Person: Hammer, Peter
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Hammer
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Peter
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Hammer, Peter
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Publication Superparamagnetic Iron Oxide Nanoparticles Function as a Long-Term, Multi-Modal Imaging Label for Non-Invasive Tracking of Implanted Progenitor Cells(Public Library of Science, 2014) Pacak, Christina A.; Hammer, Peter; MacKay, Allison A.; Dowd, Rory P.; Wang, Kai-Roy; Masuzawa, Akihiro; Sill, Bjoern; McCully, James; Cowan, DouglasThe purpose of this study was to determine the ability of superparamagnetic iron oxide (SPIO) nanoparticles to function as a long-term tracking label for multi-modal imaging of implanted engineered tissues containing muscle-derived progenitor cells using magnetic resonance imaging (MRI) and X-ray micro-computed tomography (μCT). SPIO-labeled primary myoblasts were embedded in fibrin sealant and imaged to obtain intensity data by MRI or radio-opacity information by μCT. Each imaging modality displayed a detection gradient that matched increasing SPIO concentrations. Labeled cells were then incorporated in fibrin sealant, injected into the atrioventricular groove of rat hearts, and imaged in vivo and ex vivo for up to 1 year. Transplanted cells were identified in intact animals and isolated hearts using both imaging modalities. MRI was better able to detect minuscule amounts of SPIO nanoparticles, while μCT more precisely identified the location of heavily-labeled cells. Histological analyses confirmed that iron oxide particles were confined to viable, skeletal muscle-derived cells in the implant at the expected location based on MRI and μCT. These analyses showed no evidence of phagocytosis of labeled cells by macrophages or release of nanoparticles from transplanted cells. In conclusion, we established that SPIO nanoparticles function as a sensitive and specific long-term label for MRI and μCT, respectively. Our findings will enable investigators interested in regenerative therapies to non-invasively and serially acquire complementary, high-resolution images of transplanted cells for one year using a single label.Publication Reduction and Redistribution of Gap and Adherens Junction Proteins After Ischemia and Reperfusion(Elsevier BV, 2006) Tansey, Erin E.; Kwaku, Kevin F.; Hammer, Peter; Cowan, Douglas; Federman, Micheline; Levitsky, Sidney; McCully, JamesBackground Previous studies have demonstrated that alterations in myocardial structure, consistent with tissue and sarcomere disruption as well as myofibril dissociation, occur after myocardial ischemia and reperfusion. In this study we determine the onset of these structural changes and their contribution to electrical conduction. Methods Langendorff perfused rabbit hearts (n = 47) were subjected to 0, 5, 10, 15, 20, 25, and 30 minutes global ischemia, followed by 120 minutes reperfusion. Hemodynamics were recorded and tissue samples were collected for histochemical and immunohistochemical studies. Orthogonal epicardial conduction velocities were measured, with temperature controlled, in a separate group of 10 hearts subjected to 0 or 30 minutes of global ischemia, followed by 120 minutes of reperfusion. Results Histochemical and quantitative light microscopy spatial analysis showed significantly increased longitudinal and transverse interfibrillar separation after 15 minutes or more of ischemia (p < 0.05 versus control). Confocal immunohistochemistry and Western blot analysis demonstrated significant reductions (p < .05 versus control) of the intercellular adherens junction protein, N-cadherin, and the active phosphorylated isoform of the principal gap junction protein, connexin 43 at more than 15 minutes of ischemia. Cellular redistribution of connexin 43 was also evidenced on immunohistochemistry. No change in integrin-β1, an extracellular matrix attachment protein, or in epicardial conduction velocity anisotropy was observed. Conclusions These data indicate that there are significant alterations in the structural integrity of the myocardium as well as gap and adherens junction protein expression with increasing global ischemia time. The changes occur coincident with previously observed significant decreases in postischemic functional recovery, but are not associated with altered expression of matrix binding proteins or electrical anisotropic conduction.Publication Mass-Spring Model for Simulation of Heart Valve Tissue Mechanical Behavior(Springer Nature, 2011) Hammer, Peter; Sacks, Michael S.; Del Nido, Pedro; Howe, RobertHeart valves are functionally complex, making surgical repair difficult. Simulation-based surgical planning could facilitate repair, but