From 4D medical images (CT, MRI, and Ultrasound) to 4D structured mesh models of the left ventricular endocardium for patient-specific simulations

With cardiovascular disease (CVD) remaining the primary cause of death worldwide, early detection of CVDs becomes essential. The intracardiac flow is an important component of ventricular function, motion kinetics, wash-out of ventricular chambers, and ventricular energetics. Coupling between Computational Fluid Dynamics (CFD) simulations and medical images can play a fundamental role in terms of patient-specific diagnostic tools. From a technical perspective, CFD simulations with moving boundaries could easily lead to negative volumes errors and the sudden failure of the simulation. The generation of high-quality 4D meshes (3D in space + time) with 1-to-l vertex becomes essential to perform a CFD simulation with moving boundaries. In this context, we developed a semiautomatic morphing tool able to create 4D high-quality structured meshes starting from a segmented 4D dataset. To prove the versatility and efficiency, the method was tested on three different 4D datasets (Ultrasound, MRI, and CT) by evaluating the quality and accuracy of the resulting 4D meshes. Furthermore, an estimation of some physiological quantities is accomplished for the 4D CT reconstruction. Future research will aim at extending the region of interest, further automation of the meshing algorithm, and generating structured hexahedral mesh models both for the blood and myocardial volume

Interrupting the nitrosative stress fuels tumor-specific cytotoxic T lymphocytes in pancreatic cancer

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest tumors owing to its robust desmoplasia, low immunogenicity, and recruitment of cancer-conditioned, immunoregulatory myeloid cells. These features strongly limit the success of immunotherapy as a single agent, thereby suggesting the need for the development of a multitargeted approach. The goal is to foster T lymphocyte infiltration within the tumor landscape and neutralize cancer-triggered immune suppression, to enhance the therapeutic effectiveness of immune-based treatments, such as anticancer adoptive cell therapy (ACT). METHODS: We examined the contribution of immunosuppressive myeloid cells expressing arginase 1 and nitric oxide synthase 2 in building up a reactive nitrogen species (RNS)-dependent chemical barrier and shaping the PDAC immune landscape. We examined the impact of pharmacological RNS interference on overcoming the recruitment and immunosuppressive activity of tumor-expanded myeloid cells, which render pancreatic cancers resistant to immunotherapy. RESULTS: PDAC progression is marked by a stepwise infiltration of myeloid cells, which enforces a highly immunosuppressive microenvironment through the uncontrolled metabolism of L-arginine by arginase 1 and inducible nitric oxide synthase activity, resulting in the production of large amounts of reactive oxygen and nitrogen species. The extensive accumulation of myeloid suppressing cells and nitrated tyrosines (nitrotyrosine, N-Ty) establishes an RNS-dependent chemical barrier that impairs tumor infiltration by T lymphocytes and restricts the efficacy of adoptive immunotherapy. A pharmacological treatment with AT38 ([3-(aminocarbonyl)furoxan-4-yl]methyl salicylate) reprograms the tumor microenvironment from protumoral to antitumoral, which supports T lymphocyte entrance within the tumor core and aids the efficacy of ACT with telomerase-specific cytotoxic T lymphocytes. CONCLUSIONS: Tumor microenvironment reprogramming by ablating aberrant RNS production bypasses the current limits of immunotherapy in PDAC by overcoming immune resistance

Progress towards an optimized ¹²⁹Xe / ³He Zeeman maser and a test of boost symmetry

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2006.Includes bibliographical references (p. 271-276).We report on a search for an annual variation of a daily sidereal modulation of the frequency difference between co-located ¹²⁹Xe and ³He Zeeman masers that sets a stringent limit on boost-dependent Lorentz and CPT violation involving the neutron, consistent with no effect at the level of 150 nHz. In the framework of the general Standard-Model Extension, our result provides the first clean test for the fermion sector of the symmetry of spacetime under boost transformations at a level of 10-27 GeV [1]. We also report progress on the optimization and operation of the Harvard-Smithsonian ¹²⁹Xe/³He dual noble gas maser. The ¹²⁹Xe/³He maser is the first device to sustain simultaneous active maser oscillations on distinct transitions in two intermingled atomic species, and it allows sensitive differential measurement of the ¹²⁹Xe and ³He nuclear spin-1/2 Zeeman transition frequencies [2, 3, 4]. The optimized ¹²⁹Xe /³He maser will be used for highly sensitive tests of Lorentz and CPT symmetry.by Federico Canè.Ph.D