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 When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days.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.     

Tissue specific resonance frequencies of water and metabolites within the human brain

Chemical shift imaging (CSI) without water suppression was used to examine tissue-specific resonance frequencies of water and metabolites within the human brain. The aim was to verify if there are any regional differences in those frequencies and to determine the influence of chemical shift displacement in slice-selection direction. Unsuppressed spectra were acquired at 3T from nine subjects. Resonance frequencies of water and after water signal removal of total choline, total creatine and NAA were estimated. Furthermore, frequency distances between the water and those resonances were calculated. Results were corrected for chemical shift displacement. Frequency distances between water and metabolites were consistent and greater for GM than for WM. The highest value of WM to GM difference (14ppb) was observed for water to NAA frequency distance. This study demonstrates that there are tissue-specific differences between frequency distances of water and metabolites. Moreover, the influence of chemical shift displacement in slice-selection direction is showed to be negligible.     

Selective F MR imaging of 5-fluorouracil and α-fluoro-β-alanine

A ¹⁹F MR chemical shift imaging (CSI) technique is presented which enables selective imaging of the antineoplastic drug 5-fluorouracil (5-FU) and its major catabolite α-fluoro-β-alanine (FBAL). The CSI sequence employs a chemical shift selective (CHESS) saturation pulse to suppress either the 5-FU or the FBAL resonance before the other component of the two-line ¹⁹F MR spectrum is measured. Because the transmitter frequency can always be set to the Larmor frequency of the ¹⁹F resonance to be imaged, this approach yields 5-FU and FBAL MR images free of chemical shift artifacts in read-out and slice-selection direction. In phantom experiments, selective 5-FU and FBAL images with a spatial resolution of 15 × 15 × 20 mm³ (4.5 ml) were obtained in 30 min from a model solution, whose drug and catabolite concentrations were similar to those estimated in the liver of tumor patients undergoing IV chemotherapy with 5-FU. The drug-specific MR imaging technique developed is, therefore, well-suited for the direct and noninvasive monitoring of the up-take and trapping of 5-FU in liver tumors in vivo.     

Cardiac phosphorus-31 two-dimensional chemical shift imaging in patients with hereditary hemochromatosis

Hemochromatosis is a hereditary iron overload syndrome characterized by increased iron storage, followed by liver cirrhosis and is often associated with restrictive cardiomyopathy. The purpose of this study was to detect alterations of cardiac high-energy phosphate metabolism in patients with hereditary hemochromatosis (HHC) prior to the development of structural heart diseases. Therefore cardiac phosphorus-31 two-dimensional chemical shift imaging ((31)P 2D CSI) was employed. Twenty-four male patients (mean age 47.2 +/- 12 years) homozygous for the C282Y mutation in the hemochromatosis associated HFE gene and twenty-four male healthy volunteers (mean age 47 +/- 11 years) as age-matched controls were included in this study. Using a 1.5-Tesla whole-body magnetic resonance scanner, electrocardiograph-triggered transversal 31P 2D CSI was performed. Left ventricle mean phosphocreatine (PCr) to beta-adenosine triphosphate (beta-ATP) ratios of patients with HHC (1.60 +/- 0.41) were significantly decreased in comparison to healthy volunteers (1.93 +/- 0.36; p = 0.004). Furthermore, we detected moderate, negative correlations between left ventricular PCr to beta-ATP ratios and transferrin saturation, cholesterol, low-density lipoprotein as well as triglyceride. This study shows that 31P 2D CSI permits the detection of alterations of cardiac high-energy phosphate metabolism in patients with HHC, but without any evidence for heart disease. The decreased PCr to beta-ATP ratios in HHC might be caused by mitochondrial impairment due to cardiac iron overload.     

A post-processing method for correction and enhancement of chemical shift images

Chemical shift imaging (CSI) relies on a strong and homogeneous main field. Field homogeneity ensures adequate coherence between the precessions of individual spins within each voxel. Variation of field strength between different voxels causes geometric distortion and intensity variation in chemical shift images, resulting in errors when analyzing the spatial distribution of specific chemical compounds. A post-processing method, based on detection of the spectral peak of water and baseline subtraction with Lorentzian functions, was developed in this study to automatically correct spectra offsets caused by field inhomogeneity, thus enhancing the contrast of the chemical shift images. Because this method does not require prior field plot information, it offers advantages over existing correction methods. Furthermore, the method significantly reduces geometric distortion and enhances signals of chemical compounds even when the water suppression protocol was applied during the CSI data acquisition. The experimental results of the water and glucose phantoms showed a considerable reduction of artifacts in the spectroscopic images when this post-processing method was employed. The significance of this method was also demonstrated by an analysis of the spatial distributions of sugar and water contents in ripe and unripe bananas.     

