Use of 1H/23Na and 1H/31P double frequency tuned birdcage coils to study in vivo carbon tetrachloride-induced hepatotoxicity in rats.

In vivo 1H and 23Na magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) techniques were used to study CCl4-induced acute hepatotoxicity in rats in situ. One or two hours following exposure to CCl4, a localized edematous region was detected in the liver by 1H MRI. The CCl4-induced edema was localized in a region surrounding the hepatic portal vein. With the use of a 23Na/1H double frequency tuned bird-cage imaging coil an increase in Na+ ion flux was also observed in the same region as the edematous region detected by 1H-MRI. Pretreatment with alpha-phenyl-tert-butyl nitrone (PBN), a free radical spin trap, 30 min prior to CCl4 exposure, was found to reduce the CCl4-induced edematous response in the liver observed in either 1H or 23Na-NMR images. Inhibition of the CCl4-induced edematous response in rat liver by PBN demonstrates that free radical intermediates, arising from the metabolism of CCl4, are possibly the key causal agents in the initiation of the edematous response. In addition, with the use of a 31P/1H double frequency tuned bird-cage imaging/spectroscopy coil, localized 31P spectra (ISIS) were obtained from the regions of CCl4-induced "tissue damage" observed in the 1H-MRI images. The most notable changes observed from the 31P spectra were an increase in inorganic phosphate (Pi) and a decrease in hepatocytosolic pH in the CCl4-treated rat livers in comparison to saline-treated control livers.     

Proton magnetic resonance imaging and phosphorus-31 magnetic resonance spectroscopy studies of bromobenzene-induced liver damage in the rat.

Respiratory-gated proton magnetic resonance imaging was used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity in the perihilar region of the liver was seen 24-48 hr after an intraperitoneal injection of bromobenzene. Localized proton magnetic resonance spectra from within this region indicated that the increased proton signal intensity was not due to accumulation of fat in the liver, but primarily due to a longer T2 for the proton resonance of water. This is consistent with acute edema in this localized region. In vivo 31P magnetic resonance spectroscopy studies of the same rat livers in situ were performed. Spectroscopic conditions were determined whereby localized, quantitative 31P spectra could be obtained. Using these methods, 10 mmol/kg bromobenzene was found after 24 hr to cause a number of statistically significant (p less than 0.05) effects: a decrease in adenosine 5'-triphosphate levels from 4.1 +/- 0.5 to 3.0 +/- 0.5 mM, a decrease in phosphodiester levels from 11.3 +/- 0.9 to 9.3 +/- 0.7 mM and an increase in the phosphomonoesters from 3.0 +/- 0.4 to 5.5 +/- 1.2 mM (mean +/- standard deviation). High resolution in vitro 31P spectra of perchloric acid extracts of these rat livers showed that the increased phosphomonoester resonance was due to a selective 4.3-fold increase in phosphocholine. Thus, our in vivo and in vitro 31P magnetic resonance spectra are consistent with the hypothesis that a phosphatidylcholine-specific phospholipase C (generating phosphocholine and diacylglycerol) is activated during tissue damage. Both the imaging and spectroscopy results obtained with bromobenzene closely resemble CCl4-induced liver changes previously reported, and may reflect a generalized response of the liver to any acutely acting toxic chemical.     

In vivo K, Na and H MR imaging using a triple resonant RF coil setup

The maintenance of a gradient of potassium and sodium ions across the cell membranes is essential for the physiological function of the mammal organism. The measurement of the spatial distribution of pathologically changing ion concentrations of ²³Na and ³⁹K with magnetic resonance imaging offers a promising approach in clinical diagnostics to measure tissue viability. Existing studies were focused mainly on ²³Na imaging as well as spectroscopy with only one post-mortem study for ³⁹K imaging. In this paper a triple resonant RF coil setup for the rat head at 9.4 T is presented for imaging of both nuclei (²³Na and ³⁹K) and the acquisition of anatomical proton images in the same experiment without moving the subject or the RF coil. In vivo MR images of ³⁹K and ²³Na in the rat brain were acquired as well as anatomical proton images in the same scanning session.     

