From the RSNA refresher courses: screening the cirrhotic liver for hepatocellular carcinoma with CT and MR imaging: opportunities and pitfalls.

The inherent distortion of the appearance of liver parenchyma by the underlying pathologic changes of cirrhosis can obscure and simulate malignancy at imaging. That hepatocellular carcinoma is the most common abdominal malignancy worldwide and occurs most often in patients with chronic liver disease and cirrhosis compounds this problem. Magnetic resonance (MR) imaging and, to a lesser extent, computed tomography (CT) can depict the underlying nodular and fibrotic changes in patients with cirrhosis, particularly when siderotic nodular regeneration is present. Application of state-of-the-art helical CT and MR imaging techniques has improved the ability to detect hepatocellular carcinoma in this population, but, even with these advances, fewer than 50% of small tumors are detected with either of these techniques in a screening population. Dynamic hepatic arterial-phase contrast material-enhanced imaging is essential with both CT and MR imaging to achieve even these levels of success. Benign lesions that simulate tumor tissue are encountered in many patients with cirrhosis and include focal fibrosis, infarcted regenerative nodules, arteriovenous shunts, hemangiomas, pseudoaneurysms, and focal transient hepatic enhancement. An awareness of the imaging characteristics of these lesions can help one avoid a mistaken diagnosis of hepatocellular carcinoma in many cases.

Discrimination of small hepatic hemangiomas from hypervascular malignant tumors smaller than 3 cm with three-phase helical CT.

PURPOSE: To compare the appearance of small hepatic hemangiomas at nonenhanced and contrast material-enhanced helical computed tomography (CT) with that of small (<3-cm) hypervascular malignant liver tumors and to evaluate the accuracy of multiphase helical CT for differentiating small hemangiomas from small hypervascular malignant tumors. MATERIALS AND METHODS: Radiologists reviewed multiphase helical CT liver images in 86 patients with 37 hemangiomas and 49 malignant liver tumors. They evaluated lesion type and degree of enhancement for change from arterial to portal venous phase. They rated their confidence in the discrimination of hemangiomas from malignant tumors. RESULTS: At arterial phase CT, enhancement similar to aortic enhancement was observed in 19%-32% of hemangiomas and 0%-2% of malignant tumors; globular enhancement, in 62%-68% and 4%-12%, respectively. At portal venous phase CT, enhancement similar to blood pool enhancement was observed in 43%-54% of hemangiomas and 4%-14% of malignant tumors; globular enhancement, in 46%-49% and 0%-2%, respectively. For all readers and all phases of enhancement, the area under the receiver operating characteristic curves was 0.81-0.87, indicating that inherent accuracy of CT is high and that there was no significant difference (P >.28) in overall accuracy. Readers diagnosed hemangiomas with 47%-53% mean sensitivity with all enhancement phases and diagnosed malignant lesions with 95% mean specificity. CONCLUSION: Small hemangiomas frequently show atypical appearances at CT. Two-phase helical CT does not improve sensitivity but does improve specificity for differentiating hemangiomas from hypervascular malignant tumors.

Radiologic diagnosis of hepatocellular carcinoma.

Substantial recent technologic improvements in CT scanning, US scanning, and MR imaging, together with advances in the understanding of the optimal application of contrast administration techniques, have facilitated advances in radiologic imaging detection for HCC diagnosis. Despite a large number of earlier publications reporting a high sensitivity for imaging detection of HCC, more recent screening studies of large cirrhotic populations confirm that only 37% to 45% of HCC tumor nodules are detected by CT scanning, US scanning, or MR imaging. Future investigation will include efforts to improve the detection of small tumors and to characterize with greater specificity the spectrum of nodular changes that occur with cirrhosis. Although several small series have attempted to characterize cirrhotic nodules by evaluating the relative arterial or portal blood supply, these preliminary results require substantiation with larger series. Continued technologic advances such as multidetector helical CT scanning and new US and MR contrast agents under investigation may improve the imaging characterization of cirrhotic nodules.

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.

Pretransplantation surveillance for possible hepatocellular carcinoma in patients with cirrhosis: epidemiology and CT-based tumor detection rate in 430 cases with surgical pathologic correlation.

