6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A.tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A.tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A.tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A.tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

Test-retest repeatability of ultrasonographic shear wave elastography in a rat liver fibrosis model: toward a quantitative biomarker for preclinical trials

This study evaluated the test-retest repeatability and measurement variability of ultrasonographic shear wave elastography (SWE) for liver stiffness in a rat liver fibrosis model. Methods: In 31 Sprague-Dawley rats divided into three groups (high-dose, low-dose, and control), liver fibrosis was induced by intraperitoneal administration of thioacetamide for 8 weeks. A dedicated radiographer performed SWE to measure liver stiffness in kilopascals in two sessions at a 3-day interval. We calculated correlations between liver stiffness and histopathologic results, measurement variability in each session using coefficients of variation (CoVs) and interquartile/median (IQR/M), and test-retest repeatability between both sessions using the repeatability coefficient. Results: Different levels of liver fibrosis in each group were successfully induced in the animal model. The mean liver stiffness values were 8.88±1.48 kPa in the control group, 11.62±1.70 kPa in the low-dose group, and 11.91±1.73 kPa in the high-dose group. The correlation between collagen areas and liver stiffness values was moderate (r=0.6). In all groups, the second session yielded lower CoVs (i.e., more reliable results) for liver stiffness than the first session, suggesting a training effect for the operator. The mean IQR/M values were also lower in the second session than in the first session, which had four outliers (0.21 vs. 0.12, P<0.001). The test-retest repeatability coefficient was 3.75 kPa and decreased to 2.82 kPa after removing the four outliers. Conclusion: The use of ultrasonographic SWE was confirmed to be feasible and repeatable for evaluating liver fibrosis in preclinical trials. Operator training might reduce variability in liver stiffness measurements.

Neuroimaging in Randomized, Multi-Center Clinical Trials of Endovascular Treatment for Acute Ischemic Stroke: A Systematic Review

Neuroimaging in Acute Ischemic Stroke: Role and Recent Advances

Neuroimaging plays a key role in assessing the detection of acute hemorrhage, diagnosis of infarct core, detection of steno-occlusive arteries, mismatch between infarct core and penumbra, and collateral circulation in patients with acute cerebral ischemic stroke. The recent announcement of randomized clinical trials that demonstrated the usefulness of intra-arterial mechanical thrombectomy and the guidelines of 2018 Guidelines for the Early Management of Patients with Acute Ischemic Stroke from American Heart Association/American Stroke Association led to a larger role of neuroimaging and required new neuroimaging strategy for acute cerebral ischemic stroke. In this review, we summarize the recommendation on neuroimaging from the 2018 Guidelines, and review pros and cons between CT and MR and fast scanned stroke MR. Based on the new guidelines and recent research, we discuss the appropriate neuroimaging strategy for acute cerebral ischemic stroke patients.

Radiofrequency Coil Design for in vivo Sodium Magnetic Resonance Imaging of Mouse Kidney at 9.4T

The objective of this study was to describe a radiofrequency (RF) coil design for in vivo sodium magnetic resonance imaging (MRI) for use in small animals. Accumulating evidence has indicated the importance and potential of sodium imaging with improved magnet strength (> 7T), faster gradient, better hardware, multi-nucleus imaging methods, and optimal coil design for patient and animal studies. Thus, we developed a saddle-shaped sodium volume coil with a diameter/length of 30/30 mm. To evaluate the efficiency of this coil, bench-level measurement was performed. Unloaded Q value, loaded Q value, and ratio of these two values were estimated to be 352.8, 211.18, and 1.67, respectively. Thereafter, in vivo acquisition of sodium images was performed using normal mice (12 weeks old; n = 5) with a two-dimensional gradient echo sequence and minimized echo time to increase spatial resolution of images. Sodium signal-to-noise ratio in mouse kidneys (renal cortex, medulla, and pelvis) was measured. We successfully acquired sodium MR images of the mouse kidney with high spatial resolution (approximately 0.625 mm) through a combination of sodium-proton coils.

