CARDIOVASCULAR COMPLICATIONS FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT: QUANTIFICATION AND SYSTEMATIC DIFFERENTIATION USING CLINICAL MEASUREMENTS AND IMAGE-BASED PATIENT-SPECIFIC IN SILICO MODELING

The success of TAVR procedure hinges on quantifications of the global hemodynamics (heart function metrics and workload), and the local hemodynamics (3-dimensional flow dynamics in left ventricle, aortic root, and coronary arteries). In this study, we developed an image-based framework that can quantify local and global hemodynamics for TAVR assessment. The proposed framework uses fluid-structure interaction method and lumped-parameter modeling that only needs routine non-invasive clinical patient data. The computational framework was validated against clinical cardiac catheterization data and Doppler echocardiographic measurements. One of the challenging aspects of TAVR is its common association with complex valvular, ventricular, and vascular diseases (C3VD). Treatment strategies for these patients are quite uncertain and, on a case-by-case basis. In order to examine long term risk factors and create guidelines for intervention aimed at minimizing the progression of cardiovascular disease, the impact of C3VD on ventricle fluid dynamics in patients who underwent TAVR was investigated in this thesis. Our results showed that interactions of C3VD with TAVR fluid dynamics may amplify adverse hemodynamic effects that limit the benefits of TAVR and might contribute to speed up disease progression. The results suggest that some other interventions in addition to TAVR, such as mitral valve intervention and percutaneous coronary intervention, might be required as regularly chosen current surgical techniques might not be optimal for patients with C3VD who undergo TAVR. Post-TAVR complications including paravalvular leakage, thrombosis and coronary obstruction remain as the main Achilles heels of TAVR. While coronary artery disease (CAD) is present in approximately half of TAVR candidates, correlation of post-TAVR complications such as paravalvular leakage (PVL) or misalignment with CAD are not fully understood. To effectively evaluate risk status and create guidelines for intervention, precise quantification of aortic root and coronary artery hemodynamics is required. We used a patient-specific multiscale computational-mechanics framework in both pre and post TAVR states to investigate the effect of TAVR complications such as PVL and misalignments on the coronary arteries and aortic root hemodynamics. The proposed framework could provide a platform for testing the intervention scenarios and evaluating their influences on the hemodynamics.ThesisDoctor of Philosophy (PhD)Transcatheter aortic valve replacement is an emerging less invasive intervention for patients with aortic stenosis. Although hemodynamics quantification is critical for accurate and early diagnosis of aortic stenosis, proper diagnostic methods for these diseases are still lacking because fluid-dynamics methods, that can be used as engines of new diagnostic tools, are not well developed yet. We developed an image-based patient-specific computational framework that can quantify hemodynamics in patients with aortic stenosis who received transcatheter aortic valve replacement. We also used its diagnostic abilities by providing novel analyses and interpretations of clinical data to answer clinical questions

Mixed Valvular Disease Following Transcatheter Aortic Valve Replacement: Quantification and Systematic Differentiation Using Clinical Measurements and Image-Based Patient‐Specific In Silico Modeling

Background: Mixed valvular disease (MVD), mitral regurgitation (MR) from pre‐existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre‐existing MVD, PVL, LV, and post‐TAVR recovery is meager. Methods and Results: We quantified the effects of MVD on valvular‐ventricular hemodynamics using an image‐based patient‐specific computational framework in 72 MVD patients. Doppler pressure was reduced by TAVR (mean, 77%; N=72; P<0.05), but it was not always accompanied by improvements in LV workload. TAVR had no effect on LV workload in 22 patients, and LV workload post‐TAVR significantly rose in 32 other patients. TAVR reduced LV workload in only 18 patients (25%). PVL significantly alters LV flow and increases shear stress on transcatheter aortic valve leaflets. It interacts with mitral inflow and elevates shear stresses on mitral valve and is one of the main contributors in worsening of MR post‐TAVR. MR worsened in 32 patients post‐TAVR and did not improve in 18 other patients. Conclusions: PVL limits the benefit of TAVR by increasing LV load and worsening of MR and heart failure. Post‐TAVR, most MVD patients (75% of N=72; P<0.05) showed no improvements or even worsening of LV workload, whereas the majority of patients with PVL, but without that pre‐existing MR condition (60% of N=48; P<0.05), showed improvements in LV workload. MR and its exacerbation by PVL may hinder the success of TAVR

Mixed Valvular Disease Following Transcatheter Aortic Valve Replacement: Quantification and Systematic Differentiation Using Clinical Measurements and Image-Based Patient‐Specific In Silico Modeling

