Differentiation of hepatocellular carcinomas from hyperplastic nodules induced in rat liver with ferrite-enhanced MR imaging.

The potential of superparamagnetic ferrite particles in magnetic resonance (MR) imaging to help differentiate between hyperplastic nodular lesions in the liver and hepatocellular carcinomas was evaluated with chemically induced liver tumors in cirrhotic rats. Ferrite particles decreased the signal intensity of hyperplastic nodules but not that of hepatocellular carcinomas, and stainable iron was found in the former but not in the latter with Prussian blue iron stain. T1-weighted spin-echo images made little contribution to the differentiation between these two lesions, while T2-weighted spin-echo images were effective for this purpose, since ferrite particles cause T2 shortening. Ferrite-enhanced MR imaging may be useful in differentiating these two lesion types according to their signal intensity changes on images, because Kupffer cells are present in hyperplastic nodular lesions but rarely in hepatocellular carcinomas.     

Siderotic nodules in the cirrhotic liver at MR imaging with explant correlation: no increased frequency of dysplastic nodules and hepatocellular carcinoma

PURPOSE: To determine the sensitivity of magnetic resonance (MR) imaging for detection of siderotic nodules in patients with cirrhosis and whether the frequency of hepatocellular carcinoma (HCC) and dysplastic nodules is greater if siderotic nodules are present. MATERIALS AND METHODS: MR imaging (1.5 T) was performed within 0-117 days (mean, 30 days) before liver transplantation in 77 patients. Two readers retrospectively evaluated gradient-echo (GRE) (echo time [TE], > or = 9 and 4-5 msec) and turbo short inversion time inversion-recovery or T2-weighted images for low-signal-intensity nodules. Whole-explant pathologic correlation was available in every case. RESULTS: At explantation, 28 (36%) of 77 patients had HCC, 25 (32%) had dysplastic nodules, and nine (12%) had both; 35 (45%) patients had siderotic nodules. The sensitivity of GRE imaging with 9-msec or longer TE for the detection of siderotic nodules was 80% (28 of 35) but decreased to 31% (11 of 35) with 4-5-msec TE. Frequency of HCC was not significantly higher (P =.27) in patients with (43% [15 of 35]) than in patients without (31% [13 of 42]) siderotic nodules. Frequency of dysplastic nodules also was not significantly higher (P =.42) in patients with (37% [13 of 35]) than in patients without (29% [12 of 42]) siderotic nodules. CONCLUSION: Sensitivity of MR imaging for the detection of siderotic nodules was improved with use of GRE pulse sequences with longer TEs of 9 msec or greater (80%) versus 4-5 msec (31%); however, there was no significant increased frequency of HCC or dysplastic nodules in patients with pathologically proved siderotic nodules.     

Stepwise carcinogenesis of hepatocellular carcinoma in the cirrhotic liver: demonstration on serial MR imaging

PURPOSE: To demonstrate imaging findings of stepwise carcinogenesis of hepatocellular carcinoma (HCC) in cirrhosis at serial state-of-the-art MR imaging exams. MATERIALS AND METHODS: In a retrospective search of the hospital archives, three patients were identified in which developing HCC was observed in serial MR examinations, with histopathology or alpha-fetoprotein (AFP) correlation. Image findings were assessed for signal intensity of the lesions at multiple sequences, including dynamic gadolinium-enhanced imaging. RESULTS: Initial findings in patient A showed a small nodule with fatty infiltration that developed in HCC in follow-up MRI, comprised of low-grade dysplastic nodule (DN; DN I), high-grade DN (DN II), and eventually classic HCC. In patient B, increased signal intensity on T2-weighted images in a single DN among numerous regenerative nodules was the only initial sign. Follow up MRI showed further increase in signal intensity and increased neovascularity, which suggested focal HCC in a DN II. Patient C demonstrated gradually increasing neovascularity as only initial sign, with development of classic HCC over time. CONCLUSION: MR imaging provides insight in various pathways of stepwise carcinogenesis of developing HCC in cirrhosis. This may further explain the genetic heterogeneity, and may facilitate early detection and better selection of patients for follow-up.     

