Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide a promising source for cell therapy and drug screening. Several high-yield protocols exist for hESC-CM production; however, methods to significantly advance hESC-CM maturation are still lacking. Building on our previous experience with mouse ESC-CMs, we investigated the effects of 3-dimensional (3D) tissue-engineered culture environment and cardiomyocyte purity on structural and functional maturation of hESC-CMs. 2D monolayer and 3D fibrin-based cardiac patch cultures were generated using dissociated cells from differentiated Hes2 embryoid bodies containing varying percentage (48-90%) of CD172a (SIRPA)-positive cardiomyocytes. hESC-CMs within the patch were aligned uniformly by locally controlling the direction of passive tension. Compared to hESC-CMs in age (2 weeks) and purity (48-65%) matched 2D monolayers, hESC-CMs in 3D patches exhibited significantly higher conduction velocities (CVs), longer sarcomeres (2.09 ± 0.02 vs. 1.77 ± 0.01 μm), and enhanced expression of genes involved in cardiac contractile function, including cTnT, αMHC, CASQ2 and SERCA2. The CVs in cardiac patches increased with cardiomyocyte purity, reaching 25.1 cm/s in patches constructed with 90% hESC-CMs. Maximum contractile force amplitudes and active stresses of cardiac patches averaged to 3.0 ± 1.1 mN and 11.8 ± 4.5 mN/mm(2), respectively. Moreover, contractile force per input cardiomyocyte averaged to 5.7 ± 1.1 nN/cell and showed a negative correlation with hESC-CM purity. Finally, patches exhibited significant positive inotropy with isoproterenol administration (1.7 ± 0.3-fold force increase, EC50 = 95.1 nm). These results demonstrate highly advanced levels of hESC-CM maturation after 2 weeks of 3D cardiac patch culture and carry important implications for future drug development and cell therapy studies.

Comparison of dynamic balance in adolescent male soccer players from rwanda and the United States.

PURPOSE/BACKGROUND: Dynamic balance is an important component of motor skill development. Poor dynamic balance has previously been associated with sport related injury. However, the vast majority of dynamic balance studies as they relate to sport injury have occurred in developed North American or European countries. Thus, the purpose of this study was to compare dynamic balance in adolescent male soccer players from Rwanda to a matched group from the United States. METHODS: Twenty-six adolescent male soccer players from Rwanda and 26 age- and gender-matched control subjects from the United States were screened using the Lower Quarter Y Balance Test during their pre-participation physical. Reach asymmetry (cm) between limbs was examined for all reach directions. In addition, reach distance in each direction (normalized to limb length, %LL) and the composite reach score (also normalized to %LL) were examined. Dependent samples t-tests were performed with significant differences identified at p<0.05. RESULTS: Twenty-six male soccer players from Rwanda (R) were matched to twenty-six male soccer players from the United States (US). The Rwandan soccer players performed better in the anterior (R: 83.9 ± 3.2 %LL; US: 76.5 ± 6.6 %LL, p<0.01), posterolateral (R: 114.4 ± 8.3 %LL ; US: 106.5 ± 8.2 %LL, p<0.01) and composite (R: 105.6 ± 1.3 %LL; US: 97.8 ± 6.2 %LL, p<0.01) reach scores. No significant differences between groups were observed for reach asymmetry. CONCLUSIONS: Adolescent soccer players from Rwanda exhibit superior performance on a standardized dynamic balance test as comparison to similar athletes from the United States. The examination of movement abilities of athletes from countries of various origins may allow for a greater understanding of the range of true normative values for dynamic balance. LEVELS OF EVIDENCE: 3b.

Nonlinear piezoelectricity in electroelastic energy harvesters: Modeling and experimental identification

We propose and experimentally validate a first-principles based model for the nonlinear piezoelectric response of an electroelastic energy harvester. The analysis herein highlights the importance of modeling inherent piezoelectric nonlinearities that are not limited to higher order elastic effects but also include nonlinear coupling to a power harvesting circuit. Furthermore, a nonlinear damping mechanism is shown to accurately restrict the amplitude and bandwidth of the frequency response. The linear piezoelectric modeling framework widely accepted for theoretical investigations is demonstrated to be a weak presumption for near-resonant excitation amplitudes as low as 0.5 g in a prefabricated bimorph whose oscillation amplitudes remain geometrically linear for the full range of experimental tests performed (never exceeding 0.25% of the cantilever overhang length). Nonlinear coefficients are identified via a nonlinear least-squares optimization algorithm that utilizes an approximate analytic solution obtained by the method of harmonic balance. For lead zirconate titanate (PZT-5H), we obtained a fourth order elastic tensor component of c1111p =-3.6673× 1017 N/m2 and a fourth order electroelastic tensor value of e3111 =1.7212× 108 m/V. © 2010 American Institute of Physics.

In vivo visualization of abdominal malignancies with acoustic radiation force elastography.