Imaging beta-galactosidase activity using 19F chemical shift imaging of LacZ gene-reporter molecule 2-fluoro-4-nitrophenol-beta-D-galactopyranoside

2-Fluoro-4-nitrophenol-beta-D-galactopyranoside (OFPNPG) belongs to a novel class of NMR active molecules (fluoroaryl-beta-D-galactopyranosides), which are highly responsive to the action of beta-galactosidase (beta-gal). OFPNPG has a single 19F peak (-55 ppm relative to aqueous sodium trifluoroacetate). Upon cleavage by beta-gal, the pH sensitive aglycone 2-fluoro-4-nitrophenol (OFPNP) is observed at a chemical shift of -59 to -61 ppm. The chemical shift response is sufficient to observe beta-gal activity using chemical shift imaging (CSI). 19F CSI studies of enzyme activity and lacZ gene expression in 9L-glioma and MCF7 breast cancer cells are presented, providing further evidence for the utility of OFPNPG as a gene-reporter molecule for future in vivo studies.     

Magnetic resonance cholangiopancreatography: comparison between respiratory-triggered turbo spin echo and breath hold single-shot turbo spin echo sequences

The purpose of this study was to compare the relative conspicuity of the pancreaticobiliary tree on respiratory-triggered three-dimensional turbo spin echo (3D TSE RT) and breath hold single-shot turbo spin echo (SSTSE BH) acquisitions respectively in MRCP imaging. Both techniques were applied to 61 patients with clinically suspected pancreaticobiliary disease using a 1.0 T MR system. All images were reviewed blindly. Qualitative comparison was made by grading subjectively the conspicuity of extrahepatic, intrahepatic, and main pancreatic ducts. Quantitative comparison included calculations of signal-to-noise ratio of the common bile duct, main pancreatic duct, gallbladder, liver, and contrast-to-noise ratio, relative contrast between common bile duct, gallbladder, and liver. 3D TSE RT provided significantly higher signal-to-noise ratio of the common bile duct (mean value 163.19) and main pancreatic duct (mean value 95.37) compared to SSTSE BH (mean values 76.24 and 26.22, respectively). 3D TSE RT was inferior to SSTSE BH for the depiction of intrahepatic ducts and pancreatic duct (head portion). 3D TSE RT and SSTSE BH sequences provide complimentary information in the visualization of the biliary and pancreatic ducts. Further comparative clinical studies are needed to redefine the sensitivity, specificity, and accuracy of MRCP using both sequences.     

Feasibility of proton chemical shift imaging with a stereotactic headframe

To prove feasibility of proton chemical shift imaging ((1)H CSI) during stereotactic procedure, authors performed (1)H CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, evaluated the pathologic results. The (1)H CSI directed stereotactic biopsy was performed in four patients. (1)H CSI and conventional Gd-enhancement stereotactic MRI were performed simultaneously after the fitting of a stereotactic headframe. Focal areas of increased phosphocholine(Cho)/phosphocreatine(Cr) and Lactate/Cr ratios were selected as target sites in the stereotactic MR images. (1)H CSI is possible with the stereotactic headframe in place. Pathologic samples taken from areas of increased Cho/Cr ratios and decreased NAA/Cr ratios provided information upon increased cellularity, mitoses and cellular atypism, and facilitated diagnosis. Pathologic samples taken from areas of increased Lac/Cr ratio showed predominant feature of necrosis. (1)H CSI was feasible with the stereotactic headframe in place. The final pathologic results obtained were concordant with the local metabolic information from (1)H CSI. We believe that (1)H CSI-directed stereotactic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting.     