Small hepatocellular carcinoma: differentiation from adenomatous hyperplastic nodule with color Doppler flow imaging.

Liver nodules smaller than 25 mm in diameter (19 hepatocellular carcinomas [HCCs] and nine adenomatous hyperplastic nodules [AHNs]) were examined with color Doppler flow imaging and hepatic angiography. Angiography revealed a tumor vessel in eight (42%) of the 19 HCCs, while color Doppler flow imaging revealed an arterial pulsating afferent tumor vessel in 10 (53%) of the 19 HCCs but in none of the AHNs. In addition, color Doppler flow imaging revealed a constant-flow efferent tumor vessel continuing to a portal branch in 10 (53%) of the 19 HCCs but in none of the AHNs. In 15 (79%) of the 19 HCCs, a pulsating afferent tumor vessel or a constant-flow efferent tumor vessel or both were observed. Therefore, in this series, color Doppler flow imaging was of value in distinguishing between these two lesions.     

The value of gadobenate dimeglumine-enhanced delayed phase MR imaging for characterization of hepatocellular nodules in the cirrhotic liver

OBJECTIVES: To evaluate the value of 1-hour delayed phase imaging (DPI) of gadobenate dimeglumine (Gd-BOPTA)-enhanced MR imaging for the characterization of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) in patients with cirrhosis. MATERIALS AND METHODS: A total of 37 patients with 42 HCCs and 13 DNs were included in this study and all lesions were histopathologically confirmed except for 15 HCCs. T1-weighted 3-dimensional gradient-echo images were acquired before, immediately after (30, 60, 180 s), and 1 hour after bolus injection of gadobenate dimeglumine at a dose of 0.1 mmol/kg. The lesions were classified as isointense, hypointense, or hyperintense compared with the surrounding liver parenchyma on DPI for qualitative assessment. We performed quantitative analyses of the contrast-to-noise ratio (CNR) and of the relative contrast enhancement of the lesion on the DPI. RESULTS: In the qualitative analysis, among 42 HCCs, 30 (71.4%) were hypointense on DPI, and 10 (23.8%) and 2 (4.8%) were isointense and hyperintense, respectively; only 1 of 13 DNs (7.7%) was hypointense and 10 (76.9%) and 2 (15.4%) were isointense and hyperintense, respectively. In contrast, 25 HCCs (71.4%) of 35 hypervascular HCCs were hypointense on DPI, and no hypervascular DN (0/7) was hypointense with statistical significance (P = 0.0007). When we considered the hypointensity of the hepatic lesions on delayed phase as a sign of HCC in cirrhotic liver, our results gave a sensitivity of 71.4% and a specificity of 91.7%. In the quantitative analysis, the mean CNR of the HCCs and the DNs on the 1-hour DPI was -6.32 +/- 6.27 and -0.07 +/- 3.28, respectively; the difference between the HCCs and the DNs was significant (P < 0.05). CONCLUSIONS: Delayed gadobenate dimeglumine-enhanced MR imaging allows improved characterization of HCC in cirrhotic liver. The relative hypointensity to adjacent normal liver parenchyma is a reliable predictor that this lesion favors HCC rather than DN in cirrhotic liver.     

MR Imaging of hepatocellular carcinoma in the cirrhotic liver: challenges and controversies

