Diagnostic Significance of pH-Responsive Gd³⁺-Based T₁ MR Contrast Agents

We discuss recent advances in Gd-based T₁-weighted MR contrast agents for the mapping of cellular pH. The pH plays a critical role in various biological processes. During the past two decades, several MR contrast agents of strategic importance for pH-mapping have been developed. Some of these agents shed light on the pH fluctuation in the tumor microenvironment. A pH-responsive self-assembled contrast agent facilitates the visualization of tumor size as small as 3 mm³. Optimization of various parameters is crucial for the development of pH-responsive contrast agents. In due course, the new contrast agents may provide significant insight into pH fluctuations in the human body.

Visualization of Tumor Angiogenesis Using MR Imaging Contrast Agent Gd-DTPA-anti-VEGF Receptor 2 Antibody Conjugate in a Mouse Tumor Model

OBJECTIVE: To visualize tumor angiogenesis using the MRI contrast agent, Gd-DTPA-anti-VEGF receptor 2 antibody conjugate, with a 4.7-Tesla MRI instrument in a mouse model. MATERIALS AND METHODS: We designed a tumor angiogenesis-targeting T1 contrast agent that was prepared by the bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and an anti-vascular endothelial growth factor receptor-2 (VEGFR2) antibody. The specific binding of the agent complex to cells that express VEGFR2 was examined in cultured murine endothelial cells (MS-1 cells) with a 4.7-Tesla magnetic resonance imaging scanner. Angiogenesis-specific T1 enhancement was imaged with the Gd-DTPA-anti-VEGFR2 antibody conjugate using a CT-26 adenocarcinoma tumor model in eight mice. As a control, the use of the Gd-DTPA-anti-rat immunoglobulin G (Gd-DTPA-anti-rat IgG) was imaged with a tumor model in eight mice. Statistical significance was assessed using the Mann-Whitney test. Tumor tissue was examined by immunohistochemical analysis. RESULTS: The Gd-DTPA-anti-VEGFR2 antibody conjugate showed predominant binding to cultured endothelial cells that expressed a high level of VEGFR2. Signal enhancement was approximately three-fold for in vivo T1-weighted MR imaging with the use of the Gd-DTPA-anti-VEGFR2 antibody conjugate as compared with the Gd-DTPA-rat IgG in the mouse tumor model (p < 0.05). VEGFR2 expression in CT-26 tumor vessels was demonstrated using immunohistochemical staining. CONCLUSION: MR imaging using the Gd-DTPA-anti-VEGFR2 antibody conjugate as a contrast agent is useful in visualizing noninvasively tumor angiogenesis in a murine tumor model.

Small Malignant Hepatic Tumor Detection in Gadolinium- and Ferucarbotran-Enhanced Magnetic Resonance Imaging: does Combining Ferucarbotran-Enhanced T2*-Weighted Gradient Echo and T2-Weighted Turbo Spin Echo Images have Additive Efficacy?

OBJECTIVE: To determine if a combination of ferucarbotran-enhanced T2*weighted-gradient echo (T2*W-GRE) and T2-weighted turbo spin echo (T2W-TSE) images in gadolinium- and ferucarbotran-enhanced MRI has additive efficacy compared to each image alone for detecting small (< or = 2.0 cm) hepatocellular carcinoma (HCC) lesions in a group of cirrhotic patients and metastases in a group of non-cirrhotic patients. MATERIALS AND METHODS: Two readers retrospectively analyzed gadolinium- and ferucarbotran-enhanced T2*W-GRE, T2W-TSE, and combined T2*W-GRE/T2W-TSE images of 119 patients with 157 HCCs and 32 patients with 98 metastases. The diagnostic accuracy and sensitivity for each image set and the combined set were evaluated using the alternative-free response receiver operating characteristic method. RESULTS: The mean area under the curve value of the combined set (0.966) tended to be better than that for each individual image set (T2W-TSE [0.910], T2*W-GRE [0.892]). Sensitivities in the combined set were higher than those in each individual image set for detecting HCC (mean, 93.0% versus 81.6% and 86.7%, respectively, p < 0.01). Sensitivities in the combined set and the T2W-TSE set were the same for detecting metastases, and both were higher than the sensitivity seen in the T2*W-GRE set (mean, 97.5% versus 85.2 %, p < 0.01). CONCLUSION: Combining ferucarbotran-enhanced T2*W-GRE and T2W-TSE has additive efficacy for detecting HCC in cirrhotic patients, but T2W-TSE is preferred for detecting metastases in non-cirrhotic patients.

