Measurement of <Emphasis Type="Italic">in vivo</Emphasis> Stress Resultants in Neurulation-stage Amphibian Embryos

In order to obtain the first quantitative measurements of the in vivo stresses in early-stage amphibian embryos, we developed a novel instrument that uses a pair of parallel wires that are glued to the surface of an embryo normal to the direction in which the stress is to be determined. When a slit is made parallel to the wires and between them, tension in the surrounding tissue causes the slit to open. Under computer control, one of the wires is moved so as to restore the original wire spacing, and the steady-state closure force is determined from the degree of wire flexure. A cell-level finite element model is used to convert the wire bending force to an in-plane stress since the wire force is not proportional to the slit length. The device was used to measure stress resultants (force carried per unit of slit length) on the dorsal, ventral and lateral aspects of neurulation-stage axolotl (Ambystoma mexicanum) embryos. The resultants were anisotropic and varied with location and developmental stage, with values ranging from −0.17 mN/m to 1.92 mN/m. In general, the resultants could be decomposed into patterns associated with internal pressure in the embryo, bending of the embryo along its mid-sagittal plane and neural tube closure. The patterns of stress revealed by the experiments support a number of current theories about the mechanics of neurulation.     

Tissue Elasticity Estimation with Optical Coherence Elastography: Toward Mechanical Characterization of <Emphasis Type="Italic">In Vivo</Emphasis> Soft Tissue

High-resolution imaging provides a significant means for accurate material modulus estimation and mechanical characterization. Within the realm of in vivo soft tissue characterization, particularly on small biological length scales such as arterial atherosclerotic plaques, optical coherence tomography (OCT) offers a desirable imaging modality with higher spatial resolution and contrast of tissue as compared with intravascular ultrasound (IVUS). Based on recent advances in OCT imaging and elastography, we present a fully integrated system for tissue elasticity reconstruction, and assess the benefits of OCT on the distribution results of four representative tissue block models. We demonstrate accuracy, with displacement residuals on the order of 10⁻⁶ mm (more than 3 orders of magnitude less than average calculated displacements), and high-resolution estimates, with the ability to resolve inclusions of 0.15 mm diameter.     

Identification of <Emphasis Type="Italic">I</Emphasis><Subscript>Kr</Subscript> Kinetics and Drug Binding in Native Myocytes

Determining the effect of a compound on I _Kr is a standard screen for drug safety. Often the effect is described using a single IC₅₀ value, which is unable to capture complex effects of a drug. Using verapamil as an example, we present a method for using recordings from native myocytes at several drug doses along with qualitative features of I _Kr from published studies of HERG current to estimate parameters in a mathematical model of the drug effect on I _Kr. I _Kr was recorded from canine left ventricular myocytes using ruptured patch techniques. A voltage command protocol was used to record tail currents at voltages from −70 to −20 mV, following activating pulses over a wide range of voltages and pulse durations. Model equations were taken from a published I _Kr Markov model and the drug was modeled as binding to the open state. Parameters were estimated using a combined global and local optimization algorithm based on collected data with two additional constraints on I _Kr I–V relation and I _Kr inactivation. The method produced models that quantitatively reproduce both the control I _Kr kinetics and dose dependent changes in the current. In addition, the model exhibited use and rate dependence. The results suggest that: (1) the technique proposed here has the practical potential to develop data-driven models that quantitatively reproduce channel behavior in native myocytes; (2) the method can capture important drug effects that cannot be reproduced by the IC₅₀ method. Although the method was developed for I _Kr, the same strategy can be applied to other ion channels, once appropriate channel-specific voltage protocols and qualitative features are identified. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparison of CFD and MRI Flow and Velocities in an <Emphasis Type="Italic">In Vitro</Emphasis> Large Artery Bypass Graft Model

Bypass graft failures have been attributed to various hemodynamic factors, including flow stasis and low shear stress. Ideally, surgeries would minimize the occurrence of these detrimental flow conditions, but surgeons cannot currently assess this. Numerical simulation techniques have been proposed as one method for predicting changes in flow distributions and patterns from surgical bypass procedures, but comparisons against experimental results are needed to assess their usefulness. Previous in vitro studies compared simulated results against experimentally obtained measurements, but they focused on peripheral arteries, which have lower Reynolds numbers than those found in the larger arteries. In this study, we compared simulation results against measurements obtained using magnetic resonance imaging (MRI) techniques for a phantom model of a stenotic vessel with a bypass graft under conditions suitable for surgical planning purposes and with inlet Reynolds numbers closer to those found in the larger arteries. Comparisons of flow rate and velocity profiles were performed at maximum and minimum flows at four locations and used simulation results that were temporally and spatially averaged, key postprocessing when comparing against phase contrast MRI measurements. The maximum error in the computed volumetric flow rates was 6% of the measured values, and excellent qualitative agreement was obtained for the through-plane velocity profiles in both magnitude and shape. The in-plane velocities also agreed reasonably well at most locations.