Browsing by Author "Dasi, Lakshmi Prasad, advisor"

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Open Access
A simple lumped parameter model of the cardiovascular system
(Colorado State University. Libraries, 2011) Phillips, Canek Moises Luna, author; Dasi, Lakshmi Prasad, advisor; James, Susan P., committee member; Kawcak, Christopher E., committee member
Congestive heart failure is caused when untreated heart diseases affect malfunction in the heart to a point where the heart can no longer pump enough blood to the body. The additional energy cost taxed onto the heart by heart diseases is the root cause of congestive heart failure. Currently, a disease severity guideline is used in the medical field to differentiate disease cases and their relative risk of causing congestive heart failure. The current disease severity guideline does not take into consideration workload when assessing the severity of a disease case. A zero-dimensional computational model of the left ventricle was developed to simulate physiological and pathophysiological characteristics to quantify workload of hypothetical normal and diseased patient cases. The development of the computational model has revealed that workload calculation possesses utility in differentiating the severity of risk that left ventricular diseases have on affecting congestive heart failure. Results of heart disease simulations for aortic stenosis, aortic regurgitation, mitral regurgitation, and hypertension show the energy cost the diseases impose on the left ventricle compared to a normal patient model. Additional results of simulations with combined mild cases of heart diseases show an amplified impact on energy cost - more than the energy cost of individual mild cases added together separately. The calculation of workload in computational simulations is an important step towards using workload as a universal indicator of risk of development of congestive heart failure and updating treatment guidelines so that prevention of congestive heart failure is more successful.
Open Access
Application of passive flow control to mitigate the thromboembolic potential of bileaflet mechanical heart valves: an in-vitro study
(Colorado State University. Libraries, 2014) Forléo, Márcio Henrique, author; Dasi, Lakshmi Prasad, advisor; James, Susan, committee member; Orton, Christopher, committee member; Dinenno, Frank, committee member
Implantation of a bileaflet mechanical heart valve (BMHV) continues to be associated with risk of thromboembolic complications despite anti-coagulation therapy. Mechanical heart valves have been the gold standard in valve heart replacement since the 1950s with BMHVs currently still being the valve of choice for younger patients. Given that a large body of literature points to thromboembolic complications due to poor hemodynamics, improvements to the hemodynamic performance of BMHVs are needed. In this study, we explore the concept of passive flow controls that have been widely used in aerospace industry as a novel approach towards improving BMHV design. Passive flow control elements are small features on solid surfaces, such as vortex generators (VGs), that alter flow to achieve desired performance. The specific aims of this study are (1) develop a methodology to evaluate thromboembolic potential (TEP) of BMHVs using in-vitro particle image velocimetry technique, (2) quantify the efficacy of rectangular VGs distributed on BMHV leaflets to reduce TEP, and (3) quantify the hemodynamic performance impact of rectangular VGs. An in-vitro pulsatile flow loop along with Particle Image Velocimetry (PIV) flow visualization technique was developed, validated, and utilized to acquire time-resolved velocity fields and shear stress loading: Lagrangian particle tracking analysis of the upstream and downstream flow during diastole and systole enabled the calculation of predicted shear stress history and exposure times corresponding to platelets. This information was then used in numerical models of blood damage to predict the TEP of test heart valves using established platelet activation and platelet lysis parameters. BMHV leaflets were constructed using 3D printing technology with VGs based on micro-CT scans of a model BMHV leaflet. Two configurations were constructed: co-rotating VGs and counter-rotating VGs. Co-rotating VGs consist of single features 1mm tall and 2.8mm long spaced equally apart (5mm) at an angle of attack of 23 degrees. Counter-rotating VGs consist of mirrored feature pairs 1mm from each other with the same dimensions as the co-rotating VGs. The leaflets were tested using the methodology described above to elucidate their effect on the TEP of the BMHV compared to the control leaflets. For systolic flow downstream of the valve, we report a decrease in the average platelet activation and average platelet lysis TEP (both normalized by the average exposure time) largely in the central jet, with the vortex generator equipped leaflets compared to the control leaflets at a p-value of 0.05. However, for diastolic flow upstream of the valve, we report an increase in the average platelet lysis TEP and average platelet activation TEP (both normalized by the average exposure time) largely in the regurgitant jet zone with the vortex generator equipped leaflets compared to the control leaflets at a p-value of 0.05. Also, steady and pulsatile flow experiments were conducted to calculate the transvalvular pressure drop across the model BMHV with control leaflets (no VGs) and leaflets containing VGs to calculate effective orifice area (EOA), which is an index of valve performance and is related to the degree to which the valve obstructs blood flow. We report a significant increase in EOA values for valves with leaflets containing passive flow control elements in both steady and pulsatile flow experiments compared to the control leaflets. Under steady flow, the co-rotating VGs configuration had the best EOA value compared to the control leaflet and counter-rotating vortex generator configuration. However, under pulsatile conditions, the counter-rotating VGs configuration had the best EOA value compared to the control leaflet and co-rotating vortex generator configuration. PIV measurements highlight the delay in flow separation caused by the VGs and corroborate the increased pulsatile flow EOA values. This study shows that the TEP of BMHVs can be accurately evaluated using in-vitro PIV techniques and that there is room for improvement in BMHV design using passive flow control elements. With optimization of passive flow control configuration and design, it is possible to further decrease the TEP of BMHVs while increasing their hemodynamic performance; thus creating a safer, more efficient BMHV.
