Gas-filled microbubbles as intravascular R(2)* contrast agent for liver MRI

Session 73: Contrast Agents & Microvascular Function: Methods - Oral presentationGas-filled microbubbles possess the potential to become a unique MR contrast agent because of their magnetic susceptibility effect, high biocompatibility and unique cavitation and sonoporation properties. In this study, microbubble susceptibility induced changes were investigated using custom-made albumin-coated microbubbles and a commercially available lipid-based clinical ultrasound contrast agent SonoVue® in rat livers in vivo with dynamic susceptibility weighted MRI at 7T. The results demonstrate the potential of gas-filled microbubble as an intravascular R(2)* contrast agent for liver MRI at high field.published_or_final_versionThe 17th Scientific Meeting & Exhibition of the International Society of Magnetic Resonance in Medicine (ISMRM), Honolulu, HI., 18-24 April 2009. In Proceedings of ISMRM 17th Scientific Meeting & Exhibition, 2009, p. 72

Isotope analysis in central heavy ion collisions at intermediate energies

Symmetry energy is a key quantity in the study of the equation of state of asymmetric nuclear matter. Heavy ion collisions at low and intermediate energies, performed at Laboratori Nazionali di Legnaro and Laboratori Nazionali del Sud, can be used to extract information on the symmetry energy coefficient Csym, which is currently poorly known but relevant both for astrophysics and for structure of exotic nuclei.Comment: 2 pages, 1 figure. Proceedings of 7th International Conference on Radioactive Nuclear Beams (RNB7), to be published in The European Physical Journal

A Comparison of Astronaut Near-Earth Object Missions

NASA intends to send astronauts to a near Earth object (NEO) in or around 2025. This is expected to involve a six month mission with a few weeks stay-time at the NEO. Problems with this concept include lack of abort modes, vulnerability to solar flares, and lack of resupply opportunities. Studies by the authors (the Asteroid Mining Group) and a recent workshop at JPL organized by the Keck Institute opens the door to an alternative that addresses these problems and creates additional opportunities. Both groups investigated the feasibility of bringing one of more small NEOs into Earth or Lunar orbit. Particularly for High Earth Orbits (HEO) or High Lunar Orbits (HLO), this appears feasible with near-term technology, especially high-propellant-velocity, low-thrust solar electric propulsion (SEP) inspace vehicles. This paper compares the currently planned mission with an alternative: bringing one or more NEOs into HEO or HLO using SEP and lunar gravity assist. An astronaut mission to the NEO is then similar to a mission to the Moon without a landing. Trip times are measured in days, the NEO can be used for solar flare protection for most of the mission, and resupply within a few days is practical. Furthermore, materials derived from the NEO, e.g., propellant, water, radiation shielding, metals, silicon, and others, are available for projects in cis-lunar space, including satellite refueling, habitats, and space solar power. The alternative mission also develops much of the technology, experience, and infrastructure needed to protect Earth from potentially hazardous NEOs. As an outcome of these studies we are proposing a process whereby early missions can lead to large-scale industrialization of cis-lunar space based on solar energy and asteroidal resources

Tract-based spatial statistics (TBSS): application to detecting white matter tract variation in mild hypoxic-ischemic neonates

The aim of this study is to employ tract-based spatial statistics (TBSS) to analyze the voxel-wise differences in DTI parameters between normal and mild hypoxic-ischemic (HI) neonatal brains. Forty-one full term neonates (24 normal controls and 17 with mild HI injury) and 31 preterm neonates (20 normal controls and 11 with mild HI injury) underwent T1 weighted imaging, T2 weighted imaging and diffusion tensor imaging (DTI) within 28 days after birth. The voxel differences of fractional anisotropy (FA), lambda1, lambda2, and lambda3 values between mild HI group and control group were analyzed in preterm and full term neonates respectively. The significantly decreased FA with increased lambda2, lambda3 in corticospinal tract, genu of corpus callosum (GCC), external capsule (EC) and splenium of the corpus callosum (SCC) in mild HI neonates suggested deficits or delays in both myelination and premyelination. Such impaired corticospinal tract, in both preterm and term neonates, may directly lead to the subsequent poor motor performance. Impaired EC and SCC, the additional injured sites observed in full term neonates with mild HI injury, may be causally responsible for the dysfunction in coordination and integration. In conclusion, TBSS provides an objective, independent and sensitive method for DTI data analysis of neonatal white matter alterations after mild HI injury.published_or_final_versio

Diffusion kurtosis imaging with tract-based spatial statistics reveals white matter alterations in preschool children

Diffusion kurtosis imaging (DKI), an extension of diffusion tensor imaging (DTI), provides a practical method to describe non-Gaussian water diffusion in neural tissues. The sensitivity of DKI to detect the subtle changes in several chosen brain structures has been studied. However, intuitive and holistic methods to validate the merits of DKI remain to be explored. In this paper, tract-based spatial statistics (TBSS) was used to demonstrate white matter alterations in both DKI and DTI parameters in preschool children (1-6 years; n=10). Correlation analysis was also performed in multiple regions of interest (ROIs). Fractional anisotropy, mean kurtosis, axial kurtosis and radial kurtosis increased with age, while mean diffusivity and radial diffusivity decreased significantly with age. Fractional anisotropy of kurtosis and axial diffusivity were found to be less sensitive to the changes with age. These preliminary findings indicated that TBSS could be used to detect subtle changes of DKI parameters on the white matter tract. Kurtosis parameters, except fractional anisotropy of kurtosis, demonstrated higher sensitivity than DTI parameters. TBSS may be a convenient method to yield higher sensitivity of DKI.published_or_final_versio

Principled Selection of Baseline Covariates to Account for Censoring in Randomized Trials with a Survival Endpoint

The analysis of randomized trials with time-to-event endpoints is nearly always plagued by the problem of censoring. As the censoring mechanism is usually unknown, analyses typically employ the assumption of non-informative censoring. While this assumption usually becomes more plausible as more baseline covariates are being adjusted for, such adjustment also raises concerns. Pre-specification of which covariates will be adjusted for (and how) is difficult, thus prompting the use of data-driven variable selection procedures, which may impede valid inferences to be drawn. The adjustment for covariates moreover adds concerns about model misspecification, and the fact that each change in adjustment set, also changes the censoring assumption and the treatment effect estimand. In this paper, we discuss these concerns and propose a simple variable selection strategy that aims to produce a valid test of the null in large samples. The proposal can be implemented using off-the-shelf software for (penalized) Cox regression, and is empirically found to work well in simulation studies and real data analyses

Suppression of liver tumor growth and metastasis by adiponectin in nude mice through inhibition of tumor angiogenesis and downregulation of rho kinase/IFN-inducible protein 10/matrix metalloproteinase 9 signaling

Purpose: We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms. Experimental Design: An orthotopic liver tumor nude mice model with distant metastatic potential was applied. Either Ad-adiponectin (1 × 10 8; treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by α-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration [Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9], and angiogenesis [vascular endothelial growth factor (VEGF) and angiopoietin 1] were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies. Results: Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration. Conclusion: Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway. ©2010 AACR.postprin