Faculty Bibliography

Fluid-structure interaction is ubiquitous in nature and occurs at all biological scales. Immersed methods provide mathematical and computational frameworks for modeling fluid-structure systems. These methods, which typically use an Eulerian description of the fluid and a Lagrangian description of the structure, can treat thin immersed boundaries and volumetric bodies, and they can model structures that are flexible or rigid or that move with prescribed deformational kinematics. Immersed formulations do not require body-fitted discretizations and thereby avoid the frequent grid regeneration that can otherwise be required for models involving large deformations and displacements. This article reviews immersed methods for both elastic structures and structures with prescribed kinematics. It considers formulations using integral operators to connect the Eulerian and Lagrangian frames and methods that directly apply jump conditions along fluid-structure interfaces. Benchmark problems demonstrate the effectiveness of these methods, and selected applications at Reynolds numbers up to approximately 20,000 highlight their impact in biological and biomedical modeling and simulation.

Current clinical practice for aneurysmatic interventions is often based on the maximum diameter of the vessel and/or on the growth rate, although rupture can occur at any diameter and growth rate, leading to fatality. For 27 medial samples obtained from 12 non-aneurysmatic (control) and 9 aneurysmatic human descending thoracic aortas we examined: the mechanical responses up to rupture using uniaxial extension tests of circumferential and longitudinal specimens; the structure of these tissues using second-harmonic imaging and histology, in particular, the content proportions of collagen, elastic fibers and smooth muscle cells in the media. It was found that the mean failure stresses were higher in the circumferential directions (Control-C 1474kPa; Aneurysmatic-C 1446kPa), than in the longitudinal directions (Aneurysmatic-L 735kPa; Control-L 579kPa). This trend was the opposite to that observed for the mean collagen fiber directions measured from the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C), thus suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. The difference in the mean values of the out-of-plane dispersion in the radial/longitudinal plane between the control and aneurysmatic groups was significant. The difference in the mean values of the mean fiber angle from the circumferential direction was also significantly different between the two groups. Most specimens showed delamination zones near the ruptured region in addition to ruptured collagen and elastic fibers. This study provides a basis for further studies on the microstructure and the uniaxial failure properties of (aneurysmatic) arterial walls towards realistic modeling and prediction of tissue failure. STATEMENT OF SIGNIFICANCE: A data set relating uniaxial failure properties to the microstructure of non-aneurysmatic and aneurysmatic human thoracic aortic medias under uniaxial extension tests is presented for the first time. It was found that the mean failure stresses were higher in the circumferential directions, than in the longitudinal directions. The general trend for the failure stresses was Control-C > Aneurysmatic-C > Aneurysmatic-L > Control-L, which was the opposite of that observed for the mean collagen fiber direction relative to the loading axis (Control-L > Aneurysmatic-L > Aneurysmatic-C > Control-C) suggesting that the trend in the failure stress can in part be attributed to the collagen architecture. This study provides a first step towards more realistic modeling and prediction of tissue failure.

We present a coupled left atrium - mitral valve model based on computed tomography scans with fibre-reinforced hyperelastic materials. Fluid-structure interaction is realised by using an immersed boundary-finite element framework. Effects of pathological conditions, e.g. mitral valve regurgitation and atrial fibrillation, and geometric and structural variations, namely uniform vs non-uniform atrial wall thickness and rule-based vs atlas-based fibre architectures, on the system are investigated. We show that in the case of atrial fibrillation, pulmonary venous flow reversal at late diastole disappears and the filling waves at the left atrial appendage orifice during systole have reduced magnitude. In the case of mitral regurgitation, a higher atrial pressure and disturbed flows are seen, especially during systole, when a large regurgitant jet can be found with the suppressed pulmonary venous flow. We also show that both the rule-based and atlas-based fibre defining methods lead to similar flow fields and atrial wall deformations. However, the changes in wall thickness from non-uniform to uniform tend to underestimate the atrial deformation. Using a uniform but thickened wall also lowers the overall strain level. The flow velocity within the left atrial appendage, which is important in terms of appendage thrombosis, increases with the thickness of the left atrial wall. Energy analysis shows that the kinetic and dissipation energies of the flow within the left atrium are altered differently by atrial fibrillation and mitral valve regurgitation, providing a useful indication of the atrial performance in pathological situations.

