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Magnetic resonance imaging of isolated single liposome by magnetic resonance force microscopy.

Magnetic resonance imaging (MRI) is very useful spectroscopy to visualize a three-dimensional (3D) real structure inside the sample without physical destruction. The spatial resolution of the readily available MRI spectrometer is, however, limited by a few ten to hundreds of microns due to a technological boundary of generating larger magnetic field gradient and to the insensitivity inherent to the inductive signal detection. Magnetic resonance force microscopy (MRFM) is new alternative MRI spectroscopy which is anticipated to significantly surpass the conventional MRI in both resolution and sensitivity. We report two imaging experiments on our MRFM spectrometer operated at room temperature and in vacuum approximately 10(-3)Pa. One is for approximately 20 microm liposome membrane labeled entirely by a nitroxide imaging agent and the other for approximately 15 microm DPPH particles, both are nearly the same size as that of human cell. The reconstructed images at spatial resolution approximately 1 microm were in satisfactory agreement with the scanning electron microscope images. The potential capability of visualizing intrinsic radicals in the cell is suggested to investigate redox process from a microscopic point of view.

Biphenyl Compounds↗

In vivo detection limits of magnetically labeled embryonic stem cells in the rat brain using high-field (17.6 T) magnetic resonance imaging.

Stem cell transplantation is a promising therapeutic approach for several neurological disorders. However, it has yet to fulfill its high expectations, partially due to the lack of a reliable noninvasive method for monitoring the biodistribution of the grafted stem cells in vivo. We have used high-resolution magnetic resonance imaging (MRI) at 17.6 T, combined with efficient magnetic labeling of the stem cells with iron oxide nanoparticles, in order to assess the in vivo detection limit in small animal models. Injection of different concentrations of magnetically labeled stem cells in gel phantoms led to significant reductions in image intensity from small cellular clusters of less than 10 cells. To determine the detection limit in vivo, various numbers of both labeled and unlabeled cells were injected stereotactically into the striatum of rats. Significant hypointense signal changes were observed for 100 labeled cells. After injection of approximately 20 labeled cells, signal reduction at the injection site was observed but could not be assigned unambiguously to the cells. Our results show that high-field MRI allows tracking of a minimal number of cells in vivo, well below the number used in previous studies, opening the possibility of gaining new insights into cell migration and differentiation.

Animals↗

Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation.

OBJECTIVE: Comparison of functional magnetic resonance imaging (fMRI) representational maps, that were generated during voluntary thumb abduction, hand dorsiflexion and foot elevation to amplitude maps of motor-evoked potentials (MEPs) elicited by single transcranial magnetic stimulation (TMS) administered to cortical motor representation areas of the muscles of the thenar eminence, extensor carpi radialis and tibialis anterior muscles. METHODS: Stimulus locations that produced maximal motor-evoked potential amplitudes were compared to fMRI activation maxima in three-dimensional (3D)-space and in a 2D-projection using a novel technique that allowed fMRI activation sites to be projected onto the surface of the brain. RESULTS AND CONCLUSIONS: When analyzing pooled data from all target muscles, the location of projected fMRI and TMS activation maxima on the cortical surface differed by an average 13.9 mm. The differences in 3D distances were particularly large for representation areas of lower leg muscles. 3D distances between fMRI activation maxima and highest MEP site in TMS correlated significantly with higher TMS thresholds. These observations strongly suggest that higher TMS excitation thresholds and lower MEP amplitudes are largely due to the absolute distance between the stimulation site and the excitable cortical tissue targeting this muscle. After the projection 4 out of 5 representation sites as evaluated by TMS were located anterior to the fMRI activation maxima, an observation which may due to the orientation of the magnetic field induced by the current in the coil. The representation sites as evaluated with both methods were specific for the type of movement: distances between representation maxima of the same movements were significantly smaller than those within different movements. Nevertheless, fMRI and TMS provide complementary information, which is discussed on the basis of the functional map observed with both methods.

Adult↗

Localization of the motor hand area using transcranial magnetic stimulation and functional magnetic resonance imaging.

