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Nuclear magnetic resonance study of doxorubicin binding to cardiolipin containing magnetically oriented phospholipid bilayers.

Doxorubicin (DOX) is a potent anthracycline cancer drug whose interaction with anionic membrane phospholipids, such as cardiolipin (CL), is thought to contribute to its cytotoxicity as well as induce cardiotoxic side effects. We have studied the interaction of DOX with a CL containing model membrane system using high resolution, oriented sample (31)P and (2)H NMR. The model membrane system is composed of a bilayer forming phospholipid and a detergent that breaks the extended bilayers into disc-shaped micelles (bicelles) that can orient in a magnetic field. The effects of DOX on the phospholipid bilayer were monitored using samples containing dimyristoylphosphatidylcholine (DMPC), selectively deuterated in either headgroup or acyl chain positions, and measuring the changes in (2)H quadrupolar splittings as DOX was added. Changes in quadrupolar splittings upon DOX addition provide evidence for interaction with both surface and buried sites within the membrane bilayer.

Cardiolipins↗

Axonal damage in multiple sclerosis plaques: a combined magnetic resonance imaging and 1H-magnetic resonance spectroscopy study.

The purpose of this study was to compare magnetic resonance imaging (MRI) features and proton MR spectroscopy (1H-MRS) patterns of multiple sclerosis (MS) plaques in order to define the metabolic substrate in different lesion subtypes. Combined MRI and single-voxel 1H-MRS investigation was performed in 54 MS patients (47 relapsing remitting (RR) and seven secondary progressive (SP)). Sixty-seven MS lesions were selected. Thirty-seven lesions were Gadolinium (Gd) enhancing (nine isointense and 28 hypointense on pre-contrast T(1)-weighted scans) and 30 Gd unenhancing (six isointense and 24 hypointense on pre- and post-contrast T(1)-weighted scans). Choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate were evaluated in 1H spectra acquired from MS plaques and from normal white matter (NWM) of 22 neurological controls. MS lesions of RR patients were characterized by a significant increase of Cho/Cr and decrease of NAA/Cr and NAA/Cho ratios. No significant metabolite changes were found in lesions of SP patients. Gd enhancing plaques showed lactate signal with higher frequency (37.8%) than Gd unenhancing plaques (16.7%) (p=0.04). A significant increase of Cho/Cr was found in Gd enhancing lesions when compared to controls (p<0.01), and to Gd unenhancing lesions (p<0.05). In particular, there was evidence of a significant increase of Cho/Cr in pre-contrast T(1) hypointense Gd enhancing lesions (p<0.01 vs. controls). The Gd unenhancing lesions (p<0.01), in particular the T(1) hypointense group (p<0.05), showed a significant decrease of NAA/Cr only when compared to controls. These data confirm that in vivo MRS indicates key pathological features of MS plaques. The increased Cho/Cr ratio found in Gd-enhancing plaques, in particular in the T(1) hypointense lesions, may reflect increased membrane cell turnover. The T(1) hypointense Gd unenhancing plaques better reflect axonal damage, as suggested by the decrease of NAA/Cr. Nevertheless, the lack of statistical differences in NAA/Cr between plaque subgroups suggests that axonal impairment might occur even in the early stages.

Adolescent↗

Nuclear magnetic resonance characterization of the myristoylated, N-terminal fragment of ADP-ribosylation factor 1 in a magnetically oriented membrane array.

The behavior of the N-terminal fragment of human ADP-ribosylation factor 1 (ARF1) in a membranelike environment is described. This is accomplished using heteronuclear liquid crystal NMR techniques in a magnetically oriented membrane array on a selectively 13C- and 15N-labeled peptide. After full assignment of the labeled sites, residual dipolar couplings (13C-13C, 15N-1H and, 13C-15N) and chemical shift anisotropy effects (amide 13C and 15N) were measured. The experimental data were interpreted using order matrix calculations to yield orientational and dynamic information for four separate, rigid amide planes. The experimental data obtained proves that the amphipathic peptide interacts with the bilayer in a mode that is consistent with an alpha-helix having its axis parallel to the membrane surface. Possibilities of extending the employed techniques to larger and uniformly labeled systems are discussed.

ADP-Ribosylation Factor 1↗

Magnetic susceptibility tensor and heme contact shifts determinations in the Rhodobacter capsulatus ferricytochrome c': NMR and magnetic susceptibility studies.