Ailments of the bladder are often treated via intravesical delivery-direct application of therapeutic into the bladder through a catheter. This technique is employed hundreds of thousands of times every year, but protocol development has largely been limited to empirical determination. Furthermore, the numerical analyses of intravesical delivery performed to date have been restricted to static geometries and have not accounted for bladder deformation. This study uses a finite element analysis approach with biphasic solute transport to investigate several parameters pertinent to intravesical delivery including solute concentration, solute transport properties and instillation volume. The volume of instillation was found to have a substantial impact on the exposure of solute to the deeper muscle layers of the bladder, which are typically more difficult to reach. Indeed, increasing the instillation volume from 50-100 ml raised the muscle solute exposure as a percentage of overall bladder exposure from 60-70% with higher levels achieved for larger instillation volumes. Similar increases were not seen for changes in solute concentration or solute transport properties. These results indicate the role that instillation volume may play in targeting particular layers of the bladder during an intravesical delivery.

Objective: Percutaneous VA-ECMO cannulation with placement of a distal perfusion catheter (DPC) in the superficial femoral artery (SFA) is associated with rapid initiation of support and exceptionally low rates of limb ischemia at experienced centers. Given the urgency to initiate support and the increased difficulty of percutaneous access in the actively arresting patient, we evaluated the rates of vascular injury and limb ischemia following femoral ECPR with DPC placement at our institution.
Method(s): All cases of VA-ECMO for ECPR between 1/2015 and 9/2018 were reviewed. All adult patients in whom stable VA-ECMO support could be initiated were included in the study. Cannulations were performed by attending cardiac surgeons and cardiothoracic surgery residents, with involvement of additional services as needed. Per our standard practice, patients underwent cannulation of 1 femoral vein and 1 femoral artery, after which a 6 Fr wire-reinforced introducer sheath was placed antegrade into the SFA and connected to a side port on the arterial cannula.
Result(s): A total of 41 patients were included in the study. The median age was 57 (range: 24-78 years), BMI was 29.4 (range: 1.86-2.84 kg/m2), and BSA was 2.07 (range: 1.86-2.84 m2). Survival to decannulation was 63% and survival to discharge was 34%. The most common arte-rial cannula size was 19 Fr (51%), followed by 17 Fr (32%) and 21 Fr (17%). The majority of cannulations were performed in a non-procedural area (ICU 46%, ED 17%, non-ICU unit 15%). All-percutaneous primary access was successful in 40 patients (98%) and 1 patient was cannulated via femoral cutdown. No patient was transported to the OR or cath suite for ECMO cannula-tion, though 3 patients (7%) transferred to hybrid ORs for open DPC placement after ECMO initiation. Two of these 3 patients underwent concurrent lower extremity fasciotomy. An additional 6 patients underwent open/endovascular repair of vascular injuries sustained during cannulation (n=4) or popliteal thrombectomy despite uncomplicated DPC placement (n=2). Following appro-priate cannulation and stabilization, however, no patient experienced delayed limb complications or developed clinically apparent limb ischemia.
Conclusion(s): Percutaneous vascular access with routine DPC placement can be performed reliably in the ECPR setting. Lower extremity complications were most com-monly associated arterial injury during cannulation and were promptly managed without lasting morbidity, while no patient suffered delayed ischemic complications