PURPOSE: To determine the prevalence of clinically unsuspected hepatocellular carcinoma (HCC) with advanced cirrhosis and assess the sensitivity of helical computed tomographic (CT) surveillance for tumor detection in these patients. MATERIALS AND METHODS: Prospective direct correlation of CT findings with explanted liver specimen findings was performed in 430 transplant recipients with cirrhosis. The prevalence of clinically unsuspected HCC according to liver disease cause was evaluated. Serum alpha-fetoprotein (AFP) values in patients with and those without tumor were recorded. Prospective and retrospective CT tumor detection was evaluated with respect to CT technique and time from CT to transplantation. RESULTS: HCC was found in 59 (14%) of 430 transplant recipients without suspicion of tumor before referral for transplantation. HCC was most prevalent with hepatitis B (27%) and hepatitis C (22%). Serum AFP values were not sensitive for detection of most small tumors. With triphasic helical CT, the prospective and retrospective rates of identifying patients with tumor were 59% and 68%, respectively; the prospective and retrospective tumor nodule detection rates were 37% and 44%, respectively. Tumor detection rates were highest with CT performed within 67 days before transplantation. CONCLUSION: Clinically unsuspected HCC is most prevalent with cirrhosis secondary to hepatitis B or C, and, when evaluated at CT, is best detected with triphasic contrast material-enhanced helical imaging performed within 67 days before transplantation.

Prognostic significance of arterial phase CT for prediction of response to transcatheter arterial chemoembolization in unresectable hepatocellular carcinoma: a retrospective analysis.

OBJECTIVE: The purpose of this study was to use hepatic arterial phase helical CT to assess tumor vascularity and predict the likelihood of response to transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. MATERIALS AND METHODS: Helical CT findings for 57 patients with hepatocellular carcinoma were classified into one of three patterns of vascularity on the basis of the degree of tumor or liver enhancement during the hepatic arterial phase. Cases in which hypervascular lesions predominated were classified as a type 1 pattern. Cases in which hypovascular lesions predominated were classified as a type 2 pattern. Patients were classified as responders or nonresponders on the basis of the changes of tumor size revealed on CT after three transcatheter arterial chemoembolization treatments. RESULTS: We classified the 57 patients as 37 responders (65%) and 20 nonresponders (35%). A statistically significant correlation between the type 1 hypervascular pattern and response to transcatheter arterial chemoembolization was seen; conversely, the type 2 hypovascular pattern correlated with nonresponse to transcatheter arterial chemoembolization (chi-square = 7.85, p = 0.02). Patients classified as responders lived significantly longer than those classified as nonresponders with 12-, 24-, and 36-month survival rates of 90%, 67%, and 36%, respectively, for responders and 70%, 17%, and 10%, respectively, for nonresponders. CONCLUSION: We found that patients who responded to transcatheter arterial chemoembolization had prolonged survival (p < 0.01). Response correlated closely with tumor vascularity as shown on hepatic arterial phase helical CT.

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Infarcted regenerative nodules in cirrhosis: CT and MR imaging findings with pathologic correlation.

OBJECTIVE. The purpose of this article is to present the imaging findings and correlative pathologic findings of infarcted regenerative nodules in the cirrhotic liver. CONCLUSION. Infarcted regenerative nodules exhibit a spectrum of imaging appearances in the cirrhotic liver and can resemble hypovascular hepatocellular carcinoma or other neoplasms on CT and MR imaging. Although uncommon, this abnormality must be included in the differential diagnosis of focal liver lesions in patients with cirrhosis, particularly in patients with a history of substantial gastrointestinal bleeding. Serial imaging may help differentiate these lesions from malignant tumors.

Extrahepatic metastases of hepatocellular carcinoma.

PURPOSE: To determine the relative frequency, incidence, and locations of metastases of hepatocellular carcinoma (HCC), correlate extrahepatic metastatic disease with intrahepatic tumor staging, and determine the computed tomographic (CT) manifestations of HCC metastases. MATERIALS AND METHODS: CT findings in 403 consecutive patients with HCC at our institution since 1992 were reviewed retrospectively. One hundred forty-eight patients with extrahepatic metastatic HCC were identified, and the locations, sizes, and attenuation and enhancement characteristics of the lesions were recorded. RESULTS: A majority (128 [86%] of 148) of patients with extrahepatic HCC foci had either intrahepatic stage IVA tumor (112 [76%] patients) or an intrahepatic stage III tumor (16 [11%] patients) at the occurrence of metastases. The most frequent site of the first detectable metastasis was the lung (58 [39%] patients). Tabulation of all extrahepatic metastatic sites showed the most common to be the lung in 81 (55%) patients, the abdominal lymph nodes in 60 (41%) patients, and the bone in 41 (28%) patients. CONCLUSION: The lung, abdominal lymph nodes, and bone are the most common sites of extrahepatic metastatic HCC. Most extrahepatic HCC occurs in patients with advanced intrahepatic tumor stage (stage IVA). Incidental extrahepatic lesions at CT in patients with stage I or II intrahepatic HCC are unlikely to represent metastatic HCC.