Value of Manganese-Enhanced T1- and T2-Weighted MR Cholangiography for Differentiating Cystic Parenchymal Lesions from Cystic Abnormalities which Communicate with Bile Ducts

We present a case report to show how manganese-enhanced T1- and T2-weighted MR cholangiography could differentiate cystic parenchymal lesions from cystic abnormalities which communicate with the bile ducts.

Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer Model

OBJECTIVE: We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model. MATERIALS AND METHODS: The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1-weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings. RESULTS: No statistical difference was found between the sizes of 12 metastatic (10.5+/-3.2 mm) and 24 hyperplastic (8.0+/-3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1-weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81. CONCLUSION: This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria.

The Significance of Vascular MR Contrast Enhancement in Carotid Stenosis

PURPOSE: To determine the significance of vascular MR contrast enhancement in carotid stenosis. MATERIALS AND METHODS: Forty patients that had angiographically proved carotid stenosis were selected for the study. A blind interpretation of vascular enhancement on an enhanced T1 weighted image, the lesion pattern on a DWI (diffusion weighted image), a perfusion defect on a MR perfusion image, the degree of stenosis, and collateral flow on cerebral DSA (digital subtraction angiography) was made by two observers, retrospectively. DWI lesion patterns were classified as having no high signal intensity, small PAI (perforating artery infarcts), large PAI, pial infarcts, territorial infarcts, and border zone infarcts. We evaluated the statistical correlation between vascular enhancement and the degree of stenosis, collateral flow, the DWI lesion pattern and the presence of a perfusion defect, respectively. RESULTS: The degree of carotid stenosis and the frequency of vascular enhancement correlated statistically (p=0.000). The presence of retrograde collateral flow on cerebral DSA and the border zone infarcts pattern on DWI were related with the occurrence of vascular enhancement (p=0.002, p=0.004). In 23 patients that underwent a MR perfusion study, the presence of a perfusion defect was also related to the occurrence of vascular enhancement (p=0.002). CONCLUSION: Vascular MR contrast enhancement may indicate a cerebral hypoperfusion in carotid stenosis.

Contrast Enhanced MR Findings of Lesions Associated with Radial Scar: Correlation with Histopathology

PURPOSE: To evaluate the contrast-enhanced MR findings of lesions associated with a radial scar and to compare the MR findings with the histopathology results. MATERIALS AND METHODS: From Mar. 2001 to Sep. 2005, 8 patients with a surgically proven radial scar who had undergone MRI, mammography, and ultrasonography were enrolled in this study. The morphological findings and dynamic enhancement pattern of the time-intensity curve were retrospectively reviewed using non-contrast and contrast-enhanced MRI. Mammography and ultrasonography were also analyzed according to the BI-RADS category and correlated with the histopathological diagnosis. RESULTS: The age of the patients ranged from 42 to 53 years (mean, 47 years). Five patients presented with a left breast lesion and the others presented with a right breast lesion. The histopathological diagnosis associated with the radial scar were fibrocystic changes (n=1), adenosis (n=2), atypical ductal hyperplasia (n=2), lobular carcinoma in situ (n=1), ductal carcinoma in situ (n=1), and invasive ductal carcinoma (n=1). In all patients, architectural distortion without microcalcification was observed with mammography. Irregular shaped hypoechoic lesions with an indistinct, spiculated, or angular margin was observed in all patients with ultrasonography. Posterior shadowing was observed in 4cases. MR enhancement revealed two cases with foci enhancement (adenosis and fibrocystic change), five cases with non-mass-like focal enhancement (fibrocystic change, atypical ductal hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive ductal carcinoma), and one irregular homogeneous mass enhancement (atypical ducal hyperplasia). The time-signal intensity curves are as follows: persistent type (n=2), adenosis, and fibrocystic changes, respectively; plateu type (n=4), one adenosis, two atypical ductal hyperplasia, and one ductal carcinoma in situ; and washout type (n=2), lobular carcinoma in situ, and invasive ductal carcinoma, respectively. CONCLUSION: Although a combined benign or malignant pathology with a radial scar was not predicted on the preexisting image modality, contrast-enhanced MRI can help to predict a combined benign or malignant pathology with a radial scar using the morphological findings and the dynamic enhancement type of the time-intensity curve.

