Regional distribution of manganese found in the brain after injection of a single dose of manganese-based contrast agents

Manganese (Mn) complexes are unstable and dissociate in vivo. Because of the release of this metal, there exists some concern about the potential long-term neurotoxicity associated with the use of Mn-based contrast agents. This latter problem arises because manganese is known to accumulate in specific regions of the brain of people intoxicated by this metal. It was previously demonstrated that Mn can accumulate in the mice brain after administration of 5 μmol/kg of MnCl₂, Mn-diethylenetriaminepentaacetate (Mn-DTPA), or Mn-dipyridoxal diphosphate (Mn-DPDP). In order to better characterize the behavior of Mn complexes after administration, this study assesses the regional distribution of Mn in the brain after i.v. injection of a single dose of MnCl₂ or Mn-DTPA. Male Wistar rats received an i.v. injection of 5 μmol/kg of ⁵⁴Mn as MnCl₂ or Mn-DTPA. The rats were killed at one and two weeks post exposure. The distribution of the radioactivity in the slices was monitored by autoradiography. For both MnCl₂ or Mn-DTPA, we observed that the radioactivity was dispersed in the entire brain, but the radioactivity was higher in several regions. No difference was observed between MnCl₂ or Mn-DTPA in the regional distribution of Mn, and no difference was observed between the two times of exposure (1 week or 2 weeks). The uptake of Mn was minimal in corpus callosum. Maximal Mn concentration was observed in the hippocampal region, thalamus, colliculi, amygdala, olfactory nuclei, and cerebellum.     

NMRON studies of the quasi-2-dimensional ferromagnet 54Mn-Mn(COOCH3)2·4H2O

Pulsed and continuous wave NMRON, and NMR thermally detected by Nuclear Orientation have been used to investigate the magnetic properties of the quasi-2-dimensional ferromagnet ⁵⁴Mn-Mn(COOCH₃)·4H₂O. The NMR frequencies of both the ⁵⁴Mn spins and the abundant ⁵⁵Mn spins have been determined for the two crystalline lattice sites Mn1 and Mn2. The line widths of the ⁵⁴Mn resonances are homogeneously broadened to about 300 kHz, and the ⁵⁵Mn resonances are significantly pulled down in frequency. The spin-lattice relaxation times in low applied magnetic fields are short with T₁ for the Mn2 site being much less than the value for the Mn1 site. Level crossing is observed between the Mn1 and Mn2 resonances in an applied field of 2.6 T. This revised version was published online in August 2006 with corrections to the Cover Date.     

Mri measurements of T1, T2 and D for gels undergoing volume phase transition

Gels consist of crosslinked polymer network swollen in solvent. The network of flexible long-chain molecules traps the liquid medium they are immersed in. Some gels undergo abrupt volume change, a phase transition process, by swelling-shrinking in response to external stimuli changes in solvent composition, temperature, pH, electric field, etc. We report that during volume phase transition changes of NMR longitudinal relaxation time T(1), NMR transverse relaxation time T(2), and diffusion coefficient D of the PMMA gel, and D of the NIPA gel. We describe how the gels were synthesized and the reason of using the snapshot FLASH imaging sequence to measure T(1), T(2), and D. Since T(1), T(2) and D maps have identical field of view and data are extracted from identical areas from their respective maps, these values can be correlated quantitatively on a pixel-by-pixel basis. Thus a complete set of NMR parameters is measured in-situ: the gels are in their natural state, immersed in the liquid, during the phase transition. The results of spectroscopic method agree with that of snapshot FLASH imaging method. For the PMMA gel T(1), T(2) and D decrease when gels undergo volume phase transition between deuterated acetone concentration of 30% and 40%. At its contracted state, T(1) is reduced to a little less than one order of magnitude, T(2) over two orders of magnitude, and D over one order of magnitude, smaller from values of PMMA gel at the swollen state. At an elevated temperature of 54 degrees C the thermosensitive NIPA gel is at a contracted state, with its D reduced to almost one order of magnitude smaller from that of the swollen NIPA at room temperature.     

