Award Abstract # 1263572
Collaborative Research: Advancing the Diagnosis and Quantification of Mitral Valve Regurgitation with Mathematical Modeling

NSF Org: DMS
Division Of Mathematical Sciences
Recipient: UNIVERSITY OF HOUSTON SYSTEM
Initial Amendment Date: September 17, 2013
Latest Amendment Date: April 30, 2015
Award Number: 1263572
Award Instrument: Continuing Grant
Program Manager: Junping Wang
jwang@nsf.gov
 (703)292-4488
DMS
 Division Of Mathematical Sciences
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: October 1, 2013
End Date: September 30, 2017 (Estimated)
Total Intended Award Amount: $357,106.00
Total Awarded Amount to Date: $357,106.00
Funds Obligated to Date: FY 2013 = $240,617.00
FY 2015 = $116,489.00
History of Investigator:
  • Suncica Canic (Principal Investigator)
    canics@berkeley.edu
  • Annalisa Quaini (Co-Principal Investigator)
Recipient Sponsored Research Office: University of Houston
4300 MARTIN LUTHER KING BLVD
HOUSTON
TX  US  77204-3067
(713)743-5773
Sponsor Congressional District: 18
Primary Place of Performance: University of Houston
4800 Calhoun Boulevard
Houston
TX  US  77204-2015
Primary Place of Performance
Congressional District:
18
Unique Entity Identifier (UEI): QKWEF8XLMTT3
Parent UEI:
NSF Program(s): NIGMS
Primary Program Source: 01001314DB NSF RESEARCH & RELATED ACTIVIT
01001516DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 4075
Program Element Code(s): 804700
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049

ABSTRACT

Mitral regurgitation (MR) is a valvular disease in which the mitral valve does not close properly, thereby allowing blood to flow backward from the left ventricle to the left atrium of the heart. MR is among the most prevalent valve problems in the Western world. Doppler echocardiography has recently emerged as the method of choice for the non-invasive detection and evaluation of MR severity. However, due to the various color Doppler limitations, the accurate quantification of MR remains one of the major challenges in modern echocardiography. This is particularly the case with eccentric, wall-hugging regurgitant jets, known as the Coanda effect. This form of MR is currently very difficult to quantify and may lead to gross under-estimation of regurgitant volume by inexperienced cardiovascular observers. Using mathematical modeling, bifurcation analysis, and numerical simulations, combined with the in vitro experimental modeling of MR, and clinical experience, the investigators are developing a state-of-the-art tool for accurate non-invasive assessment of mitral regurgitation. The mathematical approach utilizes the most recent advances in fluid-structure interaction, modeling the flow of an incompressible, viscous fluid, coupled with the motion of an elastic regurgitant orifice simulating the regurgitant valve. A bifurcation diagram providing the information about different types of MR is being developed. The in vitro model is based on a pulsatile flow loop incorporating a mock imaging chamber, which contains a regurgitant orifice simulating the flow conditions encountered in patients with MR.

This is an exciting, new study, addressing a significant problem in the development of non-invasive diagnostic tools for the quantification of valvular regurgitation. The interdisciplinary team of investigators is developing sophisticated novel mathematics, high performance computing, and in vitro experimental tools, which, when used together, provide novel information about the severity of mitral valve regurgitation, that could not be obtained by using each individual approach separately. Based on this collaborative endeavor, detailed information about the blood flow conditions in patient regurgitant valves will be obtained, that could not be obtained by using classical 2D or even 3D echocardiography. This information will be used to quantify the severity of MR, which is the fundamental data on which surgical interventions are decided. The complementary mathematical tools, combined with the echocardiographic images, and clinical experience, support the next step in the evolution of modern 3D echocardiography for non-invasive diagnosis of pathological complex intra-cardiac flows. The broader impacts will be achieved through student education via interdisciplinary training and interdisciplinary course preparation. Two of the investigators are women, and active recruitment of women and minorities will continue. This project contributes toward building a strong partnership between academia (University of Houston) and health/medical industry (The Methodist Hospital).