Influence of B₁-Inhomogeneity on Pharmacokinetic Modeling of Dynamic Contrast-Enhanced MRI: A Simulation Study

OBJECTIVE: To simulate the B₁-inhomogeneity-induced variation of pharmacokinetic parameters on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: B₁-inhomogeneity-induced flip angle (FA) variation was estimated in a phantom study. Monte Carlo simulation was performed to assess the FA-deviation-induced measurement error of the pre-contrast R₁, contrast-enhancement ratio, Gd-concentration, and two-compartment pharmacokinetic parameters (K(trans), v(e), and v(p)). RESULTS: B₁-inhomogeneity resulted in −23–5% fluctuations (95% confidence interval [CI] of % error) of FA. The 95% CIs of FA-dependent % errors in the gray matter and blood were as follows: −16.7–61.8% and −16.7–61.8% for the pre-contrast R₁, −1.0–0.3% and −5.2–1.3% for the contrast-enhancement ratio, and −14.2–58.1% and −14.1–57.8% for the Gd-concentration, respectively. These resulted in −43.1–48.4% error for K(trans), −32.3–48.6% error for the v(e), and −43.2–48.6% error for v(p). The pre-contrast R₁ was more vulnerable to FA error than the contrast-enhancement ratio, and was therefore a significant cause of the Gd-concentration error. For example, a −10% FA error led to a 23.6% deviation in the pre-contrast R₁, −0.4% in the contrast-enhancement ratio, and 23.6% in the Gd-concentration. In a simulated condition with a 3% FA error in a target lesion and a −10% FA error in a feeding vessel, the % errors of the pharmacokinetic parameters were −23.7% for K(trans), −23.7% for v(e), and −23.7% for v(p). CONCLUSION: Even a small degree of B₁-inhomogeneity can cause a significant error in the measurement of pharmacokinetic parameters on DCE-MRI, while the vulnerability of the pre-contrast R₁ calculations to FA deviations is a significant cause of the miscalculation.

Neurochemical Profile Quantification of Regional Adult Mice Brain Using: ex vivo 1H High-Resolution Magic Angle Spinning NMR Spectroscopy / 의학물리

The purpose of this study is to quantitate regional neurochemical profile of regional normal adult mice brain and assess regional metabolic differences by using ex vivo 1H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (1H HR-MAS NMRS). The animals were matched in sex and age. The collected brain tissue included frontal cortex, temporal cortex, thalamus, and hippocampus. Quantitative 1D spectra were acquired on 40 samples with the CPMG pulse sequence (8 kHz spectral window, TR/TE = 5500/2.2 ms, NEX = 128, scan time: 17 min 20 sec). The mass of brain tissue and D2O+TSP solvent were 8~14 mg and 7~13 mg. A total of 16 metabolites were quantified as follow: Acet, NAA, NAAG, tCr, Cr, tCho, Cho, GPC + PC, mIns, Lac, GABA, Glu, Gln, Tau and Ala. As a results, Acet, Cho, NAA, NAAG and mIns were showed significantly different aspects on frontal cortex, hippocampus, temporal cortex and thalamus respectively. The present study demonstrated that absolute metabolite concentrations were significantly different among four brain regions of adult mice. Our finding might be helpful to investigate brain metabolism of neuro-disease in animal model.

Evaluations of Spectral Analysis of in vitro 2D-COSY and 2D-NOESY on Human Brain Metabolites

