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Development of an abdominal magnetic resonance (MR) contrast agent formulation with Oral Magnetic Particles (OMP, Ferristene).

A formulation for fast dispersible granules with the magnetic resonance (MR) contrast agent, Oral Magnetic Particles (OMP), was developed. The formulation contained viscosity-increasing agents (xanthan gum and a mixture of microcrystalline cellulose and sodium carboxymethylcellulose). The granules were dispersed easily in water when stirred by hand and became a viscous OMP suspension with apparent homogeneity, but does not form granule aggregates (lump), within 10 min. The dispersibiility was greatly affected by the binder type and addition of disintegrant. Hydroxypropylcellulose and low-substituted hydroxypropylcellulose were preferable. The preparation method to incorporate OMP into the granules also greatly influenced the dispersibility of the granules. A fluidized bed granulation of the base granules containing additives and subsequent coating of OMP onto the granules was eventually utilized. The formulation was able to control the viscosity of the suspension by regulating the content of viscosity-increasing agent while maintaining dispersibility. The developed formulation gave a good MR contrast image in rats and no magnetic susceptibility artifact was observed.

Abdomen↗

A magnetic resonance imaging based method for measurement of tissue iron concentration in liver arterially embolized with ferrimagnetic particles designed for magnetic hyperthermia treatment of tumors.

Rabbit liver was loaded with ferrimagnetic particles of gamma -Fe2 O3 (designed for magnetic hyperthermia treatment of liver tumors) by injecting various doses of a suspension of the particles into the hepatic artery in vivo. Proton transverse relaxation rate (R(2)) images of the livers in vivo, excised, and dissected were generated from a series of single spin-echo images. Mean R(2) values for samples of ferrimagnetic-particle-loaded liver dissected into approximate 1 cm cubes were found to linearly correlate with tissue iron concentration over the range from approximately 0.1 to at least 2.7 mg Fe/g dry tissue when measured at room temperature. Changing the temperature of ferrimagnetic-particle-loaded samples of liver from 1 degrees C to 37 degrees C had no observable effect on tissue R(2) values. However, a small but significant decrease in R(2) was found for control samples containing no ferrimagnetic material on raising the temperature from 1 degrees C to 37 degrees C. Both chemically measured iron concentrations and mean R(2) values for rabbit livers with implanted tumors tended to be higher than those measured for tumor-free liver. This study indicates that tissue R(2) measurement and imaging by nuclear magnetic resonance may have a useful role in magnetic hyperthermia therapy protocols for the treatment of liver cancer.

Animals↗

Magnetic and gold-coated magnetic nanoparticles as a DNA sensor.

In this study, we report the chemical synthesis and functionalization of magnetic and gold-coated magnetic nanoparticles and the immobilization of single-stranded biotinylated oligonucleotides onto these particles. Selected sequences specific to the BRCA1 gene were used as a test platform. The binding of oligonucleotides to these particles was achieved through a streptavidin-biotin bridge via a carbodiimide activation protocol. Particle size and oligonucleotide attachment were confirmed by transmission electron microscopy; oligonucleotide binding was characterized by Fourier transform infrared spectroscopy and hybridization confirmed by fluorescence emission from the fluorophore attached to the target oligonucleotide strand. The rate of hybridization was measured using a spectrofluorometer and a microarray scanner. The rate of hybridization of oligonucleotides bound to the synthesized particles depends on the inorganic support material and its surface chemistry. The rate of hybridization increased concomitantly with the concentration of the probe and the target in the reaction medium. Furthermore, exposure of probe and target oligonucleotide to a combination of target and noncomplementary DNA strand reduced the rate of hybridization, possibly because of steric crowding in the reaction medium and cross-linking between reacting oligonucleotides and the noncomplementary strands. The study undertaken opens several possibilities in bioconjugate attachment to functionalized iron and iron nanocomposite structures for controlled manipulation and handling using magnetic fields.

DNA↗

Simulating the embolization of blood vessels using magnetic microparticles and acupuncture needle in a magnetic field.