Contrast Enhanced MR Findings of Lesions Associated with Radial Scar: Correlation with Histopathology

PURPOSE: To evaluate the contrast-enhanced MR findings of lesions associated with a radial scar and to compare the MR findings with the histopathology results. MATERIALS AND METHODS: From Mar. 2001 to Sep. 2005, 8 patients with a surgically proven radial scar who had undergone MRI, mammography, and ultrasonography were enrolled in this study. The morphological findings and dynamic enhancement pattern of the time-intensity curve were retrospectively reviewed using non-contrast and contrast-enhanced MRI. Mammography and ultrasonography were also analyzed according to the BI-RADS category and correlated with the histopathological diagnosis. RESULTS: The age of the patients ranged from 42 to 53 years (mean, 47 years). Five patients presented with a left breast lesion and the others presented with a right breast lesion. The histopathological diagnosis associated with the radial scar were fibrocystic changes (n=1), adenosis (n=2), atypical ductal hyperplasia (n=2), lobular carcinoma in situ (n=1), ductal carcinoma in situ (n=1), and invasive ductal carcinoma (n=1). In all patients, architectural distortion without microcalcification was observed with mammography. Irregular shaped hypoechoic lesions with an indistinct, spiculated, or angular margin was observed in all patients with ultrasonography. Posterior shadowing was observed in 4cases. MR enhancement revealed two cases with foci enhancement (adenosis and fibrocystic change), five cases with non-mass-like focal enhancement (fibrocystic change, atypical ductal hyperplasia, lobular carcinoma in situ, ductal carcinoma in situ, invasive ductal carcinoma), and one irregular homogeneous mass enhancement (atypical ducal hyperplasia). The time-signal intensity curves are as follows: persistent type (n=2), adenosis, and fibrocystic changes, respectively; plateu type (n=4), one adenosis, two atypical ductal hyperplasia, and one ductal carcinoma in situ; and washout type (n=2), lobular carcinoma in situ, and invasive ductal carcinoma, respectively. CONCLUSION: Although a combined benign or malignant pathology with a radial scar was not predicted on the preexisting image modality, contrast-enhanced MRI can help to predict a combined benign or malignant pathology with a radial scar using the morphological findings and the dynamic enhancement type of the time-intensity curve.

Relationship between the Number of SPIO-labeled Macrophage and MR Signal Intensity

PURPOSE: For the in vivo imaging of macrophages using MRI, the feasibility of labeling macrophages with iron oxide and the number of SPIO-labeled macrophage detected in 1.5 T MR, were assessed. MATERIALS AND METHODS: The MR signal intensity was measured with variable concentrations of iron oxide, ranging from 112 to 2.384x10-7 μgFe/mL. The macrophages were incubated in SPIO solution (112 μgFe/mL) for 24 hours. The MR signal intensity was measured in variable numbers of SPIO-labeled macrophages. RESULTS: The MR image signal intensity gradually increased with decreasing SPIO concentration, and reached a plateau at a concentration of 0.219 μgFe/mL. After incubation with iron oxide, the compact uptake of SPIO was detected in the cytoplasm of the macrophages using Prussian blue staining. No susceptibility effect was detected in the tubes of more than 122 macrophages. CONCLUSION: The MR signal intensity was dependent on the number of macrophages. No susceptibility effect due to a cluster of SPIO-labeled macrophages was detected in more than 488 cells.