The 1H and 15N resonances of the carbon monoxide complex of ferrocytochrome c' of Rhodobacter capsulatus, a ferrous diamagnetic heme protein, have been extensively assigned by TOCSY-HSQC, NOESY-HSQC, and HSQC-NOESY-HSQC 3D heteronuclear experiments performed on a 7 mM sample labeled with 15N. Based on short-range and medium-range NOEs and H(N) exchange rates, the secondary structure consists of four helices: helix 1 (3-29), helix 2 (33-48), helix 3 (78-101), and helix 4 (103-125). The 15N, 1HN, and 1H(alpha) chemical shifts of the CO complex form are compared to those of the previously assigned oxidized (or ferric) state. From the chemical shift differences between these redox states, the orientation and the anisotropy of the paramagnetic susceptibility tensor have been determined using the crystallographic coordinates of the ferric state. The chi-tensor is axial, and the orientation of the z-axis is approximately perpendicular to the heme plane. The paramagnetic chemical shifts of the protons of the heme ligand have been determined and decomposed into the Fermi shift and dipolar shift contributions. Magnetic susceptibility studies in frozen solutions have been performed. Fits of the susceptibility data using the model of Maltempo (Maltempo, M. M. J. Chem. Phys. 1974, 61, 2540-2547) are consistent with a rather low contribution of the S = 3/2 spin state over the range of temperatures and confirm the value of the axial anisotropy. Values in the range 10.4-12.5 cm(-1) have been inferred for the axial zero-field splitting parameter (D). Analysis of the contact shift and the susceptibility data suggests that cytochrome c' of Rb. capsulatus exhibits a predominant high-spin character of the iron in the oxidized state at room temperature.

Cytochrome c Group↗

The evaluation of human breast lesions with magnetic resonance imaging and proton magnetic resonance spectroscopy.

PURPOSE: MR spectroscopy (MRS) assists in lesion characterization and diagnosis when combined with magnetic resonance imaging (MRI). Cancerous lesions demonstrate elevated composite choline levels arising from increased cellular proliferation. Our study investigated if MR spectroscopy of the breast would be useful for characterizing benign and malignant lesions. MATERIALS AND METHODS: Single voxel proton MR spectroscopy (MRS) was acquired as part of an MR imaging protocol in 38 patients referred upon surgical consultation. The MR spectra were read independently in a blinded fashion without the MR images by three spectroscopists. The MRI exam was interpreted in two settings: (a) as a clinical exam with detailed histories and results from previous imaging studies such as mammography or ultrasound included and (b) as a blinded study without prior histories or imaging results. RESULTS: Elevated choline levels were demonstrated by MRS in 19 of the 23 confirmed cancer patients. The sensitivity and specificity for determining malignancy from benign breast disease with MRS alone were 83 and 87%, respectively, while a blinded MRI review reported 95 and 86%, respectively. CONCLUSIONS: Proton MR spectroscopy provides a noninvasive, biochemical measure of metabolism. The technique can be performed in less than 10 min as part of an MRI examination. MRI in combination with MRS may improve the specificity of breast MR and thereby, influence patient treatment options. This may be particularly true with less experienced breast MRI readers. In exams where MRI and MRS agree, the additional confidence measure provided by MRS may influence the course of treatment.

Adolescent↗

[Diagnostic value of combined conventional magnetic resonance imaging and magnetic resonance angiography in sinus venous thrombosis].

25 patients are presented, who were diagnosed with cerebral sinus venous thrombosis by a combination of Magnetic Resonance Angiography (MRA) and conventional Spin-Echo sequences. An angiography in DSA technique was carried out additionally in 12 cases. In 24 patients MR-angiographic control examinations were conducted. In seven cases MRA revealed an isolated thrombosis of the superior sagittal sinus (SSS) whereas in eleven patients there was an additional occlusion of other sinuses or cerebral veins. The transverse sinus (ST) was the second most affected. DSA essentially confirmed the MR-imaging data. Despite anticoagulation follow up MRA's showed complete recanalisation in only 7 patients, in 8 cases partial recanalisation was observed and in 9 cases a complete occlusion persisted. In contrast to these findings neurological examinations during the follow up period were unremarkable in 16 patients and the remainder revealed only mild residual symptoms. In general no further morphological alterations of the cerebral sinus system were detectable by MRA after 6 months. Follow up imaging beyond 6 months therefore appears unnecessary, unless a relapse is suspected.

