Modeling the interference between shear and longitudinal waves under high intensity focused ultrasound propagation in bone.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) is a noninvasive thermal technique that enables rapid heating of a specific area in the human body. Its clinical relevance has been proven for the treatments of soft tissue tumors, like uterine fibroids, and for the treatments of solid tumors in bone. In MR-HIFU treatment, MR-thermometry is used to monitor the temperature evolution in soft tissue. However, this technique is currently unavailable for bone tissue. Computer models can play a key role in the accurate prediction and monitoring of temperature. Here, we present a computer ray tracing model that calculates the heat production density in the focal region. This model accounts for both the propagation of shear waves and the interference between longitudinal and shear waves. The model was first compared with a finite element approach which solves the Helmholtz equation in soft tissue and the frequency-domain wave equation in bone. To obtain the temperature evolution in the focal region, the heat equation was solved using the heat production density generated by the raytracer as a heat source. Then, we investigated the role of the interaction between shear and longitudinal waves in terms of dissipated power and temperature output. The results of our model were in agreement with the results obtained by solving the Helmholtz equation and the frequency-domain wave equation, both in soft tissue and bone. Our results suggest that it is imperative to include both shear waves and their interference with longitudinal waves in the model when simulating high intensity focused ultrasound propagation in solids. In fact, when modeling HIFU treatments, omitting the interference between shear and longitudinal waves leads to an over-estimation of the temperature increase in the tissues.

Visible Blue Light Therapy: Molecular Mechanisms and Therapeutic Opportunities.

BACKGROUND: Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum. OBJECTIVE: In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions. METHODS: The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light. RESULTS: At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions. CONCLUSION: To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.

Combined in vivo and in silico investigations of activation of glycolysis in contracting skeletal muscle.

The hypothesis was tested that the variation of in vivo glycolytic flux with contraction frequency in skeletal muscle can be qualitatively and quantitatively explained by calcium-calmodulin activation of phosphofructokinase (PFK-1). Ischemic rat tibialis anterior muscle was electrically stimulated at frequencies between 0 and 80 Hz to covary the ATP turnover rate and calcium concentration in the tissue. Estimates of in vivo glycolytic rates and cellular free energetic states were derived from dynamic changes in intramuscular pH and phosphocreatine content, respectively, determined by phosphorus magnetic resonance spectroscopy ((31)P-MRS). Computational modeling was applied to relate these empirical observations to understanding of the biochemistry of muscle glycolysis. Hereto, the kinetic model of PFK activity in a previously reported mathematical model of the glycolytic pathway (Vinnakota KC, Rusk J, Palmer L, Shankland E, Kushmerick MJ. J Physiol 588: 1961-1983, 2010) was adapted to contain a calcium-calmodulin binding sensitivity. The two main results were introduction of regulation of PFK-1 activity by binding of a calcium-calmodulin complex in combination with activation by increased concentrations of AMP and ADP was essential to qualitatively and quantitatively explain the experimental observations. Secondly, the model predicted that shutdown of glycolytic ATP production flux in muscle postexercise may lag behind deactivation of PFK-1 (timescales: 5-10 s vs. 100-200 ms, respectively) as a result of accumulation of glycolytic intermediates downstream of PFK during contractions.

Speckle-initialized dynamic segmentation of the prostate.

Echography is a commonly used modality for prostate imaging. Prostate segmentation is the first step in analyzing echographic prostate images. Because of the nature of these images, traditional local image processing operators are inadequate for finding the prostate boundary. Most automated segmentations described in literature require user interaction for contour initializing or editing. Also shape templates are applied as prior knowledge. In this paper, an automatic segmentation method is presented, based on prostate specific image granulation and image intensity. First, a granulation detector is used to extract granulation. Subsequently, the Hessian is adopted to evaluate granulation shape and intensity for the extraction of the prostate-specific dot pattern. This dot pattern is used to construct the contour initialization. A smooth contour model (discrete dynamic contour; DDC) is evolved from this initialization to the final contour. The guiding vector field for the DDC deformation is the gradient vector flow field calculated from an edge map of the original image. The scale of the relevant edges (large compared to granulation) is estimated from the prostate-specific dot pattern. Comparison of automated segmentations with clinical expert manual segmentations reveals a mean sensitivity and accuracy of 0.90 and 0.93, respectively.

Computational model of excitable cell indicates ATP free energy dynamics in response to calcium oscillations are undampened by cytosolic ATP buffers.

Mitochondria in excitable cells are recurrently exposed to pulsatile calcium gradients that activate cell function. Rapid calcium uptake by the mitochondria has previously been shown to cause uncoupling of oxidative phosphorylation. To test (i) if periodic nerve firing may cause oscillation of the cytosolic thermodynamic potential of ATP hydrolysis and (ii) if cytosolic adenylate (AK) and creatine kinase (CK) ATP buffering reactions dampen such oscillations, a lumped kinetic model of an excitable cell capturing major aspects of the physiology has been developed. Activation of ATP metabolism by low-frequency calcium pulses caused large oscillation of the cytosolic, but not mitochondrial ATP/ADP, ratio. This outcome was independent of net ATP synthesis or hydrolysis during mitochondrial calcium uptake. The AK/CK ATP buffering reactions dampened the amplitude and rate of cytosolic ATP/ADP changes on a timescale of seconds, but not milliseconds. These model predictions suggest that alternative sources of capacitance in neurons and striated muscles should be considered to protect ATP-free energy-driven cell functions.

Molecular dynamics study of the influence of wall-gas interactions on heat flow in nanochannels.

Especially at the nanometer scale interfaces play an important role. The effect of the wettability on the solid-liquid interface has already been studied with molecular dynamics. In this paper we study the dependence of wetting on the solid-gas interface for different density gases and investigate the influence of wetting on the heat transport properties over such an interface using molecular dynamics. Subsequently we show how the flow profile of a gas flowing along a surface also depends on this wettability. These simulations show that wettability increases the conductivity of a solid to a stationary gas and decreases the flow velocity near the interface for a gas flow. These two effects influence the cooling of a solid achieved by a cold gas flowing along its surface in opposite ways. However, we show that a higher wettability has a positive net effect on the cooling, explaining experimental results that showed an increased heat cooling effect of hydrophilic over hydrophobic microchannels.