Hepatocellular nodules in liver cirrhosis: MR evaluation

Liver cirrhosis is a major public health problem worldwide. Common causes of cirrhosis include hepatitis C virus, hepatitis B virus, alcohol consumption, and nonalcoholic steatohepatitis. Cirrhotic livers are characterized by advanced hepatic fibrosis and the development of hepatocellular nodules such as regenerative nodules, dysplastic or neoplastic nodules. Cirrhosis is the strongest predisposing factor for hepatocellular carcinoma (HCC). For example, viral hepatitis is the main risk factor for cirrhosis and is associated with the increased incidence (1%–4% per year) of HCC after development of cirrhosis. Currently, a variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) are used in noninvasive evaluation of patients with chronic liver disease and suspected HCC. With technological development of MR scanners, MR imaging has emerged as an important imaging modality for assessing cirrhosis and its complications such as HCC. The recent advance in MR is the introduction of faster sequences which have allowed high-quality imaging of the entire liver with high intrinsic soft-tissue contrast, and also multiphasic dynamic MRI that is essential for the detection and characterization of HCC. In addition, functional MRI including diffusion-weighted MRI, MR elastography, and new MR contrast agent with dual function have been investigated for the clinical utility of detection and characterization of HCCs. In this article, we provide an overview of the state-of-the-art MR imaging techniques being used for noninvasive assessment of hepatocellular nodules including conventional dynamic imaging, liver-specific contrast-enhanced MR imaging, diffusion-weighted imaging, MR spectroscopy, and MR elastography.     

Magnetic resonance of focal liver lesions in hepatic cirrhosis and chronic hepatitis.

Detection of focal liver nodules in patients with cirrhosis continues to be a radiologic challenge despite progressive advances in liver imaging in the past 2 decades. Patients with hepatic cirrhosis have a high predisposition to develop hepatocellular carcinoma (HCC), and the early detection and diagnosis of this tumor is very important because the most effective treatment is surgical resection, transplantation, or local ablation therapy when the tumor is small. Cirrhotic livers are mainly composed of fibrosis, together with a broad spectrum of focal nodular lesions ranging from regenerative nodules to premalignant dysplastic nodules to overt HCC. Awareness of such lesions and interpretation of imaging studies in these patients requires a critical review to detect subtle tumors, and a thorough understanding of the imaging appearance of the malignant and benign masses that can occur in the cirrhotic liver. Although the recent advances in liver imaging techniques, especially computed tomography (CT) and magnetic resonance (MR), have facilitated the detection and characterization of focal liver nodules in cirrhotic patients, discriminating between HCC and precancerous nodules remains problematic with all available imaging techniques. Nevertheless, MR imaging appears to have more potential than other imaging techniques in the study of cirrhotic patients and MR may be more appropriate than the other imaging modalities for the detection of small HCCs. In this article we review the imaging characteristics of nodular focal lesions that arise in cirrhotic livers, with special attention to MR imaging features.     

MR imaging in chronic hepatitis and cirrhosis.

The role of magnetic resonance imaging (MRI) in the evaluation of diffuse parenchymal abnormalities of the liver has been expanded by recent technical advances of MR systems as well as the evolution of intravenous contrast media. Currently, MR is undoubtedly the most useful imaging modality for detecting the presence of chronic liver disease. Tailored sequences allow acurate depiction of specific disorders, including steatohepatitis and iron-overload states. Morphologic changes and signal intensity effects not only facilitate the diagnosis of chronic liver disease with MRI but they also help to distinguish between different etiologies, and they assist in staging the histologic severity of certain chronic conditions. Moreover, the faster MRI scanning techniques presently available permit the dynamic assessment of contrast enhancement, which permits improved characterization of focal hepatic lesions, including regenerative nodules, dysplastic nodules, and hepatocellular carcinoma (HCC). Although overlap in MRI findings still may exist among different types of chronic liver disease and among focal liver lesions, familiarity with certain specific imaging features may be diagnostic in the proper clinical setting. Finally, comprehensive MRI examination, including MR angiography and MR cholangiography, is the most sensitive and cost-effective technique for detecting extrahepatic disease, diagnosing vascular disorders, and evaluating the patient before or after liver transplantation. This article focuses on the current role of MR imaging in patients with chronic liver disease. The subjects covered include the detection and characterization of chronic hepatitis and cirrhosis, specific findings seen in steatohepatitis and certain metabolic diseases, the evaluation of extrahepatic vascular complications of cirrhosis, and patient assessment before and after liver transplantation. The characterization of hepatic masses is also included briefly. This subject is covered in greater depth elsewhere in this issue.     