Relaxation efficacy of paramagnetic and superparamagnetic microspheres in liver and spleen

A distinct knowledge of the relationship between physiochemical properties, cellular distribution and relaxation efficacy of particulate MR contrast media is needed for the development of tissue specific contrast compounds. To study these relations paramagnetic gadolinium labelled microspheres and superparamagnetic iron oxide microspheres (MSM) were injected intravenously to rats. The T1 and T2 relaxation times of the liver and spleen were recorded and the gadolinium tissue content quantified. A clear relationship between the gadolinium dose and the gadolinium concentration of the liver and spleen was observed while the T1 of the tissues remained unchanged. After injection of MSM, T2 of liver and both T1 and T2 of spleen decreased dose-dependently. The splenic relaxation efficacy of MSM was higher compared with that of liver, probably due to the morphology of the spleen allowing a scattered cellular sequestration of MSM. To mimic a uniform tissue distribution of the contrast agents, the liver and spleen samples were homogenized and a marked increase in the intrinsic relaxation efficacy of both the paramagnetic and superparamagnetic microspheres was observed.     

Oxygen-sensitive 19F NMR imaging of the vascular system in vivo

The fluorine nuclear magnetic resonance spin-lattice relaxation rate (1/T1) of the perfluorochemical blood substitute perfluorotripropylamine (FTPA) is very sensitive to oxygen tension. This presents the possibility of measuring blood oxygen tension by 19F MR imaging. We obtained oxygen-sensitive 19F NMR images of the circulatory system of rats infused with emulsified FTPA. Blood oxygenation was assessed under conditions of both air- and 100% O2-breathing. T1 relaxation times were derived from MR images using a partial saturation pulse sequence. The T1 times were compared with a phantom calibration curve to calculate average blood pO2 values in the lung, liver, and spleen. The results showed marked, organ-specific increases in blood oxygen tension when the rat breathed 100% O2 instead of air.     

Relaxivities of magnetoliposomes: The effect of cholesterol

We present relaxivities measurements for both the longitudinal and transverse relaxations of two types of liposomes loaded with ultra small superparamagnetic iron oxide nanoparticles. The magnetoliposome systems presented are soybean phosphatidylcholine liposomes, with and without cholesterol, in the phospholipid bilayer with different molar ratios lipid:cholesterol. In fact, cholesterol is needed to obtain stable liposomes for intravenous administration. The longitudinal and transverse relaxivities were measured with a NMR spectrometer in a 7 T magnetic field. For the studied concentrations, the liposomes show a negligible effect on the longitudinal relaxation time T₁ of the medium, but they are very efficient on decreasing the transverse relaxation time T₂, the behaviour one expects for a negative CA. We observed a lower transverse relaxivity for the magnetoliposome nanosystem with cholesterol, which strongly decreases with the cholesterol content in the liposome bilayer.     

Changes of relaxation times T1 and T2 in rat tissues after biopsy and fixation

NMR spectroscopical measurements of relaxation times were conducted on muscle, intestine, fatty tissue and cerebral cortex and white matter of the rat at various time intervals following removal of the tissue. It appeared that most tissues can be stored at 4 degrees C up to 24 hours without noticeable effects on NMR relaxation parameters. Exceptions are the T2 of muscle and the T1 and T2 of intestine, which tended to change in the first hour after biopsy. Relaxation parameters change considerably after fixation of the tissues. Therefore the effects of fixation have to be taken into account when carrying out NMR measurements on fixed tissues.     

Relaxivities of human liver and spleen ferritin

Ferritin, the iron-storing protein of mammals, is known to darken T₂-weighted magnetic resonance images. This darkening can be used to noninvasively measure an organ's iron content. Significant discrepancies exist between T₂ data obtained with ferritin-containing tissues and with aqueous solutions of horse spleen ferritin (HSF). The NMR properties of stable human ferritin have never been studied in aqueous solutions. Relaxometry results on human liver and spleen ferritin are reported here, showing that the relaxation induced in aqueous solutions by human ferritins is comparable to that induced by HSF. As a consequence, the differences between ferritin-containing human tissues and ferritin solutions cannot be attributed to different NMR properties of human and horse ferritins, but probably to a clustering of the protein in vivo.     

