• Investigative Magnetic Resonance Imaging
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• v.26 no.2
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• pp.125-134
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• 2022

Purpose: The aim of this study was to investigate the change in signal sensitivity over different acquisition start times and optimize the scanning window to provide the maximal signal sensitivity of [1-¹³C]pyruvate and its metabolic products, lactate and alanine, using spatially localized hyperpolarized 3D ¹³C magnetic resonance spectroscopic imaging (MRSI). Materials and Methods: We acquired 3D ¹³C MRSI data from the brain (n = 3), kidney (n = 3), and liver (n = 3) of rats using a 3T clinical scanner and a custom RF coil after the injection of hyperpolarized [1-¹³C]pyruvate. For each organ, we obtained three consecutive 3D ¹³C MRSI datasets with different acquisition start times per animal from a total of three animals. The mean signal-to-noise ratios (SNRs) of pyruvate, lactate, and alanine were calculated and compared between different acquisition start times. Based on the SNRs of lactate and alanine, we identified the optimal acquisition start timing for each organ. Results: For the brain, the acquisition start time of 18 s provided the highest mean SNR of lactate. At 18 s, however, the lactate signal predominantly originated from not the brain, but the blood vessels; therefore, the acquisition start time of 22 s was recommended for 3D ¹³C MRSI of the rat brain. For the kidney, all three metabolites demonstrated the highest mean SNR at the acquisition start time of 32 s. Similarly, the acquisition start time of 22 s provided the highest SNRs for all three metabolites in the liver. Conclusion: In this study, the acquisition start timing was optimized in an attempt to maximize metabolic signals in hyperpolarized 3D ¹³C MRSI examination with [1-¹³C] pyruvate as a substrate. We investigated the changes in metabolic signal sensitivity in the brain, kidney, and liver of rats to establish the optimal acquisition start time for each organ. We expect the results from this study to be of help in future studies.

• Investigative Magnetic Resonance Imaging
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• v.19 no.4
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• pp.212-217
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• 2015

Purpose: For a single time-point hyperpolarized $^{13}C$ magnetic resonance spectroscopy imaging (MRSI) of animal models, scan-time window after injecting substrates is critical in terms of signal-to-noise ratio (SNR) of downstream metabolites. Pre-scans of time-resolved magnetic resonance spectroscopy (MRS) can be performed to determine the scan-time window. In this study, based on two-site exchange model, protocol-specific simulation approaches were developed for $^{13}C$ MRSI and the optimal scan-time window was determined to maximize the SNR of downstream metabolites. Materials and Methods: The arterial input function and conversion rate constant from injected substrates (pyruvate) to downstream metabolite (lactate) were precalibrated, based on pre-scans of time-resolved MRS. MRSI was simulated using two-site exchange model with considerations of scan parameters of MRSI. Optimal scan-time window for mapping lactate was chosen from simulated lactate intensity maps. The performance was validated by multiple in vivo experiments of BALB/C nude mice with MDA-MB-231 breast tumor cells. As a comparison, MRSI were performed with other scan-time windows simply chosen from the lactate signal intensities of pre-scan time-resolved MRS. Results: The optimal scan timing for our animal models was determined by simulation, and was found to be 15 s after injection of the pyruvate. Compared to the simple approach, we observed that the lactate peak signal to noise ratio (PSNR) was increased by 230%. Conclusion: Optimal scan timing to measure downstream metabolites using hyperpolarized $^{13}C$ MRSI can be determined by the proposed protocol-specific simulation approaches.

• Investigative Magnetic Resonance Imaging
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• v.21 no.1
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• pp.1-8
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• 2017

Purpose: To investigate the exchange and redistribution of hyperpolarized $^{13}C$ metabolites between different pools by temporally analyzing the relative fraction of dual $T_2{^*}$ components of hyperpolarized $^{13}C$ metabolites. Materials and Methods: A dual exponential decay analysis of $T_2{^*}$ is performed for [1-$^{13}C$] pyruvate and [1-$^{13}C$] lactate using nonspatially resolved dynamic $^{13}C$ MR spectroscopy from mice brains with tumors (n = 3) and without (n = 4) tumors. The values of shorter and longer $T_2{^*}$ components are explored when fitted from averaged spectrum and temporal variations of their fractions. Results: The $T_2{^*}$ values were not significantly different between the tumor and control groups, but the fraction of longer $T_2{^*}$ [1-$^{13}C$] lactate components was more than 10% in the tumor group over that of the controls (P < 0.1). The fraction of shorter $T_2{^*}$ components of [1-$^{13}C$] pyruvate showed an increasing tendency while that of the [1-$^{13}C$] lactate was decreasing over time. The slopes of the changing fraction were steeper for the tumor group than the controls, especially for lactate (P < 0.01). In both pyruvate and lactate, the fraction of the shorter $T_2{^*}$ component was always greater than the longer $T_2{^*}$ component over time. Conclusion: The exchange and redistribution of pyruvate and lactate between different pools was investigated by dual component analysis of the free induction decay signal from hyperpolarized $^{13}C$ experiments. Tumor and control groups showed differences in their fractions rather than the values of longer and shorter $T_2{^*}$ components. Fraction changing dynamics may provide an aspect for extravasation and membrane transport of pyruvate and lactate, and will be useful to determine the appropriate time window for acquisition of hyperpolarized $^{13}C$ images.

