Ultrasmall superparamagnetic iron oxides enhanced MR imaging in rats with experimentally induced endometriosis

Purpose

The purpose of our study was to evaluate the feasibility of magnetic resonance imaging (MRI) using ultrasmall superparamagnetic iron oxides (USPIO) in the detection of experimentally induced endometriosis.

Materials and methods

Endometriosis was surgically induced in rats by transplanting an autologous fragment of uterine tissue onto the inner surface of the abdominal wall, the posterior surface of the uterine body and the arterial cascades of the small intestines adjacent to mesenteric blood vessels. Six weeks later, MRI using Gd-DTPA and USPIO was performed for the evaluation of the ectopic uterine tissue (EUT). A scoring system was developed for image interpretation (0=absence, 1=probably absence, 2=probably presence and 3=presence). We defined MR index (MRIx) as the sum of T1-weighted and enhanced T1-weighted and T2-weighted image scores, and USPIO MRIx (MRIx^+USPIO) as the MRIx score plus the score of USPIO-enhanced T2-weighted image.

Results

The MRIx^+USPIO was also higher in the successfully autotransplanted group than in the failed group (6.19±1.72 versus 3.94±1.20, P<.001). There was also a significant linear relationship between MRIx^+USPIO and pathologic status (R²=0.494, P<.001). Thirty-one (64.6%) of the 48 implanted uterine tissues were histologically confirmed on pathologic review. The area of MRIx and MRIx^+USPIO in the detection of EUT more than 3 mm in size was 0.739 and 0.913, respectively.

Conclusion

Our results suggest that USPIO-enhanced MRI could be a novel diagnostic tool for diagnosis in experimentally induced peritoneal endometriosis.     

Comparative analysis of the 1H NMR relaxation enhancement produced by iron oxide and core-shell iron-iron oxide nanoparticles

Physicochemical and magnetorelaxometric characterization of the colloidal suspensions consisting of Fe-based nanoparticles coated with dextran have been carried out. Iron oxide and iron core/iron oxide shell nanoparticles were obtained by laser-induced pyrolysis of Fe(CO)₅ vapours. Under different magnetic field strengths, the colloidal suspension formed by iron oxide nanoparticles showed longitudinal (R₁) and transverse (R₂) nuclear magnetic relaxation suspension (NMRD) profiles, similar to those previously reported for other commercial magnetic resonance imaging (MRI) contrast agents. However, colloidal suspension formed by ferromagnetic iron-core nanoparticles showed a strong increase of the R₁ values at low applied magnetic fields and a strong increase of the R₂ measured at high applied magnetic field. This behaviour was explained considering the larger magnetic aggregate size and saturation magnetization values measured for this sample, 92 nm and 31 emu/g Fe, respectively, with respect to those measured for the colloidal suspensions of iron oxide nanoparticles (61 nm and 23 emu/g Fe). This suspension can be used both as T₁ and T₂ contrast agent.     

Size-dependent magnetic properties of iron oxide nanoparticles

Uniform iron oxide nanoparticles in the size range from 10 to 24 nm and polydisperse 14 nm iron oxide particles were prepared by thermal decomposition of Fe(III) carboxylates in the presence of oleic acid and co-precipitation of Fe(II) and Fe(III) chlorides by ammonium hydroxide followed by oxidation, respectively. While the first method produced hydrophobic oleic acid coated particles, the second one formed hydrophilic, but uncoated, nanoparticles. To make the iron oxide particles water dispersible and colloidally stable, their surface was modified with poly(ethylene glycol) and sucrose, respectively. Size and size distribution of the nanoparticles was determined by transmission electron microscopy, dynamic light scattering and X-ray diffraction. Surface of the PEG-functionalized and sucrose-modified iron oxide particles was characterized by Fourier transform infrared (FT-IR) and Raman spectroscopy and thermogravimetric analysis (TGA). Magnetic properties were measured by means of vibration sample magnetometry and specific absorption rate in alternating magnetic fields was determined calorimetrically. It was found, that larger ferrimagnetic particles showed higher heating performance than smaller superparamagnetic ones. In the transition range between superparamagnetism and ferrimagnetism, samples with a broader size distribution provided higher heating power than narrow size distributed particles of comparable mean size. Here presented particles showed promising properties for a possible application in magnetic hyperthermia.     