The incidence of hepatocellular carcinoma (HCC) is expected to increase in the next 2 decades, largely due to hepatitis C infection and secondary cirrhosis. HCC is being detected at an earlier stage owing to the implementation of screening programs. Biopsy is no longer required prior to treatment, and diagnosis of HCC is heavily dependent on imaging characteristics. The most recent recommendations by the American Association for the Study of Liver Diseases (AASLD) state that a diagnosis of HCC can be made if a mass larger than 2 cm shows typical features of HCC (hypervascularity in the arterial phase and washout in the venous phase) at contrast material-enhanced computed tomography or magnetic resonance (MR) imaging or if a mass measuring 1-2 cm shows these features at both modalities. There is an ever-increasing demand on radiologists to detect smaller tumors, when curative therapies are most effective. However, the major difficulty in imaging cirrhosis is the characterization of hypervascular nodules smaller than 2 cm, which often have nonspecific imaging characteristics. The authors present a review of the MR imaging and pathologic features of regenerative nodules and dysplastic nodules and focus on HCC in the cirrhotic liver, with particular reference to small tumors and lesions that may mimic HCC. The authors also review the sensitivity of MR imaging for the detection of these tumors and discuss the staging of HCC and the treatment options in the context of the guidelines of the AASLD and the imaging criteria required by the United Network for Organ Sharing for transplantation. MR findings following ablation and chemoembolization are also reviewed.     

Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis

PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1-weighted gradient-echo imaging was performed before and after superparamagnetic iron oxide (SPIO) administration and immediately followed by T1-weighted gradient-echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium-based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed. Alternative-free response receiver operating characteristic (ROC) methodology was used to analyze the results, which were correlated with histopathologic findings after transplantation in 15 patients and at biopsy in 12. Lesions visualized with all three techniques were characterized as a dysplastic nodule or HCC, and ROC analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86) was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were correctly characterized with all three techniques, although observer confidence for lesion characterization was greatest with double-contrast MR imaging. CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).     

Imaging of benign hypervascular hepatocellular nodules in alcoholic liver cirrhosis: differentiation from hypervascular hepatocellular carcinoma

OBJECTIVES: To retrospectively describe imaging analyses of benign hypervascular hyperplastic liver nodules (HHN) that resulted from alcoholic liver cirrhosis and to examine the possibility of imaging differentiation between these nodules and hypervascular hepatocellular carcinoma (HCC). METHODS: Ten histopathologically confirmed HHN arise in alcoholic liver cirrhosis, and 9 HCC were examined. Magnetic resonance imaging (MRI) (10 HHN and 9 HCC), superparamagnetic iron oxide-enhanced T2-weighted MRI (6 HHN and 4 HCC), and dual-phase computed tomography hepatic arteriography (5 HHN and 6 HCC) were performed, respectively. RESULTS: On T1-weighted magnetic resonance images, 7 HHNs showed hyperintensity and 3 showed iso- to hypointensity, and all HCCs showed hypointensity compared with surrounding liver. On T2-weighted magnetic resonance images, 2 HHNs showed hyperintensity and 8 showed iso- to hypointensity. In contrast, 1 HCC showed hypointensity and 8 showed hyperintensity. On superparamagnetic iron oxide-enhanced T2 MRI, all HHNs showed iso- to hypointensity, and all HCCs showed hyperintensity. All HHN and HCCs subjected to dual-phase computed tomography hepatic arteriography showed enhancement on early-phase images and coronalike enhancement on late-phase images. CONCLUSIONS: Imaging findings of highly-well differentiated HCCs possibly overlap with HHN. So, for correct diagnosis of HHN, at first, we should suspect HHN based on clinical findings and MRI findings, and then perform core needle biopsy to verify the radiological diagnosis.     

MR imaging of the liver in primary hepatocellular carcinoma

In 10 patients with hepatoma, magnetic resonance (MR) and CT of the liver were subjectively compared and correlated with surgical or autopsy findings. In five cases MR defined the extent of the tumor better. Magnetic resonance was particularly useful in differentiating the tumor from otherwise abnormal areas of the liver, mostly focal cirrhosis. Magnetic resonance has the advantage of demonstrating major vessels in relation to the hepatoma without injection of any contrast agent. Calcifications well visualized on CT are not seen on MR. The lack of dynamic bolus CT in the majority of our cases as well as our inability to examine the entire liver with all three MR pulse sequences because of time restraint are significant limitations of this retrospective study.     

