• Journal of Biomedical Engineering Research
• /
• v.27 no.2
• /
• pp.53-58
• /
• 2006

In this study, transverse relaxation time (T2) measurement and the evaluation of the characteristics of the spectral peak related to stomach tissue metabolites were performed using ex vivo proton magnetic resonance spectroscopic imaging (MRSI) at 1.5-T MRI/S instruments. Thirty-two gastric tissues resected from 12 patients during gastric cancer surgery, of which 19 were normal tissue and 13 were cancerous tissue, were used to measure the $T_2$ of the magnetic resonance spectroscopy (MRS) peaks. The volume of interest data results from the MRSI measurements were extracted from the proper muscle (MUS) layer and the composite mucosa/submucosa (MC/SMC) layer and were statistically analyzed. MR spectra were acquired using the chemical shift imaging (CSI) point resolved spectroscopy (CSI-PRESS) technique with the parameters of pulse repetition time (TR) and echo times (TE) TR/(TE1,TE2)=1500 msec/(35 msec, 144 msec), matrix $size=24{\times}24$, NA=1, and voxel $size=2.2{\times}2.2{\times}4mm^3$. In conclusion, the measured $T_2$ of the metabolite peaks, such as choline (3.21ppm) and lipid (1.33ppm), were significantly decreased (p<0.01 and p<0.05, respectively) in the cancerous stomach tissue.

• Biomolecules & Therapeutics
• /
• v.7 no.4
• /
• pp.362-370
• /
• 1999

Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents(wax, flavonoids, phenolic compounds, etc.) and has been used in traditional medicines as early as 300 B.C. It was been demonstrated that ethanol, acetylsalicylic acid, ischemia reperfusion, non-steroidal antiin-flammatory drugs and stress induce gastric lesions by promoting the generation of reactive oxygen metabolites. Therefore, some drugs that are capable of scavenging or inhibiting the generation of reactive oxygen radicals might be expected to prevent the gastric mucosal injury. The aim of this study was 1) to examine the antiulcer effect of propolis, 2) to investigate the mechanism of action by determining gastric acid secretion, lipid per-oxidation, mucus content and proton pump ($H^+$/$K^+$-ATPase) activity on gastric mucus in varios experimental models, and finally, 3) to isolate and identify the pure compounds that exert antiulcer activity. Step 2-1 and 2-3 sub-sub fraction shoed a significant reduction of severity of gastirc damage at the dose of 25 mg/kg in various experimental models. We isolated 4 sub-sub-sub fractions by flash column chromatography of Step 2-1 sub-sub fraction and one sub-sub-sub fraction by recrystalization of Step 2-3 sub-sub fraction. The protective effects of propolis sub-sub-sub fraction manifested sifnificant effects in HCl-ethanol induced gastric erosion model and aspirin induced gastric ulcer model. These results showed that the gastric mucosal protective effect of propolis might result from the increase of mucus secretion, free radical scavenging effect as well as the reduction of acid secretion in accordance with the reduction of $H^+$/$K^+$-ATPase activitv. Three compounds were isolated and identified from sub-sub fraction of propolis which showed antiulcer effects. Subsequently, these compounds were identified as a flavonoid, namely, 2-acetoxy-5,7,-dihydroxy-flavanone, galangin and chrysin.

• BMB Reports
• /
• v.45 no.7
• /
• pp.419-424
• /
• 2012

High-fat diets (HFD) and high-carbohydrate diets (HCD)-induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ($^1H$ NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from $^1H$ NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that $^1H$ NMR-based metabolomics can identify diet-dependent perturbations in biological pathways.

• Journal of the Korean Society of Radiology
• /
• v.8 no.1
• /
• pp.35-42
• /
• 2014

The purpose of this study is to know the differences of metabolism in abnormal brain disease using a single-voxel proton MR spectroscopy(1H MRS) Together with five normal volunteers and each five patients with brain diseases, pathologically proved, underwent MRI and 1H MRS. The quantitative results of 1H MRS in adrenoleukodystrophy(ALD), hepatic encephalopathy(HE), and infarction gave unique information on the metabolite changes related with the white matter: the concentration of NAA decreased in all diseases; Cho, mI and Lac increased in ALD; Cho decreased in HE; and ${\beta}{\cdot}{\gamma}$-Glx and Lac increased in infarction. It is concluded that 1H MRS is capable of diagnosing brain diseases by monitoring metabolite changes in vivo that subsequently develope into abnormalities. 1H MRS may be a useful clinical tool for in both diagnosis and prognosis of brain diseases.