Liver imaging at 1.5 tesla: pulse sequence optimization based on improved measurement of tissue relaxation times

In order to predict the most sensitive MR imaging sequence for detecting liver metastases at 1.5 T, in vivo measurements of T1 and T2 relaxation times and proton density were obtained using multipoint techniques. Based on these measurements, two-dimensional contrast contour plots were constructed demonstrating signal intensity contrast between hepatic lesions and surrounding liver parenchyma for different pulse sequences and pulse timing parameters. The data predict that inversion recovery spin echo (IRSE) imaging should yield the greatest contrast between liver metastases and liver parenchyma at 1.5 T, followed by short tau inversion recovery (STIR) and spin-echo (SE) pulse sequences. T2-weighted SE images provided greater liver/lesion contrast than T1-weighted SE pulse sequences. Calculated T1, T2, and proton density values of the spleen were similar to those of hepatic metastatic lesions, indicating that the signal intensity of the spleen may be used as an internal standard to predict the signal intensity of hepatic metastases on T1- and T2-weighted images at 1.5 T.     

Multi-channel metabolic imaging, with SENSE reconstruction, of hyperpolarized [1-(13)C] pyruvate in a live rat at 3.0 tesla on a clinical MR scanner

We report metabolic images of (13)C, following injection of a bolus of hyperpolarized [1-(13)C] pyruvate in a live rat. The data were acquired on a clinical scanner, using custom coils for volume transmission and array reception. Proton blocking of all carbon resonators enabled proton anatomic imaging with the system body coil, to allow for registration of anatomic and metabolic images, for which good correlation was achieved, with some anatomic features (kidney and heart) clearly visible in a carbon image, without reference to the corresponding proton image. Parallel imaging with sensitivity encoding was used to increase the spatial resolution in the SI direction of the rat. The signal to noise ratio in was in some instances unexpectedly high in the parallel images; variability of the polarization among different trials, plus partial volume effects, are noted as a possible cause of this.     

Initial in vivo rodent sodium and proton MR imaging at 21.1 T

The first in vivo sodium and proton magnetic resonance (MR) images and localized spectra of rodents were attained using the wide bore (105 mm) high resolution 21.1-T magnet, built and operated at the National High Magnetic Field Laboratory (Tallahassee, FL, USA). Head images of normal mice (C57BL/6J) and Fisher rats (∼250 g) were acquired with custom designed radiofrequency probes at frequencies of 237/900 MHz for sodium and proton, respectively. Sodium MR imaging resolutions of ∼0.125 μl for mouse and rat heads were achieved by using a 3D back-projection pulse sequence. A gain in SNR of ∼3 for sodium and ∼2 times for proton were found relative to corresponding MR images acquired at 9.4 T. 3D Fast Low Angle Shot (FLASH) proton mouse images (50×50×50 μm³) were acquired in 90 min and corresponding rat images (100×100×100 μm³) within a total time of 120 min. Both in vivo large rodent MR imaging and localized spectroscopy at the extremely high field of 21.1 T are feasible and demonstrate improved resolution and sensitivity valuable for structural and functional brain analysis.     

