High-Performance Upconversion Nanoprobes for Multimodal MR Imaging of Acute Ischemic Stroke.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Electrostatics-Driven Hierarchical Buckling of Charged Flexible Ribbons.

We investigate the rich morphologies of an electrically charged flexible ribbon, which is a prototype for many beltlike structures in biology and nanomaterials. Long-range electrostatic repulsion is found to govern the hierarchical buckling of the ribbon from its initially flat shape to its undulated and out-of-plane twisted conformations. In this process, the screening length is the key controlling parameter, suggesting that a convenient way to manipulate the ribbon morphology is simply to change the salt concentration. We find that these shapes originate from the geometric effect of the electrostatic interaction, which fundamentally changes the metric over the ribbon surface. We also identify the basic modes by which the ribbon reshapes itself in order to lower the energy. The geometric effect of the physical interaction revealed in this Letter has implications for the shape design of extensive ribbonlike materials in nano- and biomaterials.

Molecular imaging of angiogenesis to delineate the tumor margins in glioma rat model with endoglin-targeted paramagnetic liposomes using 3T MRI.

PURPOSE: To evaluate the use of endoglin-targeted paramagnetic liposomes in delineating the glioma margins using magnetic resonance (MR) angiogenesis imaging in a rat model. MATERIALS AND METHODS: Four liposome preparations, including nontargeted paramagnetic liposomes (Gd-SLs), isotype control IgG-coupled paramagnetic liposomes (IgG-Gd-SLs), endoglin monoclonal antibody coupled paramagnetic liposomes (MAb-Gd-SLs), and biotinylated antibodies (Bio-MAb)/streptavidin-coupled paramagnetic liposomes (SAv-Gd-SLs) for two-step pretargeting imaging, were formulated. All animal experiments were carried out with the approval of the Shanghai Animal Care. C6 glioma-bearing Sprague-Dawley rats were intravenously injected with gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) or the previously mentioned liposomes (n = 5) and imaged with MR. T1 -weighted MRI was performed before and dynamically repeated after different contrast agents were injected. The enhancement features of the tumors were compared. RESULTS: The signal enhancement of the tumor in the two-step pretargeting group increased by 117.9 ± 5.3% at the periphery and 109.2 ± 3.5% in the center (P = 0.032) at the 8-hour timepoint after SAv-Gd-SLs injection. Ring-like enhancement margins were demonstrated at the periphery of the tumor in the two-step targeted group. The specificity of the targeted liposomes was supported by the competitive study. The signal of peak enhancement using MAb-Gd-SLs was 59% less than that of the two-step group and only slightly higher than the non-targeted groups. CONCLUSION: The two-step endoglin-targeted imaging using biotin-streptavidin interaction was demonstrated to induce intense enhancement of the tumor periphery, which implies that this advanced MR molecular contrast agent may be suitable for accurately delineating glioma tumor margins. J. Magn. Reson. Imaging 2015;41:1056-1064. © 2014 Wiley Periodicals, Inc.

Harnessing X-Ray Energy-Dependent Attenuation of Bismuth-Based Nanoprobes for Accurate Diagnosis of Liver Fibrosis.

Timely detection of liver fibrosis by X-ray computed tomography (CT) can prevent its progression to fatal liver diseases. However, it remains quite challenging because conventional CT can only identify the difference in density instead of X-ray attenuation characteristics. Spectral CT can generate monochromatic imaging to specify X-ray attenuation characteristics of the scanned matter. Herein, an X-ray energy-dependent attenuation strategy originated from bismuth (Bi)-based nanoprobes (BiF3 @PDA@HA) is proposed for the accurate diagnosis of liver fibrosis. Bi element in BiF3 @PDA@HA can exhibit characteristic attenuation depending on different levels of X-ray energy via spectral CT, and that is challenging for conventional CT. In this study, selectively accumulating BiF3 @PDA@HA nanoprobes in the hepatic fibrosis areas can significantly elevate CT value for 40 Hounsfield units on 70 keV monochromatic images, successfully differentiating from healthy livers and achieving the diagnosis of liver fibrosis. Furthermore, the enhancement produced by the BiF3 @PDA@HA nanoprobes in vivo increases as the monochromatic energy decreases from 70 to 40 keV, optimizing the conspicuity of the diseased areas. As a proof of concept, the strategically designed nanoprobes with energy-dependent attenuation characteristics not only expand the scope of CT application, but also hold excellent potential for precise imaging-based disease diagnosis.

Artificial anaerobic cell dormancy for tumor gaseous microenvironment regulation therapy.

