Ingested manganese chloride as a contrast agent for magnetic resonance imaging

Solutions of manganese chloride were force-fed to Sprague-Dawley rats. Magnetic resonance (MR) imaging was performed on (a) syringes containing different concentrations of manganese chloride, (b) rats after force feeding and (c) livers excised after sacrifice of the force-fed rats. Imaging was done with a 0.15-T resistive magnet. Multiple pulse sequences were used and T1 values were calculated. The signal intensity and T1 value obtained from a solution depended on the manganese concentration and the pulse sequence employed. At higher concentrations, no signal was produced due to extreme T2 shortening. Absorbed manganese affected the signal intensities and T1 values of the rats' livers. By appropriate selection of manganese concentration and pulse sequence, ingested manganese can serve as a combined gastrointestinal and hepatic MR contrast agent.     

Choice of contrast enhancement index for dynamic magnetic resonance mammography

Indices are often used in dynamic MRI of the breast to quantitate signal enhancement within suspicious lesions. Two indices are commonly used: one calculates the difference in pre- and postcontrast signal intensity, normalised to a base-line signal intensity such as that of fat (which does not enhance) whilst the other calculates the ratio of pre- to postcontrast signal intensity. The results of a computational simulation are presented which demonstrate the superiority of the normalised signal difference index, based on the criterion that the best index is that which is least influenced by initial tissue T₁. This hypothesis was tested by comparing the two indices in a group of patients with clinical or mammographic suspicion of recurrent breast carcinoma. Of 37 patient examinations using Gadolinium enhanced MRI of the breast, 11 patients showed 13 lesions with some degree of enhancement, which were subsequently diagnosed histologically as either benign or malignant. The normalised signal difference index showed no overlap between the benign and malignant groups, whereas some overlap was observed with the signal ratio index. The clinical findings are therefore consistent with the results of the computational simulation.     

Assessment of acute myocardial infarction in man with magnetic resonance imaging and the use of a new paramagnetic contrast agent gadolinium-bopta

To assess the feasibility of and characterize the new paramagnetic contrast agent gadolinium-BOPTA/dimeglumine (Gd-BOPTA) to detect acute myocardial infarctions with MR imaging, 24 patients (53.3 ± 8.3 yr) were examined 9.3 ± 3.6 days after a first myocardial infarction. Short-axis T₁-weighted and T₂-weighted MR imaging was performed at three slice levels. T₁-weighted images were obtained before, immediately after, 15, 30, and 45 min after injection. Patients received either 0.05 or 0.1 mmol/kg body weight Gd-BOPTA. Images were qualitatively and quantitatively analyzed. Two patients showed no signs of infarction on T₂-weighted images as opposed to contrast-enhanced T₁-weighted images. Contrast-to-noise ratio was not affected by the dosage level. Signal intensity (SI) of normal to infarcted myocardium was significantly improved by both dosages (p < .0005) but a dosage of 0.05 mmol/kg produced significantly higher SI inf/norm (1.42 ± 0.07 vs. 1.34 ± 0.06, respectively, p = .015). SI of normal and infarcted myocardium enhanced immediately after administration of 0.05 mmol/kg (29.3 ± 5.1% and 53.8 ± 9.6% respectively), which decreased thereafter to 5.3 ± 4.8% and 40.2 ± 8.5% respectively, at 45 min (p < .002 for normal myocardium). SI enhancement immediately after 0.1 mmol/kg Gd-BOPTA showed no decrease within the first 45 min. Gd-BOPTA enables the detection of myocardial infarction. Optimal infarct delineation is achieved from 15 to 45 min after administration of 0.05 mmol/kg body weight Gd-BOPTA. Gd-BOPTA at 0.05 mmol/kg does improve image quality as measured by contrast-to-noise ratio and SI enhancement as compared to 0.10 mmol/kg.     

Synthesis and electron paramagnetic resonance study of a nitroxide free radical covalently bonded on aminopropyl-silica gel

A solid spin-labeled material was obtained starting from 2-chloro-3,5-dinitro-N-(4-(2,2,6,6-tetramethyl-piperidine-1-oxyl)-benzamide) and aminopropyl-silica gel. Stability tests showed that even after several months the spin-labeled material had the same properties as immediately after synthesis. EPR properties of the TEMPO-derivatized silica were studied as a function of solvent polarity and temperature. Rotational correlation times were calculated from EPR spectra and correlated with solvent characteristics and temperature. Polar solvents induce a fast motion of the spin-label, clearly seen in the EPR spectra by the apparition of the well-known TEMPO radical triplet. The solid spin-labeled (dry) sample showed a high interspin interaction, which can be disrupted not only by different (liquid) solvents, but also by absorption of different solids, like cyclodextrins, dendrimers or polyethyleneglycols. Also, changes induced by the temperature were studied in the case of toluene wet sample. From 150 to 370 K, the spectrum is changing from a slow motion spectrum type to a fast motion regime. The preparative procedures to obtain the spin-labeled silica as well as some of its parameters are described.     

Mn[III] uroporphyrin I: a novel metalloporphyrin contrast agent for magnetic resonance imaging.