• Archives of Pharmacal Research
• /
• v.28 no.10
• /
• pp.1196-1202
• /
• 2005

Omeprazole (OMP) is a proton pump inhibitor used as an oral treatment for acid-related gastrointestinal disorders. In the liver, it is primarily metabolized by cytochrome P-450 (CYP450) isoenzymes such as CYP2C19 and CYP3A4. 5-Hyroxyomeprazole (5-OHOMP) and omeprazole sulfone (OMP-SFN) are the two major metabolites of OMP in human. Cimetidine (CMT) inhibits the breakdown of drugs metabolized by CYP450 and reduces, the clearance of coad-ministered drug resulted from both the CMT binding to CYP450 and the decreased hepatic blood flow due to CMT. Phenobarbital (PB) induces drug metabolism in laboratory animals and human. PB induction mainly involves mammalian CYP forms in gene families 2B and 3A. PB has been widely used as a prototype inducer for biochemical investigations of drug metabolism and the enzymes catalyzing this metabolism, as well as for genetic, pharmacological, and toxicological investigations. In order to investigate the influence of CMT and PB on the metabolite kinetics of OMP, we intravenously administered OMP (30 mg/kg) to rats intraperitoneally pretreated with normal saline (5 mL/kg), CMT (100 mg/kg) or PB (75 mg/kg) once a day for four days, and compared the pharmacokinetic parameters of OMP. The systemic clearance ($CL_{t}$) of OMP was significantly (p<0.05) decreased in CMT-pretreated rats and significantly (p<0.05) increased in PB-pretreated rats. These results indicate that CMT inhibits the OMP metabolism due to both decreased hepatic blood flow and inhibited enzyme activity of CYP2C19 and 3A4 and that PB increases the OMP metabolism due to stimulation of the liver blood flow and/or bile flow, due not to induction of the enzyme activity of CYP3A4.

• Investigative Magnetic Resonance Imaging
• /
• v.12 no.1
• /
• pp.20-26
• /
• 2008

Purpose : To present the T1 and T2 relaxation times of the major cerebral metabolites at 1.5T and 3.0T and compare those between 1.5T and 3.0T. Materials and Methods : Using the phantom containing N-acetyl aspartate (NAA), Choline (Cho), and Creatine (Cr) at both 1.5T and 3.0T MRI, the T1 relaxation times were calculated from the spectral data obtained with 5000 ms repetition time (TR), 20 ms echo time (TE), and 11 different mixing time (TM)s using STEAM (STimulated Echo-Acquisition Mode) method. The T2 relaxation times were obtained from the spectral data obtained with 3000 ms TR and 5 different TEs using PRESS (Point-RESolved Spectroscopy) method. The T1 and T2 relaxation times obtained at 1.5T were compared with those of 3.0T. Results : The T1 relaxation times of NAA were $2293\;{\pm}\;48\;ms$ at 1.5T and $2559\;{\pm}\;124\;ms$ at 3.0T (11.6% increase at 3.0T). The T1 relaxation times of Cho were $2540\;{\pm}\;57\;ms$ at 1.5T and $2644\;{\pm}\;76\;ms$ at 3.0T (4.1% increase at 3.0T). The T1 relaxation times of Cr were $2543\;{\pm}\;75\;ms$ at 1.5T and $2665\;{\pm}\;94\;ms$ at 3.0T (4.8% increase). The T2 relaxation times of NAA were $526\;{\pm}\;81\;ms$ at 1.5T and $468\;{\pm}\;74\;ms$ at 3.0T (11.0% decrease at 3.0T). The T2 relaxation times of Cho were $220\;{\pm}\;44ms$ at 1.5T and $182\;{\pm}\;35\;ms$ at 3.0T (17.3% decrease at 3.0T). The T2 relaxation times of Cr were $289\;{\pm}\;47\;ms$ at 1.5T and $275\;{\pm}\;57\;ms$ at 3.0T (4.8% decrease at 3.0T). Conclusion : The T1 relaxation times of the major cerebral metabolites (NAA, Cr, Cho), which were measured at the phantom, were 4.1%-11.6% longer at 3.0T than at 1.5T. The T2 relaxation times of them were 4.8%-17.3% shorter at 3.0T than at 1.5T. To optimize MR spectroscopy at 3.0T, TR should be lengthened and TE should be shortened.

• Investigative Magnetic Resonance Imaging
• /
• v.13 no.2
• /
• pp.117-126
• /
• 2009

Purpose : A numerical method of designing a multiple quantum filter (MQF) is presented for the optimum detection of myo-inositol (mI), an important brain metabolite, by using in vivo proton nuclear magnetic resonance spectroscopy ($^1$-HMRS). Materials and Methods : Starting from the characterization of the metabolite, the filter design includes the optimization of the sequence parameters such as the two echo times (TEs), the mixing time (TM), and the flip angle and offset frequency of the 3rd $90^{\circ}$ pulse which converts multiple quantum coherences (MQCs) back into single quantum coherences (SQCs). The optimized filter was then tested both in phantom and in human brains. Results : The results demonstrate that the proposed MQF can improve the signal-to-background ratio of the target metabolite by a factor of more than three by effectively suppressing the signal from the background metabolites. Conclusion : By incorporating a numerical method into the design of MQFs in $^1$-HMRS the spectral integrity of a target metabolite, in particular, with a complicated spin system can be substantially enhanced.