We develop a fluid-structure interaction (FSI) model of the mitral valve (MV) that uses an anatomically and physiologically realistic description of the MV leaflets and chordae tendineae. Three different chordae models-complex, 'pseudo-fibre' and simplified chordae-are compared to determine how different chordae representations affect the dynamics of the MV. The leaflets and chordae are modelled as fibre-reinforced hyperelastic materials, and FSI is modelled using an immersed boundary-finite element method. The MV model is first verified under static boundary conditions against the commercial finite element software ABAQUS and then used to simulate MV dynamics under physiological pressure conditions. Interesting flow patterns and vortex formulation are observed in all three cases. To quantify the highly complex system behaviour resulting from FSI, an energy budget analysis of the coupled MV FSI model is performed. Results show that the complex and pseudo-fibre chordae models yield good valve closure during systole but that the simplified chordae model leads to poorer leaflet coaptation and an unrealistic bulge in the anterior leaflet belly. An energy budget analysis shows that the MV models with complex and pseudo-fibre chordae have similar energy distribution patterns but the MV model with the simplified chordae consumes more energy, especially during valve closing and opening. We find that the complex chordae and pseudo-fibre chordae have similar impact on the overall MV function but that the simplified chordae representation is less accurate. Because a pseudo-fibre chordal structure is easier to construct and less computationally intensive, it may be a good candidate for modelling MV dynamics or interaction between the MV and heart in patient-specific applications.

Electroanatomical mapping is currently used to provide clinicians with information about the electrophysiological state of the heart and to guide interventions like ablation. These maps can be used to identify ectopic triggers of an arrhythmia such as atrial fibrillation (AF) or changes in the conduction velocity (CV) that have been associated with poor cell to cell coupling or fibrosis. Unfortunately, many factors are known to affect CV, including membrane excitability, pacing rate, wavefront curvature, and bath loading, making interpretation challenging. In this work, we show how endocardial conduction velocities are also affected by the geometrical factors of muscle thickness and wall curvature. Using an idealized three-dimensional strand, we show that transverse conductivities and boundary conditions can slow down or speed up signal propagation, depending on the curvature of the muscle tissue. In fact, a planar wavefront that is parallel to a straight line normal to the mid-surface does not remain normal to the mid-surface in a curved domain. We further demonstrate that the conclusions drawn from the idealized test case can be used to explain spatial changes in conduction velocities in a patient-specific reconstruction of the left atrial posterior wall. The simulations suggest that the widespread assumption of treating atrial muscle as a two-dimensional manifold for electrophysiological simulations will not accurately represent the endocardial conduction velocities in regions of the heart thicker than 0.5 mm with significant wall curvature.

The immersed boundary method is an approach to fluid-structure interaction that uses a Lagrangian description of the structural deformations, stresses, and forces along with an Eulerian description of the momentum, viscosity, and incompressibility of the fluid-structure system. The original immersed boundary methods described immersed elastic structures using systems of flexible fibers, and even now, most immersed boundary methods still require Lagrangian meshes that are finer than the Eulerian grid. This work introduces a coupling scheme for the immersed boundary method to link the Lagrangian and Eulerian variables that facilitates independent spatial discretizations for the structure and background grid. This approach uses a finite element discretization of the structure while retaining a finite difference scheme for the Eulerian variables. We apply this method to benchmark problems involving elastic, rigid, and actively contracting structures, including an idealized model of the left ventricle of the heart. Our tests include cases in which, for a fixed Eulerian grid spacing, coarser Lagrangian structural meshes yield discretization errors that are as much as several orders of magnitude smaller than errors obtained using finer structural meshes. The Lagrangian-Eulerian coupling approach developed in this work enables the effective use of these coarse structural meshes with the immersed boundary method. This work also contrasts two different weak forms of the equations, one of which is demonstrated to be more effective for the coarse structural discretizations facilitated by our coupling approach.

The Immersed Boundary (IB) method is a mathematical framework for constructing robust numerical methods to study fluid-structure interaction in problems involving an elastic structure immersed in a viscous fluid. The IB formulation uses an Eulerian representation of the fluid and a Lagrangian representation of the structure. The Lagrangian and Eulerian frames are coupled by integral transforms with delta function kernels. The discretized IB equations use approximations to these transforms with regularized delta function kernels to interpolate the fluid velocity to the structure, and to spread structural forces to the fluid. It is well-known that the conventional IB method can suffer from poor volume conservation since the interpolated Lagrangian velocity field is not generally divergence-free, and so this can cause spurious volume changes. In practice, the lack of volume conservation is especially pronounced for cases where there are large pressure differences across thin structural boundaries. The aim of this paper is to greatly reduce the volume error of the IB method by introducing velocity-interpolation and force-spreading schemes with the properties that the interpolated velocity field in which the structure moves is at least