OBJECTIVE: The anatomical location of the motor area of the hand may be revealed using functional magnetic resonance imaging (fMRI). The motor cortex representation of the intrinsic hand muscles consists of a knob-like structure. This is omega- or epsilon-shaped in the axial plane and hook-shaped in the sagittal plane. As this knob lies on the surface of the brain, it can be stimulated non-invasively by transcranial magnetic stimulation (TMS). It was the aim of our study to identify the hand knob using fMRI and to reveal if the anatomical hand knob corresponds to the hand area of the motor cortex, as identified by TMS, by means of a frameless MRI-based neuronavigation system. METHODS: Suprathreshold transcranial magnetic stimuli were applied over a grid on the left side of the scalp of 4 healthy volunteers. The motor evoked potentials (MEPs) were recorded from the contralateral small hand muscles, and the centers of gravity (CoG) of the MEPs were calculated. The exact anatomical localization of each point on the grid was determined using a frameless MRI-based neuronavigation system. In each subject, the hand area of the motor cortex was visualized using fMRI during sensorimotor activation achieved by clenching the right hand. RESULTS: In all 4 subjects, the activated precentral site in the fMRI and the CoG of the MEP of all investigated muscles lay within the predicted anatomical area, the so-called hand knob. This knob had the form of an omega in two subjects and an epsilon in the other two subjects. CONCLUSIONS: TMS is a reliable method for mapping the motor cortex. The CoG calculated from the motor output maps may be used as an accurate estimation of the location of the represented muscle in the motor cortex.

Adult↗

Surface modulation of magnetic nanocrystals in the development of highly efficient magnetic resonance probes for intracellular labeling.

High-quality biocompatible magnetic iron oxide (Fe3O4) nanocrystals were developed through a ligand exchange process of hydrophobically capped nanocrystals with hydrophilic molecules. By simple modulation of the nanocrystal surface ligand charge properties, we have been able to prepare magnetic nanocrystals with excellent intracellular labeling capabilities that efficiently label a variety of cell types without the need for additional transport facilitating agents. The excellent intracellular labeling capability of the newly developed cationic WSIO has further led to successful MRI monitoring of the migration of neural stem cells in rat spinal cord. The magnetic nanocrystals developed here have great potential in applications for labeling of various cell types and also the monitoring of cell-based medical treatments and cancer metastasis.

Cell Line, Tumor↗

Gold and gold-iron oxide magnetic glyconanoparticles: synthesis, characterization and magnetic properties.

The preparation, characterization and the magnetic properties of gold and gold-iron oxide glyconanoparticles (GNPs) are described. Glyconanoparticles were prepared in a single step procedure in the presence of aqueous solution of thiol functionalized neoglycoconjugates and either gold salts or both gold and iron salts. Neoglycoconjugates of lactose and maltose disaccharides with different linkers were used. Iron-free gold or gold-iron oxide GNPs with controlled gold-iron ratios were obtained. The average core-size diameters are in the range of 1.5-2.5 nm. The GNPs are fully characterized by (1)H NMR spectrometry, transmission electron microscopy (TEM), and UV-vis and X-ray absorption (XAS) spectroscopies. Inductive plasma-atomic emission spectrometry (ICP) and elemental analysis gave the average number of neoglycoconjugates per cluster. The magnetic properties were measured in a SQUID magnetometer. The most remarkable results was the observation of a permanent magnetism up to room temperature in the iron-free gold GNPs, that was not present in the corresponding gold-iron oxide GNPs.

Ferric Compounds↗

In vivo phenotyping of the ob/ob mouse by magnetic resonance imaging and 1H-magnetic resonance spectroscopy.

OBJECTIVE: We studied ob/ob and wild-type (WT) mice to characterize the adipose tissues depots and other visceral organs and to establish an experimental paradigm for in vivo phenotyping. RESEARCH METHODS AND PROCEDURES: An in vivo evaluation was conducted using magnetic resonance imaging and 1H-magnetic resonance spectroscopy (1H-MRS). We used T1-weighted images and three-dimensional spin echo T1-weighted images for the morphological analysis and 1H-MRS spectra on all body mass, as well as 1H-MRS spectra focalized on specific lipid depots [triglyceride (TG) depots] for a molecular analysis. RESULTS: In ob/ob mice, three-dimensional evaluation of the trunk revealed that approximately 64% of the volume consists of white adipose tissue, which is 72% subcutaneous and 28% visceral. In vivo 1H-MRS showed that 20.00 +/- 6.92% in the WT group and 58.67 +/- 6.65% in the ob/ob group of the total proton content is composed of TG protons. In in vivo-localized spectra of ob/ob mice, we found a polyunsaturation degree of 0.5247 in subcutaneous depots. In the liver, we observed that 48.7% of the proton signal is due to water, whereas in the WT group, the water signal amounted to 82.8% of the total proton signal. With the sequences used, the TG amount was not detectable in the brain or kidneys. DISCUSSION: The present study shows that several parameters can be obtained by in vivo examination of ob/ob mice by magnetic resonance imaging and 1H-MRS and that the accumulated white adipose tissue displays low polyunsaturation degree and low hydrolipidic ratio. Relevant anatomical alterations observed in urinary and digestive apparatuses should be considered when ob/ob mice are used in experimental paradigms.