• Korean Journal of Radiology
• /
• v.1 no.1
• /
• pp.25-32
• /
• 2000

Objective: The purpose of our study was to determine the ability of H-1 MR spectroscopy (MRS) to lateralize the lesion in patients with hippocampal sclerosis. Materials and Methods: Twenty healthy volunteers and 25 patients with intractable temporal lobe epilepsy whose MR imaging diagnosis was unilateral hippocampal sclerosis were included. This diagnosis was based on the presence of unilateral atrophy and/or high T2 signal intensity of the hippocampus. Single-voxel H-1 MRS was carried out on a 1.5-T unit using PRESS sequence (TE, 136 msec). Spectra were obtained from hippocampal areas bilaterally with volumes of interest (VOIs) of 6.0 cm³ and 2.25 cm³ in healthy volunteers, and of either 6.0 cm³ (n = 14) or 2.25 cm³ (n = 11) in patients. Metabolite ratios of NAA/Cho and NAA/Cr were calculated from relative peak height measurements. The capability of MRS to lateralize the lesion and to detect bilateral abnormalities was compared with MR imaging diagnosis as a standard of reference. Results: In healthy volunteers, NAA/Cho and NAA/Cr ratios were greater than 0.8 and 1.0, respectively. In patients, the mean values of these ratios were significantly lower on the lesion side than on the contralateral side, and lower than those of healthy volunteers (p < .05). The overall correct lateralization rate of MRS was 72% (18/25); this rate was lower with a VOI of 6.0 cm³ than of 2.25 cm³ (64% versus 82%, p < .05). Bilateral abnormalities on MRS were found in 24% (6/25) of cases. Conclusion: Although its rate of correct lateralization is low, single-voxel H-1 MRS is a useful and promising diagnostic tool in the evaluation of hippocampal sclerosis, particularly for the detection of bilateral abnormalities. To improve the diagnostic accuracy of H-1 MRS, further investigation, including the use of a smaller VOI and measurement of the absolute amount of metabolites, are needed.

• The Korean Journal of Nuclear Medicine
• /
• v.34 no.6
• /
• pp.465-477
• /
• 2000

Purpose: Thallim-201 ($^{201}Tl$) brain SPECT and proton ($^1H$) magnetic resonance spectroscopy (MRS) have been used to evaluate tumor grade and viability of glioma. We assessed the correlations between $^{201}Tl$ brain index or spectrum of metabolites of $^1H$ MRS and grade of glioma or histopathologic findings. Materials and Methods: We studied 17 patients (4 astrocytoma, 7 anaplastic astrocytoma and 6 glioblastoma). On $^{201}Tl$ Brain SPECT, $^{201}Tl$ index was measured as the ratio of average counts for region of interest to those for the contralateral normal brain. On $^1H$ MRS, we calculated choline (Cho) /creatine (Cr) ratio and N-acetylaspartate (NAA)/Cr ratio in ROI defined as tumor center. Histopathologic findings were graded by Ki-67 index, cellularity, mitosis, pleomorphism, necrosis and endothelial proliferation. An unpaired t test and statistical correlations were performed to evaluate these data. Results: Tl-index showed the best correlation with Ki-67 index (p<0.01), less correlations with cellularity, mitosis, and endothelial proliferation, but no correlation with results of MRS, pleomorphism, or necrosis. The findings of MRS did not correlate with all of the above. The cases of glioblastoma demonstrated a higher Tl-index, Cho/cr ratio, Ki-67 index and lower NAA/Cr ratio, albeit without statistical significance. Conclusion: Even though $^{201}Tl$ brain SPECT did not correlate directly with grade of malignancy, it may still be useful in determining biological aggressiveness of tumor and prognosis of patients because it correlated well with Ki-67 index, a growth fraction of glioma, cellularity, mitosis and endothelial proliferation.

• Progress in Medical Physics
• /
• v.13 no.3
• /
• pp.120-128
• /
• 2002

To investigate differences between the metabolic ratios of normal controls and brain tumors such as astrocytomas and glioblastoma multiforme (GM) by proton MR spectroscopy (MRS) at 37 high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxel technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67$\pm$018 and 1.16$\pm$0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (P=0.005). Cho/Cr ratio of glioblastoma multiforme was significantly higher than that of astrocytomas (P=0.001). Lactate was observed in all tumor cases. The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. This results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.