• Proceedings of the KSMRM Conference
• /
• 1999.11a
• /
• pp.109-109
• /
• 1999

• Investigative Magnetic Resonance Imaging
• /
• v.2 no.1
• /
• pp.73-82
• /
• 1998

Purpose : A precise NMR technique for measuring the rate of water exchange and cell membrane permeability across the hepatocyte membrane using liver-specific MR contrast agent is described. Materials and Methods : The rat hepatocytes isolated by perfusion of the livers were used for the NMR measurements. All experiments were performed on an IBM field cycling relaxometer operating from 0.02MHz to 60 MHz proton Larmor frequency. spin-echo pulse sequence was empolyed to measure spin-lattice relaxation time, T1. The continuous distribution analysis of water proton T1 data from rat hepatocytes containing low concentrations of the liver specific contrast agent, Gd-EOB-DTPA, modeled by a general two compartment exchange model. Results : The mean residence time of water molecule inside the hepatocyte was approximately 250 msec. The lower limit for the permeability of the hepatocyte membrane was $(1.3{\pm}0.1){\;}{\times}{\;}10^{-3}cm/sec$. The CONTIN analysis, which seeks the natural distribution of relaxation times, reveals direct evidence of the effect of diffusive exchange. the diffusive water exchange is not small in the intracellular space in the case of hepatocytes. Conclusions : Gd-EOB-DTPA, when combined with continuous distribution analysis, provides a robust method to study water exchange and membrane permeability in hepatocytes. Water exchange in hepatocyte is much slower thatn that in red blood cells. Therefore, tissue-specific contrast agent may be used as a functional agent to give physiological information such as cell membrane permeability.

• Proceedings of the KSMRM Conference
• /
• 2007.10a
• /
• pp.45-45
• /
• 2007

• Proceedings of the KSMRM Conference
• /
• 1997.10a
• /
• pp.17-17
• /
• 1997

• Proceedings of the KSMRM Conference
• /
• 1997.10a
• /
• pp.16-16
• /
• 1997

• Investigative Magnetic Resonance Imaging
• /
• v.6 no.1
• /
• pp.35-40
• /
• 2002

Purpose : To evaluate the NMR relaxation properties and imaging characteristics of tissue-specificity for a newly developed macromolecular MR agent. Materials and methods : Phthalocyanine (PC) was chelated with paramagnetic ion, Mn.2.01g (5.2 mmol) of Phthalocyanine was mixed with 0.37g (1.4 mmol) of Mn chloride at $310^{\circ}C$ for 36 hours and then purified by chromatography (CHC13/CH3OH 98/2 v/v, Rf, 0.76) to obtain 1.04g (46%) of MnPC (molecular weight= 2000d). The $T1}T2$ relaxivity of MnPC was measured in 1.5T(64 MHz) MR using 0.1 mM MnPC. The MR image characteristics of MnPC was evaluated using spin-echo (TR/TE=500/14 msec) and gradient-echo (FLASH) (TR/TE=80/4 msec, flip angle=60) techniques in 1.57 MR scanner. The images of rabbit liver were obtained every 10 minutes up to 4 hours. To study the effect of concentration on image, 20 mM, 50 mM, 100 mM of MnPC were tested. Results : The relaxivities of MnPC at 1.5T(64MHz) were Rl=7.28 $mM^{-1}S^{-1},{\;}R2=55.56mM^{-1}S^{-1}$. Compared to the values of Gd-DTPA (Rl[=4.8 $mM^{-1}S^{-1})$], R2[=5.2 $mM^{-1}S^{-1}])$]), both T1/T2 relaxivities of MnPC were higher than those of Gd-DTPA. For both of SE and FLASH techniques, the contrast enhancement reached maximum at 10 minutes after bolus injection and the enhancement continued for more than 2 hours. When compared with small molecular weight liver agents such as Gd-EOB-DTPA, Gd-BOPTA and MnDPDP, MnPC was characterized by more prolonged enhancement time. The time course of MR images also revealed biliary excretion of MnPC. Conclusion : We developed a new macromolecular MR agent, MnPC. The relaxivities of MnPC were higher than those of small molecular weight Gd-chelate. Hepatic uptake and biliary excretion of MnPC suggests that this agent is a new liver-specific MR agent.