PURPOSE: To investigate the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar nuclear Overhauser effect/enhancement (NOE) interaction through 2D- correlation spectroscopy (COSY) and 2D- NOE spectroscopy (NOESY) techniques. MATERIALS AND METHODS: All 2D experiments were performed on Bruker Avance 500 (11.8 T) with the zshield gradient triple resonance cryoprobe at 298 K. Human brain metabolites were prepared with 10% D2O. Two-dimensional spectra with 2048 data points contains 320 free induction decay (FID) averaging. Repetition delay was 2 sec. The Top Spin 2.0 software was used for post-processing. Total 7 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), and lactate (Lac) were included for major target metabolites. RESULTS: Symmetrical 2D-COSY and 2D-NOESY spectra were successfully acquired: COSY cross peaks were observed in the only 1.0-4.5 ppm, however, NOESY cross peaks were observed in the 1.0-4.5 ppm and 7.9 ppm. From the result of the 2-D COSY data, cross peaks between the methyl protons (CH3(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methylene protons (CH2(3,H alpha)) at 2.50ppm and methylene protons (CH2,(3,HB)) at 2.70 ppm were observed in NAA. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. From the result of 2-D NOESY data, cross peaks between the NH proton at 8.00 ppm and methyl protons (CH3) were observed in NAA. Cross peaks between the methyl protons (CH3(3)) at 1.33 ppm and methine proton (CH(2)) at 4.11 ppm were observed in Lac. Cross peaks between the methyl protons (CH3) at 3.03 ppm and methylene protons (CH2) at 3.93 ppm were observed in Cr. Cross peaks between the methylene protons (CH2(3)) at 2.11 ppm and methylene protons (CH2(4)) at 2.35 ppm, and between the methylene protons(CH2 (3)) at 2.11 ppm and methine proton (CH(2)) at 3.76 ppm were observed in Glu. Cross peaks between the methylene protons (CH2 (3)) at 2.14 ppm and methine proton (CH(2)) at 3.79 ppm were observed in Gln. Cross peaks between the methine proton (CH(5)) at 3.27 ppm and the methine proton (CH(4,6)) at 3.59 ppm, and between the methine proton (CH(1,3)) at 3.53 ppm and methine proton (CH(2)) at 4.05 ppm were observed in Ins. CONCLUSION: The present study demonstrated that in vitro 2D-COSY and NOESY represented the 3-bond and spatial connectivity of human brain metabolites by scalar coupling and dipolar NOE interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2DCOSY study.

Measurement and Assessment of Absolute Quantification from in Vitro Canine Brain Metabolites Using 500 MHz Proton Nuclear Magnetic Resonance Spectroscopy: Preliminary Results

The purpose of this study was to confirm the exactitude of in vitro nuclear magnetic resonance spectroscopy (NMRS) and to complement the defect of in vivo NMRS. It has been difficult to understand the metabolism of a cerebellum using in vivo NMRS owing to the generated inhomogeneity of magnetic fields (B0 and B1 field) by the complexity of the cerebellum structure. Thus, this study tried to more exactly analyze the metabolism of a canine cerebellum using the cell extraction and high resolution NMRS. In order to conduct the absolute metabolic quantification in a canine cerebellum, the spectrum of our phantom included in various brain metabolites (i.e., NAA, Cr, Cho, Ins, Lac, GABA, Glu, Gln, Tau and Ala) was obtained. The canine cerebellum tissue was extracted using the methanol-chloroform water extraction (M/C extraction) and one group was filtered and the other group was not under extract processing. Finally, NMRS of a phantom solution and two extract solution (90% D2O) was progressed using a 500MHz (11.4 T) NMR machine. Filtering a solution of the tissue extract increased the signal to noise ratio (SNR). The metabolic concentrations of a canine cerebellum were more close to rat's metabolic concentration than human's metabolic concentration. The present study demonstrates the absolute quantification technique in vitro high resolution NMRS with tissue extraction as the method to accurately measure metabolite concentration.

Evaluation of Antidepressant Drug Effect in a Depressive Animal Model by Proton MR Spectroscopy / 의학물리

In this study, we observed the alteration of choline signal intensity in hippocampus region of the depressive rat model induced by forced swimming test (FST). The purpose of this study was to evaluate the antidepressant efficacy in the depressive animal model using MR spectroscopy. Fourteen experimentally naive male Sprague-Dawley rats weighting 160~180 g were used as subjects. Drug injection group was exposed to the FST except for control group. The drugs were administered subcutaneously (SC) in a volume equivalent to 2 ml/kg. And three injections were administered 23, 5, and 1 h before beginning the given test. 1H MR spectra were obtained with use of a point resolved spectroscopy (PRESS) localization sequence performed according to the following parameters: repetition time, 2500 ms; echo time, 144 ms; 512 average; 2048 complex data points; voxel dimensions, 1.5x2.5x2.5 mm3; acquisition time, 25 min. There were no differences in NAA/Cr and Cho/Cr ratio between the right and the left hippocampus both normal control rats and antidepressant-injected rats. Also, no differences were observed in NAA/Cr and Cho/Cr ratio between the normal control rats and the antidepressant-injected rats both the right and the left hippocampus. In this study, we found the recovery of choline signals in the depressive animal model similar to normal control groups as injecting desipramine-HCl which was antidepressant causing anti-immobility effects. Thus, we demonstrated that MR spectroscopy was able to aid in evaluating the antidepressant effect of desipramine-HCl.

