Numerous studies have shown that cardiac diastolic dysfunction and diastolic filling play a critical role in dictating overall cardiac health and demonstrated that the filling wave propagation speed is a significant index of the severity of diastolic dysfunction [1, 2]. However, the governing flow physics underlying the relationship between propagation speed and diastolic dysfunction are poorly understood. More importantly, currently there is no reliable metric to allow clinicians the ability to diagnose cardiac dysfunction on the basis of the wave filling speed.

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).

The polymerase chain reaction (PCR) exponentially amplifies a DNA template and produces large numbers of specific DNA fragments. Because of its high sensitivity and efficiency, it becomes a common technique that is widely used in molecular biological. The addition of nano-gold particles into the template solution was found to greatly enhance the efficacy of PCR [1, 2]. Although the thermal effect has been suggested, the underlying mechanisms are still not clear, e.g. how the temperature field affects the replication of DNA at the molecular level. A typical PCR process consists of repeated cycling of three major steps: (1) fast heating to a temperature around 94°C for separating of the two strands DNA templates into single strand (Denaturation); (2) lowering the temperature to about 54°C for the primers to find the complementary part and anneal to the single stranded templates (Annealing); (3) increase of the temperature again to around 72°C for copying of the single templates with the action of the polymerase enzyme (Extension). The thermal history of the PCR determines the activity of the polymerase and rate of each reaction taken place during the process. And the motion of the primers, the DNA templates and the bases owing to both the Brownian effects and concentration gradients can also influence the specificity and reaction rates. The addition of nano-gold particles is expected to greatly alter both the heat and mass transfer efficiency. Thus, the micro-heat and mass transfer analysis of the nano-gold added PCR process has been performed. The temporal and spatial temperature distribution, and the reactants and products concentration have been numerically simulated. The influence of added nano-gold particles on the polymerase reaction rate, the efficiency and specificity of the PCR has evaluated. The possible thermal wave and resonance of the two-phase fluid at the micro-scale level has also been investigated, as well as the enhanced mass transfer of the templates and the reaction rate. The results show that both the thermal effects and physical properties of the nano-particles have contributed to the increase of the efficiency and specificity in the PCR process.

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.

The objectives of this study are to observe the behavior of Lamb waves upon encountering a defect in a bone and to provide 2-d visualizations of the process. For this purposes, measurements were conducted using a non-contact optical detection technique, scanning laser vibrometry. This technique produces 2-d graphics of the Lamb waves in the cortical layer of the bone.

Traumatic brain injuries (TBIs) involve a significant portion of human injuries resulting from a wide range of civilian accidents as well as many military scenarios. Axonal damage is one of the most common and important pathologic features of traumatic brain injury. Axons become brittle when exposed to rapid deformations associated with brain trauma. Accordingly, rapid stretch of axons can damage the axonal cytoskeleton, resulting in a loss of elasticity and impairment of axoplasmic transport. Subsequent swelling of the axon occurs in discrete bulb formations or in elongated varicosities that accumulate organelles. Ultimately, swollen axons may become disconnected [1]. The shock waves generated by a blast, subject all the organs in the head to displacement, shearing and tearing forces. The brain is especially vulnerable to these forces — the fronts of compressed air waves cause rapid forward or backward movements of the head, so that the brain rattles against the inside of the skull. This can cause subdural hemorrhage and contusions. The forces exerted on the brain by shock waves are known to damage axons in the affected areas. This axonal damage begins within minutes of injury, and can continue for hours or days following the injury [2]. Shock waves are also known to damage the brain at the subcellular level, but exactly how remains unclear. Kato et al., [3] described the effects of a small controlled explosion on rats’ brain tissue. They found that high pressure shock waves led to contusions and hemorrhage in both cortical and subcortical brain regions. Based on their result, the threshold for shock wave-induced brain injury is speculated to be under 1 MPa. This is the first report to demonstrate the pressure-dependent effect of shock wave on the histological characteristics of brain tissue. An important step in understanding the primary blast injury mechanism due to explosion is to translate the global head loads to the loading conditions, and consequently damage, of the cells at the local level and to project cell level and tissue level injury criteria towards the level of the head. In order to reach this aim, we have developed a multi-scale non-linear finite element modeling to bridge the micro- and macroscopic scales and establish the connection between microstructure and effective behavior of brain tissue to develop acceptable injury threshold. Part of this effort has been focused on measuring the shock waves created from a blast, and studying the response of the brain model of a human head exposed to such an environment. The Arbitrary Lagrangian Eulerian (ALE) and Fluid/Solid Interactions (FSI) formulation have been used to model the brain-blast interactions. Another part has gone into developing a validated fiber-matrix based micro-scale model of a brain tissue to reproduce the effective response and to capturing local details of the tissue’s deformations causing axonal injury. The micro-model of the axon and matrix is characterized by a transversely isotropic viscoelastic material and the material model is formulated for numerical implementation. Model parameters are fit to experimental frequency response of the storage and loss modulus data obtained and determined using a genetic algorithm (GA) optimizing method. The results from macro-scale model are used in the micro-scale brain tissue to study the effective behavior of this tissue under injury-based loadings. The research involves the development of a tool providing a better understanding of the mechanical behavior of the brain tissue against blast loads and a rational multi-scale approach for driving injury criteria.

