Preparation of highly dispersible and tumor-accumulative, iron oxide nanoparticles Multi-point anchoring of PEG-b-poly(4-vinylbenzylphosphonate) improves performance significantly

This paper describes the preparation of iron oxide nanoparticles, surface of which was coated with extremely high immobilization stability and relatively higher density of poly(ethylene glycol) (PEG), which are referred to as PEG protected iron oxide nanoparticles (PEG-PIONs). The PEG-PIONs were obtained through alkali coprecipitation of iron salts in the presence of the PEG-poly(4-vinylbenzylphosphonate) block copolymer (PEG-b-PVBP). In this system, PEG-b-PVBP served as a surface coating that was bound to the iron oxide surface via multipoint anchoring of the phosphonate groups in the PVBP segment of PEG-b-PVBP. The binding of PEG-b-PVBP onto the iron oxide nanoparticle surface and the subsequent formation of a PEG brush layer were proved by FT-IR, zeta potential, and thermogravimetric measurements. The surface PEG-chain density of the PEG-PIONs varied depending on the [PEG-b-PVBP]/[iron salts] feed-weight ratio in the coprecipitation reaction. PEG-PIONs prepared at an optimal feed-weight ratio in this study showed a high surface PEG-chain surface density (≈0.8 chainsnm(-2)) and small hydrodynamic diameter (<50 nm). Furthermore, these PEG-PIONs could be dispersed in phosphate-buffered saline (PBS) that contains 10% serum without any change in their hydrodynamic diameters over a period of one week, indicating that PEG-PIONs would provide high dispersion stability under in vivo physiological conditions as well as excellent anti-biofouling properties. In fact we have confirmed the prolong blood circulation time and facilitate tumor accumulation (more than 15% IDg(-1) tumor) of PEG-PIONs without the aid of any target ligand in mouse tumor models. The majority of the PEG-PIONs accumulated in the tumor by 96 h after administration, whereas those in normal tissues were smoothly eliminated by 96 h, proving the enhancement of tumor selectivity in the PEG-PION localization. The results obtained here strongly suggest that originally synthesized PEG-b-PVBP, having multipoint anchoring character by the phosphonate groups, is rational design for improvement in nanoparticle as in vivo application. Two major points, viz., extremely stable anchoring character and dense PEG chains tethered on the nanoparticle surface, worked simultaneously to become PEG-PIONs as an ideal biomedical devices intact for prolonged periods in harsh biological environments.     

Folate-targeted optical and magnetic resonance dualmodality PCL-<Emphasis Type="Italic">b</Emphasis>-PEG micelles for tumor imaging

A biodegradable tumor targeting nano-probe based on poly（ε-caprolactone）-b-poly（ethylene glycol）block copolymer（PCL-b-PEG）micelle functionalized with a magnetic resonance imaging（MRI）contrast agent diethylenetriaminepentaacetic acid-gadolinium(DTPA-Gd³⁺)on the shell and a near-infrared（NIR）dye in the core for magnetic resonance and optical dual-modality imaging was prepared.The longitudinal relaxivity（r₁）of the PCL-b-PEG-DTPA -Gd³⁺micelle was 13.4（mmol/L）^-1s^-1,three folds of that of DTPA-Gd³⁺,and higher than that of many polymeric contrast agents with similar structures.The in vivo optical imaging of a nude mouse bearing xenografted breast tumor showed that the dual-modality micelle preferentially accumulated in the tumor via the folic acid-mediated active targeting and the passive accumulation by the enhanced permeability and retention（EPR）effect.The results indicated that the dualmodality micelle is a promising nano-probe for cancer detection and diagnosis.     

A pyrophosphate-responsive gadolinium(III) MRI contrast agent

This study shows that the relaxivity and optical properties of functionalised lanthanide‐DTPA‐bis‐amide complexes (lanthanide=Gd³⁺ and Eu³⁺, DTPA=diethylene triamine pentaacetic acid) can be successfully modulated by addition of specific anions, without direct Ln³⁺/anion coordination. Zinc(II)‐dipicolylamine moieties, which are known to bind strongly to phosphates, were introduced in the amide “arms” of these ligands, and the interaction of the resulting Gd–Zn₂ complexes with a range of anions was screened by using indicator displacement assays (IDAs). Considerable selectivity for polyphosphorylated species (such as pyrophosphate and adenosine‐5′‐triphosphate (ATP)) over a range of other anions (including monophosphorylated anions) was apparent. In addition, we show that pyrophosphate modulates the relaxivity of the gadolinium(III) complex, this modulation being sufficiently large to be observed in imaging experiments. To establish the binding mode of the pyrophosphate and gain insight into the origin of the relaxometric modulation, a series of studies including UV/Vis and emission spectroscopy, luminescence lifetime measurements in H₂O and D₂O, ¹⁷O and ³¹P NMR spectroscopy and nuclear magnetic resonance dispersion (NMRD) studies were carried out.     