• Investigative Magnetic Resonance Imaging
• /
• v.21 no.2
• /
• pp.71-81
• /
• 2017

Purpose: To compare three, motion-resistant, T1-weighted MR sequences on the hepatobiliary phase for gadoxetic acid-enhanced MR imaging of the liver. Materials and Methods: In this retrospective study, 79 patients underwent gadoxetic acid-enhanced, 3T liver MR imaging. Fifty-nine were examined using a standard protocol, and 20 were examined using a motion-resistant protocol. During the hepatocyte-specific phase, three MR sequences were acquired: 1) gradient recalled echo (GRE) with controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA); 2) radial GRE with the interleaved angle-bisection scheme (ILAB); and 3) radial GRE with golden-angle scheme (GA). Two readers independently assessed images with motion artifacts, streaking artifacts, liver-edge sharpness, hepatic vessel clarity, lesion conspicuity, and overall image quality, using a 5-point scale. The images were assessed by measurement of liver signal-to-noise ratio (SNR), and tumor-to-liver contrast-to-noise ratio (CNR). The results were compared, using repeated post-hoc, paired t-tests with Bonferroni correction and the Wilcoxon signed rank test with Bonferroni correction. Results: In the qualitative analysis of cooperative patients, the results for CAIPIRINHA had significantly higher ratings for streak artifacts, liver-edge sharpness, hepatic vessel clarity, and overall image quality as compared to, radial GRE, (P < 0.016). In the imaging of uncooperative patients, higher scores were recorded for ILAB and GA with respect to all of the qualitative assessments, except for streak artifact, compared with CAIPIRINHA (P < 0.016). However, no significant differences were found between ILAB and GA. For quantitative analysis in uncooperative patients, the mean liver SNR and lesion-to-liver CNR with radial GRE were significantly higher than those of CAIPIRINHA (P < 0.016). Conclusion: In uncooperative patients, the use of the radial GRE sequence can improve the image quality compared to GRE imaging with CAIPIRINHA, despite the data acquisition methods used. The GRE imaging with CAIPIRINHA is applicable for patients without breath-holding difficulties.

• Investigative Magnetic Resonance Imaging
• /
• v.17 no.3
• /
• pp.215-223
• /
• 2013

Purpose : To evaluate the effect of gadoxetic acid on the measurement of the stiffness value of MR elastography (MRE) used to evaluate hepatic fibrosis (HF). Materials and Methods: MRE was obtained in 32 patients with clinically suspected chronic liver disease, both before and after injection of gadoxetic acid. Two independent reviewers measured the stiffness values of the liver parenchyma on elastograms. The mean liver stiffness values were compared in the pre- and post-contrast MREs using the paired t-test. Intra-rater and inter-rater correlation was assessed using the intraclass correlation coefficient (ICC). The accuracy, sensitivity, and specificity of both pre- and post-contrast MREs was evaluated for the diagnosis of significant HF (${\geq}F2$) using cut off value of 3.1 kPa. Results: There were no significant differences in the stiffness values of the liver parenchyma on pre- and post-contrast MREs (p = 0.15 and 0.38 for each reader, respectively). Regarding intra-rater correlation, excellent agreement was noted on rater 1(ICC = 0.998) and rater 2 (ICC = 0.996). Excellent correlation regarding the measured stiffness values was noted on both pre- and post-contrast MREs (ICC = 0.988 for pre-contrast, ICC = 0.993 for post-contrast). The accuracy, sensitivity, and specificity of the pre- and post-contrast MREs for differentiating significant HF (${\geq}F2$) from ${\geq}F1$ were same as 71%, 60%, and 100%, respectively. Conclusion: As there was no significant difference in the stiffness measurements seen on MREs before and after administration of gadoxetic acids, it is therefore acceptable to perform MRE after contrast injection in order to evaluate HF.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.9
• /
• pp.3595-3604
• /
• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.