Differentiation of Recently Infarcted Myocardium from Chronic Myocardial Scar: The Value of Contrast-Enhanced SSFP-Based Cine MR Imaging

The purpose of this study is to demonstrate whether the signal intensity (SI) of myocardial infarction (MI) on contrast enhanced (CE)-cine MRI is useful for differentiating recently infarcted myocardium from chronic scar. This study included 24 patients with acute MI (36-84 years, mean age: 57) and 19 patients with chronic MI (44-80 years, mean age: 64). The diagnosis of acute MI was based on the presence of typical symptoms, i.e. elevation of the cardiac enzymes and the absence of any remote infarction history. The diagnosis of chronic MI was based on a history of MI or coronary artery disease of more than one month duration and on the absence of any recent MI within the previous six months. Retrospectively, the ECG-gated breath-hold cine imaging was performed in the short axis plane using a segmented, balanced, turbo-field, echo-pulse sequence two minutes after the administration of Gd-DTPA at a dose of 0.2 mmol/kg body weight. Delayed contrast-enhanced MRI (DCE MRI) in the same plane was performed 10 to 15 minutes after contrast administration, and this was served as the gold standard of reference. The SI of the infarcted myocardium on the CE-cine MRI was compared with that of the normal myocardium on the same image. The area of abnormal SI on the CE-cine MRI was compared with the area of hyperenhancement on the DCE MRI. The area of high SI on the CE-cine MRI was detected in 23 of 24 patients with acute MI (10 with homogenous high SI, 13 high SI with subendocardial low SI, and one with iso SI). The area of high SI on the CE-cine MRI was larger than that seen on the DCE MRI (p < 0.05). In contrast, the areas of chronic MI were seen as iso-SI with thin subendocardial low SI on the CE-cine MR in all the chronic MI patients. The presence of high SI on both the CE-cine MRI and the DCE MRI is more sensitive (95.8%) for determining the age of a MI than the presence of myocardial thinning (66.7%). This study showed the different SI patterns between recently infarcted myocardium and chronic scar on the CE-cine MRI. CE-cine MRI is thought to be quite useful for determining the age of myocardial infarction, in addition to its utility for assessing myocardial contractility.

Usefulness of Post-enhanced Delayed FLAIR Imaging for Making the Diagnosis of Leptomeningitis

PURPOSE: To evaluate the usefulness of post-enhanced delayed FLAIR (fluid-attenuated inversion-recovery) images in the diagnosis of leptomeningitis. MATERIALS AND METHODS: We obtained the pre- and post-enhanced FLAIR images of 7 rabbits every hour after infusing triple doses of contrast, and we measured the signal intensities of the CSF (cerebrospinal fluid) and the brain parenchyma. Five leptomeningitis patients and 5 volunteers were enrolled to obtain the pre-enhanced FLAIR images, the early post-enhanced FLAIR images and the delayed post-enhanced FLAIR images, with using a standard dose of contrast, and to measure the signal intensities of the CSF and brain parenchyma. The statistical significances were determined by a mixed procedure and the Wilcoxon rank-sum test (p<0.05). RESULTS: In the rabbits, the signal intensities of the CSF began to increase after an hour of contrast infusion, but those of the parenchyma did not increase. The time of maximum CSF enhancement was 2 hours after contrast infusion (p<0.001; standard estimate=750.43) and we obtained the post-enhanced delayed FLAIR images for clinical studies according to this result. The signal intensities of the CSF in the subarachnoid space were higher in the patient group compared with those of the normal control group on both the early post-enhanced FLAIR images and the delayed post-enhanced FLAIR images (p=0.0096) (p=0.0391). In the patient group, changes of signal intensities of the CSF in the subarachnoid space were more conspicuous on the delayed post-enhanced FLAIR images than on the early post-enhanced FLAIR images (p=0.0042). However, those of the parenchyma were not different in either group. CONCLUSION: The post-enhanced delayed FLAIR images obtained at 2 hours after contrast infusion are more useful for making the the diagnosis of leptomeningitis than are the post-enhanced early FLAIR images.

