The arterial blood pressure waveform can be considered as the composite of a forward pressure wave, travelling from the heart to the periphery, and of a reflected pressure wave, travelling backwards towards the heart. Early return of this reflected wave boosts systolic blood pressure, increasing the load on the heart and widening the amplitude of the pressure pulse, factors that have been shown to increase cardiovascular risk.

Damage to connective tissue such as tendons can occur via stretch injuries. During stretch injury, a tendon experiences permanent subfailure damage. Provenzano et al. showed that irreversible damage to the cellular structure of tendon or ligament occurs before noticeable changes can be measured in the mechanical behavior of the tissue [1]. The same paper also showed that during loading a portion of the curve can be classified as a sub-damage region where repeated loading in that range will have no effect on mechanical properties. There is also a damage region where plastic deformation and fiber tearing occurs. In this region, the severity of damage increases as the amount of strain increases. For the same level of functional loading after damage, tissue stiffness decreases while tissue strain increases. In-vivo measurements of damage indicators, such as strain and stiffness of a tendon, prove difficult using current techniques, since many of those methods are invasive (implanted strain gages) or large and non-portable (MRI)[2]. Recent studies have shown that ultrasound can be employed to assess ligaments and tendons by measuring ultrasound wave velocity and echo reflection [3,4].

A number of concomitant factors are thought to contribute to an increase in the mean pulmonary arterial pressure (MPAP) of pulmonary arterial hypertension (PAH) patients, such as increased pulmonary vascular resistance (PVR), increased blood flow (due to septal defects), and a decrease in wall distensibility.[1] This is in contrast to the normal pulmonary circuit, which is characterized by compliant artery walls and a low PVR, resulting in a low MPAP with little flow and pressure wave reflection. The influence of pathologic MPAP’s on proximal hemodynamic factors such as artery size, flow pulse waveforms, and wall shear stress (WSS) is unclear. Since these factors are known pathophysiological stimuli in the production of molecules that alter vascular tone and matrix properties,[2] we set out to quantify the geometry, flow, and WSS of the left, right and main pulmonary arteries (LPA, RPA, & MPA) of control and PAH patients using phase-contrast magnetic resonance imaging (PC-MRI).

Focal adhesions (FAs) and their associated integrins are thought to act as mechanosensors and transducers of shear stress into intracellular biochemical signals. However, to date there exists no quantification of the magnitude of forces generated at integrin molecules in response to apically-applied fluid shear stress. Thus, we used finite element analysis of fluid dynamics and cellular stresses to compute FA stresses from solid models of focally-adhered endothelial cells. These models were developed from quantitative 3-D microscopy and total internal reflection fluorescence (TIRF) microscopy of calcein-stained endothelial cells. Extrusion coupling variables mapped stresses from the macroscale cell model to individual microscale 3-D models of FAs determined from quantitative TIRF. Included in the microscale FA model were moduli for subcellular matrix (SCM) (e.g. hyaluronan, hyaluronaic acid and other glycocalyx constituents) and extracellular matrix (ECM) (e.g. collagen, fibronectin). Integrin forces were estimated from assumed bonds densities and computed FA stresses. Maximal bond tension obtained from the simulation for a single integrin-extracellular matrix (ECM) bond was .1pN. Thus, it is unlikely that integrin-ECM bonds or chemical activities are appreciably affected by shear stress. The computational model, however, supports an alternative model of activation in and reorganization of FAs in which shear stress-induced forces cause the membrane to bend toward and away from the ECM immediately upstream and downstream of the FA, respectively. The simulation also suggests that the elasticity of the SCM plays an important role in modulating shear-induced FA reorganization. These results support a new model of endothelial cell activation by shear stress in which integrins and FAs participate in the directional biasing of force-induce signaling but do not initiate it.

The economical growth and increased welfare in the Western world have a reverse side, with an increased death toll due to cardiovascular diseases. Among these, aortic aneurysms (a local dilation) are particularly lethal as they may grow unnoticed until rupture occurs. In this study, we assessed the impact of the presence of an abdominal aortic aneurysm on arterial hemodynamics and wave reflection in particular. Experimental and numerical methods were applied. Linear wave separation was used to quantify the reflections; wave intensity analysis was applied to assess the nature of the reflected waves. In both the experimental and numerical models, negative reflections were found in the upper aorta corresponding to a backward expansion wave caused by the sudden expansion of the aorta. A numerical parameter study demonstrated that larger diameters and more compliant aneurysms generate stronger negative reflections.