Diagnostic accuracy of multi-/single-detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the milan criteria before liver transplantation

Liver transplantation has been considered to be the only causal treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC) due to its theoretical advantage of eliminating both the tumor and liver disease. However, because of the shortage of donor organs, it is strongly recommended that liver transplantations should be performed on cirrhotic patients with HCCs only when the patients meet the predetermined criteria in terms of number and extent of HCCs. Imaging is thus decisive in the patient inclusion or exclusion from transplantation lists. The imaging techniques used are CT, MRI and ultrasonography. The latter has been proven to be ineffective for HCC surveillance in transplant recipients because of its heavy operator dependence and unreliable detection of small and intermediately sized HCCs. The purpose of this article, then, is to systematically review the diagnostic performances of single-/multidetector row CT, dynamic gadolinium-enhanced MRI, superparamagnetic iron oxide (SPIO)-enhanced MRI and double-contrast MRI using both gadolinium and SPIO for the detection of HCCs with special emphasis on liver transplantation.     

Visualization of blood flow in hepatic vessels and hepatocellular carcinoma using B-flow sonography

PURPOSE: A B-flow sonographic technique was recently developed to provide direct visualization of blood flow with gray-scale sonography. Compared with color Doppler sonography, B-flow imaging has wideband resolution and a high frame rate. The purpose of this study was to evaluate the usefulness of B-flow sonography for visualizing blood flow in hepatic vessels and tumor vascularity in patients with liver cirrhosis or hepatocellular carcinoma (HCC). METHODS: Twenty-five patients with liver cirrhosis, including 15 with HCC, were studied by B-flow and color Doppler sonography. Blood-flow detection rates in portal veins and hepatic arteries and tumor vascularity in HCC were analyzed, and the 2 methods were compared. RESULTS: Using B-flow, blood flow was visualized in the portal vein in 23 (92%) of 25 patients and was visualized in the hepatic artery separately from the portal vein in 9 (36%) of 25 patients. The blood-flow signals were visualized only within vessels, never "bleeding" outside the vessel's lumen. Blood flow in the portal vein was observed with color Doppler sonography in all 25 patients, but the hepatic artery was never clearly separated from the portal vein. Vascularity within the HCC tumor was detected in 9 (60%) of 15 nodules with B-flow imaging, and fine arteries flowing into the tumor were observed in 6 nodules. Color Doppler sonography detected blood flow in 13 (87%) of the 15 HCC nodules. CONCLUSIONS: Blood flow in hepatic vessels and tumor vessels of HCC were visualized with B-flow sonography. B-flow sonography is a potentially useful technique for the evaluation of liver vascularity and intratumoral vessels.     

肝硬变的MRI诊断

笔者复习了我院９４年３～１１月经临床及ＭＲＩ诊断为肝硬变５０例，其中３７例伴有肝癌（７４％），提出肝硬变的ＭＲＩ特点：①肝内弥漫性结节，按结节大小分为小结节型．大结节型及大小结节混合型；②肝普遍增大；③肝表面凸凹不整．各叶比例失调；④肝内静脉细，稀少；⑤脾静脉扩张，胃底及脾门静脉曲张；⑥脾肿大；⑦腹水。文中着重分析肝内再生结节、脉瘤性增生结节及小肝癌三者的ＭＲＩ信号特点及其演变过程。提出ＭＲＩ诊断肝硬变的价值。     

New perspectives and strategy research biomarkers for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Cirrhosis caused by hepatitis B virus, hepatitis C virus or chronic alcohol intake is associated with major risk. Systematic screening for HCC of asymptomatic patients with cirrhosis is needed for earlier detection of small tumors requiring treatment (liver transplantation, surgical resection, percutaneous techniques). The recommended screening strategy among cirrhotic patients is based on regular liver ultrasonography associated with serum alpha-fetoprotein (AFP) assay. As the performance of AFP is not satisfactory, additional tumoral markers are proposed (des-gamma-carboxyprothrombin, glycosylated AFP-L3 fraction). Currently, diagnosis of HCC in cirrhotic patients includes non-invasive tests (imaging after contrast administration, AFP assay); diagnostic biopsy is performed when imaging is limited. After treatment, tumor recurrence is assessed by regular follow-up (AFP assay and imaging). Despite the lack of accurate markers, recent developments in genomic and proteomic approaches will allow the discovery of new biomarkers for primary tumors, as well as for recurrence. This review summarizes the current state of biomarkers for screening, diagnosis and follow-up of HCC, and highlights new perspectives in the field.     