Differentiation of Hyperplastic from Metastatic Lymph Nodes Using a Lymph Node Specific MR Contrast Agent Gadofluorine M

PURPOSE: We wanted to evaluate the value of a lymph node specific MR contrast agent, Gadofluorine M, for the differentiation of hyperplastic and metastatic lymph nodes. MATERIALS AND METHODS: This study included thirty-one rabbits. In ten rabbits, an injection of egg yolk or feces of rat into the calf muscles induced hyperplasia of the lymph node. In sixteen rabbits, metastasis of the lymph node was induced by implantation of VX2 tumor. Five rabbits were normal control models. We acquired the T1-, T2-weighted and SPGR coronal imaging before enhancement with 1.5 T MR. After injection of Gadofluorine M (5 micromol/mL, total amount: 4 mL) interstitially into the interdigital skin fold of the hind limb, we acquired the SPGR coronal imaging at 15, 30, 60 and 90 minutes. We calculated the signal-to-noise ratios on the sequential images, and we recorded the number, size and location of the popliteal and iliac lymph nodes. Three readers assessed the state of the lymph nodes according to the pattern of enhancement: they were deemed hyperplastic nodes when totally enhanced and as metastatic nodes when there was no or partial enhancement. We also compared the imaging patterns with the histopathological results. RESULTS: Among the 26 hyperplasia- or metastasis-induced rabbits, two rabbits were excluded because of failure to be enhanced. Histopathologic evaluation of the 24 rabbits detected one hundred seventeen lymph nodes: forty-six lymph nodes in nine hyperplasia-induced rabbits and seventy-one (metastasis in twenty-eight) lymph nodes in fifteen metastasis-induced rabbits. Out of one hundred two lymph nodes that were larger than 5 mm in size, MR enabled us to detect one hundred one lymph nodes (99.1%). The means of sensitivity, specificity, and the positive and negative predictive values for the diagnosis of lymph node metastasis by three readers were 97.6% (82/84), 98.2% (215/219), 95.3% (82/86), and 99.1% (215/217), respectively (p < 0.05). CONCLUSION: Interstitial MR lymphography using Gadofluorine M showed excellent results in differentiating hyperplastic from metastatic lymph nodes.

Gadobenate Dimeglumine as an Intrabiliary Contrast Agent: Comparison with Mangafodipir Trisodium with Respect to Non-dilated Biliary Tree Depiction

OBJECTIVE: To compare the efficacy of Mangafodipir trisodium (Mn-DPDP) -enhanced MR cholangiogrphy (MRC) and Gadobenate dimeglumine (Gd-BOPTA) -enhanced MRC in visualizing a non-dilated biliary system. MATERIALS AND METHODS: Eighty-eight healthy liver donor candidates underwent contrast-enhanced T1-weighted MRC. Mn-DPDP and Gd-BOPTA was used in 36 and 52 patients, respectively. Two radiologists reviewed the MR images and rated the visualization of the common duct, the right and left hepatic ducts, and the second-order branches using a 4-point scale. The contrast-to-noise ratio (CNR) of the common duct to the liver in the two groups was also compared. RESULTS: Mn-DPDP MRC and Gd-BOPTA MRC both showed similar visualization grades in the common duct (p = .380, Mann-Whitney U test). In the case of the proximal bile ducts, the median visualization grade was significantly higher with Gd-BOPTA MRC than with Mn-DPDP MRC (right hepatic duct: p = 0.016, left hepatic duct: p = 0.014, right secondary order branches: p = 0.006, left secondary order branches, p = 0.003). The common duct-to-liver CNR of the Gd-BOPTA MRC group was significantly higher (38.90+/-24.50) than that of the Mn-DPDP MRC group (24.14+/-17.98) (p = .003, Student's t test). CONCLUSION: Gd-BOPTA, as a biliary contrast agent, is a potential substitute for Mn-DPDP.