Adipose Tissue↗

Cerebral abnormalities in patients with cirrhosis detected by proton magnetic resonance spectroscopy and magnetic resonance imaging.

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child-Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 +/- .17) and white (.35 +/- .22) matter voxel were reduced significantly (P < .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 +/- .11; white matter, .64 +/- .16). In addition, patients showed a significant reduction (P = .024) in white matter choline/creatine ratio (.77 +/- .27) compared with controls (.92 +/- .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P < .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy (P < .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N-acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal-systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.

Adult↗

Methods for magnetically labeling stem and other cells for detection by in vivo magnetic resonance imaging.

Superparamagnetic iron oxide (SPIO) nanoparticles are being used for intracellular magnetic labeling of stem cells and other cells in order to monitor cell trafficking by magnetic resonance imaging (MRI) as part of cellular-based repair, replacement and treatment strategies. This review focuses on the various methods for magnetic labeling of stem cells and other mammalian cells and on how to translate experimental results from bench to bedside.

Animals↗

Encapsulation of recombinant cells with a novel magnetized alginate for magnetic resonance imaging.

Implanting recombinant cells encapsulated in alginate microcapsules to express therapeutic proteins has been proven effective in treating several mouse models of human diseases (neurological disorders, dwarfism, hemophilia, lysosomal storage disease, and cancer). In anticipation of clinical application, we have reported the synthesis and characterization of a magnetized ferrofluid alginate that potentially allows tracking of these microcapsules in vivo by magnetic resonance imaging (MRI). We now report the properties of these ferrofluid microcapsules important for applications in gene therapy. When a mouse myoblast cell line was encapsulated in these microcapsules, it showed similar viability as in regular unmodified alginate capsules, both in vitro and in vivo, in mice. The permeability of these magnetized microcapsules, a critical parameter for immunoisolation devices, was comparable to that of classic alginate in the transit of various recombinant molecules of various molecular masses (human factor IX, 65 kDa; murine IgG, 150 kDa; and beta-glucuronidase, 300 kDa). When followed by MRI in vitro and in vivo, the ferrofluid microcapsules remained intact and visible for extended periods, allowing quantitative monitoring of microcapsules. At autopsy, the ferrofluid microcapsules were mostly free within the intraperitoneal cavities, with no overt inflammatory response. Serological analyses demonstrated a high level of biocompatibility comparable to that of unmodified alginate. In conclusion, ferrofluid-enhanced alginate microcapsules are comparable to classic alginate microcapsules in permeability and biocompatibility. Their visibility and stability to MRI monitoring permitted qualitative and quantitative tracking of the implanted microcapsules without invasive surgery. These properties are important advantages for the application of immunoisolation devices in human gene therapy.

Alginates↗

Magnetic resonance imaging of implanted melanomas before and after chemotherapy. Relation to 31P magnetic resonance spectroscopy and tumor histology.

The early effects of in vivo platinum-rhodamine (PtR) chemotherapy on tumor high-energy phosphorous metabolism was investigated using phosphorus-31 (31P) magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI), and histologic examination in a subcutaneously implanted hamster melanoma model. PtR was chosen because of its potential antimitochondrial and antineoplastic properties. All melanomas were clearly observed on both T1- and T2-weighted images (T1WI and T2WI), with viable tumor regions generally characterized by low to intermediate intensity on T1WI and high intensity on T2WI. Necrotic regions were more variable in appearance, depending on the amount of cystic fluid and hemorrhage. No changes were detected on either T1WI or T2WI within 90 minutes of a tumoristatic dose of PtR (40 mg/kg) by visual examination, but slight differences were seen on calculations of relative signal intensities. However, this same dose of PtR caused a 50% drop in tumor ATP and phosphocreatine content (relative to Pi) measured by 31P MRS within 90 minutes of drug injection. Magnetic resonance spectroscopy appears to offer a sensitive means of detecting the earliest biochemical effects of chemotherapeutic agents that are known to affect tumor bioenergetics.