MR磁敏感加权成像检出肝硬化铁沉积结节的比较研究

目的:评价磁敏感加权成像(SWI)在肝硬化铁沉积结节(SN)检出中的价值。方法:40例病理证实的肝硬化患者及40例年龄、性别匹配的健康志愿者行MRI检查,扫描序列包括平扫T1WI、T2WI、T2*和SWI。2名腹部影像诊断医师共同评价,肝实质内局灶性低信号定义为SN,3mm以下SN定义为微小SN。计数SN总数目及微小SN数目,将其显示程度分为3个等级。结果:对照组均未见SN检出。40例肝硬化病例中T1WI上有10例无SN检出,T2WI、T2*和SWI均检出了SN。SWI检出SN的总数目、平均数目和微小SN明显高于T1WI、T2WI,SWI图像上表现为3级对比的SN(95%)明显高于T1WI(10%)、T2WI(10%)和T2*(33%)。结论:SWI能够较常规序列更为敏感的检出SN,且具有更好的图像对比,有望成为肝脏铁过载无创性评价的新方法。     

Differentiation of well‐differentiated hepatocellular carcinomas from other hepatocellular nodules in cirrhotic liver: Value of SPIO‐enhanced MR imaging at 3.0 Tesla

Purpose

To determine the diagnostic value of superparamagnetic iron oxide (SPIO)‐enhanced MRI for the differentiation of well‐differentiated hepatocellular carcinomas (WD‐HCCs) from other hepatocellular nodules in cirrhotic liver.

Materials and Methods

This study included 114 patients with 216 histologically confirmed hepatocellular nodules, i.e., 23 dysplastic nodules (DNs), 37 WD‐HCCs, and 156 moderately or poorly differentiated HCCs (MD‐/PD HCCs), who underwent SPIO‐enhanced MRI at 3.0T. MRI included T2‐weighted fast‐spin echo and T2*‐weighted gradient recalled echo (GRE) sequences before and after administration of ferucarbotran. The contrast‐to‐noise ratio (CNR) of the lesion was calculated. Reviewers analyzed signal intensity (SI) of the nodules and their enhancement features on SPIO‐enhanced images. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the diagnosis of WD‐HCC were also calculated.

Results

The mean CNR of WD‐HCC was significantly higher than that of DN on T2*‐weighted image. Incomplete high SI on SPIO‐enhanced T2*‐weighted images were seen in 56.8% of WD‐HCC. The most prevalent enhancement features of WD‐HCCs on SPIO‐enhanced T2*‐weighted images, were iso SI with high SI foci [32.5% (12/37)] and homogenous subtle high SI [24.3% (9/37)]. Alternatively, 22 of 23 DNs (95.7%) showed low‐ or iso SI, and 145 of 156 (94.9%) MD‐/PD HCCs showed strong high SI. When iso SI with high SI foci or subtle homogenous high SI nodule was considered as diagnostic criteria for WD‐HCC, we could identify 56.8% of the WD‐HCCs but only 4.4% of the DNs and 3.2% of the MD‐/PD HCCs.

Conclusion

WD‐HCCs have characteristic enhancement features that differentiate them from DNs and MD‐/PD HCCs on SPIO‐enhanced 3.0T MRI. The lesion conspicuity was better on T2*‐weighted images than that on T2‐weighted images. J. Magn. Reson. Imaging 2009;29:328–335. © 2009 Wiley‐Liss, Inc.     

Hepatocellular carcinoma: association with increased iron deposition in the cirrhotic liver at MR imaging.

PURPOSE: To determine whether the frequency of hepatocellular carcinoma (HCC) in patients with cirrhosis is affected by hepatic iron deposition as detected with magnetic resonance (MR) imaging. MATERIALS AND METHODS: In a retrospective search of MR imaging and histopathology records, 196 patients with histopathologically proved cirrhosis and with (n = 80) or without (n = 116) HCC who underwent T2-weighted conventional or fast spin-echo and gradient-echo (GRE) (echo time > or = 6.0 msec) imaging were identified. MR images were qualitatively and quantitatively evaluated for diffuse hepatic iron deposition and siderotic regenerative nodules to assess their correlation with the presence of HCC. RESULTS: Hepatic parenchymal iron deposition was seen in 79 (40%) patients, and iron deposition in regenerative nodules was seen in 71 (36%) at MR imaging. The mean signal intensity ratio of GRE images in patients with hepatic iron deposition was significantly lower than that in patients without it (P < .001). The frequency of HCC in patients with iron deposition in regenerative nodules (52% [37 of 71 patients]) was significantly higher (P = .015) than that in patients without iron in regenerative nodules (34% [43 of 125 patients]). CONCLUSION: The occurrence of HCC may be associated causally with iron deposition in regenerative nodules in patients with cirrhosis. MR imaging can enable detection of iron deposition in regenerative nodules as a possible risk factor for the development of HCC.     