• Journal of Korean Neurosurgical Society
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• v.29 no.9
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• pp.1233-1237
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• 2000

Objectives : In order to evaluate the metabolic changes associated with pericontusional edematous area in mild head injury, proton magnetic resonance spectroscopy(1H-MRS) was performed in mild head injury patients (initial GCS score 13-15) with focal brain contusion. Methods : Seven head injury patients with initial GCS 13-15(3 males and 4 females : age range 15-65 years, mean age 33 years) have underwent 1H-MRS evaluations. The patients were examined within 7 days after injury(n=7) and 2 months after injury(n=5). The region of interest(ROI) was selected in the edematous area adjacent to traumatic brain contusion upon T2-weighted MR images and a corresponding region of the contralateral hemisphere (ROC, region of contralateral corresponding hemisphere) was examined as well. The metabolic ratios of NAA/Cr and lactate/Cr were compared between ROIs, ROCs and control values. Results : In initial NAA/Cr ratios, the values of ROIs were significantly lower than those of the controls(p=0.009), but there was no difference either between ROIs and ROCs(p=0.410) or between ROCs of patients and the control (p=0.199). In lactate/Cr ratios, the ROIs in all seven patients and the ROCs in two showed increased lactate signals. The lactate/Cr ratios of the ROIs were significantly elevated as compared to those of the ROCs(p=0.02) and the control(p=0.015). In two months follow-up, lactate signals were absent or significantly reduced(p=0.015). In no patients, clinical or radiological deterioration has been observed. Conclusion : Our 1H-MRS results demonstrate that there are significant ischemic changes in pericontusional edematous areas as indicated by elevated lactate signals in the patients with mild head injury. But there were no consistent neural loss or dysfunction in these area. There findings suggest that pericontusional edematous areas can be vulnerable to secondary brain insults even in the patients with mild head injury.

• Investigative Magnetic Resonance Imaging
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• v.3 no.1
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• pp.47-52
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• 1999

Purpose : The purpose of this study was aimed to evaluate the BOLD(blood oxygen level dependent) contrast fMRI(functional MR imaging) in the occipital lobe and to compare with the metabolic changes based on H MRS (MR spectroscopy) and MRSI (MR spectroscopic imaging) before and after visual stimulation Materials and Methods : Healthy human volunteers (eight males and two females with 24-30 year age) participated in this study. All of the BOLD fMRI were acquired on a 1.5T MR with EPI during supervised visual stimulation in the occipital lobe. The red flicker with 8Hz was used for visual stimulation. After imaging acquisition, the MR images were transferred into unix workstation and processed with acquired from the same location based on the activation map. MRSI (magnetic resonance spectroscopic imaging) was also acquired to analyze the lactate changes before and after stimulation. Results : The activation maps were successfully produced by BOLD effect due to visual stimulation. NAA (N-acetyle aspartate)/Cr (creatine) ratio varied only from $1.79{\pm}0.28{\;}to{\;}1.88{\pm}0.20$ in activation area before and after stimulation. However, the signal intensity of lactate was elevated $9.48{\pm}4.38$ times higher than before activation. Lactate metabolite images were consistent with the activation maps. Conclusion : The BOLD contrast fMRI is enough sensitive to detect the activated area in human brain during the visual stimulation. Lactate metabolite map presents the evidence of lactate elevation on the same area of activation.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.76-76
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• 2003

Purpose: To assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating tumor malignancy at 3T high field system. Methods: 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. Results: 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 1.16:1:0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (P=0.005). Cho/Cr ratio of 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. Conclusions: 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. Acknowledgement: This study was supported by a grant of the Mid and Long Term Nuclear R/D Plan Program, Ministry of Science and Technology, Republic of Korea.