Animals↗

Evaluation of the effects of high dose irradiation on canine thigh muscle by follow-up magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate alterations of proton T1 and T2 relaxation times and phosphorus metabolites of canine thigh muscle tissue after high dose x-ray irradiation by follow-up magnetic resonance imaging (MRI) and phosphorus-31 (31P) magnetic resonance spectroscopy (MRS). METHODS: A group of 20 dogs was used for MRI and in vivo 31P MRS. Single doses of 5,000 and 10,000 cGy were delivered to the right thigh muscle of groups of 10 dogs each. All MRI and 31P MRS examinations were performed before irradiation and 1, 7, 14, 28, 42, and 56 days after irradiation. For measurement of T1, repetition time (TR) was measured at 300, 500, 1000, 1500, 2000 msec and echo time (TE) was fixed at 12 msec. Also, for measurement of T2, TE was measured at 20, 40, 60, and 80 msec and TR was fixed at 2000 msec. Image selected in vivo spectroscopy (ISIS) pulse sequence was used to obtain 31P MR spectra. Peak areas for each phosphorus metabolite were measured using a Marquart algorithm. RESULTS: Magnetic resonance imaging signal began to change at 28 days after a single dose of 10,000 cGy, whereas there was no significant MRI signal change until 56 days after a single dose of 5,000 cGy. Also, extensive MRI signal changes were observed at 42 days after a single dose of 10,000 cGy. Significant correlation was established between T2 and a lapse of time although there was no correlation between T1 and a lapse of time. T2 value increased substantially corresponding to the time period after x-ray irradiation. Although MR spectral change was not observed until 42 days after a single dose of 5,000 cGy, it began at 14 days after a single dose of 10,000 cGy. And, significant MR spectral changes were observed at 28 and 42 days. Inorganic phosphate and phosphodiesters signal intensities increased while phosphocreatine signal intensity decreased. The pH value was 7.22 +/- 0.05 at control, and 6.98 +/- 0.04 at 42 days after a single dose of 10,000 cGy. CONCLUSIONS: The postirradiation follow-up MRI and 31P MRS studies demonstrated that morphologic and metabolic changes were dependent upon the x-ray dose and a lapse of time.

Animals↗

Evaluation of gall bladder carcinoma with dynamic magnetic resonance imaging and magnetic resonance cholangiopancreatography.

The objective of this study is to evaluate the efficacy of dynamic MRI with magnetic resonance cholangiopancreatography (MRCP) in the preoperative assessment of gall bladder carcinoma. Magnetic resonance imaging and MRCP were carried out in 15 patients with gall bladder carcinoma before surgery and the imaging findings correlated with surgical and pathological findings. Gall bladder carcinoma manifested as focal or diffuse wall thickening in 73% (11/15) and as a mass replacing the gall bladder in 27% (4/15). All tumours showed enhancement in the early phase, which persisted into the delayed phase. The sensitivity and specificity of MRI with MRCP in detecting hepatic invasion, lymph node metastasis and bile duct invasion was 87.5 and 86%, 60 and 90%, and 80 and 100%, respectively. Magnetic resonance imaging correctly diagnosed duodenal invasion in only 50% and in none of the two patients with peritoneal metastasis. In conclusion, dynamic MRI with MRCP is an accurate and a reliable method of showing gall bladder carcinoma and in assessing its local and regional extent as part of preoperative assessment.

Adult↗

Combined magnetic resonance imaging and proton magnetic resonance spectroscopy of patients with acute stroke.

BACKGROUND AND PURPOSE: The prospect for a therapeutic window for treatment of ischemic stroke encourages the noninvasive investigation of metabolic changes in acute ischemia. Recently, localized proton spectroscopy became available at 1.5-T magnetic resonance systems. In this study we evaluated the usefulness of combined magnetic resonance imaging and spectroscopy on the diagnosis of acute and chronic infarctions. METHODS: Combined magnetic resonance imaging and spectroscopy investigations were carried out with a 1.5-T system in 16 volunteers, eight patients with chronic infarction (greater than 8 months), and 10 patients with acute ischemic stroke (less than 8 hours). We used a stimulated echo sequence to acquire localized spectra from image-guided volumes of interest (16-27 ml). RESULTS: There were no significant interindividual differences of choline, creatine, phosphocreatine, and N-acetyl aspartate resonances in the spectra from volunteers. In chronic infarctions, N-acetyl aspartate was decreased in relation to choline. Acute ischemic infarctions were characterized by decreased N-acetyl aspartate resonances and elevation of lactate. CONCLUSIONS: The study demonstrates the feasibility of proton spectroscopy in stroke patients. Metabolic alterations in ischemic tissue can be monitored and can distinguish acute from chronic lesions.

Aged↗

Brain abscess and glioblastoma identified by combined proton magnetic resonance spectroscopy and diffusion-weighted magnetic resonance imaging--two case reports.