Computer models were developed to simulate the capture and subsequent deposition of magnetic microparticles (MMPs) in a blood vessel adjacent to a ferromagnetic wire (e.g., acupuncture needle) magnetized by a uniform external magnetic field. Process parameter conditions were obtained to enable optimal capture of MMPs into the deposit. It was found that the maximum capture distance of the MMPs was within 0.5-2.0 mm when the particles were superparamagnetic and had large size (>1.0 microm) and relative large flow rates (2.5-5.0 cm/s) as in a healthy artery. It was also found that the deposits were asymmetrical and that their size was between 1.0 and 2.0 mm. For the case of lower flow rates as can be found in a tumor (<1.0 mm/s) and using small magnetite particles (0.25-2.0 microm) the maximum capture distance was larger, ranging between approximately 0.5 and 6.4 mm, depending on the blood flow rate, the radius of wire, and particle clustering. The range of embolization (deposition) in this later case was between 0.5 and 5.9 mm. The potential of this technique to generate MMPs deposits to embolize blood vessels inhibiting the blood supply and thus facilitating necrosis of tumors located deep within the patient (3-7 cm) is discussed.

Acupuncture Therapy↗

Fabrication of uniform magnetic nanocomposite spheres with a magnetic core/mesoporous silica shell structure.

A novel kind of magnetic core/mesoporous silica shell nanospheres with a uniform particle diameter of ca. 270 nm was synthesized. The inner magnetic core endues the whole nanoparticle with magnetic properties, while the outer mesoporous silica shell shows high enough surface area and pore volume. The synthesized material is expected to be applied to targeted drug delivery and multiphase separation. The storage and release of ibuprofen into and from the pore channels of the mesoporous silica shell, as a typical example, are demonstrated.

Magnetics↗

Effect of an oscillating magnetic field on the release properties of magnetic collagen gels.

The paper describes the effect of an oscillating magnetic field (OMF) on the morphology and release properties of collagen gels containing magnetic nanoparticles and microparticles and fluorescent drug analogues. Collagen gels were prepared through fibrillogenesis of collagen in the presence of iron oxide magnetic particles averaging 10 nm or 3 mum in diameter and rhodamine-labeled dextran (Dex-R) of molecular weights between 3000-70 000 g/mol. Dextran molecules effectively simulate protein-based drugs, since they have similar molecular weights and dimensions. The paper discusses the effect of an OMF on the release properties of the gels and proposes an empirical model to predict the release rate. It also demonstrates the self-repair capability of collagen gels following the structural damage caused by an OMF.

Animals↗

Voltage-sensitive magnetic gels as magnetic resonance monitoring agents.

Many polymer gels undergo a volume phase transition in electric fields. We report here the synthesis of a polyelectrolyte gel that incorporates magnetic particles of iron oxide into the polymer network; these particles couple the gel volume transition to the NMR relaxation times of the surrounding water. We find that the water proton relaxation rates (T2(-1)) in aqueous suspensions of particles of the magnetic gel increase significantly in an electric field. Such changes can also be induced by the hyperpolarization of red blood cells in the suspension, presumably as a result of the electric fields at the cell membrane surfaces. These gels may play a part in magnetic resonance imaging analogous to that of voltage-sensitive dyes in optical imaging.

Animals↗

Near-field imaging of ultrathin magnetic films with in-plane magnetization.

A new approach to near-field magneto-optical imaging was developed capable of visualization of in-plane magnetization of ultrathin magnetic structures. The approach relies on the magneto-optical effect specific for thin magnetic layers and employs near-field transmission measurements of longitudinal and/or transverse magneto-optical effect arising from the presence of thin film interfaces. The near-field magneto-optical contrast of in-plane domain structure of ultrathin Co film has been demonstrated in different polarization configurations.

Light↗

[Magnetic resonance tomography of focal hepatic lesions using the para-magnetic contrast medium, gadolinium DTPA. First clinical results].

The use of the para-magnetic contrast medium gadolinium DTPA for magnetic resonance tomography of focal lesions in the liver was investigated in 31 patients. Two dosage schedules of the contrast medium (0.1 and 0.2 mmol/kg body weight were used with field strengths of 0.35 and 0.5 Tesla. Using T1 sequences, gadolinium DTPA showed increased signal intensity in the liver and in tumours, but this was significantly more marked in the tumour. On T1 spin-echo sequences, previously iso-intense lesions became visible after administration of contrast. On the other hand, contrast-enhanced lesions were less well seen on inversion recovery sequences because of a reduction in the contrast between tumour and liver tissue. The contrast between tumour and liver tissue was not improved by gadolinium DTPA in comparison with precontrast inversion recovery sequences and T2 spin-echo sequences. The perfusion of intra-hepatic tumours could be elucidated by magnetic resonance tomography after the administration of gadolinium DTPA.

Adult↗

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination.

Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types.

Animals↗

Magnetic source localization in focal epilepsy. Multichannel magnetoencephalography correlated with magnetic resonance brain imaging.