MRI assessment of drug-induced fluid accumulation in humans: validation of the technology

PURPOSE: The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by different mechanisms. MATERIALS AND METHODS: Twelve young healthy male subjects were randomly assigned to one of two groups and treated with either fludrocortisone or nifedipine for 14 or 25 days, respectively. The change in sodium MRI, as well as in proton T(2) value and T(1)-weighted signal intensity in the calf following postural change [referred to here as 'postural delta signal'(PDS)], was evaluated before, during and after drug administration. The changes in MRI PDS were compared to conventional physiological parameters, including body weight, calf volume and pitting edema. RESULTS: When compared to the baseline pretreatment values, the subjects treated with fludrocortisone showed a 5.5% increase in sodium MRI PDS (P=.01), a 2-ms increase in proton T(2) PDS of the gastrocnemius muscle (P=.06) and a body weight gain of 2.3% (P=.001) within 1 week. In the nifedipine-treated subjects, the sodium MRI PDS increased by 6% versus baseline (P=.03), while the proton T(2) PDS of the gastrocnemius muscle increased by 3.7 ms (P=.01), associated with a 0.5% weight gain (P=.55), within 3 weeks. No significant changes were noted in the T(1)-weighed images following postural change. Measurements of calf circumference, volume and pitting edema did not show consistent changes associated with the drug administration. CONCLUSION: The postural change in sodium MRI and proton T(2) signals provides a sensitive method for detecting the fluid accumulation produced by fludrocortisone and nifedipine. The MRI results are consistent with treatment-induced increases in extracellular fluid volume and correlate well with the observed weight gain. These findings support the potential utility of MRI for the evaluation of medication-induced fluid retention.     

23Na TQF NMR imaging for the study of spinal disc tissue

A method for acquiring triple quantum filtered (TQF) (23)Na NMR images is proposed that takes advantage of the differences in transverse relaxation rates of sodium to achieve positive intensity, PI, NMR signal. This PITQF imaging sequence has been used to obtain spatially resolved one-dimensional images as a function of the TQF creation time, tau, for two human spinal disc samples. From the images the different parts of the tissue, nucleus pulposus and annulus fibrosus, can be clearly distinguished based on their signal intensity and creation time profiles. These results establish the feasibility of (23)Na TQF imaging and demonstrate that this method should be applicable for studying human disc tissues as well as spinal disc degeneration.     

Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response

Functional MR (fMR) imaging techniques based on blood oxygenation level dependent (BOLD) effects were developed and applied to a rat brain tumor model to evaluate the potential utility of the method for characterizing tumor growth and regression following treatment. Rats bearing 9L brain tumors in situ were imaged during inhalation of room air and after administration of 100% oxygen + acetazolamide (ACZ) injected 15 mg/kg intravenously. Pixel-to-pixel fMR maps of normalized signal intensity change from baseline values were calculated from T2 weighted spin echo (SE) images acquired pre- and post- oxygen + ACZ administration. Resultant fMR maps were then compared to gross histological sections obtained from corresponding anatomical regions. Regions containing viable tumor with increased cellular density and localized foci of necrotic tumor cells consistent with hypoxia were visualized in the fMR images as regions with decreased signal intensities, indicating diminished oxyhemoglobin concentration and blood flow as compared to normal brain. Histological regions having peritumor edema, caused by increased permeability of tumor vasculature, were visualized in the fMR images as areas with markedly increased signal intensities. These results suggest that fMR imaging techniques could be further developed for use as a non-invasive tool to assess changes in tumor oxygenation/hemodynamics, and to evaluate the pharmacologic effect of anti-neoplastic drugs.     

Sodium T2*-weighted MR imaging of acute focal cerebral ischemia in rabbits

Changes in T2*-weighted tissue sodium (23Na) signal following acute ischemia may help to identify necrotic tissue and estimate the duration of ischemia. Sodium signal was monitored in a rabbit model of acute (0-4 h) focal cerebral ischemia, using gradient echo 23Na MR images (echo time = 3.2 ms) acquired continuously in 20-min intervals on a 4-Tesla MRI. 2,3,5-Triphenyl-tetrazolium chloride staining was used to identify regions of necrosis. In necrotic tissue, average 23Na image signal intensity decreased by 11% +/- 8% during the first 40 min of ischemia followed by a linear increase (0.19%/min) to 25% +/- 14% greater than baseline after 4 h of ischemia. The time course of 23Na signal change observed in necrotic tissue following focal ischemia in this rabbit model is consistent with an initial decrease in 23Na T2* relaxation time followed by an increase in tissue sodium concentration and provides further evidence that tissue 23Na signal may offer unique information regarding tissue viability that is complementary to other MR imaging techniques.     