Islet cell tumor of the pancreas: biphasic CT versus MR imaging in tumor detection.

PURPOSE: To compare the effectiveness of biphasic computed tomography (CT) and magnetic resonance (MR) imaging in the detection of pancreatic islet cell tumors. MATERIALS AND METHODS: Retrospective quantitative, qualitative, and receiver operating characteristic analyses of biphasic CT and MR imaging were performed in 19 patients with 26 histopathologically proved islet cell tumors. Delayed arterial dominant-phase (AP) and portal venous-phase (PVP) biphasic CT was performed after the administration of contrast material. MR imaging included T1-weighted spin-echo (SE) and T2-weighted SE or fast SE imaging, fat-saturated T1-weighted SE imaging, dynamic contrast material-enhanced T1-weighted gradient-echo imaging, and delayed enhanced T1-weighted SE imaging with or without fat saturation. RESULTS: PVP CT and delayed enhanced T1-weighted MR imaging had the highest A(z) values (0.98 and 0.97, respectively; P <.05). Delayed enhanced T1-weighted MR imaging had the highest relative sensitivity (14-15 [74%-79%] of 19 lesions), followed by PVP CT (18-19 [69%-73%] of 26 lesions), AP CT (17-19 [65%-73%] of 26 lesions), fat-saturated T1-weighted MR imaging (eight to 10 [57%-71%] of 14 lesions), T2-weighted (16-17 [62%-65%] of 26 lesions), T1-weighted (15-18 [58%-69%] of 26 lesions) MR imaging, and dynamic MR imaging (nine [56%] of 16 lesions). CONCLUSION: Biphasic (especially PVP) CT and MR imaging have similar effectiveness in the detection of islet cell tumors if fat-saturated T1-weighted and delayed enhanced T1-weighted MR imaging are included.

Hepatic angiosarcoma: findings on multiphasic contrast-enhanced helical CT do not mimic hepatic hemangioma.

OBJECTIVE: The objective of our study was to identify multiphasic contrast-enhanced helical CT findings of angiosarcoma of the liver to determine whether this tumor could be confused with hemangioma of the liver. CONCLUSION: Angiosarcoma of the liver is a multifocal tumor with a variety of findings on multiphasic contrast-enhanced helical CT. None of the findings would usually be confused with the typical findings of hepatic hemangioma.

Spectrum of imaging findings of the liver in end-stage cirrhosis: Part II, focal abnormalities.

Cirrhosis, through the process of necrosis, fibrosis, regeneration, and malignant transformation, creates multiple focal benign and malignant hepatic masses. The detection and appearance of these masses varies with the severity of the cirrhotic process and the imaging technique used. Although some overlap exists in the imaging appearance of the benign and malignant masses, in most instances recognition of a few characteristic features will yield the correct diagnosis.

Delayed MR imaging of hepatocellular carcinoma enhanced by gadobenate dimeglumine (Gd-BOPTA).

The purpose of this study was to determine the efficacy of gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging for evaluation of hepatocellular carcinoma HCC. MR images were obtained in 14 patients with 31 HCC nodules as a part of a phase III clinical trial. T1- and T2-weighted images were obtained before and after iv administration of 0.1 mmol/kg of Gd-BOPTA. Two blinded readers evaluated pre- and delayed postcontrast images separately for detection of tumor nodules. Quantitative measurements of signal-to-noise (SNR) and tumor/liver contrast-to-noise (CNR) ratios were also performed. A signal/intensity ratio was calculated. Tumor enhancement was correlated with histologic findings. Consensus agreement of precontrast T1- and T2-weighted images revealed 23/31 HCC nodules in 14 patients; postcontrast T1-weighted images demonstrated 24/31 HCC nodules in the same number of patients. Combining both pre- and postcontrast images, 27/31 lesions were detected. Four patients had four well-differentiated HCC nodules detected only on postcontrast images, while three well-differentiated lesions in two patients were only seen on precontrast images. Quantitative evaluation showed an SNR ratio increase in both liver parenchyma and HCC nodules, as well as a significant increase in the absolute CNR ratio on postcontrast T1-weighted gradient-recalled images (P < 0.05). Well-differentiated HCC lesions showed a greater enhancement than poorly differentiated HCC lesions.

