McMahon, Eileen M.

Background: Myocardial reperfusion following prolonged ischemia may paradoxically cause additional injury, including edema and microvascular damage. These structural alterations augment tissue echogenicity measurable by integrated backscatter (IB). We sought to characterize alterations of myocardial IB in an ischemic and then reperfused region of the rat heart. Methods: Myocardial IB in 12 adult male Sprague-Dawley rats was studied at baseline, 60 minutes after left anterior descending coronary artery occlusion, and chronologically after coronary reopening. Short-axis scans of the mid left ventricle were acquired at a frequency of 8 MHz. Mean±SD values of IB were measured in the region of interest at baseline, ischemia, and reperfusion, and assessed by a paired t-test. Results: See figure and table. IB did not significantly change between baseline and ischemia. However, within 1 minute of reperfusion, IB significantly increased, as compared to both baseline and ischemia, and continued to increase until 10 minutes after reperfusion, when a plateau was reached. Conclusions: Myocardial reperfusion following acute prolonged ischemia in a rat heart significantly augments tissue echogenicity. A continuing increase of IB within minutes of the reperfusion onset and the subsequent plateau of elevated IB values suggest progression and completion, respectively, of reperfusion injury, detectable by a high-frequency transducer.

Two-dimensional echocardiography (echo) is the method of choice for noninvasive evaluation of the left ventricle (LV) function owing to its low cost, fast acquisition time, and high temporal resolution. However, it only provides the LV boundaries in discrete 2D planes, and the 3D LV geometry needs to be reconstructed from those planes to quantify LV wall motion, acceleration, and strain, or to carry out flow simulations. An automated method is developed for the reconstruction of the 3D LV endocardial surface using echo from a few standard cross sections, in contrast with the previous work that has used a series of 2D scans in a linear or rotational manner for 3D reconstruction. The concept is based on a generalized approach so that the number or type (long-axis (LA) or short-axis (SA)) of sectional data is not constrained. The location of the cross sections is optimized to minimize the difference between the reconstructed and measured cross sections, and the reconstructed LV surface is meshed in a standard format. Temporal smoothing is implemented to smooth the motion of the LV and the flow rate. This software tool can be used with existing clinical 2D echo systems to reconstruct the 3D LV geometry and motion to quantify the regional akinesis/dyskinesis, 3D strain, acceleration, and velocities, or to be used in ventricular flow simulations.

The left ventricle (LV) of a human heart receives oxygenated blood from the lungs and pumps it throughout the body via the aortic valve. Characterizing the LV geometry, its motion, and the ventricular flow is critical in assessing the heart’s health. An automated method has been developed in this work to generate a three-dimensional (3D) model of the LV from multiple-axis echocardiography (echo). Image data from three long-axis sections and a basal section is processed to compute spatial nodes on the LV surface. The generated surfaces are output in a standard format such that it can be imported into the curvilinear-immersed boundary (CURVIB) framework for numerical simulation of the flow inside the LV. The 3D LV model can be used for better understanding of the ventricular motion and the simulation framework provides a powerful tool for studying left ventricular flows on a patient specific basis. Future work would incorporate data from additional cross-sectional images.

The left ventricle (LV) pumps oxygenated blood from the lungs to the rest of the body through systemic circulation. The efficiency of such a pumping function is dependent on blood flow within the LV chamber. It is therefore crucial to accurately characterize LV hemodynamics. Improved understanding of LV hemodynamics is expected to provide important clinical diagnostic and prognostic information. We review the recent advances in numerical and experimental methods for characterizing LV flows and focus on analysis of intraventricular flow fields by echocardiographic particle image velocimetry (echo-PIV), due to its potential for broad and practical utility. Future research directions to advance patient-specific LV simulations include development of methods capable of resolving heart valves, higher temporal resolution, automated generation of three-dimensional (3D) geometry, and incorporating actual flow measurements into the numerical solution of the 3D cardiovascular fluid dynamics.