Guest editor's introduction: hepatocellular nodules in liver cirrhosis: imaging update 2011

These review articles will enhance the knowledge of radiologists about current imaging modalities and various contrast agents for the detection and characterization hepatocellular nodules including hepatocellular carcinoma (HCC) in liver cirrhosis, and new concepts of imaging findings, and enable to understand these nodules more completely and thus accurately diagnose HCC.     

MR弥散加权成像诊断肝硬化不典型癌变结节

目的 探讨MR弥散加权成像(DWI)对肝硬化不典型癌变结节的诊断价值.方法 对34例经临床及病理确诊的肝硬化不典型癌变结节患者行常规MR平扫、动态增强扫描及DWI(b值分别取0、500、1000 s/mm~2),比较常规扫描及DWI对肝硬化癌变结节的检出率.结果 常规扫描及动态增强扫描共发现21例肝癌28个癌结节,弥散加权成像发现27例共37个癌结节,弥散加权成像发现的病例数及结节数均多于常规MR平扫及增强扫描,两种检查方法对癌变结节检出率的比较差异有统计学意义(P=0.025).结论 DWI诊断肝硬化不典型癌变结节较MR常规及动态增强扫描更为敏感.     

Detection of recurrent hepatocellular carcinoma on post-operative surveillance: comparison of MDCT and gadoxetic acid-enhanced MRI

Objective

To compare the accuracy of multidetector computed tomography (MDCT) and gadoxetic acid-enhanced magnetic resonance imaging (MRI) for the detection of intrahepatic tumor recurrence after curative resection of hepatocellular carcinoma (HCC).

Materials and methods

Fifty-six patients who underwent MDCT and gadoxetic acid-enhanced MRI for postoperative surveillance after resection of HCC were retrospectively analyzed; 26 patients had a recurrence (36 lesions) and 30 patients did not. Recurrent HCCs were confirmed by histological examinations in two, typical dynamic imaging findings on CT and/or MRI in 28, and by demonstration of growth or tumor staining on angiography on six. Two reviewers graded the confidence for the presence of recurrence on CT and MRI, using a five-point scale. The jackknife free-response receiver operating characteristic method was used to compare diagnostic performance. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated.

Results

For 36 recurrent lesions, the figure of merit was significantly higher for MRI than MDCT for detecting recurrence for both reviewers (p < 0.005 for both reviewers). In lesion-by-lesion analysis, the sensitivity was significantly higher on MRI (100% for reviewer 1 and 97% for reviewer 2) than on MDCT (44.4% and 66.6%) for both reviewers (p < 0.005 for both reviewers). Also in patient-by-patient analysis, sensitivity was significantly higher on MRI (100% and 96.1%) than on MDCT (57.6% and 76.9%) for both reviewers (p < 0.05 for both reviewers).

Conclusion

Gadoxetic acid-enhanced MRI is superior to MDCT for detecting intrahepatic recurrence after curative resection of HCC.     

肝硬化癌变的CT、MRI表现及介入治疗

目的:探讨肝硬化癌变的CT、MRI的影像表现,提高对肝硬化癌变的诊断及介入诊疗水平。方法:对10例12个经病理证实的癌变灶的影像学病灶进行回顾分析,所有病例均接受螺旋CT三期增强扫描、MRI平扫及动态增强扫描。结果:螺旋CT增强扫描检出7个病灶,MRI平扫及动态增强扫描检出12个病灶;螺旋CT三期扫描显示,动脉早期7个病灶均出现中等度增强;MRI平扫在T1WI像上,12个病灶中,4个病灶略呈高信号,8个病灶呈略低信号,在T2WI像上9个病灶呈高信号影,增强动态扫描,动脉期9个病灶呈中度强化,3个病灶呈现小结节样强化;并对7例甲胎蛋白(AFP)升高的患者实施了介入治疗。结论:对于肝硬化癌变病灶的检出,MRI优于螺旋CT,MRI应作为肝硬化癌变检出的首选影像学方法。对影像学高度提示的肝硬化癌变病灶及早实施治疗具有十分重要的临床意义。     

Hepatocellular carcinoma: Spectrum of contrast-enhanced gray-scale harmonic sonography findings

Sonography (US) is the most commonly used tool in the assessment of patients with chronic liver disease. Nevertheless, small nodules can be overlooked. Moreover, even if the lesion is readily recognizable, difficulty persists in differentiating hepatocellular carcinoma (HCC) from pre-tumoral, dysplastic stages of nodule evolution. In addition, US is the main tool in guiding percutaneous ablation therapies for HCC and in evaluating patients after treatment, but changes are not specific and difficulties persist in recognizing residual tumor during and after the ablation procedure. Contrast-enhanced, gray-scale, harmonic US offers new possibilities in the imaging of liver tumors. The real-time, low-mechanical index technique employed in our institution allows a true dynamic assessment of the tumor during the various phases of contrast medium circulation. This pictorial essay focuses on typical and atypical appearances of HCC when imaged with contrast-specific, real-time US. Findings useful for lesion detection, differential diagnosis, posttreatment assessment, and follow-up especially are illustrated. The potential role of contrast-enhanced US in various clinical settings is emphasized.     

