We report a new type of multifunctional nanomaterials, FePt@Fe2O3 yolk-shell nanoparticles, that exhibit high cytotoxicity originated from the FePt yolks and strong MR contrast enhancement resulting from the Fe2O3 shells. Encouraged by the recently observed high cytotoxicity of FePt@CoS2 yolk-shell nanoparticles, we used Fe2O3 to replace CoS2 as the shells to further explore the applications of the yolk-shell nanostructures. The ultralow IC50 value (238 +/- 9 ng of Pt/mL) of FePt@Fe2O3 yolk-shell nanoparticles likely originates from the fact that the slow oxidation and release of FePt yolks increases the cytotoxicity. Moreover, compared with two commercial magnetic resonance imaging (MRI) contrast agents, MION and Sinerem, the FePt@Fe2O3 yolk-shell nanoparticle showed stronger contrast enhancement according to their apparent transverse relaxivity values (r2* = 3.462 (microg/mL)(-1) s(-1)). The bifunctional FePt@Fe2O3 yolk-shell nanoparticles may serve both as an MRI contrast agent and as a potent anticancer drug. This work indicates that these unique yolk-shell nanoparticles may ultimately lead to new designs of multifunctional nanostructures for nanomedicine.

In conventional diffusion tensor imaging (DTI), water diffusion distribution is described as a 2nd-order three-dimensional (3D) diffusivity tensor. It assumes that diffusion occurs in a free and unrestricted environment with a Gaussian distribution of diffusion displacement, and consequently that diffusion weighted (DW) signal decays with diffusion factor (b-value) monoexponentially. In biological tissue, complex cellular microstructures make water diffusion a highly hindered or restricted process. Non-monoexponential decays are experimentally observed in both white matter and gray matter. As a result, DTI quantitation is b-value dependent and DTI fails to fully utilize the diffusion measurements that are inherent to tissue microstructure. Diffusion kurtosis imaging (DKI) characterizes restricted diffusion and can be readily implemented on most clinical scanners. It provides a higher-order description of water diffusion process by a 2nd-order 3D diffusivity tensor as in conventional DTI together with a 4th-order 3D kurtosis tensor. Because kurtosis is a measure of the deviation of the diffusion displacement profile from a Gaussian distribution, DKI analyses quantify the degree of diffusion restriction or tissue complexity without any biophysical assumption. In this work, the theory of diffusion kurtosis and DKI including the directional kurtosis analysis is revisited. Several recent rodent DKI studies from our group are summarized, and DKI and DTI compared for their efficacy in detecting neural tissue alterations. They demonstrate that DKI offers a more comprehensive approach than DTI in describing the complex water diffusion process in vivo. By estimating both diffusivity and kurtosis, it may provide improved sensitivity and specificity in MR diffusion characterization of neural tissues.

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Cell cycle withdrawal limits proliferation of adult mammalian cardiomyocytes. Therefore, the concept of stimulating myocyte mitotic divisions has dramatic implications for cardiomyocyte regeneration and hence, cardiovascular disease. Previous reports describing manipulation of cell cycle proteins have not shown induction of cardiomyocyte mitosis after birth. We now report that cyclin A2, normally silenced in the postnatal heart, induces cardiac enlargement because of cardiomyocyte hyperplasia when constitutively expressed from embryonic day 8 into adulthood. Cardiomyocyte hyperplasia during adulthood was coupled with an increase in cardiomyoctye mitosis, noted in transgenic hearts at all time points examined, particularly during postnatal development. Several stages of mitosis were observed within cardiomyocytes and correlated with the nuclear localization of cyclin A2. Magnetic resonance analysis confirmed cardiac enlargement. These results reveal a previously unrecognized critical role for cyclin A2 in mediating cardiomyocyte mitosis, a role that may significantly impact upon clinical treatment of damaged myocardium.

Due to the well-known limitations of diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI) is used to characterize non-Gaussian diffusion processes. One approach to analyze HARDI data is to model the apparent diffusion coefficient (ADC) with higher order diffusion tensors (HODT). The diffusivity function is positive semi-definite. In the literature, some methods have been proposed to preserve positive semi-definiteness of second order and fourth order diffusion tensors. None of them can work for arbitrary high order diffusion tensors. In this paper, we propose a comprehensive model to approximate the ADC profile by a positive semi-definite diffusion tensor of either second or higher order. We call this model PSDT (positive semi-definite diffusion tensor). PSDT is a convex optimization problem with a convex quadratic objective function constrained by the nonnegativity requirement on the smallest Z-eigenvalue of the diffusivity function. The smallest Z-eigenvalue is a computable measure of the extent of positive definiteness of the diffusivity function. We also propose some other invariants for the ADC profile analysis. Experiment results show that higher order tensors could improve the estimation of anisotropic diffusion and the PSDT model can *

ObjectivesMaternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood.MethodWe used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities.ResultsPolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating.ConclusionsOur results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life.

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