Preoperative Detection of Hepatic Metastases from the colorectal Cancers: Comparison of Dual-phase CT scan, Mn-DPDP enhanced MRI, and combination of CT and MRI

PURPOSE: To determine the usefulness of additional Mn-DPDP MRI for preoperative evaluation of the patients with colorectal cancers by comparison of dual-phase CT scan, Mn-DPDP enhanced MRI and combination of CT and MRI. MATERIALS AND METHODS: Fifty-three colorectal cancer patients with 92 metastatic nodules underwent dualphase (arterial and portal) helical CT scan and Mn-DPDP MRI prior to surgery. The indication of MRI was presence or suspected of having metastatic lesions at CT scan and/or increased serum carcinoembryonic antigen (CEA) levels (10 ng/mL or more). The diagnosis was established by the combination of findings at surgery, intraoperative ultrasonography, and histopathologic examination. Two radiologists interpreted CT, MRI, and combination of CT-MRI at discrete sessions and evaluated each lesion for location, size, and intrinsic characteristics. The lesions were divided into three groups according to their diameter; 1cm 2 cm. Diagnostic accuracy was evaluated using the alternative-free response receiver operating characteristic method. Detection and false positive rate were also evaluated. RESULTS: In the lesions smaller than 1 cm, detection rate of combined CT-MRI was superior to CT or MRI alone (82%, p = 0.036). The mean accuracy (Az values) of combined CT and MRI was significantly higher than that of CT in the lesions smaller than 2 cm (1 cm <, p=0.034; 1-2 cm, p=0.045). However, there was no significant difference between MRI and combined CT-MRI. The false positive rate of CT was higher than those of combined CT-MR in the lesions smaller than 1 cm (28 %, p=0.023). CONCLUSION: Additional MRI using Mn-DPDP besides routine CT scan was helpful in differentiating the hepatic lesions (< 2 cm) and could improve detection of the small hepatic metastases (< 1 cm) from colorectal carcinoma.

Quantitative Evaluation of Liver Function with MRI Using Gd-EOB-DTPA

OBJECTIVE: Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection, Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreted via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis. MATERIALS AND METHODS: Adult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCl4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCl4. At the end of experimental period, an observer "blinded" to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCl4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL of Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, TR/TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128x128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier transform technique to calculate the hepatic extraction fraction (HEF). The presence and type of hepatic injury were determined by the histopathologic examination and statistical analysis of the changes of the hepatic enzyme levels, the ICG R15 and Gd-EOB-DTPA HEF values between the time before and after CCl4 administration with Wicoxon signed rank test. Correlation between the Gd-EOB-DTPA HEF and the change of the ICG R15 were analyzed with Pearson's correlation coefficient. RESULTS: Histopathologic examination showed findings that were compatible with hepatic fibrosis caused by chronic liver injury. The initial blood biochemical studies before the administration of carbon tetrachloride showed that the mean AST and ALT levels were 39.8+/-5.2 IU/L and 59.1+/-11.7 IU/L, respectively. The AST and ALT levels increased to 138.4+/-50.5 IU and 172.0+/-71.6 IU/L, respectively, after the three week administration of CCl4. The ALT and AST levels were significantly increased after the three weeks of CCl4 administration (p=0.018). The ICG R15 values were 4.47+/-2.08% and 19.43+/-3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p=0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 administration revealed less hepatocyte extraction efficiency with a mean value of 77.7+/-3.6. There was a significant correlation between the HEF and changes of the ICG R15 by the Pearson correlation coefficient assessment (correlation coefficient = -0.965, p=0.000). CONCLUSION: The Gd-EOB-DTPA HEF could be calculated from deconvolution analysis of aortic and hepatic parenchymal time-intensity curves obtained by dynamic MRI. The Gd-EOB-DTPA HEF was well correlated with changes of the ICG R15, which is the most common parameter used in the quantitative estimation of the hepatic function. The Gd-EOB-DTPA HEF is a direct, noninvasive technique for the quantitative evaluation of liver function. It could be a promising alternative for the determination of noninvasive hepatic function in those patients with liver disease.