Small hepatic nodules in cirrhosis: ultrasonographic, CT, and MR imaging findings

Purpose: The purpose of this study was to assess the imaging findings of pathologically-proved small hepatic nodules 2 cm in size or smaller detected with ultrasonography in cirrhotic patients with suspected hepatocellular carcinoma (HCC). Materials and Methods: We evaluated sonographically detected 32 small hepatic nodules which were pathologically confirmed in 23 consecutive cirrhotic patients who were suspected of having HCC. Twenty-six lesions were confirmed with ultrasonographically-guided aspiration needle-core biopsy, and six with definitive surgery. Ultrasonographic examination records were retrospectively reviewed. CT, and MR images obtained with various imaging techniques were retrospectively reviewed by two radiologists in a blind fashion. Results: The 32 hepatic nodules were comprised of seven focal fatty changes, two large regenerative nodules, three low-grade dysplastic nodules, five high-grade dysplastic nodules, and fifteen HCCs. Ultrasonography showed various echogenicity for the hepatic nodules. The signal-intensity characteristics with T1-weighted spin-echo, in-phase gradient-recalled-echo, and dynamic MR imagings may be useful in distinguishing HCC from nonHCC nodules. Conclusions: Nearly half of small hepatic nodules detected with ultrasonography were nonHCC nodules. Ultrasonographic findings may not be reliable in characterizing small hepatic nodules in cirrhosis. CT and MR imaging obtained with the various techniques are still insensitive to these hepatic nodules. RID="ID="<e5>Correspondence to:</e5> M. Kanematsu Received: 25 August 1997/Revision accepted: 19 November 1997     

Multidetector row CT and MR imaging in diagnosing hepatocellular carcinoma

It is important to diagnose hepatocellular carcinoma (HCC) correctly and in early stage, because viral hepatitis and liver cirrhosis are often complicated by HCC. Noncontrast and enhanced CT and MRI are very useful to visualize and diagnose HCC objectively. Especially, CT and MR imaging with dynamic study is essential to diagnose HCC, because it is usually hypervascular. Dynamic CT and MR study also improve differential diagnosis in the characterization of the tumor. However, to perform useful dynamic study, it is necessary to use a CT unit which can make a helical scan, or a MR system with fast imaging technique available that can obtain more than 15 slices within a single breath hold. Tissue specific contrast medium, such as superparamagnetic iron oxide that is available only on MRI, is also useful for diagnosis of HCC.     

Detection of hepatocellular carcinomas and dysplastic nodules in cirrhotic liver: accuracy of ultrasonography in transplant patients.

The purpose of this study was to assess the usefulness of ultrasonography in the detection of hepatocellular carcinomas and dysplastic nodules in patients with liver cirrhosis. Pretransplantation sonograms in 52 patients with liver cirrhosis who underwent orthotopic liver transplantation were evaluated retrospectively. The numbers of hepatocellular carcinomas and dysplastic nodules were assessed in the explanted liver specimens and compared with pretransplantation ultrasonographic results. Eighteen hepatocellular carcinomas in 16 patients and 20 dysplastic nodules in 11 patients were present in the explanted livers. The size of hepatocellular carcinomas ranged from 0.6 to 5.0 cm (mean, 2.1 cm) in diameter, and that of dysplastic nodules ranged from 0.5 to 1.7 cm (mean, 1.0 cm) in diameter. Pretransplantation ultrasonography enabled detection of 6 of 18 hepatocellular carcinoma and 0 of 20 dysplastic nodule lesions; lesion detection sensitivity for hepatocellular carcinomas and dysplastic nodules was 33% and 0%, respectively. Patient sensitivity and specificity for hepatocellular carcinomas were 38% (6 of 16) and 92% (33 of 36), and those for dysplastic nodules were 0% and 95% (39 of 41), respectively. On the basis of our results, ultrasonography is insensitive for detection of hepatocellular carcinomas and dysplastic nodules in patients with advanced liver cirrhosis.     

Percutaneous ethanol injection under sonographic guidance of hepatocellular carcinoma in compensated and decompensated cirrhotic patients.

