The Role of Biofluid Mechanics in the Assessment of Clinical and Pathological Observations: Sixth International Bio-Fluid Mechanics Symposium and Workshop, March 28–30, 2008 Pasadena, California

Biofluid mechanics is increasingly applied in support of diagnosis and decision-making for treatment of clinical pathologies. Exploring the relationship between blood flow phenomena and pathophysiological observations is enhanced by continuing advances in the imaging modalities, measurement techniques, and capabilities of computational models. When combined with underlying physiological models, a powerful set of tools becomes available to address unmet clinical needs, predominantly in the direction of enhanced diagnosis, as well as assessment and prediction of treatment outcomes. This position paper presents an overview of current approaches and future developments along this theme that were discussed at the 5th International Biofluid Symposium and Workshop held at the California Institute of Technology in 2008. The introduction of novel mechanical biomarkers in device design and optimization, and applications in the characterization of more specific and focal conditions such as aneurysms, are at the center of attention. Further advances in integrative modeling, incorporating multiscale and multiphysics techniques are also discussed

Model prediction of subendocardial perfusion of the coronary circulation in the presence of an epicardial coronary artery stenosis

The subendocardium is most vulnerable to ischemia, which is ameliorated by relaxation during diastole and increased coronary pressure. Recent clinical techniques permit the measuring of subendocardial perfusion and it is therefore important to gain insight into how measurements depend on perfusion conditions of the heart. Using data from microsphere experiments a layered model of the myocardial wall was developed. Myocardial perfusion distribution during hyperemia was predicted for different degrees of coronary stenosis and at different levels of Diastolic Time Fraction (DTF). At the reference DTF, perfusion was rather evenly distributed over the layers and the effect of the stenosis was homogenous. However, at shorter or longer DTF, the subendocardium was the first or last to suffer from shortage of perfusion. It is therefore concluded that the possible occurrence of subendocardial ischemia at exercise is underestimated when heart rate is increased and DTF is lower

Improved detection of fluorescently labeled microspheres and vessel architecture with an imaging cryomicrotome

Due to spectral overlap, the number of fluorescent labels for imaging cryomicrotome detection was limited to 4. The aim of this study was to increase the separation of fluorescent labels. In the new imaging cryomicrotome, the sample is cut in slices of 40 μm. Six images are taken for each cutting plane. Correction for spectral overlap is based on linear combinations of fluorescent images. Locations of microspheres are determined by using the system point spread function. Five differently colored microspheres were injected in vivo distributed over two major coronaries, the left anterior descending and left circumflex artery. Under absence of collateral flow, microspheres outside of target perfusion territories were not found and the procedure did not generate false positive detection when spectral overlap was relevant. In silico-generated microspheres were used to test the effect of background image, transparency correction, and color separation. The percentage of microspheres undetected was 2.3 ± 0.8% in the presence and 1.5 ± 0.4% in the absence of background structures with a density of 900 microspheres per color per cm3. The image analysis method presented here, allows for an increased number of experimental conditions that can be investigated in studies of regional myocardial perfusion

Hemodynamic effects of epicardial stenoses.

This chapter starts by a brief review of coronary physiology in terms of pressure-flow relationships and effects of vessel distensibility on microvascular resistance to lay the foundation for interpretation of coronary stenosis hemodynamics. The fluid dynamics of stenosis pressure gradient, resistance, and its dependency on flow and stenosis dimensions is outlined in the next section. Special consideration is given to serial lesions, stenosis compliance, and diffuse coronary narrowing. The last section discusses the hemodynamic effect of coronary epicardial stenoses on coronary blood flow and the need for integration of multiple physiological parameters to arrive at a well-founded procedural decision for an individual patient suffering from ischemic heart disease

Usefulness of Proximal Coronary Wave Speed for Wave Intensity Analysis in Diseased Coronary Vessels

Background: Wave speed is needed to separate net wave intensity into forward and backward traveling components. However, wave speed in diseased coronary arteries cannot be assessed from hemodynamic measurements obtained distal to a stenosis. Wave speed inherently depends on arterial wall properties which should be similar proximal and distal to a stenosis. Our hypothesis is that proximal wave speed can be used to separate net wave intensity obtained distal to a stenosis. Methods: We assessed coronary wave speed using the sum-of-squares single-point technique (SPc) based on simultaneous intracoronary pressure and flow velocity measurements in human coronary arteries. SPc at resting flow was determined in diseased coronary vessels of 12 patients both proximal and distal to the stenosis. In seven of these vessels, distal measurements were additionally obtained after revascularization by stent placement. SPc was also assessed at two axial locations in 14 reference vessels without a stenosis. Results: (1) No difference in SPc was present between proximal and distal locations in the reference vessels. (2) In diseased vessels with a focal stenosis, SPc at the distal location was paradoxically larger than SPc proximal to the stenosis (28.4 ± 3.7 m/s vs. 18.3 ± 1.8 m/s, p < 0.02), despite the lower distending pressure downstream of the stenosis. The corresponding separated wave energy tended to be underestimated when derived from SPc at the distal compared with the proximal location. (3) After successful revascularization, SPc at the distal location no longer differed from SPc at the proximal location prior to revascularization (21.9 ± 2.0 m/s vs. 20.8 ± 1.9 m/s, p = 0.48). Accordingly, no significant difference in separated wave energy was observed for forward or backward waves. Conclusion: In diseased coronary vessels, SPc assessed from distal hemodynamic signals is erroneously elevated. Our findings suggest that proximal wave speed can be used to separate wave intensity profiles obtained downstream of a stenosis. This approach may extend the application of wave intensity analysis to diseased coronary vessels