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past event log |
Institute of Biomedical Engineering
ETH Zürich, Switzerland
delivered a set of lectures.
According to a general paradigm, intravascular flow is mostly convective and driven by the pressure pulses generated by the beating heart while extravascular transport in organs and tissues is primarily diffusive and as such dominated by concentration gradients. Transport efficiency depends, among other, on the dynamics and typical time scales associated with convection and diffusion. Besides transport, intravascular flow patterns are of importance with respect to viscous shear loads acting on endothelial cells which decisively influences their metabolism.
First, intravascular transport is considered and arterial pulse propagation and flow characteristics on the basis of a branched arterial network are reviewed. For arterial segments with only minor lateral outflow between major bifurcations, a one-dimensional flow approximation based on the Navier-Stokes equation, conservation of mass and a nonlinear constitutive relation for the vessel wall taking into account viscoelasticity is presented. Bifurcations, in turn, are treated by a simplified approximation. It is shown that all of the nonlinear and damping effects contribute essentially and none of them can be disregarded if a realistic model of an extended branched arterial system is to be formulated. A comparison with measured flow pulses substantiates the validity of the model. In order to assess the interaction between flow and vascular endothelium, in turn, three dimensional flow simulations are necessary. Such models are confined to specific sections of the arterial tree which are of particular interest in view of vascular disease leading to atherosclerosis. Results can be substantiated thereby with the aid of measurements based on MR which lend themselves for the determination of 3D intravascular flow patterns in vivo.
Second, diffusive transport in the interstitial (extravascular and extracellular) spaces is discussed. Transport times are estimated using typical diffusion constants, distances and dimensions of conduits available for diffusion. It is furthermore established that convective flows may also be of importance in the interstitium. This is particularly the case in cortical bone, where diffusion alone cannot account for the transport capacity necessary for a healthy metabolism of osteocytes. In fact, pressure gradients which are induced in the fluid phase of the bone material by the deformations caused by the natural loading of the skeleton are experimentally and theoretically shown to produce forced convective flows (load-induced fluid flow) and to be essential for material transport. Such flows are furthermore significant in view of flow - cell interactions.
The mammalian myocardium is characterized on the one hand by the systematic spatial organization exhibited by the cardiac muscle fibers (cardiomyocytes) and on the other by the high degree of branching between them. A well-defined orthotropic architecture of the main fiber direction throughout the ventricular wall can thereby clearly be discerned under healthy conditions. Thanks to recent developments in Magentic Resonance (MR) Diffusion Tensor Imaging (DTI), the global 3D architecture of the myocardium can be visualized today particularly well in vitro.
The fact that fibers form a densely interconnected and branched orthotropic network implies that there exists a random distribution of the individual fiber orientation in a relatively narrow cone around the main direction. Histology furthermore shows, that there are not only surface-parallel orientations of the main fiber directions as is mostly assumed when cardiac mechanics are considered, but up to 20% of the fibers diverge essentially from a surface-parallel orientation to form transverse or cross-over pathways.
On the basis of a simplified mathematical model the relation between fiber orientation and forces is discussed and a comparison with stresses calculated from a Laplace-type approximation is made. It is found that the nonuniformity in the fiber direction pattern or some form of crosslinking between the myocytes is necessary to stabilize the myocardium in the sense that a functioning ventricle is feasible. Yet, large deviations from a physiologic pattern may lead to an immobilization (deadlocking) of the myocardium.
Force transducers which are inserted in the ventricular wall allow the measurement of relative fiber forces and directions in vivo during open heart surgery or in animal experiments (pigs). Examples of such measurements are shown including results obtained during volume reduction surgery and a general agreement with theoretical results is found. In particular, the course in time of the contractile forces exhibits a characteristic behavior depending on the fiber orientation. While the force in surface-parallel fibers reaches an early maximum and then decreases gradually during systole, transversely oriented fibers show in contrast an auxotonic behavior.
Medical endoscopy has become a key technology for the purposes of minimally invasive diagnostic and therapeutic procedures. With the aid of an endoscope, an external observation of a location inside the human body which may be difficult or dangerous to reach or which should be subjected to minimal traumatization associated with the intended medical treatment is facilitated through a viewing channel. A standard television system is usually attached to the distal end of an endoscope for image presentation. Of primary importance for the user are image quality, ease of application and safety-related aspects. The optical properties of various types of endocsopes are reviewed, their spatial resolution is assessed and HDTV applications are discussed.
However, minimally invasive procedures in diagnosis and therapy expose inexperienced and untrained users to situations they are not accustomed to in that there is neither a direct visual insight into the location under scrutiny nor an immediate mechanical connection to the tools applied locally. Instead, observation occurs mostly by way of video systems and tools are either manipulated through the trocar hull which leads to a reduced maneuverability or indirectly by remote or robotic control. Appropriate training is therefore necessary in order to adapt the special skills associated with operating under such conditions. Animal models and mechanical training devices are presently being in use as a help for surgeons to learn basic manipulations under television feedback.
The use of animal models, though well suited for selected training purposes, is however severely restricted due to ethical and financial reasons. Virtual Reality (VR) based mechanical simulators lend themselves to circumvent this problem. For this purpose, a mathematical formulation of the entire mechanical environment is needed which on the one hand yields verisimilitude and on the other allows for an updating of the situation, visualization and preparation of force-feedback information in real-time. For such applications rapid computational methods are to be developed. An important aspect thereby is related to the degree of accuracy of the description which has to be met in order to guarantee realistic results. This has also to be put into perspective with natural biological variability and differences in constitutive properties of tissues as the result of diseases.
The approaches to be taken for the implementation of constitutive behavior in the form of computer models include interpolation/look-up table schemes and lumped parameter approximations as well as Finite Element (FE) methods. Although FE models lead to realistic results, their applicability is restricted because of computational expense. Efficient contact detection and treatment modalities are furthermore required in order to model a realistic anatomic environment and interaction with surgical tools. Changes in model topology, associated with surgical interventions are thereby difficult to handle in real time. Mesh-free methods may be more useful for such applications.
Besides genetic, biochemical and environmental factors, mechanical loading and associated deformations and microdamage have been shown to exert a significant influence on growth, repair and remodeling of bone. Imaging procedures and mathematical modeling of bone (micro-) mechanics are therefore of importance in the investigation of bone physiology and skeletal disorders.
From a clinical point of view, the assessment of fracture risk is of primary interest. Skeletal structures mostly involved, in particular in osteoporotic patients of advanced age, are the spine, the femur and the wrist. Bone mineral content (BMC) and trabecular structure (characterized by a number of parameters) have been shown to be major determinants in view of fracture risk. While integral measurement methods such as DEXA or ultrasound allow for an assessment of the state of overall mineralization (BMC), the determination of trabecular structure requires the application of special imaging procedures. Methods to investigate the microstructure of bone samples nondestructively include Micro Computed Tomography (mCT) as well as CT based on synchrotron radiation. Both methods are explained and typical results are shown. mCT allows furthermore to analyse deformation patterns of trabecular bone samples which are subjected to controlled loading. The measurements are accompanied by large-scale finite element calculations in order to relate BMC and structure elements with mechanical properties. Such calculations can be extended today to include detailed models, e.g., of the human wrist. These procedures also allow, among other, to elucidate the effect of genetic modifications on the mechanical properties of bone in animals (mouse).
Perfusion of bone, along with osteocyte activity is a further important aspect in bone mechanics. This subject is mentioned here for completeness; it is addressed mainly in the lecture on Intra- and Extravascular Flow Dynamics and Transport Processes.