The differential diagnosis between brain abscesses and necrotic tumors such as glioblastomas is sometimes difficult to establish by conventional computed tomography and magnetic resonance imaging. Combined proton magnetic resonance spectroscopy (1H-MRS) and diffusion-weighted magnetic resonance imaging (DWI) were used to establish the preoperative diagnosis of brain abscess and glioblastoma. DWI visualized the brain abscess as a homogeneous hyperintense lesion and 1H-MRS revealed the presence of acetate, lactate, and amino acids and the absence of the normal brain components. DWI sometimes shows glioblastoma as a hyperintense lesion, but 1H-MRS reveals markedly increased lactate and decreased N-acetyl-aspartate. Combined DWI and 1H-MRS findings can distinguish brain abscess and glioblastoma.

Acetates↗

[The progress in diagnostic imaging for staging of bladder and prostate cancer: endorectal magnetic resonance imaging and magnetization transfer contrast].

We retrospectively studied the staging accuracy of endorectal magnetic resonance imaging (MRI) in comparison with transrectal ultrasound examination (TRUS) for 71 localized bladder cancers and 19 localized prostate cancers (PC) radically resected. The accuracy of clinical staging for bladder cancer in endorectal MRI and TRUS was 85.9% and 69.2%, respectively. The presence or absence of the continuity of submucosal enhancement on T2-weighted MRI images could be useful for the staging of bladder cancer. The accuracy of the seminal vesicular invasion for prostate cancer in endorectal MRI and TRUS was 95% and 63%, respectively. To determine whether magnetization transfer contrast (MTC) provides additional information in the diagnosis of prostate cancer, the magnetization transfer ratios (MTRs) were calculated in 22 patients with PC, 5 with benign prostatic hyperplasia (BPH) and 4 controls. The mean MTR in the peripheral zone of the normal prostate (8.0% +/- 3.4 [standard deviation]) showed a statistically significant decrease relative to that in the inner zone of the normal prostate (27.4% +/- 3.4, p < 0.01), BPH (25.5% +/- 3.7, p < 0.01), pre-treatment PC (30.6% +/- 5.9, p < 0.01), and PC after hormonal therapy (20.3% +/- 6.3, p < 0.01). The mean MTR in pre-treatment PC was significantly higher than that in BPH, or in PC after hormonal therapy (p < 0.01). MTC was considered to be useful for conspicuity of prostate cancer lesion.

Gadolinium DTPA↗

A comparison of magnetization transfer ratio, magnetization transfer rate, and the native relaxation time of water protons related to relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Magnetization transfer (MT) imaging and measurements of the magnetization transfer ratio (MTR) have extended our capability to depict and characterize pathologic changes associated with multiple sclerosis (MS). We wanted to investigate whether the analysis of other MT parameters, such as magnetization transfer rate (k(for)) and relative measure of water content (T1(free)), adds insight into MS-related tissue changes. METHODS: Quantitative MT imaging by use of phase acquisition of composite echoes was performed in nine patients with clinically definite relapsing-remitting MS and eight healthy control subjects on a 1.5-T MR system. We analyzed a total of 360 regions of interest and compared control white matter with various types of lesions and normal-appearing white matter in MS. RESULTS: We found a strong correlation between the MTR and k(for), but this relation was non-linear. A slight but significant reduction of the MTR in normal-appearing white matter of patients with MS was attributable to a reduced transfer rate only, whereas a lower MTR was associated with both a reduction of k(for) and an increase of T1(free) in regions of dirty white matter. Moreover, areas such as edema and T1-isointense lesions had a similar MTR but could be differentiated on the basis of Tl(free). CONCLUSION: Estimates of k(for) and T1(free) appear to complement MTR measurements for the understanding of MT changes that occur with different types of MS abnormalities in the brain.

Adult↗

Magnetization transfer contrast in magnetic resonance imaging.

Magnetization transfer contrast (MTC) in magnetic resonance imaging (MRI) is the result of selectively observing the interaction of bulk water protons with the protons contained in macromolecules of a tissue. Since different tissues have different macromolecular compositions, the MTC can generate very high tissue contrast that is based on well-defined physiochemical properties. This is accomplished by combining a saturation transfer technique with standard MRI procedures. The specific practical and theoretical aspects of saturation transfer as it applies to the generation of MTC are reviewed and discussed. In the last 3 years, MTC has been applied to the study of the body, with useful applications demonstrated in evaluating the morphology of the knee joint, eye, brain, breast, and heart. The application of MTC to accentuate MR angiography and contrast agent studies has also been demonstrated. Thus, MTC is becoming another tool towards maximizing the quality and diagnostic potential of MRI. Recent studies on isolated macromolecules have suggested that the MTC effect is specific to the surface chemistry and correlation time of the macromolecules. These latter results indicate that the magnetization transfer process may provide a unique quantitative method of MR tissue characterization based on macromolecule dynamics and chemistry.

Animals↗