Computational modeling can be used to increase the understanding of fluid dynamics and offer predictive capabilities when used in vascular surgery planning. An important consideration for studies including the pulmonary vasculature is the impact of pulmonary impedance due to respiration and vessel compliance [1]. Currently, the outlet boundary conditions for this type of model consist of a flow profile or constant pressure. These boundary conditions do not reflect the geometry of the lung, effects of respiration, or the compliance of pulmonary vessels. To improve the accuracy of computational modeling of the pulmonary circulation, a dynamic impedance boundary condition will be developed that can be used to accurately represent respiration effects and provide information regarding wave speed and reflection in compliant arteries.

Stress fractures occur in bones of athletes and soldiers due to the accumulation of microcracks [1]. Detection of precursor acoustic emissions (i.e. ultrasonic stress waves) resulting from microcrack activity may help predict failure onset before continuous physiological activity results in full-blown fracture. An acoustic emission wave generated from a microcrack in bone will be diminished by dispersion, mode separation, reflection, and viscous losses induced by the biological tissues (skin, muscle, fat) between the source and the transducer. While others have recorded waves emanating from unknown loci in human knee in vivo using acoustic emission method [2], there is no means to appreciate how far these waves can travel in the body. Several studies have characterized the ultrasound attenuation in bone [3] and muscle analog homogenates [4] in the frequency range above 300 kHz. On the other hand, acoustic emissions are prominent in the range of 20 kHz to 300 kHz. The current study focused on identifying the attenuation of acoustic emission waves in bone and muscle tissues in a frequency range which is more relevant to acoustic emissions. This information is critical for predicting whether an emission of certain magnitude at the source can reach surface mounted sensors without being totally attenuated.

Total internal reflection fluorescent microscopy (TIRFM) is a relatively well known tool used to examine the near wall region (approximately 1 μm). For years, cellular biologists have used TIRFM in a variety of experiments to examine multiple cell lines. However, much of the research has been somewhat static in nature, considering only initial and final states. With the increased ability to stain specific organelles within cells through the use of green fluorescent protein (GFP), dynamic imaging is becoming a viable solution to previously difficult problems.

Pulmonary hypertension is a potentially fatal disease, resulting from chronic obstructive or interstitial lung disease, recurrent pulmonary emboli, antecedent heart disease, hypoxia or other unknown causes [1]. Pulmonary hypertension causes vascular remodeling with smooth muscle cell (SMC) hyperplasia and hypertrophy and accumulation of collagen and elastin [2]. This remodeling increases pulmonary vascular resistance, which can lead to increases in steady right ventricular work [3]. The effects of remodeling on pulmonary vascular impedance, which determines pulsatile right ventricular work, remain incompletely described. We have previously quantified the effects of chronic hypoxia-induced pulmonary hypertension (HPH) on pulmonary vascular impedance [4] but did not investigate the role of SMC tone either before or after HPH. The aim of this study was to investigate the effects of normal and increased SMC tone on pulsatile pulmonary hemodynamics before and after HPH-induced pulmonary vascular remodeling. We hypothesized that SMC contraction would increase input resistance but decrease the speed of wave reflections. We also hypothesized that increased arteriolar muscularization after HPH would lead to greater increases in resistance and greater decreases in wave reflections with increased SMC tone.

Voiced speech involves complex fluid-structure-acoustic interactions. When a critical lung pressure is achieved, the vocal folds are pushed apart inciting self-sustained oscillations. The interplay between the aerodynamic forces and the myoelastic tissue properties produces robust oscillation of the vocal folds. The pulsatile nature of the flow as it emanates from vocal folds creates an oscillatory pressure field which acoustically excites the vocal tract and ultimately forms intelligible sound. Recently, it has been shown that the acoustic pressures are high enough in magnitude that they modulate the static fluid pressures which drive the flow. 1 This coupling effect creates a feedback loop with the fluids, acoustics, and vocal fold dynamics becoming interconnected. Consequently, speech science investigations that aim to capture the relevant physics must consider all three components to yield credible, clinically-relevant results.