Application of factor analysis to XPS valence band of superparamagnetic iron oxide nanoparticles

X-Ray photoelectron spectra of nano-sized superparamagnetic iron oxide nanoparticles were examined with the aim to discriminate the different degree of iron oxidation. Careful analysis of the valence band regions reveals the presence of both Fe₃O₄ and Fe₂O₃. The application of factor analysis enabled us to extract the relative molar concentrations of these oxides in the nanoparticles. This is of particular interest in improving the magnetic properties of iron oxide nanoparticles whose superparamagnetic character can be optimized to obtain better contrast in images from nuclear magnetic resonance. As a result, the factor analysis allows tuning the nanoparticle synthesis conditions in order to obtain the optimal magnetic properties for imaging. Results obtained by the XPS valence band analysis were compared to the transmission electron microscopy, X-ray diffraction and Raman measurements.     

Magnetic resonance in iron oxide nanoparticles: Quantum features and effect of size

In order to better understand the transition from quantum to classical behavior in spin system, electron magnetic resonance (EMR) is studied in suspensions of superparamagnetic magnetite nanoparticles with an average diameter of ∼9 nm and analyzed in comparison with the results obtained in the maghemite particles of smaller size (∼5 nm). It is shown that both types of particles demonstrate common EMR behavior, including special features such as the temperature-dependent narrow spectral component and multiple-quantum transitions. These features are common for small quantum systems and not expected in classical case. The relative intensity of these signals rapidly decreases with cooling or increase of particle size, marking gradual transition to the classical ferromagnetic resonance (FMR) behavior.     

Magnetic properties of iron adatoms and small iron clusters on Ag(1 0 0)

A Green's function embedding technique based on the fully relativistic spin-polarized Screened Korringa–Kohn–Rostoker method is used to calculate the electronic and magnetic properties of magnetic nanostructures. Strongly enhanced spin and orbital moments are obtained for an Fe adatom and for small clusters of Fe on a Ag(1 0 0) surface. As a consequence, for an Fe adatom a magnetic anisotropy energy is found that is about 10 times larger than for an Fe monolayer. Furthermore, the exchange coupling energy between two Fe adatoms is calculated in terms of the force theorem, showing a very rapid decay with increasing distance.     

Magnetic and relaxometric properties of polyethylenimine-coated superparamagnetic MRI contrast agents

Novel systems to be employed as superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI) have been synthesized. These compounds are composed of an iron oxide magnetic core coated by polyethylenimine (PEI) or carboxylated polyethylenimine (PEI-COOH). The aim of the present work was to prepare and study new nanostructured systems (with better or at least comparable relaxivities, R₁ and R₂, with respect to the commercial ones) with controlled, almost monodisperse average dimensions and shape, as candidates for molecular targeting. By means of atomic force microscopy (AFM) measurements we determined the average diameter, of the order of 200 nm, and the shape of the particles. The superparamagnetic behavior was assessed by SQUID measurements. From X-ray data the estimated average diameters of the magnetic cores were found to be 5.8 nm for PEI-COOH60 and 20 nm for the compound named PEI25. By NMR-dispersion (NMRD), we found that PEI-COOH60 presents R₁ and R₂ relaxivities slightly lower than Endorem^®. The experimental results suggest that these novel compounds can be used as MRI CA.     

