• Proceedings of the Korean Society of Medical Physics Conference
• /
• 2002.09a
• /
• pp.345-351
• /
• 2002

The purpose of this study was to assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating brain tumor malignancy at 3T high field system. Using 3T MRI/MRS system, localized water-suppressed single-voxe1 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), but Cho/Cr ratio of all tumor tissue was significantly higher (p=0.001). Cho/Cr ratio of high-grade gliomas was significantly higher than that of low-grade gliomas (P=0.001). Except 4 menigiomas, lactate signal 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. Our results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.8
• /
• pp.2413-2418
• /
• 2013

Forensic and legal medicine require reliable data to indicate excessive alcohol consumption. Ethanol is oxidatively metabolized to acetate by alcohol dehydrogenase and non-oxidatively metabolized to ethyl glucuronide (EtG), ethyl sulfate (EtS), phosphatidylethanol, or fatty acid ethyl esters (FAEE). Oxidative metabolism is too rapid to provide biomarkers for the detection of ethanol ingestion. However, the non-oxidative metabolite EtG is a useful biomarker because it is stable, non-volatile, water soluble, highly sensitive, and is detected in body fluid, hair, and tissues. EtG analysis methods such as mass spectroscopy, chromatography, or enzyme-linked immunosorbent assay techniques are currently in use. We suggest that nuclear magnetic resonance (NMR) spectroscopy could be used to monitor ethanol intake. As with current conventional methods, NMR spectroscopy doesn't require complicated pretreatments or sample separation. This method has the advantages of short acquisition time, simple sample preparation, reproducibility, and accuracy. In addition, all proton-containing compounds can be detected. In this study, we performed $^1H$ NMR analyses of urine to monitor the ethanol and EtG. Urinary samples were collected over time from 5 male volunteers. We confirmed that ethanol and EtG signals could be detected with NMR spectroscopy. Ethanol signals increased immediately upon alcohol intake, but decreased sharply over time. In contrast, EtG signal increased and reached a maximum about 9 h later, after which the EtG signal decreased gradually and remained detectable after 20-25 h. Based on these results, we suggest that $^1H$ NMR spectroscopy may be used to identify ethanol non-oxidative metabolites without the need for sample pretreatment.

• Korean Journal of Agricultural Science
• /
• v.45 no.3
• /
• pp.447-454
• /
• 2018

Zearalenone (ZEN), a mycotoxin produced by Fusarium in food and feed, causes serious damage to the health of humans and livestock. Therefore, we compared the metabolomic profiles in the liver, serum, and urine of piglets fed a ZEN-contaminated diet using proton nuclear magnetic resonance ($^1H-NMR$) spectroscopy. The spectra from the three different samples, treated with ZEN concentrations of 0.8 mg/kg for 4 weeks, were aligned and identified using MATLAB. The aligned data were subjected to discriminating analysis using multivariate statistical analysis and a web server for metabolite set enrichment analysis. The ZEN-exposed groups were almost separated in the three different samples. Metabolic analysis showed that 28, 29, and 20 metabolites were profiled in the liver, serum, and urine, respectively. The discriminating analysis showed that the alanine, arginine, choline, and glucose concentrations were increased in the liver. Phenylalanine and tyrosine metabolites showed high concentrations in serum, whereas valine showed a low concentration. In addition, the formate levels were increased in the ZEN-treated urine. For the integrated analysis, glucose, lactate, taurine, glycine, alanine, glutamate, glutamine, and creatine from orthogonal partial least squares discriminant analysis (OPLS-DA) were potential compounds for the discriminating analysis. In conclusion, our findings suggest that potential biomarker compounds can provide a better understanding on how ZEN contaminated feed in swine affects the liver, serum, and urine.

• Journal of the Korean Society of Radiology
• /
• v.5 no.6
• /
• pp.401-407
• /
• 2011