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. In fact, when a blast wave interacts with nearby structures, reflected shock waves are generated and complex three-dimensional shock waves are formed. Complex shock wave overpressure-time traces are significantly different from free-field profiles because reflections can cause super-positioning of shock waves resulting in increased pressure magnitudes and multiple pressure peaks. Very importantly, the shocks arrive from different directions which would invoke a different biomechanical response than a one-dimensional exposure. It has been reported that in complex wave environments, the extent of the injuries becomes a function of the location related to the surrounding structures rather than a function of the distance from the center of the explosion, as it is for free-field conditions (Yelverton et al. 1993; Mayorga 1997; Stuhmiller 1997). Furthermore, the resulting injuries when the individual is in confined spaces are noted to be more severe (Yelverton et al. 1993; Leibovici et al. 1996). The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment. Furthermore, we explored the effects of head orientation in the same environment.

Aortic coarctation is a congenital disease, characterized by a narrowing of the upper descending aorta, obstructing the blood flow from the heart towards the lower part of the body. The treatment can be minimally invasive using a stent and/or a balloon catheter to dilate the coarctation zone, or the narrow section can be removed surgically. Even after a successful treatment, a high risk of cardiovascular morbidity and mortality remains. Two aspects contribute to this increased risk: (1) a residual narrowing, leading to an additional resistance in the arterial system and (2) a local stiffening after treatment, disturbing the buffer function of the aorta. Moreover, these residual narrowing and stiffening lead to an impedance mismatch and are a source of wave reflections that reach the heart fast, given the short distance to the heart.

Pulse wave velocity (PWV) is the propagation speed of pressure and flow waves in the arterial system induced by the contracting left ventricle. PWV is a measure of arterial stiffness, and has been shown to predict cardiovascular events. In a clinical setting, PWV is usually associated with carotid-femoral PWV, reflecting the propagation speed over the aorta. It is, however, also possible to assess local PWV at a given measuring location, which reflects the stiffness of the artery under investigation at that particular location. When locally assessing PWV, single-location techniques are commonly used, which rely on the fact that in uniform elastic tubes, the relationship between a change in pressure (dP) and velocity (dU) is constant in the absence of wave reflections. As such, when plotting the pressure P as a function of the velocity U in an artery, a PU-loop is obtained, where reflection-free instants emerge as a straight line (typically during early systole), with a slope given by ρPWV (ρ = blood density). The original method relied on pressure and velocity data ( PU-method ), but alternative methods have been introduced based on cross-sectional area (A) and flow (Q) ( QA-method ), or diameter (D) and velocity (U) ( ln(D)U-method ).

The distribution of inhaled air throughout human lungs is determined by the pressure losses in lung airways. These losses are reflections of patient health; alterations in measured pressure drops can indicate the presence of respiratory disease [1]. Pressure losses also have implications for the effective treatment of such diseases, as they affect how effectively inhaled medication can be distributed throughout the lung.

Recently, Ultrasonic Perpendicular Velocimetry (UPV) based algorithms, as opposed to commonly used Doppler technique (Figure 1), were applied to Radio Frequency (RF)-data acquired in an in-vitro setup [1,3]. Thus, the estimation of velocity components perpendicularly to the ultrasound beam and the simultaneous and accurate assessment of wall position and axial velocity profiles were made feasible. By integrating the measured velocity profile an accurate flow estimation was made possible. Furthermore, the ratio between the changes in flow Q(t) and the changes in cross-sectional area of the vessel A(t) was found to offer an accurate estimation of the local Pulse Wave Velocity (PWV). By combining the PWV with the diameter waveform, accurate local pressure estimation was obtained indicating that a non-invasive pressure assessment by means of ultrasound is feasible [3]. However, the abovementioned method is time consuming due to the data size and the post-processing procedure required. Additionally, the Fast Fourier Transform (FFT) on Butterworth Band Pass Filters (BPF) for vessel’s wall removal requires contrast agents dispersion in the fluid for the application of UPV. A real-time approach, of the previously described techniques, was applied [2] in-vitro using a Blood Mimicking Fluid (BMF), as contrast agent, resembling the rheological (shear thinning) and acoustical (backscattering) properties of blood and ex-vivo using BMF or contrast-free real blood implementing Wavelet Transform (WT) filtering. The use of a Graphics Processing Unit (GPU) [4], succeeded in considerable acceleration and WT [5] filtering on the rough RF-data, in improvement of the discrimination between reflections from the vessel wall and scattering from small particles. In this research the method is extended to include in-vivo measurements.

