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Biomechanics and Modeling in Mechanobiology

, Volume 18, Issue 1, pp 219–243 | Cite as

Hemodynamic assessment of pulmonary hypertension in mice: a model-based analysis of the disease mechanism

  • M. Umar Qureshi
  • Mitchel J. Colebank
  • L. Mihaela Paun
  • Laura Ellwein Fix
  • Naomi Chesler
  • Mansoor A. Haider
  • Nicholas A. Hill
  • Dirk Husmeier
  • Mette S. OlufsenEmail author
Original Paper

Abstract

This study uses a one-dimensional fluid dynamics arterial network model to infer changes in hemodynamic quantities associated with pulmonary hypertension in mice. Data for this study include blood flow and pressure measurements from the main pulmonary artery for 7 control mice with normal pulmonary function and 5 mice with hypoxia-induced pulmonary hypertension. Arterial dimensions for a 21-vessel network are extracted from micro-CT images of lungs from a representative control and hypertensive mouse. Each vessel is represented by its length and radius. Fluid dynamic computations are done assuming that the flow is Newtonian, viscous, laminar, and has no swirl. The system of equations is closed by a constitutive equation relating pressure and area, using a linear model derived from stress–strain deformation in the circumferential direction assuming that the arterial walls are thin, and also an empirical nonlinear model. For each dataset, an inflow waveform is extracted from the data, and nominal parameters specifying the outflow boundary conditions are computed from mean values and characteristic timescales extracted from the data. The model is calibrated for each mouse by estimating parameters that minimize the least squares error between measured and computed waveforms. Optimized parameters are compared across the control and the hypertensive groups to characterize vascular remodeling with disease. Results show that pulmonary hypertension is associated with stiffer and less compliant proximal and distal vasculature with augmented wave reflections, and that elastic nonlinearities are insignificant in the hypertensive animal.

Keywords

Pulmonary hypertension 1D fluid dynamics model Linear and nonlinear wall model Parameter estimation Statistical model selection Wave intensity analysis Impedance analysis 

Notes

Funding

This study was supported by the National Science Foundation (NSF) awards NSF-DMS # 1615820, NSF-DMS # 1246991 and Engineering and Physical Sciences Research Council (EPSRC) of the UK, grant reference number EP/N014642/1.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • M. Umar Qureshi
    • 1
  • Mitchel J. Colebank
    • 1
  • L. Mihaela Paun
    • 2
  • Laura Ellwein Fix
    • 3
  • Naomi Chesler
    • 4
  • Mansoor A. Haider
    • 1
  • Nicholas A. Hill
    • 2
  • Dirk Husmeier
    • 2
  • Mette S. Olufsen
    • 1
    Email author
  1. 1.Department of MathematicsNorth Carolina State UniversityRaleighUSA
  2. 2.School of Mathematics and StatisticsUniversity of GlasgowGlasgowUK
  3. 3.Department of Mathematics and Applied MathematicsVirginia Commonwealth UniversityRichmondUSA
  4. 4.Department of Biomedical EngineeringUniversity of Wisconsin-MadisonMadisonUSA

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