Perfluorocarbon imaging in vivo: a 19F MRI study in tumor-bearing mice

Multiresonance perfluorocarbon emulsions (Oxypherol and Fluosol-DA) were imaged in tumor-bearing mice using 19F spin-echo magnetic resonance imaging in vivo. Multiple thin-slice fluorine images free of chemical shift artifacts were obtained in 13 minutes and these were correlated with proton images obtained during the same experiment to delineate the anatomic distribution of perfluorocarbons. Sequential images were used to determine the time course of the distribution and the retention of the compounds in tumors and organs. 19F MR spectroscopy was used ex vivo to determine with high sensitivity the relative concentration of perfluorocarbons in different tissues and organs and to confirm the results obtained from imaging experiments. The fluorine images visually demonstrated the preferential localization of the perfluorocarbons in the liver and spleen; shortly after injection, the images also revealed the highly vascularized tumor-chest wall interface. Imaging and spectroscopy together showed that the perfluorocarbons were removed from the blood pool within hours and remained sequestered in tissues at later times; the highest concentrations were found in the spleen and liver, where the agents were retained without spectral changes for the duration of these studies. The perfluorocarbons accumulated within tumors at dose-dependent concentrations, one to two orders of magnitude smaller than those observed in the spleen and liver.     

Multichannel transceiver dual-tuned RF coil for proton/sodium MR imaging of knee cartilage at 3 T

Sodium magnetic resonance (MR) imaging is a promising technique for detecting changes of proteoglycan (PG) content in cartilage associated with knee osteoarthritis. Despite its potential clinical benefit, sodium MR imaging in vivo is challenging because of intrinsically low sodium concentration and low MR signal sensitivity. Some of the challenges in sodium MR imaging may be eliminated by the use of a high-sensitivity radiofrequency (RF) coil, specifically, a dual-tuned (DT) proton/sodium RF coil which facilitates the co-registration of sodium and proton MR images and the evaluation of both physiochemical and structural properties of knee cartilage. Nevertheless, implementation of a DT proton/sodium RF coil is technically difficult because of the coupling effect between the coil elements (particularly at high field) and the required compact design with improved coil sensitivity. In this study, we applied a multitransceiver RF coil design to develop a DT proton/sodium coil for knee cartilage imaging at 3 T. With the new design, the size of the coil was minimized, and a high signal-to-noise ratio (SNR) was achieved. DT coil exhibited high levels of reflection S11 (～-21 dB) and transmission coefficient S12 (～-19 dB) for both the proton and sodium coils. High SNR (range 27-38) and contrast-to-noise ratio (CNR) (range 15-21) were achieved in sodium MR imaging of knee cartilage in vivo at 3-mm(3) isotropic resolution. This DT coil performance was comparable to that measured using a sodium-only birdcage coil (SNR of 28 and CNR of 20). Clinical evaluation of the DT coil on four normal subjects demonstrated a consistent acquisition of high-resolution proton images and measurement of relative sodium concentrations of knee cartilages without repositioning of the subjects during the same MR scanning session.     