End-stage primary sclerosing cholangitis: CT findings of hepatic morphology in 36 patients.

PURPOSE: To determine if there is a significant difference in the hepatic morphology depicted on computed tomographic (CT) scans in patients with end-stage cirrhosis caused by primary sclerosing cholangitis versus that in patients with end-stage cirrhosis caused by other factors. MATERIALS AND METHODS: The frequency of five morphologic findings of the liver parenchyma and two intrahepatic biliary findings identified on CT scans in 36 patients with end-stage cirrhosis caused by primary sclerosing cholangitis were compared with the frequency of the same findings in 472 patients with end-stage cirrhosis caused by other factors. The morphologic findings were lobulation of the liver contour, atrophy of the lateral or posterior hepatic segments, hypertrophy of the caudate lobe, and pseudotumor of the caudate lobe. Lobulation, atrophy, and hypertrophy were subclassified as mild-moderate or severe. The biliary findings were ductal dilatation and calculi. RESULTS: Each of the 11 findings occurred more frequently (P < .05) in patients with primary sclerosing cholangitis than in the other 472 patients. Six findings occurred more frequently (P < .05) in patients with primary sclerosing cholangitis than in patients with cirrhosis caused by any other single agent. CONCLUSION: There is a significant difference in the hepatic morphology observed in patients with primary sclerosing cholangitis-induced end-stage cirrhosis versus that in patients with end-stage cirrhosis of other causes.

Undetected hepatocellular carcinoma: clinical features and outcome after liver transplantation.

The aim of the study was to define the clinical characteristics and outcome of patients found to have an undetected hepatocellular carcinoma (HCC) at liver transplantation. Patients who underwent liver transplantation and were found to have a hepatoma with a prior workup showing normal alpha-fetoprotein levels and no corresponding lesion on radiological evaluation were defined as having an undetected HCC. Detailed information was collected, and the last abdominal computed tomographic (CT) scan before transplantation was performed was retrospectively reviewed. Thirty-nine patients had a tumor that met the criteria for an undetected hepatoma. The most common causes for pretransplantation liver disease were hepatitis C virus (HCV) (49%) and alcohol use (28%). Tumor size was 2 cm or less in 85% of the patients, vascular invasion was detected in 31% of the patients, and tumor, node, metastasis (TNM) classification was stage I or II in 77% of the patients. Review of the last CT scan before transplantation showed that the lesion was evident in retrospect in only 15% of the patients. Thirty-two patients (82%) remained alive at the time of the study with a mean follow-up of 30 months. Metastatic HCC was detected in 1 patient 7 months after transplantation. There were no other tumor recurrences. Survival analysis showed no significant differences when tumor size, stage, presence of vascular invasion, or causes of pretransplantation liver disease were compared. Undetected HCCs represent a significant percentage of total hepatomas in patients undergoing liver transplantation. Most patients have small, early-stage tumors, but tumors greater than 2 cm or of advanced stage are also frequently found in this population. Overall and tumor-free survival appear to be favorable.

Gadobenate dimeglumine (BOPTA) enhanced MR imaging: patterns of enhancement in normal liver and cirrhosis.

To determine whether gadobenate dimeglumine (BOPTA) will adequately enhance cirrhotic liver parenchyma, and to document the enhancement patterns in cirrhosis, 14 cirrhotic and 20 non-cirrhotic patients were evaluated before and 60-120 minutes after gadolinium-BOPTA. Proof of liver cirrhosis was biopsy (6), surgical resection (3), and clinical follow-up (5). Enhancement effects were compared quantitatively by determining the liver signal-to-noise ratio (SNR) and signal enhancement in both populations. Qualitatively assessment of the liver enhancement was performed and classified as homogeneous or heterogeneous. Quantitative analysis: cirrhotic liver parenchyma presented a higher increase in SNR values, relative to non-cirrhotic liver parenchyma, on postcontrast images. Likewise the signal enhancement of cirrhotic liver parenchyma was superior to non-cirrhotic liver on T1-weighted SE images (P = .02) and in-phase GRE images (P < .001). There was no statistical difference on out-of-phase GRE images. Qualitative analysis: on T1-weighted SE postcontrast images, cirrhotic liver parenchyma showed a homogeneous enhancement in 7 patients and heterogeneous in 7. Whereas on GRE images, cirrhotic parenchyma showed heterogeneous enhancement in 9 patients and homogeneous in 5 patients. The heterogeneous enhancement was due to the presence of hypointense nodules in 7 patients and hyperintense nodules in 2 patients. In conclusion, our study has shown that the hepatobiliary contrast agent Gd-BOPTA is effective in the cirrhotic liver, demonstrating an increased liver enhancement compared with non-cirrhotic patients.