Initial results of magnetic source localization by means of multichannel recording using a 10 or a 31 channel system are reported. Simultaneous magnetoencephalographic (MEG) and electroencephalographic (EEG) (scalp, sphenoidal and foramen oval) recording, as well as magnetic resonance imaging (MRI) with a fixed head position, permits the projection of brain structures and the source localized from MEG into a three-dimensional coordinate system. From 8 patients investigated it can be clearly seen that the method is of diagnostic relevance for patients with temporal lobe epilepsy. Results are demonstrated for 3 patients with interesting findings concerning the anatomical correlation with source localization. The findings indicate that MRI-correlated magnetic source localization by means of multichannel recordings provides important advantages in epilepsy research. (1) Increased precision permits noninvasive localization. Deeper sources in the temporal lobe are localized from MEG combined with scalp or minor invasive EEG. (2) Investigation time is considerably shortened. (3) Single events can be localized for supplementary presurgical information concerning the three-dimensional anatomical localization of focal epileptic activity in the brain.

Adult↗

Electron holography on remanent magnetization distribution of melt-spun Nd-Fe-B magnets.

Microstructures and magnetic domain structures of melt-spun Nd-Fe-B permanent magnets were investigated in detail by analytical electron microscopy and electron holography. While the crystal orientation of matrix Nd2Fe14B grains was analyzed by nanobeam electron diffraction, precipitates of a few tens of nanometers at grain boundaries were identified to be alpha-Fe by energy-dispersive X-ray spectroscopy. The detailed magnetization distribution in Nd2Fe14B grains and at their boundaries was visualized by electron holography. Ex situ experimentation with an electromagnet revealed that the domain walls in the demagnetized state and remanent states were pinned at grain boundaries, and Fe precipitates at the grain boundary were situated at the center of the closure domain.

Boron↗

High spatial resolution functional magnetic resonance imaging at very-high-magnetic field.

Although neuroimaging methods have been used successfully to map large-scale neurocognitive networks distributed across the human cortex, functional mapping and differentiation of localized brain organization within a small structure has been limited by inadequate sensitivity for high spatial resolution imaging. Functional magnetic resonance imaging (fMRI) technique based on blood oxygenation level-dependent (BOLD) contrast has become one of the most useful neuroimaging techniques. It has been used extensively to study human brain function from sensory perception to cognitive performance. However, the majority of these studies used a relatively low spatial resolution (typically with a voxel size of 3.1 x 3.1 x 5.0 mm3), which is incapable of mapping on the millimeter and submillimeter spatial scale. In this article, we review the technical aspects of the high-resolution fMRI technique and the sensitivity and spatial specificity of BOLD-based fMRI. We demonstrate applications of high-resolution fMRI in studying the human visual pathway from the lateral geniculate nucleus in the thalamus to the ocular dominance columns in the primary visual cortex. Most results were obtained at very-high-magnetic fields (3.0 and 4.0 Tesla). They reveal that high-resolution fMRI at very-high-magnetic field is promising for functional mapping of brain organization from large cortical networks, small nuclei, and even to cellular layer structures.

Brain↗

Mini hemoreliable axial flow LVAD with magnetic bearings: part 3: modeling of demo-magnetic bearing and verification.

This paper discusses my previous work on aerospace magnetic bearings during the 1970s and 1980s. Modeling of the magnetic field in the bearing is discussed and stiffness test data are provided, which verifies the model. An LVAD this small was made possible by the use of axial field fringing ring magnetic bearings that are much stronger than the radial field bearings currently used in turbo pumps. The analytical design of a first prototype bearing is discussed in detail that is mainly of interest to bearing designers. Modeling was accurately done without finite element analysis (FEA), which readily provided design insights not easily obtained through FEA. This bearing was not meant to satisfy all specifications of a blood pump. The next prototype, to be reported at the 2001 ASAIO conference, will meet these specifications.

Equipment Design↗

Comparison of T1-enhancing and magnetic susceptibility magnetic resonance contrast agents for demarcation of the jeopardy area in experimental myocardial infarction.