Over last two decades lasers have been used for the treatment of subsurface tumors. Various techniques such as Laser-induced Hyperthermia, Laser Interstitial Thermal Therapy (LITT), and Laser Immunotherapy have been developed for the successful ablation of subsurface tumors by different researchers. All these techniques use photo-thermal mechanism for tumor ablation by delivering thermal energy at the tumor site. In all these existing techniques, either continuous wave (CW) or long pulse laser source has been used, which often produces larger heat affected zone as compared to that produced by short pulse laser. Moreover, the delivery of laser beam at the target site is achieved through fiber optic probes which often require perforation of the skin. These drawbacks can be eliminated if a converging laser beam from a short pulse laser source is directly focused at the subsurface location to ablate the tumor.

Non-invasive measurement of pulse wave velocity (PWV) in the cerebrospinal fluid (CSF) system is of interest as a potential indicator of subarachnoid space pressure and compliance, both of which play a role in the development of craniospinal diseases. However, measurement of PWV has eluded researchers primarily due to either a lack of access to CSF velocity measurements or to poor temporal resolution. Here, we present PWV measurements using a novel MR technique that acquires unsteady velocity measurements during the cardiac cycle with a time interval <10 ms. Axial CSF velocity measurements were obtained in the sagittal plane of the cervical spinal region on three patients without cranio-spinal disorders. PWV was estimated by using the time shift identified by the maximum temporal velocity gradient during the cardiac cycle. Based on the maximum velocity gradient, the mean PWV in the three cases was calculated to be 4.6 m/s (stdev 1.7 m/s, p<0.005) during systolic acceleration. The measurements of PWV agree with previously published values.

Most blast-related injuries happen as a result of complex pressure waves generated by the explosion. In this paper, we model the explosion from detonation and examine the blast propagation in air using Arbitrary Lagrangian–Eulerian (ALE) finite element formulation. The results of the simulation agree well with those of physical data obtained from blast wave experiments. Such results set the circumstances necessary for an examination of brain injury exposed to such situations. Thus the model will be coupled with a Fluid/Structure Interaction (FSI) algorithm to implicitly examine the blast wave interactions with a human head and to study the creation of high regions of biomechanics pressure and stress gradients.

Filamentous actin (F-actin) is a stiff biopolymer that is tightly crosslinked in vivo by actin-binding proteins (ABPs) to form stiff bundles that form major constituents of a multitude of slender cytoskeletal processes including stereocilia, filopodia, microvilli, neurosensory bristles, cytoskeletal stress fibers, and the acrosomal process of sperm cells (Fig. 1). The mechanical properties of these cytoskeletal processes play key roles in a broad range of cellular functions — the bending stiffness of stereocilia mediates the mechanochemical transduction of mechanical stimuli such as acoustic waves to detect sound, the critical buckling load of filopodia and acrosomal processes determines their ability to withstand compressive mechanical forces generated during cellular locomotion and fertilization, and the entropic stretching stiffness of cytoskeletal bundles mediates cytoskeletal mechanical resistance to cellular deformation. Thus, a detailed understanding of F-actin bundle mechanics is fundamental to gaining a mechanistic understanding of cytoskeletal function.

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.

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.

Blast wave overpressure from detonations can injure physiological systems ‘silently.’ Experimental and clinical studies have revealed the damaging effects of shock waves on different physiological systems, such as ears, lungs and gastrointestinal tracts [1, 2]. Despite the improved helmet and body armor, many veterans returning from wars suffered from neurological disorders that are being diagnosed as mild traumatic brain injury. Warden (2006) reported that most of these veterans were exposed to blast [3]. In vivo study illustrated neuronal degeneration in the brain after exposure to blast waves [4]. As with many neuronal diseases, blast-induced neuronal injury may be related to microglia and astrocyte activation. However, the underlying mechanism is not clearly understood. This study was aimed at investigating the effects of short duration overpressure on astrocytes, in terms of cell proliferation and mRNA expression of several apoptotic genes and glial fibrillary acidic protein (GFAP).

