to the plane of motion. Magnetic robots act as cargo carriers, and multiple robots can be controlled simultaneously and in opposing directions using a single stationary electromagnet. The scalable approach to fabrication and control of magnetic soft robots invites their future ap...
Soft pneumatic artificial muscles are increasingly popular in the field of soft robotics due to t... more Soft pneumatic artificial muscles are increasingly popular in the field of soft robotics due to their light-weight, complex motions, and safe interfacing with humans. In this paper, we present a Vacuum-Powered Artificial Muscle (VPAM) with an adjustable operating length that offers adaptability throughout its use, particularly in settings with variable workspaces. To achieve the adjustable operating length, we designed the VPAM with a modular structure consisting of cells that can be clipped in a collapsed state and unclipped as desired. We then conducted a case study in infant physical therapy to demonstrate the capabilities of our actuator. We developed a dynamic model of the device and a model-informed open-loop control system, and validated their accuracy in a simulated patient setup. Our results showed that the VPAM maintains its performance as it grows. This is crucial in applications such as infant physical therapy where the device must adapt to the growth of the patient duri...
Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with... more Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient’s cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients’ hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD)...
Aortic stenosis (AS) affects approximately 1.5 million people in the US and is associated with a ... more Aortic stenosis (AS) affects approximately 1.5 million people in the US and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need of high-fidelity testing platforms for these devices. We propose a soft robotic model of AS capable of recapitulating patient-specific hemodynamics of AS and secondary ventricular remodeling, validated against clinical data. The model leverages 3D printed replicas of each patient’s cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients’ hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, while a left ventricular sleeve recapitulates loss of ventricular compliance, and impaired filling associate...
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Papers by Ellen Roche