Gadolinium oxide: a protoype agent for contrast enhanced imaging of the liver and spleen with magnetic resonance

Gd2O3 particles (less than 2 microns) in suspension were evaluated as a potential contrast agent for liver-spleen imaging with magnetic resonance. The agent was administered IV to rabbits in doses ranging from 10 to 120 mumol/kg and the tissues removed after sacrifice for in vitro T1 and T2 analysis. The temporal response was determined in liver and spleen samples of rabbits given a fixed dose (60 mumol/kg) and sacrificed at intervals from 15 min to 60 hr later. Documentation of the subanatomic location of Gd2O3 particles in tissue was accomplished by electron microscopy and x-ray dispersion microanalysis. T1 weighted images were obtained at 0.12T on a prototype resistive scanner. The liver, spleen, and lung relaxation times are very responsive to Gd2O3 IV and the effect is dose related. A peak effect is observed between 3-7 hr after injection and relaxation times may normalize by 60 hr. By electron microscopic and x-ray analysis, Gd2O3 is most prominently found in the hepatic and splenic sinusoids. The images show marked enhancement of liver and splenic tissues, aiding in the clear delineation of these tissues from neighboring structures.     

Spin-wave description of nuclear spin-lattice relaxation in Mn12O12 acetate

In response to recent nuclear-magnetic-resonance (NMR) measurements on the molecular cluster Mn12O12 acetate, we study the nuclear spin-lattice relaxation rate 1/T(1), developing a modified spin-wave theory. Our microscopic new approach, which is distinct from previous macroscopic treatments of the cluster as a rigid spin of S=10, not only excellently interprets the observed temperature and applied-field dependences of 1/T(1) for 55Mn nuclei but also strongly supports the 13C NMR evidence for spin delocalization over the entire molecule.     

T1rho Dispersion profile of rat tissues in vitro at very low locking fields

The purpose of this study was to show the T(1rho) dispersion profile in various rat tissues (liver, brain, spleen, kidney, heart and skeletal muscle) at low (0.1 T) B(0) field at very low locking field B1, starting from 10 microT. The T(1rho) dispersion profile showed a quite similar pattern in all tissues. The highest R(1rho) relaxation rates were seen in the liver and muscle followed by the heart, whereas the values for spleen, kidney and brain were rather similar. The greatest difference between R2 relaxation rate and R(1rho) relaxation rate at B1=10 microT was seen in the liver and muscle. The steepest slope for a dispersion curve was seen in the muscle. The value of T(1rho) approximately approached the value of T2 when the locking field B1 approached 0. Except for the liver, the calculated apparent relaxation rate R2' was slightly larger than the calculated one. The potential value of T(1rho) imaging is to combine high R1 contrast of low-field imaging with the high signal-to-noise ratio (SNR) of high static field imaging. T(1rho) relaxation and dispersion data presented in the current study help to optimize the rotating-frame MR imaging.     

Two-phase character of metallic ferromagnetism in manganites

(55)Mn NMR spectra of several ferromagnetic manganites, including La(0.7)Ca(0.3)MnO(3) and La(0.7)Sr(0.3) MnO(3), were measured as a function of temperature. A thorough analysis of the spin-spin relaxation and the NMR line shape revealed that in these compounds two different ferromagnetic phases coexist below T(C) in a certain temperature interval which depends on the composition. The phase with lower hyperfine field has faster nuclear relaxation, its characteristic dimension is a few nm, and its volume decreases with decreasing temperature. The NMR lines of both phases are motionally narrowed, i.e., the electron holes are mobile.     

NMR study of water exchange across the hepatocyte membrane

An understanding of the cellular permeability for water is needed to evaluate MR images of complex tissues, such as liver, and to interpret the effects of contrast agents. To obtain data essential for such an understanding we measured water exchange across the isolated rodent hepatocyte membrane by proton NMR relaxation with dextranmagnetite as a relaxation agent. The results are treated as water exchange in a two-compartment system, and possible reasons for deviations from that behavior are analyzed. The mean residence time of intracellular water was approximately 40 ms at 37 degrees C. We found the lower limit for the diffusional permeability of the hepatocyte membrane to be 8 x 10(-3) cm s-1. These results, combined with consideration of hepatic anatomy indicate that the failure to observe effects on the T1 of liver from particulate contrast agents such as magnetite, Gd-starch, and liposome encapsulated Mn2+ is due to the localization of these agents in the Kupffer cells. Also, the nonexponential T1 decay observed in normal liver is unlikely to be due to slow exchange of water between compartments.     