Bi-exponential proton transverse relaxation rate (R2) image analysis using RF field intensity-weighted spin density projection: potential for R2 measurement of iron-loaded liver

A bi-exponential proton transverse relaxation rate (R(2)) image analysis technique has been developed that enables the discrimination of dual compartment transverse relaxation behavior in systems with rapid transverse relaxation enhancement. The technique is particularly well suited to single spin-echo imaging studies where a limited number of images are available for analysis. The bi-exponential R(2) image analysis is facilitated by estimation of the initial proton spin density signal within the region of interest weighted by the RF field intensities. The RF field intensity-weighted spin density map is computed by solving a boundary value problem presented by a high spin density, long T(2) material encompassing the region for analysis. The accuracy of the bi-exponential R(2) image analysis technique is demonstrated on a simulated dual compartment manganese chloride phantom system with relaxation rates and relative population densities between the two compartments similar to the bi-exponential transverse relaxation behavior expected of iron loaded liver. Results from analysis of the phantoms illustrate the potential of bi-exponential R(2) image analysis with RF field intensity-weighted spin density projection for quantifying transverse relaxation enhancement as it occurs in liver iron overload.     

In vivo sodium-23 magnetic resonance surface coil imaging: Observing experimental cerebral ischemia in the rat

Sodium-23 magnetic resonance imaging can be used to detect and assess experimental cerebral ischemia in the rat. An imaging technique utilizing a surface coil is described to produce sodium magnetic resonance images of good quality and resolution within 10 min. A novel method of hemispheric occlusion showed edema in the right brain of the rat head within 3 hr after injury. The edema was especially pronounced by 12 hr with effects in the right brain, eye and surrounding muscle evident.     

Ethanol-induced fatty liver in the rat examined by in vivo 1H chemical shift selective magnetic resonance imaging and localized spectroscopic methods.

In vivo 1H magnetic resonance imaging (MRI), chemical shift selective imaging (CSI), and localized (VOSY) 1H magnetic resonance spectroscopy (MRS) were used to study fatty infiltration in the livers of rats chronically fed an ethanol-containing all-liquid DeCarli-Lieber diet. Conventional total proton MRI showed a somewhat hyperintense liver for ethanol-fed rats, compared with pair-fed controls. CSI showed a dramatic increase in the fat signal intensity for ethanol-treated rats that was fairly homogeneous throughout the liver. However, CSI also showed a substantial decrease in the water signal intensity for the ethanol-treated rats compared to pair-fed control rats. 1H VOSY MR spectra also showed a 5.5-fold increase in the methylene resonance (1.3 ppm) of fat and a 50-70% decrease in the water resonance (4.8 ppm). Relative in vivo proton T1 and T2 relaxation times for the water resonance separate from the fat resonance, determined from modified VOSY experiments, were found to tend to increase and decrease, respectively, for ethanol-treated rat livers compared with controls. The decrease in hepatic water signal intensity could be accounted for by the decrease in T2 and decrease in water density due to the presence of accumulated hepatic fat (approximately 25 mg/g wet weight of liver). When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days. By day 16, however, the signal intensity for hepatic fat was still significantly higher than control levels. In vitro 1H MRS studies of chloroform-methanol extracts confirmed the 5.5-fold increase in total hepatic fat induced by the chronic ethanol treatment, and showed further that triacylglycerols were increased 7.7-fold, cholesterol was increased fourfold, and phospholipids were increased 3.3-fold, compared with liver extracts from pair-fed control rats.     

Width determination of SiO2-films in Si-based devices using low-loss EFTEM: image contrast as a function of sample thickness

Energy filtering transmission electron microscopy (EFTEM) has become one of the most efficient tools for specimen characterization at nanometer length scales. EFTEM imaging is most often carried out in the core-loss region but image intensity becomes more and more a limiting factor with decreasing feature size. Alternatively, it is possible to record EFTEM images in the low-loss region, where intensities are essentially higher and where in many cases the images contain material specific contrasts. In this paper we investigate the influence of the important parameters on the material contrast between silicon and silicon dioxide, e.g. specimen thickness, specimen orientation, energy-loss and energy selecting slit width. We show that sample thickness plays an important role and present two methods to calculate material contrast as a function of energy-loss and sample thicknesses. The first method uses spectra taken from both materials at different sample thickness by electron energy-loss spectroscopy, the second calculates contrast directly from a series of energy filtered images. From the results we determine the ideal acquisition parameters for the Si/SiO(2) system and demonstrate imaging at sufficient resolution below 2nm with a test sample of thin SiO(2) layers on Si.     