We have used an intracranial 9L rat brain tumor model to determine whether a novel metalloporphyrin, Mn[III] uroporphyrin I (MnUROP-I), could function as an intravenous MRI contrast agent for brain tumors. In several experiments, 24 male Fischer 344 rats were inoculated intracranially with 9L brain tumor cells. On day 15 postinoculation, animals were anesthetized and the femoral vein exposed. Prior to the intravenous injection of the contrast agent, a precontrast scan (1 Tesla in a standard head coil) was performed. Thirty min after injection of the contrast agent, a postcontrast scan was performed. Although there was only a suggestion of abnormality on the precontrast scans, the presence of tumor was visibility enhanced in the postcontrast scans. In 3 animals scanned at 24 hr postinjection, persistent tumor enhancement was demonstrated. Measured tumor sizes on the MRI scans were consistent with sizes measured at autopsy and histologically. These results demonstrate that MnUROP-I is an effective MRI contrast agent for the detection of an intracranial brain tumor in the rat model.     

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.     

Quantitative assessment of Gd-DTPA contrast agent from signal enhancement: an in-vitro study

Quantitative determination of in-vivo gadolinium diethylenetriamine-pentaacid (Gd-DTPA) concentration is attractive in various studies involving perfusion, tracer kinetics and permeability constants. Using a 1.5 T clinical system and a 7 T small-bore system, we evaluated a method for absolute determination of Gd-DTPA concentrations in plasma solutions. Different solutions of Gd-DTPA and (99m)Tc-DTPA were mixed in human plasma and concentrations in the range of 0-5.0 mmol/l (1.5 T system) or 0-3.0 mmol/l (7 T system) of Gd-DTPA were divided into thirteen tubes. All MRI measurements were carried out using conventional sequences (SE, FLASH and GRASS). The MR measured intensity was converted to Gd-DTPA concentration by mathematical interpretation of the sequences. All MRI sequences showed, that the measured concentrations of Gd-DTPA revealed a slight non-linear difference compared with the calculated Gd-DTPA concentrations determined by the plasma (99m)Tc-DTPA using gamma counting. This non-linearity was most pronounced at high Gd-DTPA concentrations, suggesting that the discrepancy could be a result of an increased plasma relaxivity at higher concentrations. Adjustment of measured Gd-DTPA concentration was therefore performed using a selected power function, A[Gd-DTPA](a), which yielded the best linear relationship. Regression analysis showed that the scaling constant (A) varied from 0.11 to 97.45 and the power constant (a) varied from 0.83 to 1.6. Based on these constants, the MRI measured concentrations of Gd-DTPA did not differ from the calculated concentrations of Gd-DTPA obtained from reference measurements of (99m)Tc-DTPA. In the 1.5 T system, a linear relationship (r(2) > or = 0.95) was demonstrated in the range of 0-5.0 mmol/l Gd-DTPA, and in the 7 T system, a linear relationship (r(2) > or = 0.92) was demonstrated in the range of 0-3.0 mmol/l Gd-DTPA. Additionally, the effect of signal-to-noise on measured concentrations of Gd-DTPA was simulated using MR data of the mixed solutions of Gd-DTPA in plasma and the analytical expression of the pulse sequences. The simulations showed that the concentrations were most sensitive to noise in the GRASS sequence. In conclusion, this study demonstrates a novel approach to quantify accurately the Gd-DTPA concentration directly from MRI signal data using different routine sequences.     

Novel mineral contrast agent for magnetic resonance studies of bone implants grown on a chick chorioallantoic membrane

Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds.     

Nuclear magnetic resonance study of iron overload in liver tissue

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.     

Nuclear magnetic resonance study of the smectic-cholesteric phase transition in a dimesogenic liquid crystal

Nuclear magnetic resonance (NMR) spectroscopy has provided a unique opportunity to study the characteristic smectic-A to chiral nematic phase transition in a dimesogenic liquid crystal (“KI-5S”). The order parameters in the liquid crystalline phases were obtained from the ²H NMR quadrupole splitting and ¹³C NMR chemical shift measurements, manifesting a first-order smectic-nematic phase transition.     

典型荷载条件下淤泥孔径分布特征核磁共振试验研究

模拟了淤泥地基加固工况对应的几种典型荷载效应,并利用核磁共振测试寻求典型荷载水平和速率下,淤泥孔隙及其孔径分布的变化规律,以探讨淤泥地基典型加固条件下微细观结构的三维响应.结果表明:在一定压力作用下,淤泥中最大孔隙数将会减少,应力水平越高,减少量越大,而当冲击荷载达到更高的某一水平时,淤泥中最大孔隙和最小孔隙所占比例均会减小,孔隙更趋于均匀;约束样品的侧限刚度将会增加淤泥土的总受力水平,进而更易减小大孔隙所占比例;当荷载水平680 kPa时,加载速率是决定相对最大孔隙占总孔隙数比例的关键因素,速率较小会使得该比例增大,速率较大则使得该比例减小,其界限值在0.8 MPa/s与1.6 MPa/s之间;一定的冲击荷载和速率水平下,随着作用次数即总能量的提高,淤泥中的相对大孔隙和最大孔隙部分会明显减少,而当间隔时间较短的作用次数再提高时,上述效应会降低;对于有效减少较大孔隙而言,淤泥受冲击的次数存在某个合适的量值.上述规律有助于从内部本质上寻求和掌握各种静动力排水固结法处理淤泥类软基的微观机理,为其科学设计及施工优化提供了进一步的依据.     