Adolescent↗

Diffusion-weighted magnetic resonance imaging and magnetic resonance spectroscopy in the evaluation of focal cerebral tubercular lesions.

PURPOSE: To review magnetic resonance (MR) diffusion-weighted imaging (DWI) and spectroscopy findings in patients with focal cerebral tuberculosis and to assess whether these techniques can adequately characterize focal cerebral tubercular lesions. MATERIAL AND METHODS: Sixteen patients with single or multiple lesions were evaluated on a 1.5T MR system. DWI was performed with three 'b' values of 50, 500, and 1000 s/mm2 and the apparent diffusion coefficient maps were calculated. MR spectroscopy was performed using the point-resolved single-voxel technique with 2 echo time values of 135 ms and 270 ms. The signal intensities of the tubercular lesions on diffusion images and the apparent diffusion coefficients (ADCs) of their centers, along with MR spectroscopy findings, were analyzed in relation to their T2-weighted MR appearances. RESULTS: DWI identified 17 of the 20 lesions evaluated. Increased signal intensity was seen in 9 of the 17 lesions. The ADCs of the lesions ranged from 0.406 to 2.64 x 10(-3) mm2/s (mean +/- SD: 1.038 +/- 0.609 mm2/s). Most of the lesions with hyperintense centers on T2-weighted images were of increased intensity on diffusion images, while those with hypointense centers on T2-weighted images were of decreased signal intensity on diffusion images. However, no statistical difference in the ADCs was found between lesions with increased and those with decreased signal intensity centers on T2-weighted images. MR spectroscopy revealed a lipid peak at 0.9-1.3 ppm in all of the 14 lesions evaluated. An increase in normalized choline:creatine ratio was found in all the lesions in which the spectra were obtained with the voxel, including a variable portion of the lesion wall. CONCLUSION: DWI and MR spectroscopy help in determining the nature of cerebral tubercular lesions; however, since the findings are varied, they do not help in specific characterization.

Adolescent↗

Sturge-Weber syndrome: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy findings.

We report on the diffusion magnetic resonance imaging (MRI) and proton MR spectroscopy findings of a 26-year-old female patient with Sturge-Weber syndrome. Echo-planar trace diffusion MRI revealed mildly high signal intensity changes at parieto-occipital lobes on b = 1000 s/mm2 images, suggesting restricted diffusion. On corresponding apparent diffusion coefficient maps, those areas had moderately high signal intensity and high apparent diffusion coefficient values (around 0.9 x 10(-3) mm2/s) compared with the contralateral symmetrical normal side of the brain (0.776 x 10(-3) mm2/s). This finding was consistent with increased motion of water molecules (disintegration of the neural tissue) in these regions. Proton MR spectroscopy revealed decreased N-acetyl aspartate and increased choline peaks, indicating disintegration of neural tissue associated with neuronal loss as well.

Adult↗

Comparison of thermal damage calculated using magnetic resonance thermometry, with magnetic resonance imaging post-treatment and histology, after interstitial microwave thermal therapy of rabbit brain.

Clinical application of high-temperature thermal therapy as a treatment for solid tumours requires an accurate and close to real-time method for assessing tissue damage. Imaging methods that detect structural changes during heating may underestimate the extent of thermal damage. This is due to the occurrence of delayed damage manifested at tissue locations exposed to temperatures lower than those required to cause immediate structural changes. An alternative approach is to measure temperature and then calculate the expected damage based on the temperature history at each tissue location. Magnetic resonance (MR) imaging methods now allow temperature maps of the target and surrounding tissues to be generated in almost real-time. The aim of this work was to evaluate whether thermal damage zones calculated on the basis of MR thermometry maps measured during heating correspond to actual tissue damage as measured after treatment by histological methods and MR imaging. Four male rabbits were treated with high-temperature thermal therapy delivered in the brain by a single microwave antenna operating at 915 MHz. MR scanning was performed before, during and after treatment in a 1.5 T whole-body scanner. Temperature maps were produced using the proton resonance frequency (PRF) shift method of MR thermometry. In addition, conventional T1-weighted and T2-weighted spin-echo images were acquired after treatment. Thermal damage zones corresponding to cell death, microvascular blood flow stasis and protein coagulation were calculated using an Arrhenius analysis of the MR temperature/time course data. The calculated zones were compared with the lesions seen on histopathological examination of the brains which were removed within 6-8 h of treatment. The results showed that calculated damage zones based on MR thermometry agreed well with areas of damage as assessed using histology after heating was completed. The data suggest that real-time calculations of final expected thermal damage based on an Arrhenius analysis of MR temperature data may provide a useful method of real-time monitoring of thermal therapy when combined with conventional T2-weighted images taken after treatment.