RATIONALE AND OBJECTIVES: This study compared the areas demarcated by a T1-enhancing agent, Gd-DTPA-BMA, and a magnetic susceptibility agent, Dy-DTPA-BMA, with 201thallium autoradiography (indicator of perfusion) and postmortem histochemical staining with triphenyltetrazolium chloride (TTC)(indicator of infarction). METHODS: Thirteen rats were subjected to coronary artery occlusion for 3 to 4 hours before acquisition of four sets of electrocardiogram-gated spin-echo magnetic resonance (MR) images: T1-weighted images before and after 0.2 mmol/kg Gd-DTPA-BMA; and T2-weighted images before and after 0.3 mmol/kg Dy-DTPA-BMA. After MR imaging, intravenous 201thallium delineated the area of decreased myocardial perfusion. At autopsy, TTC staining delineated the area of myocardial infarction. RESULTS: A myocardial region in the distribution of the occluded artery was delinated as a hyperintense area ("hot-spot") by Dy-DTPA-BMA and as a hypointense area ("cold-spot") by Gd-DTPA-BMA. The hyperintense area demarcated by Dy-DTPA-BMA (51 +/- 3% of the area of the midequitorial slice of the left ventricle) showed a closer relationship to the area of decreased myocardial perfusion (jeopardized area) (46 +/- 3%), determined by 201thallium autoradiography, than the area of myocardial infarction (36 +/- 4%), determined by histochemical staining. However, the hypointense area demarcated by Gd-DTPA-BMA (29 +/- 2%) did not relate as closely to the area of decreased myocardial perfusion (slope = 0.54) or the area of myocardial infarction (r = 0.46). CONCLUSIONS: The abnormal myocardial area delineated by the magnetic susceptibility agent showed a closer relationship to the area of deficient myocardial perfusion (jeopardy area) after coronary occlusion than that defined by T1-enhancing contrast media.

Animals↗

Interventional magnetic resonance. Initial clinical experience with a 1.5-tesla magnetic resonance system combined with c-arm fluoroscopy.

RATIONALE AND OBJECTIVES: The authors evaluate the feasibility of performing magnetic resonance (MR) procedures on a 1.5-tesla (T) system combined with conventional c-arm fluoroscopy. METHODS: A 1.5-T MR imaging system was combined with a conventional c-arm fluoroscopy unit in one room. The two systems were connected via a floating table top. Twenty-six interventional procedures (biopsies, MR-portography, percutaneous alcohol injection, laser ablation, fluid aspiration, and breast marking) were performed in 22 patients under MR, fluoroscopic control, or both. For MR guidance, fast gradient echo sequences were used, initiated from a panel at the front of the magnet. Images were displayed on an liquid crystal display screen positioned on the magnet. RESULTS: All MR-guided procedures were performed successfully without complications. The addition of c-arm fluoroscopy was useful for bone interventions and MR-portography. All diagnostic biopsies yielded sufficient amounts of tissue for histologic diagnosis. In breast lesions, the target identified on dynamic MR imaging was marked correctly in each case. In interstitial laser thermotherapy the laser effect could be visualized, and in percutaneous ethanol injection the distribution of the alcohol could be seen. Both imaging systems worked without image distortions and high-quality MR images were obtained. CONCLUSIONS: The combination of a 1.5-T MR imager with a c-arm fluoroscopy system seems to be a promising technical solution for performing interventional MR procedures.

Adult↗

Contrast-enhanced magnetic resonance cholangiography versus heavily T2-weighted magnetic resonance cholangiography.

RATIONALE AND OBJECTIVES: To investigate the feasibility of contrast-enhanced magnetic resonance cholangiography (CE-MRC) and compare it with single-shot turbo spin-echo magnetic resonance cholangiography (SSTSE-MRC). METHODS: Fifteen patients with suspected metastatic liver disease (n = 10) or biliary tree abnormalities (n = 5) underwent a magnetic resonance imaging (1.5-T system) examination before and after mangafodipir administration. Contrast-enhanced MRC with a three-dimensional fast low-angle shot sequence after mangafodipir trisodium administration was compared with SSTSE-MRC. Four anatomic segments were evaluated: the intrapancreatic and extrapancreatic common bile duct segments, the cystic duct, and the area of hepatic bifurcation. Contrast-enhanced MRC and SSTSE-MRC were separately analyzed on a 5-point grading scale in terms of ductal segment visualization and lumen narrowing or dilatation. RESULTS: There was no difference (P = 0.375) in segment visualization between CE-MRC and SSTSE-MRC; 56 of the 60 segments were visualized by both techniques. In the evaluation of ductal narrowing or dilatation, nonsignificant differences (P = 0.500) were observed. Contrast-enhanced MRC was not influenced by fluid superimposition and provided additional information from background tissues. CONCLUSIONS: Contract-enhanced MRC is a feasible technique showing anatomic correlation with SSTSE-MRC, and it can in addition provide functional information. Contrast-enhanced MRC may be used in selected patients when traditional SSTSE-MRC is inconclusive.

Bile Ducts↗