## Section: Scientific Foundations

### Multiscale modeling

Multiscale modeling is a necessary step for blood and respiratory flows. In this section, we focus on blood flows. Nevertheless, similar investigations are currently carried out on respiratory flows.

#### Arterial tree modeling

Problems arising in the numerical modeling of the human cardiovascular
system often require an accurate description of the flow in a specific
sensible subregion (carotid bifurcation, stented artery, *etc.*).
The description of such local phenomena is better addressed by means
of three-dimensional (3D) simulations, based on the numerical
approximation of the incompressible Navier-Stokes equations, possibly
accounting for compliant (moving) boundaries. These simulations
require the specification of boundary data on artificial boundaries
that have to be introduced to delimit the vascular district under
study. The definition of such boundary conditions is critical and, in
fact, influenced by the global systemic dynamics. Whenever the
boundary data is not available from accurate measurements, a proper
boundary condition requires a mathematical description of the action
of the reminder of the circulatory system on the local district. From
the computational point of view, it is not affordable to describe the
whole circulatory system keeping the same level of detail. Therefore,
this mathematical description relies on simpler models, leading to the
concept of *geometrical multiscale* modeling of the circulation
[73] . The underlying idea consists in coupling
different models (3D, 1D or 0D) with a decreasing level of accuracy,
which is compensated by their decreasing level of computational
complexity.

The research on this topic aims at providing a correct methodology and a mathematical and numerical framework for the simulation of blood flow in the whole cardiovascular system by means of a geometric multiscale approach. In particular, one of the main issues will be the definition of stable coupling strategies between 3D and reduced order models.

To model the arterial tree, a standard way consists of imposing a
pressure or a flow rate at the inlet of the aorta, *i.e.* at the
network entry. This strategy does not allow to describe important
features as the overload in the heart caused by backward traveling
waves. Indeed imposing a boundary condition at the beginning of the
aorta artificially disturbs physiological pressure waves going from
the arterial tree to the heart. The only way to catch this
physiological behavior is to couple the arteries with a model of
heart, or at least a model of left ventricle.

A constitutive law for the myocardium, controlled by an electrical command, has been developed in the CardioSense3D project (http://www-sop.inria.fr/CardioSense3D/ ). One of our objectives is to couple artery models with this heart model.

A long term goal is to achieve 3D simulations of a system including heart and arteries. One of the difficulties of this very challenging task is to model the cardiac valves. To this purpose, we plan to mix arbitrary Lagrangian Eulerian and fictitious domain approaches, or simplified valve models based on an immersed surface strategy.

#### Heart perfusion modeling

The heart is the organ that regulates, through its periodical contraction, the distribution of oxygenated blood in human vessels in order to nourish the different parts of the body. The heart needs its own supply of blood to work. The coronary arteries are the vessels that accomplish this task. The phenomenon by which blood reaches myocardial heart tissue starting from the blood vessels is called in medicine perfusion. The analysis of heart perfusion is an interesting and challenging problem. Our aim is to perform a three-dimensional dynamical numerical simulation of perfusion in the beating heart, in order to better understand the phenomena linked to perfusion. In particular the role of the ventricle contraction on the perfusion of the heart is investigated as well as the influence of blood on the solid mechanics of the ventricle. Heart perfusion in fact implies the interaction between heart muscle and blood vessels, in a sponge-like material that contracts at every heartbeat via the myocardium fibers.

Despite recent advances on the anatomical description and measurements of the coronary tree and on the corresponding physiological, physical and numerical modeling aspects, the complete modeling and simulation of blood flows inside the large and the many small vessels feeding the heart is still out of reach. Therefore, in order to model blood perfusion in the cardiac tissue, we must limit the description of the detailed flows at a given space scale, and simplify the modeling of the smaller scale flows by aggregating these phenomena into macroscopic quantities, by some kind of “homogenization” procedure. To that purpose, the modeling of the fluid-solid coupling within the framework of porous media appears appropriate.

Poromechanics is a simplified mixture theory where a complex
fluid-structure interaction problem is replaced by a superposition of
both components, each of them representing a fraction of the complete
material at every point. It originally emerged in soils mechanics with
the work of Terzaghi [76] , and Biot [68] later
gave a description of the mechanical behavior of a porous medium using
an elastic formulation for the solid matrix, and Darcy's law for the
fluid flow through the matrix. Finite strain poroelastic models have
been proposed (see references in [69] ), albeit with *ad hoc* formulations for which compatibility with thermodynamics laws and incompressibility conditions is not established.

#### Tumor and vascularization

The same way the myocardium needs to be perfused for the heart to beat, when it has reached a certain size, tumor tissue needs to be perfused by enough blood to grow. It thus triggers the creation of new blood vessels (angiogenesis) to continue to grow. The interaction of tumor and its micro-environment is an active field of research. One of the challenges is that phenomena (tumor cell proliferation and death, blood vessel adaptation, nutrient transport and diffusion, etc) occur at different scales. A multi-scale approach is thus being developed to tackle this issue. The long term objective is to predict the efficiency of drugs and optimize therapy of cancer.

#### Respiratory tract modeling

We aim to develop a multiscale modeling of the respiratory tract. Intraprenchymal airways distal from generation 7 of the tracheabronchial tree (TBT), which cannot be visualized by common medical imaging techniques, are modeled either by a single simple model or by a model set according to their order in TBT. The single model is based on straight pipe fully developed flow (Poiseuille flow in steady regimes) with given alveolar pressure at the end of each compartment. It will provide boundary conditions at the bronchial ends of 3D TBT reconstructed from imaging data. The model set includes three serial models. The generation down to the pulmonary lobule will be modeled by reduced basis elements. The lobular airways will be represented by a fractal homogenization approach. The alveoli, which are the gas exchange loci between blood and inhaled air, inflating during inspiration and deflating during expiration, will be described by multiphysics homogenization.