Body Temperature Mapping by Magnetic Resonance Imaging

Abstract

There are numerous clinical situations, such as hyperthermia cancer therapy, under which body temperature has to be accurately evaluated. Magnetic Resonance Imaging presently offers the best set of non-invasive methods for body temperature mapping, including diffusion imaging, relaxation time measurement, magnetization transfer contrast and chemical shift spectroscopic imaging. The basic NMR parameters involved in each are first analyzed. The role of temperature in their physical variation is then presented and finally the different practical MRI methods are briefly discussed. In the present slate of available technology and for basic physical reasons, the T 1 method appears the best compromise at low and medium magnetic field in a limited temperature range. Chemical shift could be theoretically more promising but strictly depends from the homogeneity and stability of the magnet and will be available only at high or very high field.

     

Proton magnetic resonance spectroscopic images and MRI volumetric studies for lateralization of temporal lobe epilepsy

We obtained 2D magnetic resonance (MR) spectroscopic images (MRSI) and MRI volumetric measurements (MRIV) of amygdala and hippocampus in 30 consecutive patients with temporal lobe epilepsy (TLE) being evaluated for surgical treatment. Both MRSI and MRIV lateralization showed good agreement with the current gold standard of clinical-EEG lateralization. Each exam separately correctly lateralized 25 out of 30 patients with no false lateralization. Combining both exams, lateralization could be achieved in 28 out of 30 patients. The two patients with no significant asymmetry had bitemporal EEG abnormalities, and bilateral damage on both MRIV and MRSI. There was a good correlation between the magnitude of the MRSI and MRIV asymmetry (Pearson COEFFICIENT = 0.83; p < .0001). Both MRSI and MRIV were normal in our patients with seizures originating outside the temporal lobes. Both MRIV and MRSI can lateralize TLE in 83% of patients. Combination of the two modalities allows lateralization in 93% of patients. Patients who cannot be lateralized generally have symmetrical bitemporal abnormalities; they are not incorrectly lateralized. The structural and chemical pathologic abnormalities seen in TLE seem to be associated with the seizure focus, and may be as, or even more, reliable than a few recorded seizures in predicting the side from which most seizures originate.     

大白鼠抑郁症模型的MRI方法研究

用核磁共振成象方法研究对比了抑郁症大白鼠与对照组正常大白鼠脑部的核磁共振信号强度的差别.从大白鼠大脑的核磁共振图象出发,经过数据分析,发现抑郁症大白鼠多个脑组织的核磁共振信号相对强度普遍比正常大白鼠高.另外,模型组大白鼠大脑的脑裂比对照组大白鼠的脑裂更深且更宽.     

Quantitative cerebral magnetic resonance imaging during ACTH treatment of multiple sclerosis

Serial MR scans were performed with the 2DFT imaging method and the filtered backprojection imaging method on 12 patients with multiple sclerosis in acute phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before, during and after ACTH treatment. Both T₁ and T_2mono relaxation times, obtained by fitting transverse magnetization decay curves with a monoexponential function within the apparently normal white matter and the areas of increased signal, were measured. With the backprojection method it was possible to fit the transverse magnetization decay curve with a biexponential function and obtain T_2long and T_2short relaxation times. The T_2mono and T₁ relaxation times of the apparently normal white matter were significantly different from those obtained for volunteers, but no significant differences were found before, during, or after treatment. The transverse magnetization decay curves of the areas of increased signal were better fitted by a biexponential function. No significant changes in these relaxation times were observed after ACTH treatment. These results argue against an anti-oedematous action of ACTH and may suggest that it has an immunosuppressant effect.     

A novel editing technique for F MRI: Molecule-specific imaging

A novel technique is proposed to facilitate the selective imaging of specific molecules from a mixture. The application of the technique presented here demonstrates the ability to selectively produce ¹⁹F MR images of either trifluoroacetic acid or the perfluorocarbon emulsion Oxypherol-ET (perfluorotributylamine), when both molecules are present simultaneously. Selective detection is based on the presence of homonuclear J-modulation in one molecule and differential spin-spin relaxation time (T₂). Perfluorotributylamine, an A₃B₂ system, is subject to homonuclear J-modulation, which produces a null signal from the antiphase components of the triplet (A₃) when an echo time is used in a spin-echo image. At this echo time the second molecule, in this example trifluoroacetic acid, a non-coupled spin system, is selectively imaged. At longer echo times, e.g., TE = 1/J there is substantial recovery of the J-modulated signal, which may be solely observed due to T₂ decay of the trifluoroacetic acid signal. The method is demonstrated both using phantoms and in vivo.