The utility of acoustic radiation force impulse (ARFI) imaging for real-time visualization of abdominal malignancies was investigated. Nine patients presenting with suspicious masses in the liver (n = 7) or kidney (n = 2) underwent combined sonography/ARFI imaging. Images were acquired of a total of 12 tumors in the nine patients. In all cases, boundary definition in ARFI images was improved or equivalent to boundary definition in B-mode images. Displacement contrast in ARFI images was superior to echo contrast in B-mode images for each tumor. The mean contrast for suspected hepatocellular carcinomas (HCCs) in B-mode images was 2.9 dB (range: 1.5-4.2) versus 7.5 dB (range: 3.1-11.9) in ARFI images, with all HCCs appearing more compliant than regional cirrhotic liver parenchyma. The mean contrast for metastases in B-mode images was 3.1 dB (range: 1.2-5.2) versus 9.3 dB (range: 5.7-13.9) in ARFI images, with all masses appearing less compliant than regional non-cirrhotic liver parenchyma. ARFI image contrast (10.4 dB) was superior to B-mode contrast (0.9 dB) for a renal mass. To our knowledge, we present the first in vivo images of abdominal malignancies in humans acquired with the ARFI method or any other technique of imaging tissue elasticity.

Intracardiac acoustic radiation force impulse imaging: a novel imaging method for intraprocedural evaluation of radiofrequency ablation lesions.

BACKGROUND: Arrhythmia recurrence after cardiac radiofrequency ablation (RFA) for atrial fibrillation has been linked to conduction through discontinuous lesion lines. Intraprocedural visualization and corrective ablation of lesion line discontinuities could decrease postprocedure atrial fibrillation recurrence. Intracardiac acoustic radiation force impulse (ARFI) imaging is a new imaging technique that visualizes RFA lesions by mapping the relative elasticity contrast between compliant-unablated and stiff RFA-treated myocardium. OBJECTIVE: To determine whether intraprocedure ARFI images can identify RFA-treated myocardium in vivo. METHODS: In 8 canines, an electroanatomical mapping-guided intracardiac echo catheter was used to acquire 2-dimensional ARFI images along right atrial ablation lines before and after RFA. ARFI images were acquired during diastole with the myocardium positioned at the ARFI focus (1.5 cm) and parallel to the intracardiac echo transducer for maximal and uniform energy delivery to the tissue. Three reviewers categorized each ARFI image as depicting no lesion, noncontiguous lesion, or contiguous lesion. For comparison, 3 separate reviewers confirmed RFA lesion presence and contiguity on the basis of functional conduction block at the imaging plane location on electroanatomical activation maps. RESULTS: Ten percent of ARFI images were discarded because of motion artifacts. Reviewers of the ARFI images detected RFA-treated sites with high sensitivity (95.7%) and specificity (91.5%). Reviewer identification of contiguous lesions had 75.3% specificity and 47.1% sensitivity. CONCLUSIONS: Intracardiac ARFI imaging was successful in identifying endocardial RFA treatment when specific imaging conditions were maintained. Further advances in ARFI imaging technology would facilitate a wider range of imaging opportunities for clinical lesion evaluation.

Acoustic radiation force impulse imaging (ARFI) on an IVUS circular array.

Our long-term goal is the detection and characterization of vulnerable plaque in the coronary arteries of the heart using intravascular ultrasound (IVUS) catheters. Vulnerable plaque, characterized by a thin fibrous cap and a soft, lipid-rich necrotic core is a precursor to heart attack and stroke. Early detection of such plaques may potentially alter the course of treatment of the patient to prevent ischemic events. We have previously described the characterization of carotid plaques using external linear arrays operating at 9 MHz. In addition, we previously modified circular array IVUS catheters by short-circuiting several neighboring elements to produce fixed beamwidths for intravascular hyperthermia applications. In this paper, we modified Volcano Visions 8.2 French, 9 MHz catheters and Volcano Platinum 3.5 French, 20 MHz catheters by short-circuiting portions of the array for acoustic radiation force impulse imaging (ARFI) applications. The catheters had an effective transmit aperture size of 2 mm and 1.5 mm, respectively. The catheters were connected to a Verasonics scanner and driven with pushing pulses of 180 V p-p to acquire ARFI data from a soft gel phantom with a Young's modulus of 2.9 kPa. The dynamic response of the tissue-mimicking material demonstrates a typical ARFI motion of 1 to 2 microns as the gel phantom displaces away and recovers back to its normal position. The hardware modifications applied to our IVUS catheters mimic potential beamforming modifications that could be implemented on IVUS scanners. Our results demonstrate that the generation of radiation force from IVUS catheters and the development of intravascular ARFI may be feasible.

Contrast in intracardiac acoustic radiation force impulse images of radiofrequency ablation lesions.

We have previously shown that intracardiac acoustic radiation force impulse (ARFI) imaging visualizes tissue stiffness changes caused by radiofrequency ablation (RFA). The objectives of this in vivo study were to (1) quantify measured ARFI-induced displacements in RFA lesion and unablated myocardium and (2) calculate the lesion contrast (C) and contrast-to-noise ratio (CNR) in two-dimensional ARFI and conventional intracardiac echo images. In eight canine subjects, an ARFI imaging-electroanatomical mapping system was used to map right atrial ablation lesion sites and guide the acquisition of ARFI images at these sites before and after ablation. Readers of the ARFI images identified lesion sites with high sensitivity (90.2%) and specificity (94.3%) and the average measured ARFI-induced displacements were higher at unablated sites (11.23 ± 1.71 µm) than at ablated sites (6.06 ± 0.94 µm). The average lesion C (0.29 ± 0.33) and CNR (1.83 ± 1.75) were significantly higher for ARFI images than for spatially registered conventional B-mode images (C = -0.03 ± 0.28, CNR = 0.74 ± 0.68).