Dae Woo Park

Decellularized zebrafish cardiac extracellular matrix induces mammalian heart regeneration

Mammalian heart regeneration after acute heart attacks can be induced by decellularized zebrafish cardiac extracellular matrix. Heart attack is a global health problem that leads to significant morbidity, mortality, and health care burden. Adult human hearts have very limited regenerative capability after injury. However, evolutionarily primitive species generally have higher regenerative capacity than mammals. The extracellular matrix (ECM) may contribute to this difference. Mammalian cardiac ECM may not be optimally inductive for cardiac regeneration because of the fibrotic, instead of regenerative, responses in injured adult mammalian hearts. Given the high regenerative capacity of adult zebrafish hearts, we hypothesize that decellularized zebrafish cardiac ECM (zECM) made from normal or healing hearts can induce mammalian heart regeneration. Using zebrafish and mice as representative species of lower vertebrates and mammals, we show that a single administration of zECM, particularly the healing variety, enables cardiac functional recovery and regeneration of adult mouse heart tissues after acute myocardial infarction. zECM-treated groups exhibit proliferation of the remaining cardiomyocytes and multiple cardiac precursor cell populations and reactivation of ErbB2 expression in cardiomyocytes. Furthermore, zECM exhibits pro-proliferative and chemotactic effects on human cardiac precursor cell populations in vitro. These contribute to the structural preservation and correlate with significantly higher cardiac contractile function, notably less left ventricular dilatation, and substantially more elastic myocardium in zECM-treated hearts than control animals treated with saline or decellularized adult mouse cardiac ECM. Inhibition of ErbB2 activity abrogates beneficial effects of zECM administration, indicating the possible involvement of ErbB2 signaling in zECM-mediated regeneration. This study departs from conventional focuses on mammalian ECM and introduces a new approach for cardiac tissue regeneration.

High‐Resolution Ultrasound Elasticity Imaging to Evaluate Dialysis Fistula Stenosis

Accurate, noninvasive characterization of arterial wall mechanics and detection of fibrotic vascular lesions could vastly improve the ability to predict patient response to local treatments such as angioplasty. Current imaging and other techniques for determining wall compliance rely on imprecise or indirect estimates of wall motion. This study used high‐resolution ultrasound imaging with phase‐sensitive speckle tracking to obtain detailed and direct measurements of arterial stiffness in two subjects with dialysis fistula dysfunction. In both subjects, the absolute values of strain were much higher in normal regions of fistula than in regions of stenosis. The lower values of strain in stenotic fistula indicate greater stiffness of the vessel wall. The ultrasound speckle tracking technique used here may have potential to determine vascular mechanical properties noninvasively with a level of precision and accuracy not currently available.

Arterial elasticity imaging: Comparison of finite-element analysis models with high-resolution ultrasound speckle tracking

BackgroundThe nonlinear mechanical properties of internal organs and tissues may be measured with unparalleled precision using ultrasound imaging with phase-sensitive speckle tracking. The many potential applications of this important noninvasive diagnostic approach include measurement of arterial stiffness, which is associated with numerous major disease processes. The accuracy of previous ultrasound measurements of arterial stiffness and vascular elasticity has been limited by the relatively low strain of nonlinear structures under normal physiologic pressure and the measurement assumption that the effect of the surrounding tissue modulus might be ignored in both physiologic and pressure equalized conditions.MethodsThis study performed high-resolution ultrasound imaging of the brachial artery in a healthy adult subject under normal physiologic pressure and the use of external pressure (pressure equalization) to increase strain. These ultrasound results were compared to measurements of arterial strain as determined by finite-element analysis models with and without a surrounding tissue, which was represented by homogenous material with fixed elastic modulus.ResultsUse of the pressure equalization technique during imaging resulted in average strain values of 26% and 18% at the top and sides, respectively, compared to 5% and 2%, at the top and sides, respectively, under physiologic pressure. In the artery model that included surrounding tissue, strain was 19% and 16% under pressure equalization versus 9% and 13% at the top and sides, respectively, under physiologic pressure. The model without surrounding tissue had slightly higher levels of strain under physiologic pressure compared to the other model, but the resulting strain values under pressure equalization were > 60% and did not correspond to experimental values.ConclusionsSince pressure equalization may increase the dynamic range of strain imaging, the effect of the surrounding tissue on strain should be incorporated into models of arterial strain, particularly when the pressure equalization technique is used.