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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(Showing: 1 - 10 of 44)
A. Cesmelioglu, H. Lee, A. Quaini, K. Wang, S.-Y. Yi "Optimization-based decoupling algorithms for a fluid-poroelastic system" The IMA Volumes in Mathematics and its Applications , v.160 , 2016 , p.79
a. Kheradrvar, S. Little, S. Canic, B. Griffith et al. "Emerging Trends in Heart Valve Engineering: Part IV. Computational Modeling and Experimental Studies" Annals of Biomedical Engineering , v.43 , 2015 , p.2314
A. Kheradvar, S. Canic, S.H. Little et al. "Emerging Trends in Heart Valve Engineering: Part III. Novel Technologies for mitral valve repair and replacement." Annals of Biomedical Engineering , 2014
A. Kheradvar, S. Canic, S. Little et al. "Emerging Trends in Heart Valve Engineering: Part III. Novel Technologies for mitral valve repair and replacement" Annals of Biomedical Engineering , v.43 , 2015 , p.858
A. Kheradvar, S. Canic, S. Little et al. "Emerging Trends in Heart Valve Engineering: Part II. Novel and Standard Technologies for Aortic Valve Replacement" Annals of Biomedical Engineering , v.43 , 2015 , p.844
A. Kheradvar, S. Canic, S. Little et al. "Emerging Trends in Heart Valve Engineering: Part I. Solutions for Future" Annals of Biomedical Engineering , v.43 , 2015 , p.833
A. Kheradvar, S. Little, S. Canic, et al. "Emerging Trends in Heart Valve Engineering: Part III. Novel Technologies for mitralvalve repair and replacement" Annals of Biomedical Engineering , v.43 , 2014 , p.858
Annalisa Quaini, Ph.D.; Suncica Canic, PhD; Roland Glowinski, PhD; Stephen Igo; Craig J Hartley, PhD; William Zoghbi, M.D.; Stephen Little, M.D. "Validation of a 3D computational fluid-structure interaction model simulating flow through an elastic aperture." Journal of Biomechanics. , v.45 , 2012 , p.310-318
A. Quaini, R. Glowinski, S. Canic "A computational study on the generation of the Coanda effect in a mock heart chamber" RIMS Kokyuroku series , 2016
A. Quaini, R. Glowinski, S. Canic. "Symmetry breaking and preliminary results about a Hopf bifurcation for incompressible viscous flow in an expansion channel." Int. J. Comput. Fluid Dyn. , v.30 , 2016 , p.7
Arash Kheradvar (Corresponding Author), Elliott M Groves, M.D., M.Sc.; craig J Goergen, Ph.D.; S. Hamed Alavi, Ph.D.; Robert T Tranquillo, Ph.D.; Craig A Simmons, Ph.D.; Lakshmi P Dasi, Ph.D.; K. Jane Grande-Allen, Ph.D.; Mohammad R K Mofrad, Ph.D.; Ahmad "Emerging Trends in Heart Valve Engineering: Part II. Novel and Standard Technologies for Aortic Valve Replacement." Annals of Biomedical Engineering. , v.43 , 2015 , p.844
(Showing: 1 - 10 of 44)

PROJECT OUTCOMES REPORT

Disclaimer

This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.

The results from this project provide a new understanding of the behavior of intracardiac flows during a valvular disease known as the mitral valve regurgitation (MR). Mitral regurgitation is a disease in which the mitral valve does not close properly, thereby allowing blood to flow backward from the left ventrice to the left atrium of the heart. MR can lead to atrial arrhythmias, pulmonary artery hypertehsion, congestive heart failure, and death. MR is among the most prevalent valve problems in the western world. Doppler echocardiography has recently emerged as the method of choice for the non-invasive detection and evaluation of MR severity. However, due to the various color Doppler limitations, the accurate quantification of MR remains one of the major challenges in modern echocardiography. This is particularly the case with eccentric, wall-hugging regurgitant jets, also known as Coanda effect, which appear smaller on the echocardiographic image of MR, leading to a gross under-estimation of regulrgitant volume by inexperienced cardiovascular observers.