Hepatic Enhancement on Gd-BOPTA-enhanced MR Imaging: Comparison between Cirrhotic and Normal Livers

PURPOSE: To compare the enhancement features of hepatic parenchyma between cirrhotic and normal liver, using Gd-BOPTA-enhanced delayed MR imaging. MATERIALS AND METHODS: The 60 patients (35 with cirrhotic and 25 with normal liver) included in our study underwent Gd-BOPTA-enhanced MR imaging using a 1.5T system with a phase-array multicoil. In all cases, T1-weighted in-phase and opposed-phase gradient-echo MR imaging was performed before and 60 minutes after intravenous administration of a bolus of Gd-BOPTA. All images were quantitatively analysed by comparing the signal-to-noise ratio (SNR) and signal enhancement (SE) of cirrhotic and normal liver before and after contrast enhancement, and in cirrhotic patients, SNR and SE were also compared in terms of the Child-Pugh classification. For qualitative analysis, the hepatic enhancement patterns of cirrhotic and normal liver were classified as homogeneous or heterogeneous according to the consensual findings of two radiologists. RESULTS: At contrast-enhanced imaging, both cirrhotic (p<0.001) and normal liver (p<0.001) showed substantially increased SNR relative to unenhanced images, and the SNR of cirrhotic liver was significantly lower than that of normal livers at both in-phase (p<0.001) and opposed-phase (p<0.001) imaging. The SE of cirrhotic liver was significantly lower than that of normal liver (in-phase: p=0.002; opposed phase: p=0.011). Both Child-Pugh class A (p<0.001) and B (p<0.001) cirrhotic liver showed a substantial increase in SNR at contrast-enhanced imaging relative to unenhanced imaging and the SNR of Child-Pugh class A was significantly higher than that of Child-Pugh class B at both in-phase (p<0.001) and opposed-phase (p=0.022) imaging. In addition, the SE of class A was significantly higher than that of class B at in-phase imaging (p=0.004). Cirrhotic liver showed heterogeneous enhancement in 20 of 35 patients (57%), whereas normal liver showed homogeneous enhancement in all patients. CONCLUSION: At Gd-BOPTA-enhanced delayed MR imaging, cirrhotic liver showed less enhancement than normal liver. In cirrhotic patients, hepatic enhancement and hepatic function decreased in tandem. Gd-BOPTAenhanced delayed MR imaging may be useful for evaluating the functional reserve of the liver.

Are the Delay Images Necessary to Evaluate the Liver Metastatic Lesions on Mangafodipir Trisodium Enhanced Liver MRI?: Comparison with Hepatocellular Carcinomas

PURPOSE: To assess whether ring enhancements of liver metastases on Mn-DPDP enhanced, early MR images were well visualized on delayed images, as compared with those of hepatocellular carcinomas (HCC), and to investigate the detection accuracy and conspicuity of each tumor. MATERIALS AND METHODS: Twenty patients with liver metastases and 15 with HCC were studied by Mn-DPDP enhanced, T1-weighted MR images. Peripheral ring enhancement and conspicuity were investigated. Differences in detection accuracy and frequency of ring enhancement in liver metastases and HCC were assessed. RESULTS: In liver metastases (n=69), 44 cases (63.8%) without ring enhancement and 25 (36.2%) with were noted on early images. Sixteen cases (23.2%) without ring enhancement, 38 (55.1%) with ring enhancement similar to the early images, and 15 (21.7%) with prominent ring enhancement were noted on delayed images. In HCC (n=37), 36 cases (97.3%) without ring enhancement and 1 case (2.7%) with were noted on early images. There was no difference of detection accuracy in liver metastases or HCC between the 2 readings. Ring enhancement and conspicuity of each tumor were superior on delayed images. Ring enhancement in liver metastases was better seen on delayed images. CONCLUSION: Ring enhancement in liver metastases was well presented on Mn-DPDP enhanced, delayed MR images, which was useful to differentiate liver metastases from HCC.