The purpose of this study is to know the differences of MR spectra, obtained from normal volunteers by variable TE value, through the quantitative analysis of brain metabolites by peak integral and SNR between 1.5T and 3.0T, together with PRESS and STEAM pulse sequence. Single-voxel MR proton spectra of the human brain obtained from normal volunteers at both 3.0T MR system (Magnetom Trio, SIEMENS, Germany) and 1.5T MR system (Signa Twinspeed, GE, USA) using the STEAM and PRESS pulse sequence. 10 healthy volunteers (3.0T:3 males, 2 females; 1.5T : 3 males, 2 females) with the range from 22 to 30 years old (mean 26 years) participated in our study. They had no personal or familial history of neurological diseases and had a normal neurological examination. Data acquisition parameters were closely matched between the two field strengths. Spectra were recorded in the white matter of the occipital lobe. Spectra were compared in terms of resolution and signal-to-noise ratio(SNR), and echo time(TE) were estimated at both field strengths. Imaging parameters was used for acquisition of the proton spectrum were as follow : TR 2000msec, TE 30ms, 40ms, 50ms, 60ms, 90ms, 144ms, 288ms, NA=96, VOI=$20{\times}20{\times}20mm3$. As the echo times were increased, the spectra obtained from 3.0T and 1.5T show decreased peak integral and SNR at both pulse sequence. PRESS pulse sequence shows higher SNR and signal intensity than those of STEAM. Especially, Spectra in normal volunteers at 3.0T demonstrated significantly improved overall SNR and spectral resolution compared to 1.5T(Fig1). The spectra acquired at short echo time, 3T MR system shows a twice improvement in SNR compared to 1.5T MR system(Table. 1). But, there was no significant difference between 3.0Tand 1.5T at long TE It is concluded that PRESS and short TE is useful for quantification of the brain metabolites at 3.0T MRS, our standardized protocol for quantification of the brain metabolites at 3.0T MRS is useful to evaluate the brain diseases by monitoring the systematic changes of biochemical metabolites concentration in vivo.

• Investigative Magnetic Resonance Imaging
• /
• v.16 no.1
• /
• pp.40-46
• /
• 2012

Purpose : To investigate the feasibility of in vivo proton magnetic resonance spectroscopy (MRS) for evaluation of lung cancer. Materials and Methods: This prospective study was approved by the institutional review board of our hospital and informed consent was obtained in all patients. Ten patients (7 men, 3 women; mean age, 64.4) with pathologicallyproven lung cancer (mean, 56.8 mm; range, 44-77 mm) were enrolled to 1.5 T MRS using a single-voxel respiration-triggered point-resolved spectroscopic sequence. Technical success rate and the reason of technical failure, if any, were investigated. Results: Out of 10 lung cancers, analyzable MRS spectra were obtained in 8 tumors (technical success rate, 80%). Two MRS datasets were not able to be analyzed due to serious baseline distortion. Choline and lipid signals were detected as major metabolites in analyzable MRS spectra. Conclusion: In vivo proton MRS method using a single-voxel respiration-triggered point-resolved spectroscopic sequence is feasible in obtaining the MR spectra of lung cancer because these spectra were analyzable and high success rate was shown in our study although there was the limitation of small patient group.

• Biomolecules & Therapeutics
• /
• v.26 no.1
• /
• pp.4-9
• /
• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• Proceedings of the KOSOMBE Conference
• /
• v.1998 no.11
• /
• pp.121-122
• /
• 1998

To induce perturbed magnetic field variations in the range of auto prescans permitted, we chose artificially shim values and applied manualy as DC offsets to X, Y, Z gradient amplifiers. The STEAM spectra were obtained from a localized region (8ml) of phantom's center and a Marquart Algorithm is employed to quantify MRS spectra. Results indicated that Creatine (Cr) which had a good correlation between a signal intensity and an area, changed little bit and showed extremly a stabilized state in perturbed magnetic field variations. Therefore, during the MRS experiments, to minimize the SNR reduction by means of unavoidable inhomogeneous magnetic fields, the present study suggested that the quantification method of relative ratios produced by replacing Cr concentration with standard quantify was most desirable.

• Progress in Medical Physics
• /
• v.11 no.1
• /
• pp.73-83
• /
• 2000

In this study, we investigate the effects of poor shimming on quantitative measurement of ratios of metabolite levels by proton magnetic resonance spectroscopy ($^1$H MRS). Coefficient of variation (COV) of metabolite ratios for point resolved spectroscopy (PRESS) and stimulated-echo acquisition mode (STEAM) spectra was evaluated from a phantom containing in vivo levels of metabolites using a conventional whole body 1.5T MR system and conventional acquisition and analysis protocol. A statistical P-value was also calculated from a linear regression for relationship of metabolite ratios. N-acetylaspartate (NAA)/ creatine (Cr) and NAA/ choline (Cho) had low COV values for the long and short TE spectra (29.1 and 27.5%; 23.8 and 12.6 %), whereas Cho/Cr and Cr/Cho had high COV values (50.0 and 68.6 %; 27.5 and 29.3 %). A linear relationship between NAA/Cr and Cho/Cr, and between NAA/Cho and Cr/Cho revealed the statistical significance in the long and short TE spectra, respectively (P < 0.0001 and P < 0.0001; P = 0.015 and P = 0.005). There was no significant relationship between Cho/NAA and Cr/NAA in the measurement (P = 0.159; P = 0.910). The present study suggested that NAA/Cr and NAA/Cho could be useful for data with poor shimming in $^1$H MR spectroscopy. In conclusion, statistical significance of metabolite ratios indicated that the Cr and Cho levels could be interpreted as a significant alteration factor in the long and short TE spectra, and then should be used with care to provide precise metabolite quantification.