Development of a Kinematic Hand Model for Study and Design of Hose Installation

Kinematic hand models can be used to predict where workers will place their fingers on work objects and the space required by the hand. Hand postures can be used to predict hand strength. Kinematic models also can be used to predict tissue stresses and to study work-related musculoskeletal disorders. Study and design of manual hose installation is an important application for kinematic hand models. Hoses are widely used in many mechanical systems such as autos, aircraft and home appliance, which are all mass-produced on assembly lines. Studies of automobile assembly jobs show that hose installations are one of the most physically demanding jobs that workers perform. Hoses are a good starting point for kinematic model development because they can be characterized as simple cylinders.

Characterization of vascular strain during in-vitro angioplasty with high-resolution ultrasound speckle tracking

BackgroundUltrasound elasticity imaging provides biomechanical and elastic properties of vascular tissue, with the potential to distinguish between tissue motion and tissue strain. To validate the ability of ultrasound elasticity imaging to predict structurally defined physical changes in tissue, strain measurement patterns during angioplasty in four bovine carotid artery pathology samples were compared to the measured physical characteristics of the tissue specimens.MethodsUsing computational image-processing techniques, the circumferences of each bovine artery specimen were obtained from ultrasound and pathologic data.ResultsUltrasound-strain-based and pathology-based arterial circumference measurements were correlated with an R2 value of 0.94 (p = 0.03). The experimental elasticity imaging results confirmed the onset of deformation of an angioplasty procedure by indicating a consistent inflection point where vessel fibers were fully unfolded and vessel wall strain initiated.ConclusionThese results validate the ability of ultrasound elasticity imaging to measure localized mechanical changes in vascular tissue.

Quantification of Ultrasound Correlation-Based Flow Velocity Mapping and Edge Velocity Gradient Measurement

This study investigated the use of ultrasound speckle decorrelation‐ and correlation‐based lateral speckle‐tracking methods for transverse and longitudinal blood velocity profile measurement, respectively. By studying the blood velocity gradient at the vessel wall, vascular wall shear stress, which is important in vascular physiology as well as the pathophysiologic mechanisms of vascular diseases, can be obtained. Decorrelation‐based blood velocity profile measurement transverse to the flow direction is a novel approach, which provides advantages for vascular wall shear stress measurement over longitudinal blood velocity measurement methods. Blood flow velocity profiles are obtained from measurements of frame‐to‐frame decorrelation. In this research, both decorrelation and lateral speckle‐tracking flow estimation methods were compared with Poiseuille theory over physiologic flows ranging from 50 to 1000 mm/s. The decorrelation flow velocity measurement method demonstrated more accurate prediction of the flow velocity gradient at the wall edge than the correlation‐based lateral speckle‐tracking method. The novelty of this study is that speckle decorrelation‐based flow velocity measurements determine the blood velocity across a vessel. In addition, speckle decor‐relation‐based flow velocity measurements have higher axial spatial resolution than Doppler ultrasound measurements to enable more accurate measurement of blood velocity near a vessel wall and determine the physiologically important wall shear.

Methods for using 3-D ultrasound speckle tracking in biaxial mechanical testing of biological tissue samples.

Being multilayered and anisotropic, biological tissues such as cardiac and arterial walls are structurally complex, making the full assessment and understanding of their mechanical behavior challenging. Current standard mechanical testing uses surface markers to track tissue deformations and does not provide deformation data below the surface. In the study described here, we found that combining mechanical testing with 3-D ultrasound speckle tracking could overcome this limitation. Rat myocardium was tested with a biaxial tester and was concurrently scanned with high-frequency ultrasound in three dimensions. The strain energy function was computed from stresses and strains using an iterative non-linear curve-fitting algorithm. Because the strain energy function consists of terms for the base matrix and for embedded fibers, spatially varying fiber orientation was also computed by curve fitting. Using finite-element simulations, we first validated the accuracy of the non-linear curve-fitting algorithm. Next, we compared experimentally measured rat myocardium strain energy function values with those in the literature and found a matching order of magnitude. Finally, we retained samples after the experiments for fiber orientation quantification using histology and found that the results satisfactorily matched those computed in the experiments. We conclude that 3-D ultrasound speckle tracking can be a useful addition to traditional mechanical testing of biological tissues and may provide the benefit of enabling fiber orientation computation.

