Nanoscale metal-organic frameworks (NMOFs) based on Gd3+ centers and benzenedicarboxylate and benzenetricarboxylate bridging ligands were synthesized using reverse microemulsions and characterized using SEM, PXRD, and TGA. These NMOFs exhibit extraordinarily large R1 and R2 relaxivities because of the presence of up to tens of millions of Gd3+ centers in each nanoparticle and are thus efficient T1 and T2 contrast agents for MRI. The NMOFs can also be made highly luminescent by doping with Eu3+ or Tb3+ centers. The results from this work suggest that NMOFs can be used as potential contrast agents for multimodal imaging.

Emerging evidence indicates that microRNAs (miRNAs) have important roles in regulating osteogenic differentiation and bone formation. Thus far, no study has established the pathophysiological role for miRNAs identified in human osteoporotic bone specimens. Here we found that elevated miR-214 levels correlated with a lower degree of bone formation in bone specimens from aged patients with fractures. We also found that osteoblast-specific manipulation of miR-214 levels by miR-214 antagomir treatment in miR-214 transgenic, ovariectomized, or hindlimb-unloaded mice revealed an inhibitory role of miR-214 in regulating bone formation. Further, in vitro osteoblast activity and matrix mineralization were promoted by antagomir-214 and decreased by agomir-214, and miR-214 directly targeted ATF4 to inhibit osteoblast activity. These data suggest that miR-214 has a crucial role in suppressing bone formation and that miR-214 inhibition in osteoblasts may be a potential anabolic strategy for ameliorating osteoporosis.

No abstract

SummaryA quantitative estimate of cerebral blood oxygen saturation is of critical importance in the investigation of cerebrovascular disease because of the fact that it could potentially provide information on tissue viability in vivo. In the current study, a multi-echo gradient and spin echo magnetic resonance imaging sequence was used to acquire images from eight normal volunteer subjects. All images were acquired on a Siemens 1.5T Symphony whole-body scanner (Siemens, Erlangen, Germany). A theoretical signal model, which describes the signal dephasing phenomena in the presence of deoxyhemoglobin, was used for postprocessing of the acquired images and obtaining a quantitative measurement of cerebral blood oxygen saturation in vivo. With a regionof-interest analysis, a mean cerebral blood oxygen saturation of 58.4% ± 1.8% was obtained in the brain parenchyma from all volunteers. It is in excellent agreement with the known cerebral blood oxygen saturation under normal physiologic conditions in humans. Although further studies are needed to overcome some of the confounding factors affecting the estimates of cerebral blood oxygen saturation, these preliminary results are encouraging and should open a new avenue for the noninvasive investigation of cerebral oxygen metabolism under different pathophysiologic conditions using a magnetic resonance imaging approach.

All of the proposed novel methods have an average global performance within likely acceptable limits (±5% of CT-based reference), and the main difference among the methods was found in the robustness, outlier analysis, and clinical feasibility. Overall, the best performing methods were MR-ACBOSTON, MR-ACMAXPROB, MR-ACRESOLUTE and MR-ACUCL, ordered alphabetically. These methods all minimized the number of outliers, standard deviation, and average global and local error. The methods MR-ACMUNICH and MR-ACCAR-RiDR were both within acceptable quantitative limits, so these methods should be considered if processing time is a factor. The method MR-ACSEGBONE also demonstrates promising results, and performs well within the likely acceptable quantitative limits. For clinical routine scans where processing time can be a key factor, this vendor-provided solution currently outperforms most methods. With the performance of the methods presented here, it may be concluded that the challenge of improving the accuracy of MR-AC in adult brains with normal anatomy has been solved to a quantitatively acceptable degree, which is smaller than the quantification reproducibility in PET imaging.

Lighting things up: Multifunctional silica nanoparticles containing a luminescent core and a paramagnetic coat are prepared, and their utility as multimodal imaging probes is demonstrated in vitro. Monocyte cells can be labeled with the hybrid nanoparticles with greater than 98 % efficiency and do not experience measurable toxicity even at a high loading of 0.123 mg per 5000 cells.

Multifunctional nanoparticles (MFNPs) have shown great promise as new probes for biomedical imaging and carriers for drug delivery. 1 MFNPs can not only carry large payloads of imaging and/or therapeutic agents, but also be rendered target-specific by conjugation to affinity molecules which have avidity for cell surface markers. Although a number of strategies have been developed to synthesize target-specific MFNPs, most of them rely on covalent attachment of affinity molecules to their surfaces. 2 Since such bioconjugation steps can be tedious, there exists a need for new synthetic strategies toward imaging and/or therapeutic MFNPs that can specifically target diseased cells. Herein we wish to report a noncovalent, electrostatic layer-by-layer (LbL) self-assembly strategy for the synthesis of cancer-specific MFNPs that are efficient contrast agents for multimodal imaging. TEM images indicated alternate deposition of 1 and PSS onto the nanoparticles (Figure 1a-c); the average diameters for NP1A, NP3A, and NP6A are 37±1, 41±1, and 43±2 nm, respectively.

Quantitative estimates of brain oxygen extraction fraction (OEF) and venous cerebral blood volume (vCBV) using a 2D multiecho gradient echo/spin echo (MEGESE) sequence have been reported previously in normal subjects (1,2). While estimates of OEF and vCBV with an MEGESE sequence are in accordance with those reported in the literature using other imaging modalities, this method suffers from several major limitations, including lengthy data acquisition time, inability to cover a large region-of-interest (ROI), and sensitivity to motion artifacts, making it difficult for routine clinical applications. In addition, owing to the inherent limitations of the MEGESE sequence, the potential contribution of the intravascular signal in the estimates of vCBV and OEF cannot be determined. Therefore, imaging sequences that minimize these technical difficulties while allowing quantitative estimates of OEF and vCBV are highly desirable.Since its inception (3,4), the asymmetric spin echo (ASE) technique has been widely used to probe signal alterations induced by susceptibility perturbers. Through a line-width mapping technique, local magnetic field inhomogeneities were evaluated (5,6). More recently, Stables et al. (7) employed the ASE technique in a phantom study to examine the sensitivities of gradient echo and spin echo to different magnetic field perturber sizes. In addition, Houston et al. (8) have observed MR signal changes during hypoxia with respect to baseline condition by using an ASE sequence with a fixed time offset between the spin echo and the gradient echo readout. Thus far, only relative measurements have been obtained, with little attention to the quantitative measurements of the susceptibility with the ASE approaches. In this study, an ASE EPI sequence was employed to acquire images that have different susceptibility weighting. Subsequently, based on the theoretical model proposed by Yablonskiy and Haacke (9) for characterizing signal changes in the presence of deoxyhemoglobin, vCBV and OEF were estimated from the acquired images. In addition, images with and without flow dephasing gradients were also acquired to determine the effects of intravascular signal contributions in the measurements of vCBV and OEF. Finally, a well-characterized experimental paradigm, hypercapnia, which is known to induce predictable alterations in cerebral blood oxygenation in normal subjects, was employed to verify the sensitivity of the ASE approach in measuring OEF and vCBV under a pathophysiologically relevant condition. THEORYDeoxyhemoglobin, a microscopic magnetic susceptibility source residing in venous blood vessels and capillaries of the brain parenchyma, can induce signal alterations in both T 2 -and T * 2 -weighted images (10,11). A two-compartment model, in which the extravascular and intravascular compartments correspond to brain tissue and venous blood vessels, respectively, can be used to characterize the MR signal. The total MR signal is depicted as a weighted sum of signals from these two compartments. Assuming the si...