Animals↗

Magnetic resonance imaging and magnetic resonance spectroscopy of bone tumors and bone marrow disease.

The authors have made use of an integrated magnetic resonance imaging/spectroscopy (MRI/MRS) examination to study seven patients with a variety of bone tumors. The spatial localization method used in the 31P portion of the examination was surface coil localization and a one-dimensional chemical shift imaging method (3 cases). The authors found that the precision of spatial localization was critical in many of these cases, since most of these bone tumors were surrounded by muscle tissue that contained high concentrations of phosphocreatine (PCr). For this reason, they suggest that the metabolite ratios should be referenced to the adenosine triphosphate (beta-NTP) resonance rather than PCr. The phosphate monoester (PME) to beta-NTP ratio was elevated as compared with normal muscle in all of the bone tumors studied. The authors found that all of these tumors exhibited pHs between 7.0 and 7.2, which are similar to the values found for normal muscle. They also show the feasibility of using a line-selective proton chemical shift imaging sequence with high spatial resolution for investigating changes in the fatty composition of bone marrow. This method is illustrated in an example of a patient with advanced avascular necrosis in the femoral heads.

Adolescent↗

Magnetic starch microspheres, biodistribution and biotransformation. A new organ-specific contrast agent for magnetic resonance imaging.

The biodistribution and elimination of magnetic starch microspheres (MSM) were studied qualitatively and quantitatively by radioiron tracer studies and relaxation time measurements. One hour after injection of MSM (1 mg/kg of Fe), 85% +/- 5% of the dose was accumulated in the liver and 6.5% +/- 1.3% [corrected] in the spleen. The hepatic clearance led to 50% reduction in the T2 relaxation time of liver tissue. This T2 effect was halved after 24 hours and T2 reversed to baseline value within 5 days after injection. The radioiron was gradually cleared from the liver with a t1/2 of 4 to 5 days. Six weeks after injection of MSM, 72% +/- 7% of the radioiron dose was detected in the circulation in a nonsuperparamagnetic form associated with the erythrocytes. The results indicate a redistribution of iron from the liver and spleen via the erythroid bone marrow to the erythrocytes after injection of MSM.

Animals↗

Fusion of cine magnetic resonance and contrast-enhanced first-pass magnetic resonance data in patients with coronary artery disease: a feasibility study.

RATIONALE AND OBJECTIVES: The left ventricle (LV) myocardial wall contractibility can be evaluated using cine magnetic resonance imaging (MRI) in a qualitative or quantitative manner. Meanwhile, myocardial perfusion can be assessed using contrast-enhanced first-pass MRI. The authors propose a method of automatically fusing the complementary information from these two cardiac MRI modalities into one single image, from which a match or mismatch between contraction and perfusion could be extracted. METHODS: The authors developed a registration algorithm based on the combined use of the global affine transformation and intrinsic landmarks to match images from the same sequence or from two imaging sequences. Contraction and perfusion information was fused by combining a myocardial contour image and a parametric image of the slope of the intensity-time curve, respectively. The fusion paradigm was applied to four patients' data as a demonstration of feasibility of the proposed approach and as a preliminary evaluation. RESULTS: Cine MR and contrast-enhanced MR images were well aligned. The contractibility of the LV was displayed by the myocardial contour image. The parametric slope image was consistent with the known coronary artery status of each patient. The combined contraction-perfusion representation of the LV showed the correspondence between regional LV contraction and myocardial perfusion at a one slice level. CONCLUSIONS: Left ventricle contraction and myocardial perfusion can be represented conjointly in one single fused image. The fusion paradigm should be evaluated for a larger number of patients to evaluate the clinical relevance of this approach in assessing coronary artery disease.