In Vivo Vascular Wall Shear Rate and Circumferential Strain of Renal Disease Patients

This study measures the vascular wall shear rate at the vessel edge using decorrelation based ultrasound speckle tracking. Results for nine healthy and eight renal disease subjects are presented. Additionally, the vascular wall shear rate and circumferential strain during physiologic pressure, pressure equalization and hyperemia are compared for five healthy and three renal disease subjects. The mean and maximum wall shear rates were measured during the cardiac cycle at the top and bottom wall edges. The healthy subjects had significantly higher mean and maximum vascular wall shear rate than the renal disease subjects. The key findings of this research were that the mean vascular wall shear rates and circumferential strain changes between physiologic pressure and hyperemia that was significantly different between healthy and renal disease subjects.

Quantification of Coupled Stiffness and Fiber Orientation Remodeling in Hypertensive Rat Right-Ventricular Myocardium Using 3D Ultrasound Speckle Tracking with Biaxial Testing

Mechanical and structural changes of right ventricular (RV) in response to pulmonary hypertension (PH) are inadequately understood. While current standard biaxial testing provides information on the mechanical behavior of RV tissues using surface markers, it is unable to fully assess structural and mechanical properties across the full tissue thickness. In this study, the mechanical and structural properties of normotensive and pulmonary hypertension right ventricular (PHRV) myocardium through its full thickness were examined using mechanical testing combined with 3D ultrasound speckle tracking (3D-UST). RV pressure overload was induced in Sprague–Dawley rats by pulmonary artery (PA) banding. The second Piola–Kirchhoff stress tensors and Green-Lagrangian strain tensors were computed in the RV myocardium using the biaxial testing combined with 3D-UST. A previously established non-linear curve-fitting algorithm was applied to fit experimental data to a Strain Energy Function (SEF) for computation of myofiber orientation. The fiber orientations obtained by the biaxial testing with 3D-UST compared well with the fiber orientations computed from the histology. In addition, the re-orientation of myofiber in the right ventricular free wall (RVFW) along longitudinal direction (apex-to-outflow-tract direction) was noticeable in response to PH. For normotensive RVFW samples, the average fiber orientation angles obtained by 3D-UST with biaxial test spiraled from 20° at the endo-cardium to -42° at the epi-cardium (Δ = 62°). For PHRV samples, the average fiber orientation angles obtained by 3D-UST with biaxial test had much less spiral across tissue thickness: 3° at endo-cardium to -7° at epi-cardium (Δ = 10°, P<0.005 compared to normotensive).

Elastic modulus contrast enhancement in shear wave imaging using mechanical nonlinearity: In vitro tissue mimicking phantom study

Shear wave elasticity imaging (SWEI) has been widely used to assess the elasticity of tissues. However, the shear modulus estimated in SWEI is often less sensitive in some cases, especially to a subtle change of the stiffness that produces only small mechanical contrast to the background tissues. This small mechanical contrast can be enhanced if the tissues are compressed, exhibiting mechanical nonlinearity. In this study, we propose a new approach of nonlinear SWEI and evaluate its feasibility through experiments using a tissue mimicking phantom. SWEI was performed while a tissue mimicking phantom was continually deformed over a relatively large dynamic range of strains. A 1.5% agar mixed with 5% gelatin inclusion of a long cylinder (D: 8 mm, hard) embedded in 0.5% agar mixed with 5% gelatin phantom block (soft) was fabricated. The average shear modulus of the inclusion exhibited noticeable nonlinearity after >10% overall applied strain and sharply increased to 40 kPa at 30% overall applied strain. On the other hand, the average shear modulus of the surrounding phantom block increased almost linearly from 4 to 16 kPa over the same applied strain range. The elastic modulus contrast of the inclusion to the surrounding phantom block was increased from 0.40 at 0% overall applied strain to 1.52 at 30% applied strain, which displays detecting the inclusion better.