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spinspin relaxation time (T₂), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T₂ value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between “free” and “bound” water protons as measured by MTC imaging is at least partially responsible for the elevation in T₂ values observed during ischemia, and may accompany breakdown of cellular structure.     

An ESR-CT imaging of the head of a living rat receiving an administration of a nitroxide radical.

Three-dimensional ESR imaging of a living rat has been performed by an L-band ESR system, which is composed of an L-band ESR spectrometer, a field gradient coil, and a data processor. The imaging was carried out by Lauterbur's method. A nitroxide, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (Carbamoyl-PROXYL), was used as an imaging agent in saline solution at a concentration of 0.2 M and administered intraperitoneally to obtain a constant concentration in the head for about an hour. It took about 40 min to obtain one set of ESR-CT images. The cross-sectional images were made, both as coronal and horizontal images. In the images of the rat head the nitroxide-rich region was clearly distinguished from the deficient region. The nitroxide-deficient areas corresponded well to the brain of the rat.     

Evaluation of STIR imaging as a complement to spin-echo MR and CT of the porta hepatis/hepatoduodenal ligament

Short TI inversion-recovery (STIR) imaging provides specific advantages over standard spin-echo (SE) MR sequences by producing additive effects of T1 and T2 brightening of pathology and suppression of the signal from surrounding fat. We retrospectively evaluated 12 patients with abnormalities, primarily neoplastic, of the porta hepatis/hepatoduodenal ligament (PH/HdL) with CT and MR imaging, including SE and STIR imaging. Masses on CT were of slightly decreased density compared to liver and seen in contrast to surrounding fat in the PH/HdL region. On MR, T1-weighted images provided comparable anatomic detail to CT, with masses clearly distinguished from surrounding fat due to the low signal intensity of masses as compared to fat. T2-weighted images clearly depicted intrahepatic lesions because of their high signal intensity relative to liver. Increased signal in extrahepatic lesions made them less distinctly seen from surrounding fat. STIR images best demonstrated tumor relative to fat. In six cases, CT was equivalent in demonstrating pathology to the best MR sequence. At least one MR sequence demonstrated pathology better than CT in 6 of 12 cases. In five of these six cases, the STIR sequence was better than CT. Thus, MR, particularly STIR imaging, provides a useful technique in imaging of PH/HdL pathology.     

Microimaging of hairless rat skin by magnetic resonance at 900 MHz

Purpose

Quantitative imaging of the rat skin was performed using magnetic resonance imaging (MRI) at 900 MHz.

Materials and methods

A number of imaging techniques utilized for multiple contrast included magnetization transfer contrast, spin-lattice relaxation constant (T1-weighting), combination of T2-weighting with magnetic field inhomogeneity (T2*-weighting), magnetization transfer weighting and diffusion tensor weighting. These were used to obtain 2D slices and 3D multislice-multiecho images with high magnetic resonance contrast. These 2D and 3D imaging techniques were combined to achieve high-resolution MRI.

Results

Oil–water phantom showed distinct fat-water contrast. The dermis and epidermis, including the stratum corneum remnants, of nude rat skin were distinct due to their proton magnetic resonance as a result of proton interactions with the skin interstitial tissue. Combined details obtained from high-resolution, high-quality ex vivo skin images with different multicontrast characteristics generated better differentiation of skin layers, sublayers and significant correlation (r²=0.4927 for MRI area, r²=0.3068 for histology area; P<.0148) of MR data with co-registered histological areas of the epidermis as well as the hair follicle.

Conclusion

The multiple contrast approach provided a noninvasive ex vivo MRI visualization with semi-quantitative assessment of the major skin structures including the stratum corneum remnants, epidermis, hair, papillary dermis, reticular dermis and hypodermis.