Oxygen is known as an irreplaceable gas in the lives of most eukaryotic cells, yet researchers underestimate its importance, as in the case in many studies of tumors. The variable oxygen content of malignant solid tumors increases the difficulty of treatment. Thus, it could be reasonably inferred that the tumor oxygen microenvironment, if efficiently and completely regulated, could bring certain changes to existing therapies. Based on this speculation, an acid-responsive, oxygen-scavenging and anaerobic-sensitizing nanoparticle was designed to regulate the oxygen level of solid tumor by creating an artificial anaerobic environment in our study. The Mg2Si core, which acted as a deoxygenating agent, was able to consume tumor oxygen and cause cell dormancy, while the incorporated hydrophobic tirapazamin (TPZ) helped to kill the now-dormant tumor cells. This simple and nontoxic nanoparticle achieved controllable factitious anaerobic circumstance in solid tumor for the first time, displaying the considerable potential and promising application of tumor gaseous microenvironment regulation therapy.

PEGylated NaHoF4 nanoparticles as contrast agents for both X-ray computed tomography and ultra-high field magnetic resonance imaging.

It is well-known that multimodal imaging can integrate the advantages of different imaging modalities by overcoming their individual limitations. As ultra-high field magnetic resonance imaging (MRI) will be inevitably used in future MRI/X-ray computed tomography (CT) scanner, it is highly expected to develop high-performance nano-contrast agents for ultra-high field MR and CT dual-modality imaging, which has not been reported yet. Moreover, specific behavior of nano-contrast agents for ultra-high field MRI is a challenging work and still remains unknown. Herein, a novel type of NaHoF4 nanoparticles (NPs) with varied particle sizes were synthesized and explored as high-performance dual-modality contrast agents for ultra-high field MR and CT imaging. The specific X-ray absorption and MR relaxivity enhancements with varied nanoparticle diameters (3 nm, 7 nm, 13 nm and 29 nm) under different magnetic field (1.5/3.0/7.0 T) are investigated. Based on experimental results and theoretical analysis, the Curie and dipolar relaxation mechanisms of NaHoF4 NPs are firstly separated. Our results will greatly promote the future medical translational development of the NaHoF4 nano-contrast agents for ultra-high field MR/CT dual-modality imaging applications.

Packing of charged chains on toroidal geometries.

We study a strongly adsorbed flexible polyelectrolyte chain on tori. In this generalized Thomson problem, the patterns of the adsorbed chain are analyzed in the space of the toroidal coordinates and in terms of the orientation of each chain segment. Various patterns are found, including double spirals, disclination-like structures, Janus tori, and uniform wrappings, arising from the long-range electrostatic interaction and the toroidal geometry. Their broken mirror symmetry is quantitatively characterized by introducing an order parameter, an integral of the torsion. The uniform packing, which breaks the mirror symmetry the least, has the lowest value of the order parameter. In addition, it is found that the electrostatic energy of confined chains on tori conforms to a power law regardless of the screening effect in some typical cases studied. Furthermore, we study random walks on tori that generate chain configurations in the large screening limit or at large thermal fluctuation; some features associated with the toroidal geometry are discussed.

[Report of a case with Joubert syndrome and literature review].

OBJECTIVE: To explore the clinical feature, imaging and their diagnostic value for Joubert syndrome (JS). METHOD: The clinical data, imaging feature, and 31 references from China Biomedical literature database (CBMdise) were reviewed and analyzed. RESULT: The age of onset of 32 patients including male 20 and female 12 ranged from 3 days to 6 years (mean 2.2 years). All the 32 patients with Joubert syndrome showed "slow growth" and "reduced muscle tension", 26 cases (81.3%) showed "gasp for breath", 26 cases (81.3%) showed "unusual motion of eyeball", 2 cases (6.3%) showed additional fingers (toes), 6 cases (18.8%) showed stretching tongue with agape. The typical imaging features of Joubert syndrome included "molar tooth sign", "midline cleavage" between cerebellar hemispheres and "bat-wing" like fourth ventricle, all the 32 patients with Joubert syndrome showed "midline cleavage", "molar tooth sign" was present in 29 cases (90.1%), and "bat-wing" like fourth ventricle in 30 cases (93.8%). CONCLUSION: Joubert syndrome is a rare congenital brain malformation. The typical clinical manifestations included "gasp for breath", "reduced tension of muscle", "slow growth" and "unusual motion of eyeball", and at the same time the patients had the following typical imaging features of brain: "molar tooth sign", "midline cleavage" and "bat-wing" like fourth ventricle.