Background: Mixed valvular disease (MVD), mitral regurgitation (MR) from pre‐existing disease in conjunction with paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR), is one of the most important stimuli for left ventricle (LV) dysfunction, associated with cardiac mortality. Despite the prevalence of MVD, the quantitative understanding of the interplay between pre‐existing MVD, PVL, LV, and post‐TAVR recovery is meager. Methods and Results: We quantified the effects of MVD on valvular‐ventricular hemodynamics using an image‐based patient‐specific computational framework in 72 MVD patients. Doppler pressure was reduced by TAVR (mean, 77%; N=72; P<0.05), but it was not always accompanied by improvements in LV workload. TAVR had no effect on LV workload in 22 patients, and LV workload post‐TAVR significantly rose in 32 other patients. TAVR reduced LV workload in only 18 patients (25%). PVL significantly alters LV flow and increases shear stress on transcatheter aortic valve leaflets. It interacts with mitral inflow and elevates shear stresses on mitral valve and is one of the main contributors in worsening of MR post‐TAVR. MR worsened in 32 patients post‐TAVR and did not improve in 18 other patients. Conclusions: PVL limits the benefit of TAVR by increasing LV load and worsening of MR and heart failure. Post‐TAVR, most MVD patients (75% of N=72; P<0.05) showed no improvements or even worsening of LV workload, whereas the majority of patients with PVL, but without that pre‐existing MR condition (60% of N=48; P<0.05), showed improvements in LV workload. MR and its exacerbation by PVL may hinder the success of TAVR

Design of Smart Barb of Honeybee-Inspired Surgery Needle

Needles are among the most common used instruments in surgery by medical professionals either for diagnosing the disease such as biopsy or for medical intervention such as drug delivery. Generally, needles are assumed to be minimally invasive, however it is desirable to decrease the insertion and pulling out force in order to prevent tissue damages. The hypothesis is that reducing the resistance forces caused by needle-tissue interaction leads to less tissue damage and less pain. Bioinspired needles mimicking insect stingers have been designed to reduce this resistance force and this design could provide to a more sophisticated steering of needle. Although our earlier study on honeybee-mimicking needle has shown the reduction of insertion force by having barbs on the needle body, the pull-out force is a big concern in particular during the extraction of the needle. A special mechanism to control the barbs at the end of the insertion procedure is designed. In this study, we investigated the use of SMA to control the barb functions so that it will reduce the pull-out force of the bioinspired needles. In this work, smart barb design is proposed. Circular barbs are divided to two symmetric parts connected by a ring around the central axis of the needle and the rings are connected to form the base part of its structure. Barbs are designed to have parallel faces with a desired angle through the insertion mechanism and are connected with a SMA wire at their bottom that is connected to the rear and front part of the needle. After insertion, actuating the SMA wires force the barbs to rotate around the rings due to the torque provided by wire shrinkage. As a result, barbs have now the same angle along the movement of needle for pulling out as they have for insertion mechanism.</jats:p

Design and Evaluation of Advanced Smart Needles for Brain Biopsy

Biopsy involves removing a piece of tissues for further medical examination. Brain biopsy is generally performed using different techniques, such as open biopsy, stereotactic core biopsy, and needle biopsy. Open biopsy is the most common and the most invasive form of the brain biopsy. During the procedure, a piece of the skull is removed and the brain is exposed. Stereotactic core and needle biopsies are minimally invasive. In these procedures, a hole is usually drilled into the skull and a needle is inserted through the hole to extract the tissue. Brain biopsy has its risks and complications due to the vulnerability of the brain tissue. Although using needle or stereotactic biopsies reduce the risks, brain biopsy may cause swelling or bleeding in the brain, and in some cases, can result in infection, stroke, seizure or even coma. A needle biopsy with conventional needles involves pulling or pushing the cutting stylet inside the needle hollow body (cannula). The manual pulling and pushing procedure induces lateral movement of the needle, which increases the damage in brain tissue. The goal here is to completely remove the needle harmful lateral movement. In this work, design of smart biopsy needles is proposed and demonstrated by incorporating nitinol wires and springs to control the lateral movement of the cutting stylet. The first design comprises of two parts. The first part of the needle is a 360° tissue cutting stylet, and the second part is the cannula. The cutting stylet can slide inside the cannula and a nitinol wire is embedded at the end of the stylet and the end of the cannula. As the electric current is applied on the nitinol wire, it shrinks and pulls the cutting stylet. The second design is almost similar to the first design, but it has a 180° tissue cutting stylet with a similar actuating mechanism. The last design uses a nitinol torsion spring that is attached to the cutting stylet. It cuts tissue samples by activating the nitinol spring to rotate the cutting stylet.</jats:p