To address this problem, we developed complementary in silico (mathematical and computational) models, and in vitro (experimental) models of the left atrium, the left ventricle, and several different regurgitant mitral valve orifices. Flow conditions corresponding to mild, moderate and severe MR were generated in the experimental set up at the Methodist DeBakey Heart and Vascular Center. At the same time, mathematical models of blood flow throught regurgitant orifices were generated based on the Navier-Stokes equations for an incompressible, viscous fluid. A model for fluid-structure interaction describing the interaction between blood flow and regulrgitant orifice was developed and implemented computationally. Using mathematical bifurcation theory, solutions to the Navier-Stokes equations for an incompressible, viscous fluid were investigated for symmetry breaking leading to the Coanda effect. Based on the information provided by the mathematical bifurcation theory, a regurgitant orifice was manufactured at the Methodist DeBakey Heart and Vascular Center, and the corresponding flow rate was generated in the in vitro set up to produce regurgitant flow exhibiting Coanda effect. Novel computational approaches were developed to simulate the corresponding moderate-to-high Reynolds number flows. Numerical simulations provided detailed information about the complex flow features of regurgitant Coanda flow in the left atrium. Echocardiographic images were obtained of the same flow and compared with the numerical simulations. The following conclusions were obtained:

1.  Regurgitant jets associated with prolapsed mitral valves can be classified into two categories: deflected jets and Coanda jets. Deflected jets follow the direction of flow determined by the prolapsed orifice,  while Coanda jets exhibit strong wall-hugging behavior.

2. Coanda jets typically occur for larger orifice aspect ratios and larger Reynolds numbers, which are associated with larger regurgitant volumes.

3. Using a single plane 2D color Doppler jet area size methodology to estimate the severity of mitral regurgitation is not a reliable tool for estimation of regurgitant volume.

4. Regurgitant jets passing though prolapsed orifices with small aspect ratio exhibiting large regurgitant volumes, have significant 3D flow features that cannot be captured by single plane 2D color Doppler screening. Such jets are more likely to be under-estimated in severity of mitral regurgitation.

5. Vortex rolls appear in the left atrium for regurgitant jets passing through orifices with larger Reynolds numbers. The smaller the orifice aspect ratio, the larger the 3D vortex roll effects. This is the first time vortex rolls have been associated with regurgitant jets in the left atrium. The role of regurgitant vortex dynamics in the left atrium (LA) on LA remodeling is completely unexplored.

In conclusion, the work performed in this study presents the first comprehensive analysis of regurgitant mitral valve flows in a mock left atrium.  A two-parameter study of flow showing transition to eccentric, wall-hugging Coanda jets was performed, explaining the role of orifice aspect ratio and regurgitant volume in the formation of Coanda jets in vitro. For the first time the role of vortex rolls on the under-estimation of regurgitant volume using 2D color Doppler echocardiography was explained. While the role of vortices in the left ventricle has been studied in the past, the identification of the presence of vortex rolls in the left atrium during regurgitation is new. It would be interesting to see if the presence of vortex rolls in the left atrium during regurgitation is associated with the known LA remodeling in patients with severe MR. Perhaps one of the goals of a successful  mitral valve repair sould be to minimize (or optimize) LA vortex dynamics that may speed up reverse remodeling of LA.


This work has introduced a new concept in clinical imaging which emphasizes that the quality and not only the quantity of regurgitant flow matters in the assessment of severity of mitral valve regurgitation.

 


Last Modified: 01/02/2018
Modified by: Suncica Canic

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