Open Access
Biomechanical analysis of aortic valve calcification and post-procedural paravalvular leak
(Colorado State University. Libraries, 2016) Zebhi, Banafsheh, author; Dasi, Lakshmi Prasad, advisor; Orton, Christopher, committee member; Gao, Xinfeng, committee member
Cardiovascular disease is a leading cause of death accounted for 17.3 million people annually. Aortic valve calcification (AVC) and stenosis are the most common diseases among valvular heart diseases. Severe AVC and stenosis will need the standard surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) for patients who are at high risk for open heart surgery. Post-procedural paravalvular leak (PVL) is a common complication which occurs around the implanted stent in a significant population of patients who undergo valve replacement, requiring significant interventions. The overarching hypothesis of this research is that anatomic characteristics of patients’ native aortic valve play an important role in both calcification processes and post-procedural PVL occurrence. This hypothesis is studied through two specific Aims. Aim 1 was designed to determine what anatomic and biological parameters as well as hemodynamic factors are associated with severity of aortic valve calcification. In this aim, patient-specific geometric characteristics were extracted using 3D image reconstruction of patient CT data, and their relation with cusp specific calcification was evaluated using multiple regression analysis. The results of this analysis indicated that severity of calcification is significantly correlated with coronary calcification as well as the size of sinus of valsava and sinotubular junction (all p-values<0.05). In Aim 2, we investigated the relationship among patients’ calcification level and anatomic parameters of their native aortic valve as well as the risk of post-procedural PVL occurrence. Using a logistic regression analysis model we show that large calcification deposition (p-value<0.001) and large ratio of sinus of valsava to annulus (p-value<0.02) of native aortic valve can predict probability of post-procedural PVL occurrence. The overall significance of this study is that bioengineering analysis of pre-procedural CT data can be utilized towards better TAVR planning as well as basic understanding of the pathogenesis of AVC.
Open Access
Biomechanics of transapical mitral valve implantation
(Colorado State University. Libraries, 2014) Koenig, Evan Kienholz, author; Dasi, Lakshmi Prasad, advisor; Prasad, Ashok, committee member; Orton, Christopher, committee member
Heart disease is the number one killer in the United States. Within this sector, valve disease plays a very important role: Approximately 6% of the entire population has either prolapse or stenosis of the mitral valve and this percentage only increases when looking only at the elderly population. Transapical mitral valve implantation has promised to be a potential therapy for high-risk patients presenting with MR; however it is unclear what the best method of securing a valve within the mitral annulus may be to provide a safe and efficient valve replacement. The objective of this research is to study and understand the underlying biomechanics of fixation of transapical mitral valves within the native mitral annulus. Two different transapical mitral valve prosthesis designs were tested: One valve design has a portion of the leaflets atrialized such that it has a shorter stent height and the valve itself sits within the native annulus, the other design is not atrialized and protrudes further into the left ventricle. The valves were implanted in a left heart simulator to assess leaflet kinematics and hemodynamics using high speed imagery and particle image velocimetry techniques. An in vitro passive beating heart model was then used to assess the two different fixation methods (namely, anchored at the apex vs. anchored at the annulus) with respect to paravalvular regurgitation. Leaflet kinematics and hemodynamics revealed proper leaflet coaptation and acceptable pressure gradients and inflow fillings; however, both designs yielded elevated turbulence stresses within the ventricle. At 60 beats per minute, leaflet opening and closing times were both under 0.1 seconds, max Reynolds shear stresses were between 40 and 60 N/m2 and maximum velocities were approximately 1.4 m/s. Assessment of the different fixation methods during implantation revealed the superiority of the atrialized valve when anchored at the annulus (p<0.05), but showed no such comparison during tethered implantation. In addition to the results of statistical testing, observations show that the importance of the relationship between ventricular stent height and fixation method compared with native anatomy plays an important role in overall prosthesis function regardless of implantation method.