Serial magnetic resonance imaging in a non-traumatic rabbit osteonecrosis model: an experimental longitudinal study

We investigated the time-dependent natural course of experimental osteonecrosis (ON), including initial changes in ON and the reparative process, using in vivo serial repetitive magnetic resonance imaging (MRI) in a non-traumatic rabbit serum sickness ON model. Some necrotic lesions were detected at 1 week (3 of 16 femora with necrotic lesions) and some in the metaphysis were detected by 12 weeks (2 of 6 femora with lesions) on T(1)-weighted, T(2)-weighted, and fat suppression T(1)-weighted images. On contrast-enhanced MRI, extravasation of the erythrocytes was detected at 72 h (7 of 26 femora with lesions) as a small, focal enhanced area. Necrotic lesions were detected in all abnormal femora by 6 weeks (16 of 16 femora with lesions) as focal, homogeneously or inhomogeneously enhanced areas. Reparative tissue replaced with new vascular and trabecular formation in necrotic areas was detected as an extended marginal enhanced area at 12 weeks. These results suggest that the enhancement patterns on contrast-enhanced MRI may provide helpful information about the developmental and reparative process of clinical ON.     

Gated magnetic resonance imaging of acute myocardial ischemia in dogs: application of multiecho techniques and contrast enhancement with GD DTPA

ECG gated magnetic resonance images were obtained in six canines prior to and immediately following occlusion of either the LAD or circumflex coronary artery using a surgically placed snare. Multiecho and single-echo acquisition techniques were utilized 0.25 mmol/kg Gd DTPA was injected as an IV bolus 1 hr following coronary artery ligation. In two animals, the region of ischemic myocardium was clearly visualized on multiecho technique without the use of intravenous contrast. The ischemic zone could be best identified on images with a long TE of 120 msec. Contrast enhancement with Gd DTPA enabled visualization of the ischemic myocardium in all six canines. Administration of Gd DTPA, a perfusion agent, improved both detectability and definition of the myocardial lesions.     

The oral administration of MnCl2: A potential alternative to IV injection for tissue contrast enhancement in magnetic resonance imaging

Mn⁺² (as MnCl₂) was administered to rabbits intravenously and orally (a route of administration which based upon our previous experiments in rats⁷ promises to give selective hepatobiliary enhancement with less systemic toxicity). Nuclear magnetic relaxation dispersion or T₁ (NMRD) was performed on selected tissues (heart, liver, kidney, serum, and bile) in both animal groups to examine possible qualitative and semiquantitative differences in T₁ relaxation at equivalent sacrifice times. One animal was given an oral dose of MnCl₂ (620 micromoles/kg) and imaged sequentially (T₁ weighted sequence, .12T) for 30 minutes. The NMRD curves for organ tissues show an increase in relaxation efficacy in the 10–20MHz range characteristic of Mn-macromolecular complexes and are similar irrespective of the route of administration. The lack of increased relaxation enhancement for bile in this frequency range reflects cleavage of this complex upon excretion. Decreased overall relaxation in the liver is observed when oral Mn⁺² is compared to IV Mn⁺² due to the small fraction of administered dose that is absorbed. However, the images document a significant increase in the intensity of liver signal after the oral dose. We suspect this dose may ultimately be adjusted downward to give selective hepatobiliary effects.     

Co-existing responses and stochastic resonance in post-buckled structures: A combined numerical and experimental study

Much of what is known about co-existing responses in nonlinear systems under both deterministic and random dynamic loading is limited to phenomenological investigations of discrete systems, most commonly, the Duffing equation. From these results alone, it is difficult to extrapolate the behavior of the distributed nonlinear systems more commonly seen in real structures such as buckled beams and curved panels. This is because, beyond the simple increase in dimension, real systems bring with them imperfections and more complex forms of energy dissipation. The possibility of co-existing responses, particularly in the case of simultaneous “safe” and “unsafe” solutions (e.g. snap-through and non-snap-through), poses potential problems for engineers as it multiplies the workload, since one must be very careful to ensure that a particular simulation or experiment has captured the most critical response. Even in the case where random forces dominate the overall loading of a system, a situation in which one might anticipate an equally random response, a very small harmonic component can have an influence beyond its proportion. This effect, known as stochastic resonance, is quite counterintuitive to the analyst more familiar with linear systems where the principles of superposition and scalar multiplication of solutions make this impossible. In this paper, the effect of the damping and noise level on the number of co-existing responses in nonlinear systems is investigated. Stochastic resonance is also demonstrated, first with a double-well Duffing oscillator, and then it is shown to exist experimentally, we believe for the first time, on a macroscopic structure, that being, an (imperfect) buckled beam.