Magnetic resonance imaging with superparamagnetic iron oxide particles for the detection of myocardial reperfusion

The effect of superparamagnetic iron oxide particles on magnetic resonance myocardial signal intensity was examined in order to define the ability of this agent to identify normal, ischemic, and reperfused myocardium. Data were obtained from 6 normal rats (group 1) and from 6 heterotopic isogenic rat heart transplants (group 2) at 4.7 T with a multislice spin-echo sequence. Images were acquired in (a) normal rats before and after the infusion of 36 μmol Fe/kg of AMI-25 (group 1) and (b) rat heart transplants during control, global myocardial ischemia (before and after the injection of 72 μmol Fe/kg of AMI-25), and following reperfusion (group 2). Myocardial signal intensity decreased by 36 ± 4%, p < 0.001, following contrast infusion in normal hearts (group 1). The intensity remained constant in the rat heart transplants (group 2) during coronary occlusion, both before and after the infusion of AMI-25 and decreased by 61 ± 7%, p < 0.001, upon reperfusion. The larger effect of AMI-25 in reperfused as compared to normal myocardium suggests the presence of ischemia-induced hyperemia. There was no significant difference (analysis of variance) among intensities from different myocardial regions in either group at any stage of the experiment. We conclude that the use of AMI-25 permits identification of normal, ischemic, and reperfused myocardium and may therefore be helpful for the early detection of reperfusion following thrombolytic therapy for acute myocardial infarction.     

Synthesis and magnetic properties of size-selected CoPt nanoparticles

CoPt nanoparticles are widely studied, in particular for their potentially very high magnetic anisotropy. However, their magnetic properties can differ from the bulk ones and they are expected to vary with the particle size. In this paper, we report the synthesis and characterization of well-defined CoPt nanoparticle samples produced in ultrahigh vacuum conditions following a physical route: the mass-selected low energy cluster beam deposition technique. This approach relies on an electrostatic deviation of ionized clusters which allows us to easily adjust the particle size, independently from the deposited equivalent thickness (i.e. the surface or volume particle density in a sample). Diluted samples made of CoPt particles, with different diameters, embedded in amorphous carbon are studied by transmission electron microscopy and superconducting interference device magnetometry, which gives access to the magnetic anisotropy energy distribution. We then compare the magnetic properties of two different particle sizes. The results are found to be consistent with an anisotropy constant (including its distribution) which does not evolve with the particle size in the range considered.     

Formation of multifunctional Fe_3O_4/Au composite nanoparticles for dual-mode MR/CT imaging applications

Recent advances with iron oxide/gold(Fe3O4/Au) composite nanoparticles(CNPs) in dual-modality magnetic resonance(MR) and computed tomography(CT) imaging applications are reviewed. The synthesis and assembly of "dumbbelllike" and "core/shell" Fe3O4/Au CNPs is introduced. Potential applications of some developed Fe3O4/Au CNPs as contrast agents for dual-mode MR/CT imaging applications are described in detail.     

Magnetic properties of SiO2-coated iron oxide nanoparticles studied by polarized small angle neutron scattering

The structural and magnetic properties of non-coated and SiO₂-coated iron oxide (Fe₃O₄) nanoparticles (NPs) were investigated by a polarized small-angle neutron scattering (P-SANS) method. Measurement of the P-SANS allowed us to obtain nuclear and magnetic scattering cross sections of the NPs under applied magnetic field. The analysis of the scattering intensity provided the structural parameters and the spatial magnetization distribution of the non-coated and the SiO₂ coated core–shell NPs. The measured radius of both NPs and the shell thickness of the core–shell NPs were in consistent with those measured by the transmission electron microscopy. In comparison, the magnetic core radii of both NPs were 0.12–0.6 nm smaller than the nuclear radii, indicating the magnetization reduction in the surface region of core Fe₃O₄ in both NPs. However, the reduced magnetization region, which is the surface spin canting region, of the SiO₂-coated NPs was relatively narrower than that of the non-coated NPs. We suggest that the SiO₂ coating on the Fe₃O₄ NPs may stabilize the spin order of atoms and prohibit the oxidation or defect formation at the surface region of the Fe₃O₄ NPs, and enhance the corresponding magnetization of the Fe₃O₄ NPs by the reduction of the spin canting layer thickness.     