current finite element (FE) studies are prohibitively slow for rapid, clinically oriented simulations. Mass-spring (M-S) models are fast but can be inaccurate. We quantify speed and accuracy differences between an anisotropic, nonlinear M-S and an efficient FE membrane model for simulating both biaxial and pressure loading of aortic valve (AV) leaflets. The FE model incurs approximately 10 times the computational cost of the M-S model. For simulated biaxial loading, mean error in normal strains is <1% for both FE and M-S models for equibiaxial loading but increases for non-equibiaxial states for the M-S model (7%). The M-S model was less able to simulate shear behavior, with mean strain error of approximately 80%. For pressurized AV leaflets, the M-S model predicts similar leaflet dimensions to the FE model (within 2.6%), and the coaptation zone is similar between models. The M-S model simulates in-plane behavior of AV leaflets considerably faster than the FE model and with only minor differences in the deformed mesh. While the M-S model does not allow explicit control of shear response, shear does not strongly influence shape of the simulated AV under pressure.Publication On the design of an interactive, patient-specific surgical simulator for mitral valve repair(IEEE, 2011) Tenenholtz, Neil Arturo; Hammer, Peter; Schneider, Robert J.; Vasilyev, Nikolay; Howe, RobertSurgical repair of the mitral valve is a difficult procedure that is often avoided in favor of less effective valve replacement because of the associated technical challenges facing non-expert surgeons. In the interest of increasing the rate of valve repair, an accurate, interactive surgical simulator for mitral valve repair was developed. With a haptic interface, users can interact with a mechanical model during simulation to aid in the development of a surgical plan and then virtually implement the procedure to assess its efficacy. Sub-millimeter accuracy was achieved in a validation study, and the system was successfully used by a cardiac surgeon to repair three virtual pathological valves.Publication Fast Interactive Simulations of Mitral Valve Repair(2012) Tenenholtz, Neil Arturo; Hammer, Peter; Howe, RobertPublication Anisotropic Mass-Spring Method Accurately Simulates Mitral Valve Closure from Image-Based Models(Springer Science + Business Media, 2011) Hammer, Peter; Del Nido, Pedro; Howe, RobertHeart valves are functionally complex, making surgical repair difficult. Simulation-based surgical planning could facilitate repair, but current finite element studies are prohibitively slow for rapid, clinically-oriented simulations. An anisotropic, nonlinear mass-spring (M-S) model is used to approximate the behavior of valve leaflets and applied to fully image-based mitral valve models to simulate valve closure for fast applications like intraoperative surgical planning. This approach is used to simulate a technique used in valve repair and to assess the role of chordae in determining the closed configuration of the valve. Direct image-based comparison is used for validation. Results of M-S model simulations showed that it is possible to build fully image-based models of the mitral valve and to rapidly simulate closure with sub-millimeter accuracy. Chordae, which are presently difficult to image, are shown to be strong determinants of closed valve shape.Publication Fast Image-Based Model of Mitral Valve Closure for Surgical Planning(MIDAS, 2008) Hammer, Peter; Vasilyev, Nikolay; Perrin, Douglas; Del Nido, Pedro; Howe, RobertSurgical repair of the mitral valve results in better outcomes than valve replacement, yet diseased valves are often replaced due to the technical difficulty of the repair process. A surgical planning system based on patient-specific medical images that allows surgeons to simulate and compare potential repair strategies could greatly improve surgical outcomes. The system must simulate valve closure quickly and handle the complex boundary conditions imposed by the chords that tether the valve leaflets. We have developed a process for generating a triangulated mesh of the valve surface from volumetric image data of the opened valve. The closed position of the mesh is then computed using a mass-spring model of dynamics. In the mass-spring model, triangle sides are treated as linear springs supporting only tension. Chords are also treated as linear springs, and self-collisions are detected and handled inelastically. The equations of motion are solved using implicit numerical integration. The simulated closed state is compared with an image of the same valve taken in the closed state to assess accuracy of the model. The model exhibits rapid valve closure and is able to predict the closed state of the valve with reasonable accuracy.