Algorithms↗

L-2 hydroxyglutaric aciduria: proton magnetic resonance spectroscopy and diffusion magnetic resonance imaging findings.

A 10-month-old boy was reported with the diagnosis of L-2 hydroxyglutaric aciduria. Amino acid chromatographic analysis revealed an 80-fold increase of hydroxyglutaric acid in the urine. Proton magnetic resonance (MR) spectroscopy of the brain obtained with the hybrid chemical shift imaging sequence (repetition time = 1,500 milliseconds, echo time = 40 milliseconds) revealed prominent peaks resonating at 2.50 ppm, which were attributable to L-2 hydroxyglutaric acid. Diffusion MR imaging was obtained using the echo-planar trace sequence (repetition time = 5,700 milliseconds, echo time = 139 milliseconds). Two different diffusion patterns were evident: a restricted diffusion pattern in the globi pallidi and an increased diffusion pattern in the white matter.

Brain↗

Phenylketonuria: diffusion magnetic resonance imaging and proton magnetic resonance spectroscopy.

Two patients with phenylketonuria are reported with white matter lesions. Diffusion magnetic resonance (MR) imaging revealed restricted diffusion patterns (high signal) on b = 1000 s/mm2 images associated with low apparent diffusion coefficient values ranging between 0.44 x 10-3 mm2/s and 0.56 x 10-3 mm2/s. On proton MR spectroscopy obtained in 1 of the patients, a prominent peak resonating at approximately 3.80 ppm was consistently present attributable to the peak rising from the alpha-proton of the phenylalanine molecule.

Adult↗

Inter- and intratumoral variability in magnetic resonance imaging of pleomorphic adenoma: an attempt to interpret the variable magnetic resonance findings.

OBJECTIVES: The purpose of our study was to describe the various magnetic resonance (MR) findings of pleomorphic adenoma and to interpret these findings. METHODS: MR studies of 33 pleomorphic adenomas and 13 malignant tumors in the major salivary glands were reviewed. RESULTS: High signal intensity on short-inversion-time inversion recovery (STIR) and T2-weighted (T2W) images, progressive enhancement on dynamic MR images, and high apparent diffusion coefficient (ADC) values on diffusion-weighted (DW) images reflected myxoid-dominant components in pleomorphic adenomas. Hypercellularity with less-myxoid stroma showed reduced signal intensity on STIR and T2W images and also reduced ADC values on DW images, and the peak of time versus signal intensity curves (TICs) was reached earlier on dynamic MR images. CONCLUSIONS: The MR images of hypercellularity components in pleomorphic adenoma overlap with those of malignant parotid tumors. Detecting myxoid components by STIR, T2W, DW, and dynamic MR images is useful for predicting whether salivary gland tumors are pleomorphic adenoma or not.

Adenoma, Pleomorphic↗

Combined magnetic resonance tractography and functional magnetic resonance imaging in evaluation of brain tumors involving the motor system.

The goal of neuro-oncologic surgery is to maximize tumor resection while preserving vital brain functions. Identification of the relation between the tumor and adjacent functional cortical areas as well as efferent subcortical white matter tracts is important for preservation of function. Combined diffusion tensor imaging with magnetic resonance (MR) tractography and functional blood oxygen level-dependent MR imaging were applied successfully for preoperative planning and guidance in 2 patients with tumors near the motor cortex. The combination of these novel functional imaging techniques can provide new information for presurgical planning.

Adult↗

In vivo prostate magnetic resonance imaging and magnetic resonance spectroscopy at 3 Tesla using a transceive pelvic phased array coil: preliminary results.

Magnetic resonance (MR) systems operating at 3 Telsa (T) and above have demonstrated considerable potential in human studies, offering improved signal-to-noise ratio and spectral resolution. However, because of radiofrequency limitations and concerns, and the lack of large volume body coils, most studies have been limited to the head. In this study we describe the design and construction of a transceive pelvic phased array coil with which MR images and spectra of the human prostate at 3 T have been obtained. Comparison with 1.5 T instruments with different hardware configurations is difficult; however, in a preliminary comparison the signal-to-noise ratio is improved in phantoms and humans when compared with a 1.5 T receive-only pelvic phased array coil, and high quality spectral resolution is demonstrated through the delineation of the citrate quadruplet in localized 1H prostate spectra. Higher fields offer the potential for MR prostate studies without the use of an endorectal coil.

Adult↗