Open Access
Design and fabrication of a flow chamber for the study of cell adhesion and hemocompatibilty in dynamic conditions
(Colorado State University. Libraries, 2011) Migita, Kevin, author; Popat, Ketul, advisor; Dasi, Lakshmi Prasad, advisor; Prasad, Ashok, committee member
Cell adhesion is a well characterized condition of both biomaterial and tissue engineering research. It plays a role in biocompatibility and the proliferation, differentiation and viability of seeded cells. With respect to hemocompatibility, platelet adhesion and subsequent activation is a driving factor in the failure of blood contacting medical devices. Platelets aggregates are vital components in the wound healing and foreign body responses and display various forms of adhesion based on blood flow. However, the study of platelet adhesion on implantable tissue engineering scaffolds under dynamic conditions is very limited, particularly with directional flow. A flow chamber which incorporates a tissue engineering scaffold or functionalized biomaterial was designed and fabricated for investigation of flow patterns and cellular adhesion in response to dynamic conditions on these surfaces. The device utilizes a combination of aspects from both tissue engineering bioreactors and microfluidics platforms to result in a flow chamber which provides the directional flow of a perfused flow bioreactor with the advantages of controlling chamber shape and real time monitoring presented by Polydimethylsiloxane microfluidics chambers. Results of fluid flow study in the chamber modeled for laminar and shear gradient simulated flow show the ability of the device to manipulate flow patterns. Dynamic and static studies of platelet adhesion to poly-(ε-caprolactone) flat and electrospun nanofiber surfaces utilizing the flow chamber provide insight into the hemocompatibility of tissue engineering scaffolds in a dynamic flow setting.
Open Access
Effect of large-scale anisotropy on the small-scale structure of turbulence
(Colorado State University. Libraries, 2014) Morshed, Khandakar Niaz, author; Dasi, Lakshmi Prasad, advisor; Kirkpatrick, Allan, committee member; Gao, Xinfeng, committee member; Venayagamoorthy, Subhas Karan, committee member
Even though the small-scale structure of turbulence has been hypothesized to be locally isotropic with universal properties, numerous studies document the departure from local isotropy and universality in the presence of strong mean shear (or large-scale anisotropy). The goal of this work is to elucidate the effects of strong shear on the small-scale structure with emphasis on the physical mechanism through which mean shear deviates local structure from isotropy. Two dimensional time-resolved particle image velocimetry (PIV) experiments were performed in a stationary turbulent flow past a backward facing step at Reynolds numbers 13600 and 5500 based on the maximum velocity and step height. Large-scale anisotropic properties of the flow along with local turbulence characteristics were quantified in detail. Special points of interest distributed within the measurement domain for varying large-scale anisotropic characteristics were probed to analyze small-scale structure. Results show that velocity structure functions and their scaling exponents systematically align with the principal directions of deformation of the mean flow field. Furthermore, the probability density function (PDF) of the instantaneous dissipative scales indicate a potentially universal mechanism of how mean shear affects the distribution of dissipative scales captured through a local Reynolds number based on mean shear and dissipation rate. PDFs of the instantaneous dissipative scales in all directions demonstrate that mean shear strength and local principal axis directions dictate the behavior of structure functions, correlation functions, thereby influencing the dissipative scale PDFs in a directionally dependent manner.
Open Access
Effects of structure on flow mechanics in the human left ventricle and respiratory tract
(Colorado State University. Libraries, 2011) Moore, Brandon L., author; Dasi, Lakshmi Prasad, advisor; Orton, Christopher, committee member; Sakurai, Hiroshi, committee member
Cardiac and respiratory dysfunctions represent a large portion of healthcare problems in the United States. Many of these problems are caused by abnormal flow mechanics due to altered anatomical structure. This structure in the human body is very complex and ranges over many different scales. At relatively small scales, one facet that is still not well understood is the role of trabeculae on the biomechanics of the left ventricle. Similarly, large-scale airflow through the respiratory tract has not been fully investigated as a function of age or mechanical ventilation. This research has revealed some of the flow patterns caused by these different scale structures. Fractal geometry was used to help characterize the inner surface of the left ventricle at different times during the cardiac cycle. The fractal dimension of the ventricle was determined using a custom box-counting algorithm developed in MATLAB, and it was shown that trabeculae do indeed play a role in the biomechanics of heart pumping. Computational fluid dynamics (CFD) was also run on the respiratory tracts of three different patients to determine airflow effects due to age and intubation. Three dimensional models were constructed from computed tomography (CT) scans and simulations were run in ANSYS Fluent. Results of the study were validated through grid and time step sensitivity studies as well as comparison to previous studies. It was shown that flow mechanics in the airways of children change with age as well as with the introduction of an intubation tube.