Effect of hyperosmotic mannitol on magnetic resonance relaxation parameters in reperfused canine myocardial infarction

To determine how administration of a hyperosmotic agent alters regional nuclear magnetic resonance (NMR) relaxation parameters and imaging characteristics in ischemic-reperfused myocardium, 7 dogs were infused with mannitol for 15 minutes before and after the release of a 3 hour left anterior descending coronary artery (LAD) occlusion. Nine control animals received normal saline during the 3 hour occlusion and 1 hour reperfusion periods. Normal posterior left ventricular (LV) wall and the ischemic anterior LV wall (risk area) myocardium was sampled for calculation of segmental microsphere myocardial blood flow, % tissue water content, NMR relaxation times (T1, T2) and myocyte ultrastructure using electron microscopy. Mean infarct T1 values were 14% greater than normal segments in saline-treated controls, but only 5% greater after mannitol. The difference in tissue water content between infarcted and normal segments was 4% in saline-treated (83 vs. 79%) compared to 2% in mannitol-treated dogs (79 vs. 77%). T1, T2 and % water content of control infarct segments were greater than treated infarcts (p less than 0.01). T1 and T2 rose as occlusion flow fell below 0.5 ml/min/g in control hearts but did not rise until flows were reduced to 0.1 ml/min/g in mannitol-treated hearts. Areas of increased signal in T1 and T2 NMR images correlated well with histochemical infarct volume (r = 0.98, SEE = 1.1 cc) in mannitol-treated dogs, but infarct borders were qualitatively less well-defined than in controls. We concluded that mannitol (1) diminishes tissue edema and reduces NMR relaxation parameters (T1, T2) in infarcted myocardium; and (2) attenuates the rise in T1 and T2 and ultrastructural myocyte injury in ischemic-reperfused myocardium.     

Effect of a gadodiamide contrast agent on the reliability of brain tissue T1 measurements

To determine whether brain spin-lattice relaxation time (T1) can routinely be measured after contrast-agent injection, we measured T1 by a precise and accurate inversion-recovery (PAIR) method in five brain tumor patients, before and again after contrast-agent injection. The T1 in at least 20 regions of interest (ROIs) was measured in each patient, avoiding areas of contrast enhancement visible by conventional MR imaging. Contrast-agent injection reduced T1 in 51 regions of interest in white matter by less than 1% (not significant), and in 50 regions of interest in gray matter by less than 2% (p = 0.001). Pixel-by-pixel plots demonstrate that T1 is reduced substantially in extra-parenchymal tissues, but not in brain tissues. Therefore, T1 mapping with the precise and accurate inversion-recovery method can routinely be done after contrast injection. Our results suggest that the precise and accurate inversion-recovery method is not sensitive to the T1 of blood in the presence of an intact blood-brain barrier, although a substantial T1 reduction does occur in the absence of a blood-brain barrier.     

氟喹诺酮类抗菌药物与过渡金属离子Cr3+, Mn2+和Fe3+形成配合物配位位置的研究

通过1D ¹H NMR, ¹³C NMR和1H自旋-晶格弛豫时间T₁对氟喹诺酮类抗菌药物与过渡金属离子Cr³⁺, Mn²⁺和Fe³⁺形成配合物的位置进行了研究, 合成了固体配合物对其进行了元素分析. 实验结果表明过渡金属离子Cr³⁺, Mn²⁺和Fe³⁺与氟喹诺酮类抗菌药物形成1∶2的配合物, 并确定了配位位置.     

pH-sensitive paramagnetic liposomes as MRI contrast agents: in vitro feasibility studies.