Small hepatocellular carcinoma and cavernous hemangioma: differentiation with dynamic FLASH MR imaging with Gd-DTPA

Forty patients with hepatocellular carcinoma (HCC) (n = 22) or cavernous hemangioma (diameter, 3 cm or less) (n = 18) were examined with serial magnetic resonance (MR) imaging at 1.5 T with the fast low-angle shot (FLASH) technique and an intravenously administered bolus injection of 0.05 mmol/kg Gd-DTPA. Two images per minute were obtained for 5 minutes, and one per minute thereafter until about 10 minutes. Dynamic MR studies revealed five criteria for differentiating these tumors. With HCC there was a hyperintense mass before contrast material enhancement (32%), peak contrast enhancement at about 10 seconds after injection (55%), slight to moderate peak contrast enhancement (73%), absent or minimal delayed enhancement (100%), and, at morphologic study, a capsule or nodules-in-nodule appearance (59%). With hemangioma there was a hypointense mass before contrast enhancement (72%), peak contrast enhancement more than 2 minutes after injection (72%), marked peak contrast enhancement (83%), moderate to marked delayed enhancement (100%), and, at morphologic study, spreading phenomenon (39%). Seventy-seven percent of HCCs and 83% of hemangiomas satisfied three or more criteria and thus could be differentiated from each other with certainty.     

Regenerating nodules of liver cirrhosis: MR imaging

A large number of tiny (0.5-1.5 cm), low-intensity nodules of the liver were retrospectively observed on T2-weighted magnetic resonance (MR) images of eight patients with cirrhosis of the liver. The lesions were not detected with other imaging modalities and were considered to be regenerating nodules. Twenty-five consecutive cases of liver cirrhosis referred for MR examination were prospectively investigated to study the detectability of regenerating nodules and the optimal pulse sequence for detection. A large number of small, low-intensity nodules were demonstrated in nine of 25 cases on T2-weighted spin-echo (SE) images, in nine of 22 cases on T1-T2 complex fast low-angle shot (FLASH) images, and in one of eight cases on T1-weighted SE images. FLASH images obtained with respiratory suspension most clearly revealed regenerating nodules. However, T2-weighted SE images clearly permit differentiation of high-intensity hepatocellular carcinoma, including small daughter lesions, from low-intensity regenerating nodules.     

Hepatocellular carcinoma in the cirrhotic liver with helical CT and MRI: imaging spectrum and pitfalls of cirrhosis-related nodules

OBJECTIVE: This article reviews the imaging spectrum of cirrhosis-related nodules on CT and MRI and differentiates between hepatocellular carcinoma (HCC) and common focal lesions that can simulate HCC in the cirrhotic liver. CONCLUSION: Knowledge of cirrhotic nodules and focal lesions and how they mimic HCC will improve the diagnosis and characterization of focal lesions in cirrhotic liver on CT and MRI.     

Spin-echo echo-planar MR imaging of hepatocellular carcinoma arising from chronic liver damage: comparison with turbo spin-echo imaging.

The aim of this work was to evaluate the value of echo-planar imaging (EPI) in the detection of hepatocellular carcinomas arising in a chronic liver damage to respiratory triggered turbo spin-echo (TSE) imaging. With spin-echo EPI sequences, better lesion-liver contrast was obtained than TSE imaging. Although severe artifact is seen, this imaging produce good contrast, and may be useful as an adjunct to TSE imaging in evaluating patients with chronic liver damage.