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.

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.

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.

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.

Pulse Sequence Optimization for Superparamagnetic Iron Oxide-enhanced MR Imaging in the Detection of Hepatic VX2 Tumors in Rabbits

PURPOSE: The purpose of this experimental study was to determine the optimal pulse sequences for SPIO-enhanced MR imaging in the evaluation of multiple hepatic tumors. MATERIALS AND METHODS: Twelve rabbits with multiple VX2 liver tumors underwent SPIO-enhanced MRI using the following nine pulse sequences: TSE T2-weighted imaging (T2WI), TSE proton density-weighted imaging (PDWI), and GRE T2*-weighted imaging (T2*WI) with seven different echo times (TE). Liver-lesion contrastto-noise ratios (CNRs) were calculated, and images were also assessed qualitatively by two radiologists, who reached a consensus as to lesion conspicuity and imaging artefacts using a four-level scale. By means of pathologic correlation, the sensitivity and positive predictive value of each sequence was calculated. RESULTS: TSE T2WI and long-TE (35 msec) FLASH T2*WI showed the highest liver-lesion CNR. The best lesion conspicuity was seen at TSE T2WI and medium-TE (12 msec) GRE T2*WI. Short TE GRE T2*WI showed the least imaging artefacts. The four sequences which demonstrated the best sensitivity were medium-TE (12 msec), GRE T2*WI (FLASH, 84%; FISP, 82%), TSE T2WI (79%), and TSE PDWI (76%). All nine sequences showed overall high positive predictive value (86-97%), with no statistically significant difference (p>0.05). CONCLUSION: In terms of image quality and the detection of sensitivity, TSE T2WI and medium TE (12 msec) GRE T2*WI were the top two pulse sequences among the various sequences used for on SPIO-enhanced MRI. They are thus considered to be the optimal sequences for evaluating multiple malignant hepatic tumors.

Detection of Malignant Primary Hepatic Neoplasms with Gadobenate Dimeglumine (Gd-BOPTA) Enhanced T1-Weighted Hepatocyte Phase MR Imaging: Results of Off-site Blinded Review in a Phase-II Multicenter Trial

OBJECTIVE: To investigate the efficacy of gadobenate dimeglumine (Gd-BOPTA) enhanced MR imaging for the detection of liver lesions in patients with primary malignant hepatic neoplasms. MATERIALS AND METHODS: Thirty-one patients with histologically proven primary malignancy of the liver were evaluated before and after administration of Gd-BOPTA at dose 0.05 or 0.10 mmol/kg. T1-weighted spin echo (T1W-SE) and gradient echo (T1W-GRE) images were evaluated for lesion number, location, size and confidence by three off-site independent reviewers and the findings were compared to reference standard imaging (intraoperative ultrasound, computed tomography during arterial portography or lipiodol computed tomography). Results were analyzed for significance using a two-sided McNemar's test. RESULTS: More lesions were identified on Gd-BOPTA enhanced images than on unenhanced images and there was no significant difference in lesion detection between either concentration. The largest benefit was in detection of lesions under 1 cm in size (7 to 21, 9 to 15, 16 to 18 for reviewers A, B, C respectively). In 68% of the patients with more than one lesion, Gd-BOPTA increased the number of lesions detected. CONCLUSION: Liver MR imaging after Gd-BOPTA increases the detection of liver lesions in patients with primary malignant hepatic neoplasm.

Proton MR Spectroscopic Features According to Change of Hepatic Parenchymal Iron Content after SPIO Injection

PURPOSE: To determine the effect of iron on proton MR spectra (1H-MRS) by evaluating changes in 1H-MRS of the liver according to changes in hepatic parenchymal iron content. MATERIALS AND METHODS: We evaluated serial changes in 1H-MRS of the liver after intravenous infusion of SPIO in 40 rabbits. These were divided into eight groups of five, and in each group, respectively, 1H-MRS and T2WI MR images were acquired prior to SPIO infusion, just after infusion, and at 15 minutes and 1, 2, 4, 24 and 96 hours after infusion. MR spectra were evaluated with particular attention to the curve pattern observed at specific times after the infusion of SPIO, and the results were correlated with the signal intensity observed on T2W1 images and the histologic giade of ilon content of samples of resected liver parenchyma. RESULTS: As observed on T2WI, the mean signal intensity of rabbit liver in its pre-SPIO infusion state, just after infusion, at 15 minutes, and at 1, 2, 4, 24 and 96 hours after SPIO infusion was 121.3 +/-15.5, 41.5 +/-12.7, 30.3 +/-7.9, 31.3 +/-3.5, 33.6 +/-9.4, 45.5 +/-10.9, 80.3 +/-15.7 and 110.4 +/-22.9, respectively(p<0.05). Mean standard deviation of the ratio of the area of the peak (3.9-4.1 ppm) / lipid peak (1.3 ppm) peak at each of the above times except for the pre-infusion state was 1.10 +/-0.13, 1.86 +/-0.21, 1.80 +/-0.30, 1.76 +/-0.27, 1.74 +/-0.20, 0.07 +/-0.02 and 0.03 +/-0.01, respectively(p<0.05). The hepatic parenchymal iron content increased rapidly from just after SPIO infusion, reaching its maximal level (as revealed by histologic specimens) at 15 minutes, sustaining this for up to 4 hours, and then decreasing gradually over periods of 24 and 96 hours. These results show that serial changes in patterns of MR spectra and the signal intensity seen on T2WI images correlate closely with changes in hepatic parenchymal iron content. CONCLUSION: Elevated hepatic parenchymal iron content leads to increases in the relative intensity of unknown peaks at around 4.0 ppm and decreases in the relative intensity of lipid peaks.

Superparamagnetic Iron Oxide Enhanced MR Imaging: Influence of Hepatic Dysfunction in Cirrhotic Patients

PURPOSE: To determine the influence of liver dysfunction on the detection of focal hepatic nodules, and to investigate the loss of signal intensity of hepatic parenchyma occurring after superparamagnetic iron oxide (S-PIO)-induced contrast enhancement in patients with liver cirrhosis. MATERIALS AND METHODS: In 68 patients with liver cirrhosis, we evaluated MR images before and after the administration of SPIO. Clinical information and laboratory data indicated that the liver was normal in ten patients (nine hemangiomas and one hepatic cyst), while Child's A was diagnosed in 25 cases [22 of which were hepatocellular carcinomas (HCCs)], Child's B in 15 (11 HCCs), and Child's C in 18 (10 HCCs). Before and after SPIO administration, conventional T2-weighted spin-echo, respiratory-triggered T2-weighted turbo spin-echo, and breathhold T2-weighted turbo spin-echo images were obtained. After the administration of SPIO, degrees of liver dysfunction and laboratory data were correlated with reductions in signal intensity of the liver, and, in addition, the state of hepatic dysfunction was corelated with inhomogeneous parenchymal change and lesion conspicuity. RESULTS: After the administration of SPIO, percentage signal loss in liver parenchyma was significantly higher on conventional T2-weighted spin-echo images than on T2-weighted turbo spin-echo and breathhold T2-weighted turbo spin-echo (p 0.05). CONCLUSION: SPIO uptake by hepatic parenchyma correlated closely with Child's degree of liver cirrhosis and laboratory data such as albumin and total bilirubin levels, and prothrombin time. In the Child's B and Child's C group, SPIO-enhanced MR imaging revealed inhomogeneous hepatic parenchyma, but the pattern observed did not affect the detection of hepatic nodules.