A novel type of pH-sensitive paramagnetic contrast agent is introduced; a low molecular weight gadolinium (Gd) chelate (GdDTPA-BMA) encapsulated within pH-sensitive liposomes. The in vitro relaxometric properties of the liposomal Gd chelate were shown to be a function of the pH in the liposomal dispersion and the membrane composition. Only a minor pH-dependency of the T1 relaxivity (r1) was observed for liposomal GdDTPA-BMA composed of the unsaturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (OA). On the other hand, the r1 of GdDTPA-BMA encapsulated within saturated dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomes demonstrated a strong pH-dependency. At physiological pH and above, the r1 of this system was significantly lowered compared to that of non-liposomal Gd chelate, which was explained by an exchange limited relaxation process. Lowering the pH below physiological value, however, gave a sharp and 6-7 fold increase in r1, due to liposome destabilisation and subsequent leakage of entrapped GdDTPA-BMA. The pH-sensitivity of the DPPE/PA liposome system was confirmed in an in vitro magnetic resonance imaging (MRI) phantom study.     

Methodology for the measurement and analysis of relaxation times in proton imaging

Measurements of proton T1 and T2 were performed on GdCl3 solutions (20 less than T2 less than 500 msec, 90 less than T1 less than 1000 msec) on large-bore NMR imaging systems operating at 1.0T and 1.5T. CPMG multi-echo (ME), multiple saturation recovery (MSR) and modified fast inversion recovery (MFIR) pulse sequences as well as a sequence that combines and interleaves T1 and T2 weighted data acquisition (which we call "multiple saturation-recovery multiple-echo" (MSRME) were used. The relaxation data are compared to those obtained on a small bore NMR spectrometer operated at 1.5T. T1 and T2 values for the solutions were found to be the same within 10% for the two fields. Reproducibility of measurements of T1, T2 and the unnormalized spin density of the solutions was better than 5%. Systematic errors, amenable to correction through calibration, are noted in the imager T1 and T2 values. T1 and T2 values for some typical neural tissues at 1.5T and body tissue at 1.0T for human volunteers were obtained and are tabulated.     

T1rho dispersion of rat tissues in vitro.

The purpose of this study was to demonstrate T1rho dispersion in different rat tissues (liver, brain, spleen, kidney, heart, and skeletal muscle), and to compare the 1/T1rho data to previous 1/T1 data and magnetization transfer of rat tissues at low (0.1 T) B0 field. The 1/T1rho dispersion showed a fairly similar pattern in all tissues. The highest 1/T1rho relaxation rates were seen in liver and muscle followed by heart, whereas the values for spleen, kidney, and brain were quite similar. Compared to 1/T2 relaxation rate, the greatest difference was seen in liver and muscle. The rank order 1/T1rho value at each locking field B1 was the same as the transfer rate of magnetization from the water to the macromolecular pool (Rwm) for liver, muscle, heart, and brain. The potential value T1rho imaging is to combine high T1 contrast of low field imaging with the high signal to noise ratio of high static field imaging. When the T1rho value for a given tissue is known, the contrast between different tissues can be optimized by adjusting the locking time TL. Further studies are encouraged to fully exploit this. Targets for more detailed research include brain infarct, brain and liver tumors.     

The effect of ultrasound treatment on the interaction of brine with pork meat proteins

The objective of the study is to elucidate the effect of ultrasound treated salt solution on curing of pork meat. The interactions of salt (NaCl) solutions of 3 and 25% with the proteins of pork meat are studied. High intensity ultrasound operating at 20 kHz was used. The differential scanning calorimetry (DSC), NMR spin-spin relaxation time, unfrozen water and water diffusion coefficient measurements were carried out in meat cured with ultrasound treated and untreated salt solutions. The effect of ultrasonication was most evident from measured spin-spin relaxation times T₂₁, the rate of chemical exchange of water protons k and the amount of unfrozen water W_unf in the meat. The measured diffusion coefficient of water D_w in meat cured with ultrasound treated and control salt solution did not show significant difference. The nuclear magnetic resonance (NMR) relaxation data, differential scanning calorimetry (DSC) and the diffusion coefficient data reliably show that the possible action of ultrasound to salt solution was manifested on the first 2 days of the experiment with a 3% salt solution.