How size evaluation of lymph node is protocol dependent in MRI when using ultrasmall superparamagnetic iron oxide nanoparticles

In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions.     

Surface morphology and local magnetic properties of electrodeposited thin iron layers

Thin iron layers with different thickness were prepared by electrodeposition on the polycrystalline substrate. The surface morphology of the layers, their structure and local magnetic properties were studied using scanning tunneling microscopy (STM), X-ray diffraction (XRD) and conversion electron Mössbauer spectroscopy (CEMS). STM studies revealed the granular structure of the surface of the electrodeposited iron layers with the roughness up to 10 nm. XRD analysis proved that these layers were highly strained. The CEMS spectra showed an in-plane magnetic anisotropy in the iron layers. Isomer shift of the electrodeposited iron was different than that of the -Fe. This difference was attributed to the internal stresses existing in the electrodeposited layers.     

Magnetic properties of novel superparamagnetic MRI contrast agents based on colloidal nanocrystals

Novel systems based on colloidal magnetic nanocrystals (NCs), potentially useful as superparamagnetic (SP) contrast agents for magnetic resonance imaging (MRI) have been investigated. The NCs we have studied comprise organic-capped single-crystalline maghemite (γ-Fe₂O₃) cores possessing controlled sizes and shapes. We have comparatively examined spherical and tetrapod-like NCs, the latter being branched particles possessing four arms which depart out at tetrahedral angles from a central point. The as-synthesized NCs are passivated by hydrophobic surfactant molecules and thus are fully dispersible in nonpolar media only. The NCs have been made soluble in aqueous solution by applying a procedure based on the surface intercalation and coating with an amphiphilic polymer shell. NMR relaxivities R₁ and R₂ were compared with ENDOREM^®, one of the standard commercial SP-MRI contrast agent. We found that the spherical NCs exhibit R₁ and R₂ relaxivities slightly lower than those of ENDOREM^®, over the whole frequency range; on the contrary, tetrapods show relaxivities about one order of magnitude lower. The physical origin of such difference in relaxivities between tetrapod- and spheres-based nanostructures is under investigation and it is possibly related to different sources of the magnetic anisotropy.     

Time resolved spectroscopic NMR imaging using hyperpolarized Xe

We have visualized the melting and dissolution processes of xenon (Xe) ice into different solvents using the methods of nuclear magnetic resonance (NMR) spectroscopy, imaging, and time resolved spectroscopic imaging by means of hyperpolarized ¹²⁹Xe. Starting from the initial condition of a hyperpolarized solid Xe layer frozen on top of an ethanol (ethanol/water) ice block we measured the Xe phase transitions as a function of time and temperature. In the pure ethanol sample, pieces of Xe ice first fall through the viscous ethanol to the bottom of the sample tube and then form a thin layer of liquid Xe/ethanol. The xenon atoms are trapped in this liquid layer up to room temperature and keep their magnetization over a time period of 11 min. In the ethanol/water mixture (80 vol%/20%), most of the polarized Xe liquid first stays on top of the ethanol/water ice block and then starts to penetrate into the pores and cracks of the ethanol/water ice block. In the final stage, nearly all the Xe polarization is in the gas phase above the liquid and trapped inside the pores. NMR spectra of homogeneous samples of pure ethanol containing thermally polarized Xe and the spectroscopic images of the melting process show that very high concentrations of hyperpolarized Xe (about half of the density of liquid Xe) can be stored or delivered in pure ethanol.     