Wavelet Encoding Spectroscopic Imaging in Small FOV Regime: Comparison to Chemical Shift Imaging at 3?Tesla

We have recently proposed a new magnetic resonance spectroscopic imaging (MRSI) technique called wavelet encoding spectroscopic imaging (WE-SI), and described its implementation on a clinical 1.5?T scanner. This technique is proposed as an alternative to chemical shift imaging (CSI), to decrease acquisition time, and voxel contamination. The proposed method is implemented here on a clinical 3?T scanner. Phantom and in vivo studies are chosen to validate the technique at higher field, as well as to fully explore the usefulness of this technique, and find its niche of application in the chain of existing MRSI techniques. In wavelet encoding, a set of dilated and translated wavelets are used to span a localized space by dividing it into a set of sub-spaces with pre-determined sizes and locations. Due to their simple shapes, Haar wavelets are chosen. They are represented in the modified PRESS sequence by the selective excitation and refocusing radio-frequency (RF) pulses. The wavelets dilation and translation are achieved by changing the strength of the localization gradients and frequency shift of the RF pulses, respectively. Data acquisition time is reduced using the minimum recovery time when successive MR signals from adjacent sub-spaces are collected. The results obtained at 3?T confirm those obtained at 1.5?T, and demonstrate that despite the low signal-to-noise ratio, the proposed WE-SI provides accurate results and reduces both voxel contamination and acquisition time as compared to CSI. This applies especially in the small field-of-view regime where only a small number of voxels is required.     

In vivo determination of 31P spin relaxation times (T1, T2, T1 rho) in rat leg muscle. Use of an off-axis solenoid coil

A probe using a solenoid coil tilted 45 degrees off-axis has been used to study the 31P NMR relaxation characteristics of the resonances arising from phosphorus metabolites in rats in vivo. T1, T1 rho and T2 values have been determined for phosphocreatine and ATP in leg muscle. The ratio of 31P T1(1700ms) to T2(12ms) for ATP was in excess of 200:1 compared with a ratio of 5:1 for 1H T1:T2. Of major significance was the observation that T2 values for phosphocreatine (230ms) were markedly longer than T2 values for ATP (12ms). Thus by use of appropriate delay times in spin echo sequences ATP signals can be nulled, and discrete 31P imaging of phosphocreatine in muscle may be possible provided the overall signal-to-noise is satisfactory.     

Theoretical Evaluation and Comparison of Fast Chemical Shift Imaging Methods

Magnetic resonance chemical shift imaging (CSI) is becoming the method of choice for localized NMR spectroscopic examinations, allowing simultaneous detection of NMR spectra from a large number of voxels. The main limitation of these methods is their long experimental duration. A number of fast CSI experiments have been presented, promising to reduce that duration. In this contribution the criteria for evaluating and optimizing the sensitivity of fast CSI experiments are elaborated. For a typical experiment in the human brain, the performance of various methods is compared. While conventional CSI provides optimal sensitivity per unit time, it is shown in which circumstances fast sequences allow a shorter experimental duration. Using these results, the best method for any experimental requirements can be selected.     

Dissociation between lactate accumulation and acidosis in middle cerebral artery-occluded rats assessed by P and H NMR metabolic images under A 2-T magnetic field

The relationships among tissue edema, lactate accumulation, and intracellular pH in middle cerebral artery (MCA)-occluded rats were investigated with multiecho ¹H magnetic resonance imaging and spatially resolved metabolic images constructed by ¹H and ³¹P nuclear magnetic resonance (NMR) chemical shift imaging (CSI). For the effective and sensitive detection of NMR signals from the brain, outer volume suppression (OVS), reduced k-space sampling and proton irradiation were incorporated into the CSI sequences. The consecutive three measurements of calculated T₂ image, lactate image, and pH image which were required for 3.75 h were repeated for four cycles of 1–16 h after MCA occlusion. Tissue edema and lactate accumulation in the infarcted region were gradually and consistently increased during the 15-h observation period. In contrast, severe acidosis was already detected on the first pH image (2–4.7 h after MCA occlusion); thereafter, the degree of acidosis became milder and showed no further progression. The dissociation between the time courses of the lactate accumulation and pH decrease was clearly demonstrated by the NMR metabolic images. Acid-base balance in cerebral infarction might be affected not only by lactate production but also by complicated interactions with tissue edema and some other factors.     

