Integrating multi-scale data to create a virtual physiological mouse heart

Abstract

One contribution of 25 to a Theme Issue 'The virtual physiological human: integrative approaches to computational biomedicine'. While the virtual physiological human (VPH) project has made great advances in human modelling, many of the tools and insights developed as part of this initiative are also applicable for facilitating mechanistic understanding of the physiology of a range of other species. This process, in turn, has the potential to provide human relevant insights via a different scientific path. Specifically, the increasing use of mice in experimental research, not yet fully complemented by a similar increase in computational modelling, is currently missing an important opportunity for using and interpreting this growing body of experimental data to improve our understanding of cardiac function. This overview describes our work to address this issue by creating a virtual physiological mouse model of the heart. We describe the similarities between human-and mouse-focused modelling, including the reuse of VPH tools, and the development of methods for investigating parameter sensitivity that are applicable across species. We show how previous results using this approach have already provided important biological insights, and how these can also be used to advance VPH heart models. Finally, we show an example application of this approach to test competing multi-scale hypotheses by investigating variations in length-dependent properties of cardiac muscle.

Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition

“…55.2%) 23 , 43 . Such an approach is not uncommon as for example the parametrization of the virtual physiological rat and mouse heart models include data from other species as well 44 , 45 . The average wet weight of the mouse small intestine was reported to be 1.094 g, of which 76% was water 46 .…”

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

“…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]. These models have the advantage that they can be used to link changes in sub-cellular properties to whole organ contractile performance, predicting key indicators of cardiac function from changes to individual channels or proteins involved in calcium regulation and contractile dynamics.…”

Comprehensive Analysis of Animal Models of Cardiovascular Disease using Multiscale X-Ray Phase Contrast Tomography

“…Knowing how the microstructural components of the heart arrange, organise and integrate at a macroscopic level is crucial in order to better understand the cardiac (dys)function both in healthy and pathological conditions. Moreover, this information is of prime importance for the development of more realistic and accurate cardiac computational models, for which 3D high-resolution imaging techniques such as PB-X-PCI are needed 38,39 . Therefore, the processing and analysis of images such the ones acquired with the presented protocol, can be used as input for models with the goal of better understanding the effects of anatomical alteration on cardiac function.…”