Forty-six patients with cirrhosis and 75 biopsy-proved hepatocellular carcinoma (HCC) nodules underwent percutaneous ethanol injection (PEI) regardless of number (up to five) and size (mean diameter, 3.6 cm) of tumoral lesions and clinical severity of cirrhosis (11 patients in Child's class C were included). Ethanol was injected under sonographic guidance through 20 to 22 gauge needles so as to obtain homogeneous hyperechogenicity of lesions. A total of 271 PEI sessions were carried out, delivering 2 to 14 ml per session. All nodules but one decreased in size, and seven were no longer appreciable on sonography. Recurrence was detected in two patients. The 3 year survival rate of all cases was 86%. Child's classes A and B patients fared better (3 yr survival 100%); 2 year survival of subjects with HCC < or = 3 cm was 92%. Multifocality did not affect survival. Most patients experienced mild pain at the site of injection, but only two major complications were encountered: partial chemical thrombosis of the left portal vein and cholangitis. Both cases were managed conservatively. In conclusion, PEI seems to offer a safe and valuable tool for therapy of HCC, especially in patients with good functional liver reserve and small (< or = 3 cm) tumors.     

肝细胞癌MRI动态增强表现的血供基础研究

目的明确肝细胞癌MRI动态增强表现的微血管基础.方法用二乙基亚硝胺长期小剂量灌喂大鼠诱发肝细胞癌,于不同时间行MRI动态增强扫描,并且在相应部位取材做病理、电镜及MVD测定.结果 41个结节做MRI动态增强扫描,绘制时间-信号强度曲线,可见曲线形态与肿瘤MVD有关,快速上升型曲线肿瘤的MVD值高,缓慢上升型曲线肿瘤的MVD值低.结论 MRI动态增强扫描可以客观的反映肿瘤的血供情况,有助于临床进一步治疗.     

多排螺旋CT及MRI在肝门部胆管癌术前评价中的应用

目的探讨多排螺旋CT(MDCT)及MRI在肝门部胆管癌(HHC)术前评价中的应用价值,以期提高HHC手术切除率。方法回顾性分析26例经临床手术病理证实的HHC,分析术前MDCT及MRI改变,并与手术病理对照。结果 26例HHC中,肿块型8例,浸润型16例,管内结节乳头型2例,增强后动脉期及门静脉期表现为边缘轻中度强化,延迟期呈渐进性强化;与手术病理对照,MDCT及MRI分型符合率分别为76.9%及84.6%;MDCT正确评价胆管侵犯范围20例,MRI正确评价胆管侵犯范围22例;MDCT正确评价血管侵犯8例,MRI正确评价血管侵犯7例;淋巴结转移及肝脏侵犯13例,MDCT正确评价10例,MRI正确评价11例。结论 MDCT及MRI对HHC的分型及手术前评估具有重要价值,对于外科手术治疗具有较高的指导作用。     

Evaluation of transcatheter arterial embolization therapy on hepatocellular carcinomas using contrast-enhanced harmonic power Doppler sonography: comparison with CT,power Doppler sonography,and dynamic MRI

Purpose The aim of this study was to assess and compare the sensitivity of power Doppler sonography, contrast-enhanced sonography, plain computed tomography (CT), and dynamic magnetic resonance imaging (MRI) for detecting hepatocellular carcinoma (HCC) nodules incompletely treated with transcatheter arterial embolization (TAE). Methods A total of 63 unresectable HCC nodules were examined in this study. The HCCs were treated with TAE. All patients underwent plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI 1 week after TAE. The sensitivity of each modality to incompletely treated HCC nodules was compared. Detection of the residual viable HCC on angiography or tumor biopsy was regarded as the gold standard for the diagnosis of incomplete treatment. Results Twenty-four nodules (38%) were diagnosed as incompletely treated. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these incompletely treated nodules were 42% (10/24), 46% (11/24), 88% (21/24), and 79% (19/24), respectively. Eighty percent (19 nodules) of the 24 incompletely treated nodules were located within a depth of less than 8 cm. The sensitivities of plain CT, power Doppler sonography, contrast-enhanced harmonic power Doppler sonography, and dynamic MRI to these superficial incompletely treated nodules were 37% (7/19), 53% (10/19), 100% (19/19), and 74% (14/19), respectively. In contrast, the sensitivities of each modality to deeply located nodules were 60% (3/5), 20% (1/5), 40% (2/5), and 100% (5/5), respectively. Conclusion Plain CT and power Doppler sonography had a low sensitivity to HCC nodules incompletely treated with TAE. Except for those that were deeply located, contrast-enhanced harmonic sonography showed the highest sensitivity in detecting incompletely treated HCC nodules.