Assessment on Gastrointestinal Transit Movement of Capsule Endoscopy in Beagle Dogs / 의학물리

The object of this study is to measure the transit time and passage rate of capsule endoscopy (CE) in the gastrointestinal tract in medium sized beagle dogs (7~13 kg). Animals were divided into four groups: only capsule (group 1, n=10), capsule+water (group 2, n=10), mettoclopramide+capsule (group 3, n=10), metoclopramide +capsule+water (group 4, n=10). The capsule transit times through the stomach and small bowel were evaluated by radiography findings. Gastric transit time (GTT), small intestinal transit time (SITT) and complete passage rate were measured in four groups. GTT's for each group were as follows; 45+/-20 min (group 1), 117+/-35 min (group 2), 150+/-40 min (group 3), and 154+/-65 min (group 4), while SITT's were 75+/-20 min (group 1), 195+/-55 min (group 2), 70+/-15 min (group 3), and 76+/-15 min (group 4). The complete passage rates were 20% (group 1), 40% (group 2), 20% (group 3), 50% (group 4). In all groups, if CE could pass through the pylorus, it passed all small intestinal tracts within 8 hours (battery life). Administration of water helped CE to pass pylori, except in case of metoclopramide administration. These results indicate that CE could be an useful tool for examining gastrointestinal diseases in the veterinary medicine.

Development of Solenoid RF Coil for Animal Imaging in 3T High Magnetic Field MRI

PURPOSE: The purpose of the present study was to develop and optimize solenoid coil for animal- model in 3 T MRI system and investigate and compare with the birdcage coil concerning the image quality with the various parameters such as SNR and Q-factor. MATERIALS AND METHODS: Solenoid coil for animal-model was made on the acryl structure (diameter 4 cm, length 10 cm) 3 times-winding cooper tape of width 2 cm , thickness 0.05 cm and length 10 cm with 2 cm interval between winded tapes. Capacitors from 2 pF to 100 pF were used, and the solenoid coil was designed for receiver only coil. RESULTS: SNR of the developed solenoid was 985 in CuSO4 0.7 g/L and 995 in rat experiment. Q-factor was 84-89 in unloaded condition and 203-206 in loaded condition. CONCLUSION: The resolution of the image obtained from solenoid was relatively higher than that of the conventional birdcage coil. In addition, the homogeneity of RF field by coil simulation was significantly excellent. The present study demonstrated that the solenoid coil could be useful to obtain small animal images with better contrast, resolution, visibility than images from birdcage.

Investigation of Varied MR Spectra by TE and Metabolite Amount in the Localized Voxel using the MR Cone-shape Phantom / 의학물리

The purpose of this study is to investigate the spectra of a magnetic resonance spectroscopy (MRS) in accordance with the variance of TE and the volumes of metabolites in a localized voxel for the quality assurance using a designed single voxel spectroscopy QA phantom. Because a cone-shape phantom is designed as the volume of metabolite in a localized voxel is changeable, we try to analyze the peaks of each metabolite (NAA, Cr, Cho, Lac, etc.) in accordance with metabolite volume in a localized voxel as well as echo time (TE). All data were obtained using a 3T MRI/MRS machine and analyzed using jMRUI(R). The results of this study show that TE is in inverse proportion to the noise of MRS and the longer TE and the less metabolite volume in the localized voxel, the peak intensities of each metabolite decrease. In case of the lactate, its peak was observed on the all TE only if the greatest metabolite is included in the localized voxel. Then, the intensity of a metabolite is more sensitive to the metabolite volume in the localized voxel than the TE. These obtained in vitro MRS data is provide the guideline that is important for in vivo metabolite quantification. But, in the edge of cone-shape vial air bubbles were observed and spectrum could not obtained. Therefore our cone-shape MRS phantom needs to be modified in order to solve these problems.