Many planar connective tissues exhibit complex anisotropic matrix fiber arrangements that are critical to their biomechanical function. This organized structure is created and modified by resident fibroblasts in response to mechanical forces in their environment. The directionality of applied strain fields change dramatically during development, aging, and disease, but the specific effect of strain direction on matrix remodeling is less clear. Current mechanobiological inquiry of planar tissues is limited to equibiaxial or uniaxial stretch, which inadequately simulate many in vivo environments. In this study, we implement a novel bioreactor system to demonstrate the unique effect of controlled anisotropic strain on fibroblast behavior in 3D engineered tissue environments, using aortic valve interstitial fibroblast cells (VIC) as a model system. Cell seeded 3D collagen hydrogels were subjected to cyclic anisotropic strain profiles maintained at constant areal strain magnitude for up to 96 hours at 1Hz. Increasing anisotropy of biaxial strain resulted in increased cellular orientation and collagen fiber alignment along the principal directions of strain and cell orientation was found to precede fiber reorganization. Cellular proliferation and apoptosis were both significantly enhanced under increasing biaxial strain anisotropy (P < 0.05). While cyclic strain reduced both vimentin and alpha-smooth muscle actin compared to unstrained controls, vimentin and alpha-smooth muscle actin expression increased with strain anisotropy and correlated with direction (P < 0.05). Collectively, these results suggest that strain field anisotropy is an independent regulator of fibroblast cell phenotype, turnover, and matrix reorganization, which may inform normal and pathological remodeling in soft tissues.
Our study demonstrates that left ventricular diastolic dysfunction is associated with an abnormal CAC score even after adjusting for Framingham Risk Score or clinical risk factors. Patients without known coronary artery disease that present with chest pain and have normal perfusion imaging with evidence of abnormal diastolic function on echocardiogram may warrant more thorough evaluation for coronary atherosclerotic disease with CAC score assessment.
We sought to determine the relation between myocardial extracellular volume (ECV), left ventricular (LV) diastolic function, and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM). Forty five HCM patients with an ejection fraction >50% and no previous septal reduction therapy underwent imaging by CMR and transthoracic echocardiography. CMR was used to quantify LV volumes, mass, EF, LA volumes, scar burden, pre and post contrast T1 relaxation times and ECV. Echocardiography was used to measure outflow tract gradients, mitral inflow and annular velocities, circumferential strain, systolic, early and late diastolic strain rates. Exercise duration and peak oxygen consumption were noted. HCM patients had increased native T1 relaxation time and ECV vs. controls [ECV controls: 24.7 (23.2-26.4) vs. HCM: 26.8 (24.6-31.3)%, P = 0.014]. Both parameters were significantly associated with LV diastolic dysfunction, circumferential strain, diastolic strain rate and peak oxygen consumption (r = -0.73, P < 0.001). Compared to controls, HCM patients have significantly longer native T1 relaxation time and higher ECV. These structural changes lead to worse LV global and segmental diastolic function and in turn reduced exercise tolerance.
As a part of an ongoing project, in this paper we introduce the first version of a system which has a novel methodology for Cine (as in cinema) MRI based control of a cardiac robot for beating heart surgeries. The system uses the preoperative planning approach that we developed earlier, and integrates it to the intraoperative algorithms for controlling a robot and tracking some specific landmarks of a highly dynamical surgical field. In particular, our late studies presented herein aim to demonstrate the feasibility of integrating appropriate computational tools to achieve the volumetric image guidance for minimally invasive surgeries in the beating heart. We conceive of the system as practicable for in vitro experiments upon the completion of the first physical prototype, which may pave the way for expansion of the approach for other complex surgeries as well.
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