Open Access
Influence of anatomic valve conditions and coronary flow on aortic sinus hemodynamics
(Colorado State University. Libraries, 2015) Moore, Brandon L., author; Dasi, Lakshmi Prasad, advisor; Gao, Xinfeng, advisor; Kirkpatrick, Allan, committee member; Orton, Christopher, committee member
Heart disease is the leading cause of death in the US, and aortic valve stenosis represents a significant portion of this disease. While the specific causes of stenosis are not entirely clear, its development has been strongly linked to mechanical factors such as localized solid and fluid stresses and strains, especially on the aortic side of the valve leaflets. These mechanical cues can be tied to valvular hemodynamics, however the factors regulating these hemodynamics are relatively unknown. Therefore, the overarching hypothesis of this research is that aortic valve sinus hemodynamics are regulated by anatomic valve conditions and presence of coronary flow. This hypothesis is explored through three specific aims: 1) to develop methodologies for quantifying hemodynamics within the aortic sinuses, 2) to characterize the differences in native valve flow patterns that occur due to patient and sinus variability, and 3) to evaluate the hemodynamic impacts of different prosthetic aortic valve implantations. In this work, experimental methods have been developed to study a broad range of aortic valve conditions, and computational models were also employed to validate and enhance experimental findings. An in vitro setup is presented using a surgical bioprosthesis as a native aortic valve model, while additional valve implantations were also tested. Physiological pressures and flow rates were imposed across these valves via an in-house pumping loop, which included a novel coronary flow branch. Two-dimensional time-resolved particle image velocimetry (PIV) protocols were developed and employed to analyze sinus vorticity dynamics. Computationally, both 2D and 3D simulations were run in ANSYS Fluent to enhance experimental findings. Results from this research demonstrate that aortic sinus hemodynamics are indeed regulated by anatomic valve conditions and coronary flow. From a clinical perspective, average valve geometric parameters tend to produce hemodynamics that are least likely to initiate disease than those near the upper or lower anatomical limits. Coronary flow was likewise found to increase sinus velocities and shear stresses near the leaflets, which is also beneficial for valve health. The prosthetic valves tested – transcatheter and sutureless – both severely limited sinus perfusion, which could help explain an increased risk of thrombus formation in the transcatheter case and suggests similar risk for sutureless valves. These findings could help educate clinicians on proper courses of treatment based on patient-specific valve parameters, and could also provide useful information for engineers when designing new valve prostheses.
Open Access
Quantitative analysis of the mechanical environment in the embryonic heart with respect to its relationship in cardiac development
(Colorado State University. Libraries, 2015) Bulk, Alexander T., author; Dasi, Lakshmi Prasad, advisor; Garrity, Deborah, advisor; Popat, Ketul, committee member; Orton, Christopher, committee member
In order to understand the causes of congenital heart defects, which afflict at least 4 infants per 1,000 live births, research has implemented the use of animal models to study embryonic heart development. Zebrafish (Danio rerio) have become one of the more prominent of these animal models due to the fact that their heart morphology at the earliest stages of development is remarkably similar to humans, and because embryos lack pigmentation, rendering them transparent. This transparency allows for high-speed images of blood flow to be acquired in the developing heart so that the mechanotransductive relationship between the intracardiac flow environment and myocardial progenitor cell differentiation can be understood. One particular aspect of the flow environment, a cyclic retrograde flow at the junction of the forming atrium and ventricle, has been shown to be necessary for valve formation, though the mechanisms causing it to occur had previously been unknown. By comparing the results of two-dimensional spatiotemporal analysis applied to embryos both with normal retrograde flow and inhibited retrograde flow, this study shows that a particular range of pressures associated with the pumping mechanics of the heart as well as resistance due to systolic contractile closure must exist in order to maintain adequate retrograde flow to induce valve formation. The use of two-dimensional spatiotemporal analysis was sufficient to acquire these results, however when applied to analysis of other aspects of the intracardiac flow environment, this computational method is subject to critical limitations. Therefore, this study includes the development of methodology to integrate the results of spatiotemporal analysis on multiple focal planes bisecting the heart into a more accurate, three-dimensional result. The results of this study not only increase our understanding of the mechanics behind an important factor in embryonic development, but also enable future experiments pertaining to the measurement of embryonic intracardiac blood flow to be performed with increased certainty.