A chemical shift imaging study on regional metabolite distribution in a CADASIL family

A chemical shift imaging (CSI) study was performed to directly assess relative concentrations of N-acetylaspartate (NAA), Cho and Cr metabolites in normal- and abnormal-appearing brain tissue of asymptomatic and symptomatic members of a single family with a neuropathologic, genetic and electrophysiological confirmed diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The aim of the investigation was to evaluate clinical findings and metabolite abnormalities as early appearance of axonal injury in this syndrome. The main findings related statistically significant decreases in the mean metabolite ratios for NAA/Cr, NAA/Cho and Cho/Cr in the anterior parts in comparison with the posterior parts of the centrum semiovale in symptomatic and asymptomatic patients. The effect was considerably greater in the symptomatic patients, indicating a strong correlation between CSI and pathology results. No differences were found between the two areas in the control group. Although lactate signals were hardly detectable in individual spectra, there was a trend toward increased Lac/Cr values in the anterior parts with respect to the posterior parts in the patient group, with the effect particularly evident in the asymptomatic subjects with the gene mutation.     

Localized Spectroscopy from Anatomically Matched Compartments: Improved Sensitivity and Localization for CardiacP MRS in Humans

Several pioneering studies have demonstrated that localized³¹P NMR spectroscopy of the human heart might become an important diagnostic tool in cardiology. The main limitation is due to the low sensitivity of these experiments, allowing only crude spatial resolution. We have implemented a three-dimensional version of SLOOP (“spectral localization with optimal pointspread function”) on a clinical instrument. SLOOP takes advantage of all availablea prioriinformation to match the size and the shape of the sensitive volumes to the anatomical structures in the examined subject. Thus, SLOOP reduces the contamination from adjacent organs and improves the sensitivity compared to conventional techniques such as ISIS or chemical shift imaging (CSI). Initial studies were performed on six healthy volunteers at 1.5 T. The good localization properties are demonstrated by the absence of resonances from blood in the heart spectra, and by PCr-free spectra from the liver. Compared to conventional CSI, the signal-to-noise ratio of the SLOOP heart spectra was improved by approximately 30%. Taking into account the varying excitation angle in the inhomogeneous B₁field of the surface coil, the SLOOP model computes the local spin saturation at every point in space. Therefore, no global saturation correction is required in the quantitative evaluation of local spectra. In this study, we found a PCr/γ-ATP ratio in the left ventricular wall of 1.90 ± 0.33 (mean ± standard deviation).     

Application of compressed sensing to in vivo 3D ¹⁹F CSI

This study shows how applying compressed sensing (CS) to (19)F chemical shift imaging (CSI) makes highly accurate and reproducible reconstructions from undersampled datasets possible. The missing background signal in (19)F CSI provides the required sparsity needed for application of CS. Simulations were performed to test the influence of different CS-related parameters on reconstruction quality. To test the proposed method on a realistic signal distribution, the simulation results were validated by ex vivo experiments. Additionally, undersampled in vivo 3D CSI mouse datasets were successfully reconstructed using CS. The study results suggest that CS can be used to accurately and reproducibly reconstruct undersampled (19)F spectroscopic datasets. Thus, the scanning time of in vivo(19)F CSI experiments can be significantly reduced while preserving the ability to distinguish between different (19)F markers. The gain in scan time provides high flexibility in adjusting measurement parameters. These features make this technique a useful tool for multiple biological and medical applications.     

Elimination of chemical shift artifacts of thoracic spine with contrast-enhanced FLAIR imaging with fat suppression at 3.0 T

The purpose of this study was to assess the effect of chemical shift artifacts and fat suppression between contrast-enhanced T1-weighted fast spin-echo (FSE) sequence with fat suppression and contrast-enhanced T1-weighted fluid attenuated inversion recovery (FLAIR) sequence with fat suppression in magnetic resonance imaging (MRI) of the thoracic spine at 3.0T. Forty patients, who underwent MRI examination, were recruited and analyzed both qualitatively and quantitatively. Due to chemical shift artifacts in the T1-weighted FSE, 14 of the patients were found to be of non-diagnostic value. On the contrary, in 11 of those 14 patients, no chemical shift artifacts were observed in the T1-weighted FLAIR sequence. Regarding the efficiency of fat suppression, both sequences achieved successful fat suppression. Consequently, the use of T1-weighted FLAIR fat suppression after contrast administration sequence seems to eliminate or significantly reduce image quality deterioration stemming from chemical shift artifacts in thoracic spine examinations.     