Wave dissipation in arteries was intensively studied previously in the frequency domain, which focused on the waves with “pushing effect”. Meanwhile, we noted that waves with “suction effect” are observed in pulmonary veins [1], and in coronary arteries [2]. In spite of this, the dissipation of “suction waves” has not been studied before.

Correlating In vivo temperatures to the radio-frequency (RF) coil induced total RF power is necessary to ensure human safety in an ultra high field magnetic resonance (MR) application. Thus to ensure human safety in an ultra high field MR head imaging experiment, temperatures were measured as a function of time in the brain and surrounding cutaneous layer of twelve human sized, anesthetized swine (mean animal weight = 52kg, SD = ±6.7kg). In vivo temperatures were correlated to the RF power by developing coil and geometry specific normalized temperatures such that the RF coil induced cranial temperature change could be obtained during an MR exam by measuring only the whole head average specific absorption rate (ASAR) and the duration of the RF deposition. Thus, the feasibility of the thermal characterization of an RF volume head coil was shown. More specifically, a continuous wave (CW) RF was deposited in porcine cranium using a four loop RF head coil at 400 MHz (proton larmor frequency at 9.4T). Temperatures were recorded continuously using an inline probe placed at a predetermined location of 15mm inside the brain and a separate probe in the cutaneous layer. To differentiate the temperature response caused by the RF from that of anesthesia, the temperatures were recorded in four unheated, anesthetized swine for the complete duration of experiments (∼8hours). To study the effect of the spatial distribution of the RF as well as the tissue thermal/electrical properties and blood perfusion, the inline temperature probe was placed at two locations (N = 4 for each location). Results showed that the thermal characterization of an RF coil was possible such that the normalized temperature maps when multiplied by the ASAR and the RF heating time would predict In vivo temperature change during heating. Further, it was shown that at 9.4 T 1) the RF heating caused an inhomogeneous normalized temperature distribution in the brain; and 2) the skin temperature change was an unreliable parameter to assess In vivo temperature change.

Aortic pressure and flow result from the interaction between the ventricle and the arterial circulation. However, prior three-dimensional simulations of aortic blood flow have either assumed a prescribed velocity profile at the inlet or have computed aortic flow and pressure using an upstream heart model implemented with an explicit approach. In this work, we describe an implicit approach which strongly couples a lumped-parameter heart model with a three-dimensional finite element model of the vascular system. We demonstrate that this approach can be used to compute physiologically-realistic blood flow and pressure waves in three-dimensional arterial models and study the interactions between the heart and the vascular system.

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.

Because the left ventricle (LV) is not completely emptied during systole, oxygenated blood from the left atrium interacts with residual blood from preceding cycles. It is hypothesized that LV flow is optimal for transporting blood under normal conditions; yet proving this remains a challenge. Furthermore, clinical evaluation of LV hemodynamics has tremendous diagnostic importance for patients with cardiomyopathy. We have performed Doppler-echocardiography on 6 patients with dilated cardiomyopathy and 6 healthy volunteers. Using novel processing of the color-Doppler data, bi-directional velocity field maps in the apical long axis plane were derived. Resulting flow data was used to perform Lagrangian coherent structure (LCS) computation, which enabled novel characterization of the transport topology in the LV during filling and ejection. This framework was used to quantify stasis in the LV, which can be used as a surrogate for diagnosing pumping deficiencies and thrombosis risk. This framework also enables characterization of LV vortices, which have previously received much attention using Eulerian characterizations. The framework presented here uncovers the well-defined boundaries to both E-wave and A-wave filling vortices, which has not been previously reported.

High intensity focused ultrasound (HIFU) is a noninvasive medical procedure during which a large amount of energy is deposited in a short duration which causes sudden localized rise in tissue temperature, and ultimately, cell necrosis. In assessing the influence of HIFU on biological tissue, semi-empirical mathematical models can be useful for predicting thermal effects. These models require values of the pressure amplitude in the tissue of interest, which can be difficult to obtain experimentally. One common method for estimating the pressure amplitude in tissue is to operate the HIFU transducer in water, measure the pressure amplitude, then multiply by a scaling factor that accounts for the difference in attenuation between water and tissue. This procedure can be accurate when the ultrasound amplitude is low, and the pressure trace in tissue is proportional to that in water. Because of this proportionality, the procedure for reducing the amplitude from water to tissue is called linear derating. At higher intensities, however, harmonics of the fundamental frequency are generated due to nonlinear propagation effects. Higher harmonics are attenuated differently in water and tissue (Hamilton and Blackstock [1]), and the pressure waves in water and tissue are no longer proportional to one another. Techniques for nonlinearly transforming pressure amplitudes measured in water to values appropriate for tissue are therefore desirable when bioeffects of higher intensity procedures are being studied. These techniques are labeled “nonlinear derating”.