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

• Investigative Magnetic Resonance Imaging
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• v.20 no.1
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• pp.53-60
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• 2016

Purpose: To develop a technique for quantifying the $^{13}C$-metabolites by performing frequency-selective hyperpolarized $^{13}C$ magnetic resonance spectroscopy (MRS) in vitro which combines simple spectrally-selective excitation with spectrally interleaved acquisition. Methods: Numerical simulations were performed with varying noise level and $K_p$ values to compare the quantification accuracies of the proposed and the conventional methods. For in vitro experiments, a spectrally-selective excitation scheme was enabled by narrow-band radiofrequency (RF) excitation pulse implemented into a free-induction decay chemical shift imaging (FIDCSI) sequence. Experiments with LDH / NADH enzyme mixture were performed to validate the effectiveness of the proposed acquisition method. Also, a modified two-site exchange model was formulated for metabolism kinetics quantification with the proposed method. Results: From the simulation results, significant increase of the lactate peak signal to noise ratio (PSNR) was observed. Also, the quantified $K_p$ value from the dynamic curves were more accurate in the case of the proposed acquisition method compared to the conventional non-selective excitation scheme. In vitro experiment results were in good agreement with the simulation results, also displaying increased PSNR for lactate. Fitting results using the modified two-site exchange model also showed expected results in agreement with the simulations. Conclusion: A method for accurate quantification of hyperpolarized pyruvate and the downstream product focused on in vitro experiment was described. By using a narrow-band RF excitation pulse with alternating acquisition, different resonances were selectively excited with a different flip angle for increased PSNR while the hyperpolarized magnetization of the substrate can be minimally perturbed with a low flip angle. Baseline signals from neighboring resonances can be effectively suppressed to accurately quantify the metabolism kinetics.

• Progress in Medical Physics
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• v.7 no.1
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• pp.37-52
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• 1996

Image-guided localized, water-suppressed in vivo $^1$H MR spectroscopic studies were performed on the patients with brain tumors, acute cerebral infarction and schizophrenia, and dogs. GE Signa 1.5 T whole-body MRI/MRS system using STEAM pulse sequence was used. Proton metabolite ratios relative to creatine (Cr) were obtained using a Marquart algorithm. In vivo $^1$H MR spectra in brain neoplastic tissues revealed the changes of signal intensities of N-acetylaspartate (NAA), choline (Cho) and lactate (Lac) resonances. The present results suggest that the observed metabolite alterations from localized, water-suppressed in vivo $^1$H MR spectroscopy can be useful as an index of brain tumors, cerebral infarction and schizophrenia, and provide good quality metabolic information of cerebral tissue in the field of thanato-chronology.

• Animal Bioscience
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• v.37 no.1
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• pp.61-73
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• 2024

Objective: The main objective of this study was to define molecular mechanisms associated with thermal stress responses of chickens from commercial broilers (BR, Ross 308), Thai native chickens (NT) and crossbreeds between BR×NT (H75). Methods: Twenty days before reaching specific market age, chickens from each breed were divided into control and thermal-stressed groups. The stressed groups were exposed to a cyclic thermal challenge (35℃±1℃ for 6 h, followed by 26℃±1℃ for 18 h) for 20 days. Control group was raised under a constant temperature of 26℃±1℃. Pectoralis major (n = 4) from each group was collected for transcriptome analysis using HiSeq Illumina and analysis of glycogen and lactate. Gene expression patterns between control and thermal-stressed groups were compared within the same breeds. Results: Differentially expressed transcripts of 65, 59, and 246 transcripts for BR, NT, and H75, respectively, were revealed by RNA-Seq and recognized by Kyoto encyclopedia of genes and genomes database. Pathway analysis underlined altered glucose homeostasis and protein metabolisms in all breeds. The signals centered around phosphatidylinositol 3-kinase (PI3K)/Akt signaling, focal adhesion, and MAPK signaling in all breeds with slight differences in molecular signal transduction patterns among the breeds. An extensive apoptosis was underlined for BR. Roles of AMPK, MAPK signaling and regulation of actin cytoskeleton in adaptive response were suggested for H75 and NT chickens. Lower glycogen content was observed in the breast muscles of BR and NT (p<0.01) compared to their control counterparts. Only BR muscle exhibited increased lactate (p<0.01) upon exposure to the stress. Conclusion: The results provided a better comprehension regarding the associated biological pathways in response to the cyclic thermal stress in each breed and in chickens with different growth rates.