Biliary tract carcinoma complicating primary sclerosing cholangitis: evaluation with CT, cholangiography, US, and MR imaging.

PURPOSE: To assess the value of computed tomography (CT), cholangiography, ultrasonography (US), and magnetic resonance (MR) imaging in the demonstration of biliary tract carcinoma complicating primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: Thirty patients were studied who had PSC and biliary tract carcinoma. Twenty-six patients had cholangiocarcinoma, and four had gallbladder carcinoma. Sixty-four CT scans, 41 cholangiograms, 40 US studies, and seven MR studies were reviewed retrospectively for evidence of tumor and PSC. Imaging results were correlated with pathologic findings from whole liver specimens and biopsies. Presence of mass was rated as definite, probable, possible, or doubtful or absent. RESULTS: On CT scans, cholangiocarcinomas produced hypoattenuating masses in 17 of 23 cases, delayed contrast enhancement in six of 12, progressive biliary dilatation in five of 15, and thickened bile duct wall in two of 23. On cholangiograms, dominant strictures were present in 18 of 21 cases of cholangiocarcinoma; 13 were malignant, and five were benign. Cholangiocarcinoma formed polypoid bile duct masses in two of 21 cases. Biliary dilatation was caused by cholangiocarcinoma in 10 of 12 cases and by benign stricture in two. Gallbladder carcinomas demonstrated masses on CT scans, cholangiograms, and US images, and wall thickening on CT and US images. Overall, definite or probable tumor was demonstrated in 25 of 30 patients (83%). CONCLUSION: Most biliary tract carcinomas complicating PSC can be demonstrated on imaging studies.

MR imaging patterns of gadolinium retention within liver neoplasms.

BACKGROUND: To determine the spectrum of appearances of gadolinium retention within cholangiocarcinoma (CCA) and other liver neoplasms. METHODS: Two hundred ten patients underwent hepatic magnetic resonance imaging (MRI) at 1.5 T with precontrast T1- and T2-weighted spin-echo (SE) images and delayed Gd-DTPA- or gadoteridol- (0.1 mmol/kg) enhanced T1-weighted SE images. Postcontrast images were evaluated for lesions suspicious for tumors, and lesion signal intensity was characterized as homogeneously or heterogeneously hypo-, iso-, mildly hyper-, or markedly hyperintense to liver. Data from 94 patients with benign or malignant neoplasms are presented. RESULTS: Imaging demonstrated 237 malignant neoplasms (121 hepatocellular carcinoma [HCC], 26 CCA, 17 colon carcinoma metastases, 73 other tumors) and 28 benign neoplasms (22 hemangioma, six focal nodular hyperplasia [FNH]). One hundred forty malignant lesions appeared as homogeneous postcontrast (29 hypointense, 75 isointense, 17 mildly hyperintense, 19 markedly hyperintense) and 97 as heterogeneous (15 isointense, 50 mildly hyperintense, 32 markedly hyperintense). Malignant lesions showing homogeneous, mildly or markedly hyperintense signal intensity postcontrast included 10 CCA, seven HCC, six epithelioid hemangioendothelioma, eight neuroendocrine tumor metastases, three adenocarcinoma metastases of unknown origin, and one breast carcinoma metastasis. Hemangiomas appeared as homogeneous postcontrast in 19 lesions (six isointense, one mildly hyperintense, 12 markedly hyperintense) and as heterogeneous in three lesions (markedly hyperintense). FNH appeared as homogeneous postcontrast in one lesion (isointense) and as heterogeneous in five lesions (one isointense, four mildly hyperintense). CONCLUSION: Homogeneous gadolinium retention on delayed postcontrast images of malignant hepatic neoplasms is seen in a high percentage of CCA lesions and less commonly with other neoplasms.