Synthesis and characterization of nanoparticles with an iron oxide magnetic core and a biologically active trialkylsilylated aliphatic alkanolamine shell

Water-soluble double-coated magnetic nanoparticles (NPs) containing cytotoxic decyldimethyl(β$\beta$-dimethylaminoethoxy)silane methiodide (AA) molecule sorbed at biocompatible magnetic particles, which consist of magnetite pre-coated with oleic acid (OA), have been prepared. X-ray line profile broadening analysis was used for crystallite size determination. The method of magnetogranulometry has been used for determination of diameter of iron oxide magnetic core and magnetic properties of NPs prepared. In vitro cytotoxicity on monolayer tumor cell lines HT-1080 (human fibrosarcoma), MG-22A (mouse hepatoma) and normal mouse fibroblasts (NIH 3T3) has been studied. It was revealed that all the water-based colloidal solutions obtained are non-toxic and possess high NO-induction ability.     

Mössbauer effect studies on the formation of iron oxide phases synthesized via microwave–hydrothermal route

Microwave–hydrothermal (MH) route was employed to synthesize various iron oxide phases in ultra-fine crystalline powders by using ferrous sulphate and sodium hydroxide as starting chemicals. All chemical reactions were carried out under identical MH conditions, namely, at 190°C, 154 psi, 30 min, by varying the molar ratio (MR) of FeSO₄/NaOH in the aqueous solutions. The variation of MR has a dramatic effect on the crystallization behavior of various phases of iron oxides under MH processing conditions. For example, spherical agglomerates of Fe₃O₄ powder were obtained if MR equal to 0.133 (pH?>?10 sample A). On the other hand non-stoichiometric Fe₃O₄ powders (Sample B) were obtained for all higher MR of FeSO₄/NaOH between 0.133 and 4.00 (6.6?2O₃ powders (sample C) were produced. Fe⁵⁷ Mössbauer spectra were recorded for all the three sets of samples at room temperature. In the case of sample B, temperature dependent Mössbauer spectra were recorded in the range of 77–300 K to understand the non-stoichiometric nature of Fe₃O₄ powders. All these results are discussed in the present paper.     

Structural and photoluminescence properties of terbium-doped zinc oxide nanoparticles

We present in this paper a study of the structural and photoluminescence （PL） properties of terbium （Tb） doped zinc oxide （ZnO） nanoparticles synthesized by a simple low temperature chemical precipitation method, using zinc acetate and terbium nitrate in an isopropanol medium with diethanolamine （DEA） as the capping agent at 60 ℃. The as-prepared samples were heat treated and the PL of the annealed samples were studied. The prepared nanoparticles were characterized with X-ray diffraction （XRD）. The XRD patterns show the pattern of typical ZnO nanoparticles and correspond with the standard XRD pattern given by JCPDS card No. 36-1451, showing the hexagonal phase structure. The PL intensity was enhanced due to Tb^3＋ doping, and it decreased at higher concentrations of Tb^3＋ doping after reaching a certain optimum concentration. The PL spectra of Tb^3＋ doped samples exhibited blue, bluish green, and green emissions at 460 nm （5^D3 - 7^F3）, 484 nm （5^D4 - 7^F6）, and 530 nm （5^D4 - 7^F5）, respectively, which were more intense than the emissions for the undoped ZnO sample. Based on the results, an energy level schematic diagram was proposed to explain the possible electron transition processes.     

Effect of hydrogen plasma implantation on the micro-structure and magnetic properties of hcp-Co_(80)~(57)Fe_4Ir_(16) thin films

We present detailed investigations of structural and static/dynamic magnetic properties of hydrogenated hcpCo_(80)~(57)Fe_4Ir_(16) soft magnetic thin films. Two different kinds of defects, i.e., destructive and non-destructive, were demonstrated by controlling the negative bias voltage of the hydrogenation process. Our results show that the structure and magnetic properties of our sample can be tuned by the density of the induced defects. These results provide better understanding of the hydrogenation effect and thus can be used in the future for materials processing to meet the requirements of different devices.