MRI and 1H MRS evaluation for the serial bile duct changes in hamsters after infection with Opisthorchis viverrini

A 3 T MR scanner was used to investigate the relationship between the alteration of bile duct lesions and the hepatic metabolic changes in hamsters infected with Opisthorchis viverrini by using 3 T MRI and ¹H MR spectroscopy. Animals were divided into control and infected groups. Five normal hamsters were used as control; fifty-five hamsters were infected with O. viverrini to induce bile duct lesions and hepatic metabolic changes. T2-weighted image sequence in three orthogonal planes were conducted by MRI scans. Single-voxel ¹H MRS was performed to obtain the relative choline-to-lipid ratios. The livers and bile ducts were excised for the histologic examination. The progression of bile duct changes by histology and metabolic changes in O. viverrini infected hamsters were co-investigated. In the O. viverrini-infected group, the T2-weighted images revealed the time-dependent intra- and extra-hepatic duct dilatations in the liver. The mean (± SD) choline-to-lipid ratios were 0.11 ± 0.035 in the control group, whereas the ratio in the infected group increased significantly with the progression of time. Histologic grading of hepatic inflammation and fibrosis were correlated well with the MRI grading (Spearman rank correlation test; r = 0.746 and p < 0.001). The control group showed no dilatation of the bile ducts and showed normal liver patterns. Noninvasive technique, MRI and ¹H MRS can demonstrated and applied to evaluate not only the inflammation-related fibrosis in the small bile ducts but also the metabolic changes in the liver induced by O. viverrini infection. A significant increase in the choline-to-lipids ratios were observed in parallel with the time-course of infection. O. viverrini infected in human is detected by stool examination. Hepatobiliary morbidity is detected and followed up by ultrasonography. MRI and MRS can be used in conjunction with ultrasonography for evaluation of progression of the disease.     

ViP-CSI: Virtual Phantom Chemical Shift Imaging

To apply the Virtual Phantom (ViP) method for generating reference signals, to the chemical shift imaging (CSI) technique. The ViP method, previously used for generating reference images in magnetic resonance imaging (MRI), was here extended to generate reference peaks in the MR spectra acquired with a 2D-CSI sequence. Theoretical analysis was carried out to design the ViP signal. ViP-2D-CSI experiments were performed on a 4.7 Tesla MR scanner. Data analysis was carried out with the jMRUI software to fit the ViP peaks to determine their amplitude and frequency. Based on the theoretical analysis, it was found that the ViP peak could be generated by transmitting the ViP signal only in one repetition time of the 2D-CSI sequence. The amplitude and frequency of the ViP peak could be precisely adjusted and fine-tuned. The ViP peak was uniform over all CSI voxels, both in amplitude and in frequency. Furthermore, a good stability of the ViP reference amplitude and frequency was observed. The ViP method provides a means to generate a reference MR peak in 2D-CSI experiments. This could be of interest for signal quantification in CSI experiments.     

H MR spectroscopy monitoring of changes in choline peak area and line shape after Gd-contrast administration

Fifteen percent loss in the peak area of choline containing compounds (Cho) was recently observed in ¹H MR spectra of contrast-enhancing tumor at 5–10 min after Gd-contrast administration [Magn. Reson. Med. 37:222–225, 1997]. In this study, chemical shift imaging (CSI, 1500/135 ms PRESS) was used to assess the spectral changes in 47 Gd-enhancing glial brain tumors and metastatic brain tumors measured at 0–5, 5–10, and/or 10–15 min after administration of Gd-contrast. Percent Cho peak area losses measured at these times, 3 ± 3, 12 ± 2, and 14 ± 3 SEM, respectively, coincided with trends of line narrowing and up-field shift of the Cho peak. Significant changes in creatine and N-acetyl acetate signals were not observed. It is concluded that the Gd-induced loss of tumor Cho signal measured after 5 min, typically required for post contrast-MRI and the positioning of the CSI volume on tumor, shows little further change with time, if any.     

小动物高分辨扩散加权成像在临床 MRI 上的实现

在临床用MRI系统上对小动物扩散加权成像一般采用回波平面成像序列,但是回波平面成像易受偏共振效应的影响,得到的图像伪影大、几何变形严重、图像分辨率低,无法探究微小的生物组织结构. 该文报道了在临床用3 T MRI系统上采用自旋回波序列实现了高分辨扩散加权成像. 为减少运动伪影,序列中整合了导航回波矫正技术. 对脑缺血模型大鼠脑部的扫描结果显示,自旋回波扩散加权序列获得的图像基本没有发生形变,并且具有较高的分辨率和较好的信噪比.