• Investigative Magnetic Resonance Imaging
• /
• v.7 no.1
• /
• pp.31-38
• /
• 2003

Purpose : To analyze the serial changes of proton magnetic resonance (MR) spectra in the abscess and to determine the effect of the antibiotic treatment on the metabolite patterns. Materials and Methods : MR imaging and MR spectroscopy of an experimentally induced abscess were performed sequentially for four weeks at interval of one week in both the control group (n=5) and the antibiotic treatment group (n=5). On MR imaging, the shape and the size of the abscess were analyzed. On MR spectroscopy, the resonance peaks of metabolites were assigned on the basis of reported peaks in the literature. The metabolite ratios measured by using N-acetyl alanine as an external reference and by using lipid as an internal reference were compared in both the control and treatment g roups. Results : The abscesses were seen as cystic masses on MR imaging. On MR spectroscopy, the variable peaks of acetate, succinate and various amino acids, which are the metabolites of infection, were identified in the control and antibiotic treatment groups. The most frequent peak was that of acetate at 1.92ppm (70%). Both the peak ratios of acetate to lipid and acetate to external reference tended to decrease in the treatment group while the ratios did not change significantly in the control group. Conclusion : MR spectroscopy is useful not only for the diagnosis of abscess but also for monitoring the evolution of the abscess by using the acetate peak.

• Journal of Korean Neurosurgical Society
• /
• v.29 no.11
• /
• pp.1421-1428
• /
• 2000

Objectives : The aim of this study is to evaluate the sequential metabolic changes in experimental hydrocephalus and the clinical applicability to the diagnosis and prognosis of hydrocephalus using proton MR spectroscopy. Methods : Hydrocephalus was experimentally induced in 30 cats(2-3kg body weight) by injecting 1ml of sterile kaolin suspension(250mg/ml) into the cisterna magna. Proton MRS was performed with a 1.5 T MRI/MRS unit (Vision Plus, Siemens) at pre-treatment and at 1, 3, 7, 14, 21, and 28 days after the kaolin injection. PRESS(TR/TE＝1500/270msec) technique was employed. The major metabolites which include N-acetyl aspartate (NAA), creatine(Cr), choline(Cho), and lactate(Lac) were quantitatively analyzed and the relative concentrations ratios were evaluated. Multislice $T_2$-weighted images were also obtained using fast spin echo sequence(TR/TE＝ 2500/96msec) to monitor the morphologic changes along with progression of hydrocephalus. Results : Hydrocephalus was successfully induced in all 30 cats. Twenty five cats died within 3 days and one at the end of the second week. In all animals, the NAA/Cr ratios initially decreased during the acute stage. In 4 surviving cats, the NAA/Cr ratios initially decreased during the acute stage(<14 days) and then gradually increased to the prekaolin level as follows : pre-kaolin($1.49{\pm}0.04$), day 1($1.11{\pm}0.07$), day 7($1.17{\pm}0.04$), day 14($1.40{\pm}0.03$), day 21 ($1.46{\pm}0.06$), day 28($1.43{\pm}0.03$). These levels were relatively well correlated with the symptomatologic improvement. Lactate peak, which reflects the evidence of ischemia, did not appear throughout the entire period except in one case which expired at the end of the second week. Conclusions : The NAA/Cr ratio of the sequential proton MRS in kaolin-induced hydrocephalic cats reflects a metabolic aspect of the hydrocephalus at each stage. A decreased NAA level at the early stage is from both neuronal and axonal damage which may provide diagnostic information in the acute stage of hydrocephalus. In addition, the initial fall of NAA/Cr ratio and recovery in the late stage, when no lactate peak emerges, may suggest that the main insult of the parenchyma is not to the neuron itself but to the axon, which may be related to a good prognosis. However, emergence of the lactate peak and unrecoverable NAA/Cr at the end of the acute phase may be a poor prognostic factor. In the chronic stage, recovery of NAA/Cr ratio may provide a diagnostic clue for the differentiation between hydrocephalus and cortical atrophy.