Arterial stiffness is an independent predictor of cardiovascular risk [1]. It is therefore crucial to accurately estimate the arterial mechanical properties. The mechanical properties are reflected in the pulse wave velocity (PWV), which can be estimated from the blood pressure (BP) waveforms measured at two locations (tonometry). However, accuracy of tonometry is limited by reflections in the BP waveforms and errors in distance estimation between the measurement sites.

The analysis of wave travel and reflection has gained increased interest in the clinical community. The speed of the pressure pulse, PWV, (assessed from the time delay of the foot of the wave measured at two distant locations), is considered the gold standard method to assess the stiffness of arterial segments and has been shown to be of prognostic value for cardiovascular disease. Also, analysis of wave reflections has been suggested as diagnostic tool, a.o. to estimate the effect of the treatment of aortic coarctation (a congenital disease characterized by an obstructive narrowing of the upper descending aorta) on the load on the heart. The presence of a residual narrowing and/or local stiffening after treatment of aortic coarctation leads to an impedance mismatch and generates wave reflections that reach the heart very fast, given the short distance to the heart. The exact interplay between arterial stiffness, wave travel and reflection is, however, still relatively poorly understood due to the complexity of the arterial tree leading to scattered wave reflection, rather than discrete reflection.

Ultrasound waves, transmitted by a transducer into a body, are reflected and scattered by the materials they encounter in the body. In case of blood flow measurements in an artery, the received signal will contain the information not only from the moving red blood cells, but the reflections from the vessel wall of other soft tissue structures as well. The discrimination between ultrasound signals originating from scattering of red blood cells and reflection of tissue is one of the major problems for blood velocity assessment. Traditionally, in Doppler processing, where the highest blood velocities in the middle of the vessel are estimated, this discrimination is obtained via a high pass filter with a static cut-off frequency related to the maximum frequency content of the reflections. This is illustrated in Fig.1 (top). As illustrated in Fig. 1 (bottom), problems occur for velocity estimation of slowly moving blood cells close to the vessel wall and in case of perpendicular insonification [1]. In these cases, there is no frequency shift in the signal received from scattering on blood cells. Furthermore, the intensity of the reflections from the vessel wall is highest in case of perpendicular insonification. Filtering in these cases is very challenging since it allows the assessment of blood velocity profiles without contrast agents.

Molecular and cellular interactions with foreign surfaces can be noninvasively measured by isotope imaging techniques. Long available for probing cell behavior, these techniques are now employed in molecular studies of disease progression, such as Alzheimer’s [1]. This paper reviews results obtained by noninvasive dual label gamma scintigraphy for the transient adhesion of platelets and neutrophils to pump-oxygenators during cardiopulmonary bypass (CPB). In this application, characteristic cell-foreign surface adhesion and release patterns are observed during CPB in the pig, as a function of oxygenator design and surface chemistry. Cell distributions in internal organs post-CPB are also affected by these processes. This method can be adapted to other settings where the understanding of protein-cell interactions with native and foreign surfaces is at issue, including fibrinogen-cell interactions, bacterial colonization, etc.

In vivo studies have revealed that aortic grafts augment heart load and alter blood pressure and flow waveforms [1]. A one-dimensional model of the arterial tree was developed in order to analyze the different mechanisms by which proximal and distal aortic grafts affect hemodynamics. Graft compliance and properties were based on in vitro tests. Predicted pressures at the aortic root were compared for the control, proximal and distal graft case. Pulse pressure increased by 21% and 10% in presence of a proximal and distal graft, respectively. The distal graft resulted in a wave reflection coefficient of 0.62 while for the proximal graft the wave reflection coefficient was 0.46. The physiological mechanism behind the rise of pressure is dual and it is critically affected by the graft’s compliance and position. In case of a proximal graft, the primary reason for aortic pressure increase is the augmentation of aortic characteristic impedance, which augments the forward running pressure wave, while for the distal graft the wave reflections are major contributors to the total pressure wave. Overall, the proximal graft altered hemodynamics to a greater extent than a distal aortic graft.