The Usefulness of Dynamic MR Imaging for the Evaluation of Cervical Cancer

PURPOSE: We wished to evaluate the diagnostic usefulness of dynamic MRI in assessing tumor visualization and the parametrial invasion of cervical cancer, and we also wished to determine the most adequate enhancing time by comparing the T2-weighted image (T2WI) and enhanced T1-weighted image (Gd-T1WI). MATERIALS AND METHODS: Fifty-three women with histopathologically proven cervical cancer underwent a preoperative MRI. Using a 1.5 T magnet, the fast spin echo axial T2WI without fat saturation was taken; after contrast administration, 20, 40, 60, 90, 120 sec-dynamic MRIs were taken using fast SPGR and spin echo axial Gd-T1WI. Tumor conspicuity and parametrial invasion in each pulse sequence and the most adequate enhancing time for the evaluation of the tumor on dynamic MRI were evaluated prospectively by three radiologists working at three separate sessions. The results were then correlated with the histopathologic findings. RESULTS: The conspicuity of tumor on dynamic MRI (99.4%) and T2WI (95.6%) were better than on Gd-T1WI (89.3%). In the assessment of parametrial invasion of the tumor, the diagnostic accuracy of dynamic MRI, Gd-T1WI and T2WI was 79.9%, 78% and 76.1%, respectively; the highest values were for the dynamic MRI, but there was no statistically significant difference among three pulse sequences. The most adequate enhancing time on dynamic MRI was between 90 seconds and 120 seconds. CONCLUSION: Dynamic MRI is useful for the assessment of tumor visualization of cervical cancer, and the most appropriate scan time on dynamic MRI is between 90 seconds and 120 seconds. For the determination of parametrial invasion, the dynamic MRI revealed a higher diagnostic accuracy than that of T2WI or Gd-T1WI, but the differences were statistically insignificant.

MR Imaging with Gd-DTPA Enhancement in the Testicular Ischemia in Rat Model: Evaluation of Testicular Viability

PURPOSE: To find the magnetic resonance (MR) imaging patterns and to determine the viability in normal, infracted and reversible ischemic testis of the rat. MATERIALS AND METHODS: Fifteen Sprague-Dawley rats were examined and they were divided into four groups. Group 1 was the control group, group 2 had a complete testicular artery ligation, group 3 had a complete ligation with reperfusion after 1 hour and group 4 had a complete ligation with reperfusion after 12 hours. All four groups were imaged every 5 minutes for 30 minutes. Delayed MR imaging was obtained every 30 minutes for 90 minutes. Two follow-up MR images were performed in all groups at a one-week interval. The signal intensity was measured in the normal testis, ischemic testis, and in muscle, water and fat in every rat at each time, with the phantom attached near the scrotum during the scanning. The signal intensities were analyzed statistically. RESULTS: On initial and 2-week follow-up examinations, the pattern of change differed among four groups (p<0.001). Group 1 and Group 3 did not show any marked change over time at each examination. Group 3 showed strong enhancement at the first week follow-up. Group 2 showed steadily delayed enhancement at each examination. Group 4 had same pattern with the Group 2 with higher enhancement intensity in parallel. CONCLUSION: MR images with Gd-DTPA could be useful for the diagnosis of damaged testicular tissue and for the determination of testicular viability.

Double Contrast Media enhanced MRI with Ferumoxides-Gadolinium on Hepatocellular Carcinoma

PURPOSE: To evaluate the effects of Ferumoxides on Gadolinium (Gd) enhanced dynamic liver magnetic resonance imaging (MRI) in cirrhotic patients and also for the diagnosis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: 29 patients with liver cirrhosis were examined at 1.5T. 12 patients had HCC. The imaging protocol included GE T1 in and opposed phases, and a breath-hold TSE T2 before and 30-60 min following 0.05 ml/kg Ferumoxides. Four dynamic in-phase GE series were also acquired after an injection of 20 ml of Gd at 2 ml/sec. SNR and CNR were calculated for liver lesion relative to the muscle and background liver respectively. Statistical analysis was performed using the paired t-test. RESULTS: The SNR of the liver decreased by 8.6+/-1.20 (p<0.001) after Ferumoxides injection. At the peak of the Gd effect, the liver increased by 6.09+/-1.15 relative to the post Ferumoxides, but it was not significantly different from the pre-Ferumoxides study (p<0.01). Although there was no significant change in post Ferumoxides SNR of HCC, CNR of HCC relative to the liver increased by 7.54+/-1.61 (p<0.05). After the Gd injection, CNR of HCC increased by 15.6+/-3.87 (p<0.05). CONCLUSION: The administration of Ferumoxides made HCC CNR increase, and it canceled the effect of Gd enhancement of the cirrhotic liver. The combination of Ferumoxides and Gd makes HCC CNR increase.