Myocardial Stiffness Estimation: A Novel Cost Function for Unique Parameter Identification

Nasopoulou, Anastasia; Blazevic, Bojan; Crozier, Andrew; Shi, Wenzhe; Shetty, Anoop; Rinaldi, Christopher Aldo; Lamata, Pablo; Niederer, Steven A.

doi:10.1007/978-3-319-20309-6_41

Cited by 3 publications

(4 citation statements)

References 21 publications

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“…We use parameters C 2 = 8, C 3 = 3, C 4 = 4 based on Nasopoulou et al [48] and C 1 = 1 kPa to match end-diastolic volume. Meshes were 'deflated' to the reference configuration using the backward displacement method [6].…”

Section: Multi-scale Modelmentioning

confidence: 99%

“…These complex multi-physics and multi-scale cardiac simulations combine models that represent the distinct physiology of the material properties, cellular electrical activity and cellular contraction. When constructing multi-scale models of human function, there are currently many options for characterizing the cellular electrophysiology [19,52] or material properties [66,48]. Detailed biophysical models of cardiac contraction do exist for other species [56,8,36] and have been used to great effect in multi-scale computational models, particularly in the mouse [59,40] and rat [51,39].…”

Section: Introductionmentioning

confidence: 99%

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A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Land

Park-Holohan

Smith

et al. 2017

Journal of Molecular and Cellular Cardiology

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110

147

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Experimental data from human cardiac myocytes at body temperature is crucial for a quantitative understanding of clinically relevant cardiac function and development of whole-organ computational models. However, such experimental data is currently very limited. Specifically, important measurements to characterize changes in tension development in human cardiomyocytes that occur with perturbations in cell length are not available. To address this deficiency, in this study we present an experimental data set collected from skinned human cardiac myocytes, including the passive and viscoelastic properties of isolated myocytes, the steady-state force calcium relationship at different sarcomere lengths, and changes in tension following a rapid increase or decrease in length, and after constant velocity shortening. This data set is, to our knowledge, the first characterization of length and velocity-dependence of tension generation in human skinned cardiac myocytes at body temperature.We use this data to develop a computational model of contraction and passive viscoelasticity in human myocytes. Our model includes troponin C kinetics, tropomyosin kinetics, a three-state crossbridge model that accounts for the distortion of crossbridges, and the cellular viscoelastic response. Each component is parametrized using our experimental data collected in human cardiomyocytes at body temperature. Furthermore we are able to confirm that properties of length-dependent activation at 37• C are similar to other species, with a shift in calcium sensitivity and increase in maximum tension. We revise our model of tension generation in the skinned isolated myocyte to replicate reported tension traces generated in intact muscle during isometric tension, to provide a model of human tension generation for multi-scale simulations. This process requires changes to calcium sensitivity, cooperativity, and crossbridge transition rates. We apply this model within multi-scale simulations of biventricular cardiac function and further refine the parametrization within the whole organ context, based on obtaining a healthy ejection fraction. This process reveals that crossbridge cycling rates differ between skinned myocytes and intact myocytes.

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Section: Multi-scale Modelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Land

Park-Holohan

Smith

et al. 2017

Journal of Molecular and Cellular Cardiology

Self Cite

110

147

View full text Add to dashboard Cite

show abstract

“…The passive mechanical behavior was governed via the transverse-isotropic strain-energy functional ( 68 )

where E is the Lagrangian strain tensor expressed relative to the muscle fiber and sheet directions and the parameters c 2 = 8, c 3 = 2, and c 4 = 4 characterized the tissue anisotropy ( 69 ). Treating the prefactor c 1 as a phenomenological scaling factor for the overall passive tissue stiffness, we allowed it to vary to preserve the ratios between the different stiffness components.…”

Section: Appendix A: Tissue Mechanicsmentioning

confidence: 99%

Balance of Active, Passive, and Anatomical Cardiac Properties in Doxorubicin-Induced Heart Failure

Lewalle

Land

Merken

et al. 2019

Biophysical Journal

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Late-onset heart failure (HF) is a known side effect of doxorubicin chemotherapy. Typically, patients are diagnosed when already at an irreversible stage of HF, which allows few or no treatment options. Identifying the causes of compromised cardiac function in this patient group may improve early patient diagnosis and support treatment selection. To link doxorubicin-induced changes in cardiac cellular and tissue mechanical properties to overall cardiac function, we apply a multiscale biophysical biomechanics model of the heart to measure the plausibility of changes in model parameters representing the passive, active, or anatomical properties of the left ventricle for reproducing measured patient phenotypes. We create representative models of healthy controls (N ¼ 10) and patients with HF induced by (N ¼ 22) or unrelated to (N ¼ 25) doxorubicin therapy. The model predicts that HF in the absence of doxorubicin is characterized by a 2-to 3-fold stiffness increase, decreased tension (0-20%), and ventricular dilation (of order 10-30%). HF due to doxorubicin was similar but showed stronger bias toward reduced active contraction (10-30%) and less dilation (0-20%). We find that changes in active, passive, and anatomical properties all play a role in doxorubicin-induced cardiotoxicity phenotypes. Differences in parameter changes between patient groups are consistent with doxorubicin cardiotoxicity having a greater dependence on reduced cellular contraction and less anatomical remodeling than HF not caused by doxorubicin.

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“…The current methodological limitation for the clinical translation is the need for catheterized pressure data (Xi et al 2014). Research is also needed to uniquely identify material parameters, a problem that can be reduced by an adequate choice of the constitutive law (Hadjicharalambous et al 2014;Nasopoulou et al 2015). Other methodologically critical aspects are the choice of a mechanical reference configuration, and the correct temporal alignment of pressure and deformation data.…”

Section: Mechanical Models Decouple Diastolic Biomarkersmentioning

confidence: 99%

Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology

2015

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Computational modelling of the heart is rapidly advancing to the point of clinical utility. However, the difficulty of parameterizing and validating models from clinical data indicates that the routine application of truly predictive models remains a significant challenge. We argue there is significant value in an intermediate step towards prediction. This step is the use of biophysically based models to extract clinically useful information from existing patient data. Specifically in this paper we review methodologies for applying modelling frameworks for this goal in the areas of quantifying cardiac anatomy, estimating myocardial stiffness and optimizing measurements of coronary perfusion. Using these indicative examples of the general overarching approach, we finally discuss the value, ongoing challenges and future potential for applying biophysically based modelling in the clinical context.

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Myocardial Stiffness Estimation: A Novel Cost Function for Unique Parameter Identification

Cited by 3 publications

References 21 publications

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

A model of cardiac contraction based on novel measurements of tension development in human cardiomyocytes

Balance of Active, Passive, and Anatomical Cardiac Properties in Doxorubicin-Induced Heart Failure

Clinical Diagnostic Biomarkers from the Personalization of Computational Models of Cardiac Physiology

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