Impact of TAVR on coronary artery hemodynamics using clinical measurements and image‐based patient‐specific in silico modeling

Abstract In recent years, transcatheter aortic valve replacement (TAVR) has become the leading method for treating aortic stenosis. While the procedure has improved dramatically in the past decade, there are still uncertainties about the impact of TAVR on coronary blood flow. Recent research has indicated that negative coronary events after TAVR may be partially driven by impaired coronary blood flow dynamics. Furthermore, the current technologies to rapidly obtain non-invasive coronary blood flow data are relatively limited. Herein, we present a lumped parameter computational model to simulate coronary blood flow in the main arteries as well as a series of cardiovascular hemodynamic metrics. The model was designed to only use a few inputs parameters from echocardiography, computed tomography and a sphygmomanometer. The novel computational model was then validated and applied to 19 patients undergoing TAVR to examine the impact of the procedure on coronary blood flow in the left anterior descending (LAD) artery, left circumflex (LCX) artery and right coronary artery (RCA) and various global hemodynamics metrics. Based on our findings, the changes in coronary blood flow after TAVR varied and were subject specific (37% had increased flow in all three coronary arteries, 32% had decreased flow in all coronary arteries, and 31% had both increased and decreased flow in different coronary arteries). Additionally, valvular pressure gradient, left ventricle (LV) workload and maximum LV pressure decreased by 61.5%, 4.5% and 13.0% respectively, while mean arterial pressure and cardiac output increased by 6.9% and 9.9% after TAVR. By applying this proof-of-concept computational model, a series of hemodynamic metrics were generated non-invasively which can help to better understand the individual relationships between TAVR and mean and peak coronary flow rates. In the future, tools such as these may play a vital role by providing clinicians with rapid insight into various cardiac and coronary metrics, rendering the planning for TAVR and other cardiovascular procedures more personalized

Study of Bioinspired Surgery Needle Advancing in Soft Tissues

Although needle-based surgeries are considered as minimally invasive surgeries, the damage caused by the needle insertion in soft tissues, namely brain needs to be reduced. Any minor damage, swelling or bleeding in the brain tissue can lead to a long-lasting traumatic brain injury. Our approach to this challenge is to search for a proper solution in nature such as honeybees. In our previous studies, some new bioinspired needles (passive/active) mimicking honeybee stingers have been proposed and tested by conducting needle insertion tests in tissue gel phantoms. The main feature of the bioinspired needles is specially-design barbs on the needle structures. It was discovered that the insertion forces of the bioinspired needles are decreased by as much as 35%, which means that there is a decrease in tissue gel phantom damages. It was also observed that the needle path deflection in the tissue was greatly affected by the reduction in needle bending stiffness and the insertion force. The reduction in the bending stiffness would require lower forces of Nitinol actuators to navigate our smart/active needle inside the tissues. This work specifically aims to investigate the mechanics of the bioinspired needles in bovine brain tissues. The needle insertion tests in real tissues are designed and performed. The insertion mechanics of the bioinspired needles in bovine brain is studied and presented.</jats:p

Towards non-invasive computational-mechanics and imaging-based diagnostic framework for personalized cardiology for coarctation

AbstractCoarctation of the aorta (COA) is a congenital narrowing of the proximal descending aorta. Although accurate and early diagnosis of COA hinges on blood flow quantification, proper diagnostic methods for COA are still lacking because fluid-dynamics methods that can be used for accurate flow quantification are not well developed yet. Most importantly, COA and the heart interact with each other and because the heart resides in a complex vascular network that imposes boundary conditions on its function, accurate diagnosis relies on quantifications of the global hemodynamics (heart-function metrics) as well as the local hemodynamics (detailed information of the blood flow dynamics in COA). In this study, to enable the development of new non-invasive methods that can quantify local and global hemodynamics for COA diagnosis, we developed an innovative fast computational-mechanics and imaging-based framework that uses Lattice Boltzmann method and lumped-parameter modeling that only need routine non-invasive clinical patient data. We used clinical data of patients with COA to validate the proposed framework and to demonstrate its abilities to provide new diagnostic analyses not possible with conventional diagnostic methods. We validated this framework against clinical cardiac catheterization data, calculations using the conventional finite-volume method and clinical Doppler echocardiographic measurements. The diagnostic information, that the framework can provide, is vitally needed to improve clinical outcomes, to assess patient risk and to plan treatment.</jats:p