Pharmacokinetics of drugs may differ between small and large mammals (including humans); therefore, drug testing in animal models must be carefully designed. Sprague–Dawley rats were used in cardiac experiments, during which the lopinavir concentration in serum had to match human therapeutic levels (4–10 μg/mL). Lopinavir was administered as a co-formulated drug of lopinavir and ritonavir. It was found that after a single administration of a standard human peroral dose (lopinavir 13.3 mg/kg of body weight), the serum concentration of lopinavir was only one-tenth of the target level. It remained below the minimum target level even after 10-fold the standard dose was administered. After initial pilot tests, a dose escalation study was conducted with oral doses 10- and 15-fold the standard clinical dose of lopinavir (i.e. 133 and 200 mg/kg, respectively). A second administration 2 h later effectively increased and maintained higher concentrations during the experimental ischaemia and reperfusion periods. A dose-dependent increase in serum concentration of the drug was observed. Thus, the target therapeutic serum level of lopinavir in the rats was achieved by administrating 10- to 15-fold the standard human dose twice, separated by a 2 h interval.

Ultrasonic contrast agents consisting of microbubbles are used to assess tissue perfusion. The microbubbles are highly reflective and nonlinear and thus produce harmonics that are stronger than those from tissues. However, the magnitude of harmonic signals resulting from a region with microbubbles also depends on the acoustic pressure of incident ultrasound and the attenuation of intervening tissues in the ultrasound path. Therefore, the harmonic magnitude, as used in traditional harmonic imaging, may not be a reliable indicator of the presence or absence of microbubbles, and hence, tissue perfusion. To compensate for these effects, we present two parameters defined as the ratio of the harmonic to the fundamental component ( HFR) and the ratio of the harmonic to squared fundamental ( HSFR). A simplified model is used to illustrate the usefulness of these two parameters. Experiments show that both parameters improve detection of microbubbles and that HSFR performs better than HFR.

As both fluid flow measurement techniques and computer simulation methods continue to improve, there is a growing need for numerical simulation approaches that can assimilate experimental data into the simulation in a flexible and mathematically consistent manner. The problem of interest here is the simulation of blood flow in the left ventricle with the assimilation of experimental data provided by ultrasound imaging of microbubbles in the blood. The weighted least-squares finite element method is used because it allows data to be assimilated in a very flexible manner so that accurate measurements are more closely matched with the numerical solution than less accurate data. This approach is applied to two different test problems: a flexible flap that is displaced by a jet of fluid and blood flow in the porcine left ventricle. By adjusting how closely the simulation matches the experimental data, one can observe potential inaccuracies in the model because the simulation without experimental data differs significantly from the simulation with the data. Additionally, the assimilation of experimental data can help the simulation capture certain small effects that are present in the experiment, but not modeled directly in the simulation.

Background— Onset of myocardial relaxation is highly energy dependent. Perfusion and therefore energy substrate delivery are predominantly reduced in the subendocardial myocardium in the early stages of progressive ischemia. We hypothesized that delayed onset of subendocardial diastolic thinning will functionally identify regionally hypoperfused resting myocardium. Methods and Results— Progressive left anterior descending coronary artery stenosis was induced by an ameroid occluder and maintained for 1 or 2 weeks (end point) in 12 dogs. M-mode tissue Doppler images of the anterior apical and middle segments (testing region) and middle inferior segment (control region) were acquired selectively in the subendocardium and subepicardium. The time to the onset of thinning was measured with the use of tissue Doppler velocity (TOTv) and a thickness function (TOTt). At the end point in the testing region, myocardial flow was significantly lower in the subendocardial layer ( P <0.05) in all animals, whereas viability staining showed preserved transmural viability in 10 dogs and thin subendocardial necrosis in 2 dogs. Both TOTv and TOTt were significantly ( P <0.01) prolonged in the testing region. The mean difference between subendocardial and subepicardial TOTv values versus that in the control region identified the ischemic region, even when only dogs with hypoperfused but transmurally viable myocardium were considered ( P <0.05). Systolic and diastolic myocardial velocities did not identify subendocardial hypoperfusion. Conclusions— In resting myocardium subtended to progressive coronary stenosis, a delayed onset of subendocardial thinning suggests an early stage of hypoperfusion, before the development of local wall motion abnormalities.