Improved diagnosis of well‐differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid‐enhanced magnetic resonance imaging and Sonazoid contrast‐enhanced ultrasonography

Aim: Two new imaging modalities have been developed recently that are directed at the focal liver lesions: gadolinium ethoxybenzyl diethylene triamine pentaacetic acid (Gd‐EOB‐DTPA)‐enhanced magnetic resonance imaging (MRI) and Sonazoid contrast‐enhanced ultrasonography (CEUS). We investigated the usefulness of these modalities for the diagnosis of small (<2 cm), well‐differentiated hepatocellular carcinoma (HCC). Methods: A total of 15 nodules from 13 patients, which were histologically diagnosed as well‐differentiated HCC, were subjected to this study. Lesions that showed hypervascularity in the arterial phase and washout in the portal or late non‐hemodynamic phase were regarded as HCC in the dynamic studies of all imaging modalities. Results: By multidetector computed tomography (MDCT), six of 15 (40%) nodules were diagnosed as HCC. Gd‐EOB‐DTPA‐enhanced MRI diagnosed HCC in nine of the 15 (60%) nodules. Of the nine nodules that were not diagnosed by MDCT, four could be diagnosed by Gd‐EOB‐DTPA‐enhanced MRI. In Sonazoid CEUS, 10 of 15 nodules (67%) were diagnosed as HCC. Four of nine nodules that could not be diagnosed as HCC by MDCT, were diagnosed by Sonazoid CEUS. A total of 11 of the 15 (73%) nodules were diagnosed as HCC by Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS in addition to MDCT. Conclusion: Gd‐EOB‐DTPA‐enhanced MRI and Sonazoid CEUS had greater diagnostic value for small, well‐differentiated HCC than did conventional MDCT.     

Contrast-enhanced intraoperative ultrasound for hepatocellular carcinoma: high sensitivity of diagnosis and therapeutic impact

Background

Postoperative early recurrence is a crucial issue in the treatment of hepatocellular carcinoma (HCC) patients. Some early recurrences seem to occur from minute tumors which were overlooked during both preoperative and intraoperative investigations. Therefore, it is urgently necessary to increase detectability of minute HCCs during operation. If they could be detected and resected during surgery, the prognosis should be improved. The purpose of this study is to investigate the usefulness of contrast-enhanced intraoperative ultrasound (CEIOUS) for the diagnosis and treatment of HCC.

Methods

Institutional ethics committee approval and informed consent were obtained. Fifty-two patients (mean age 65 years; 38 males and 14 females) who underwent liver resection with either preoperative computed tomography during angiography (CTA) or CEIOUS with Sonazoid (perflubutane microbubble contrast agent) were studied. We determined the presence of HCC on the basis of the histopathological findings of resected specimens.

Results

The sensitivity of CEIOUS [97.6% (95% CI 91.8–99.4)] was higher than that of CTA [89.4% (95% CI 81.1–94.3)]. The positive predictive values of CEIOUS [91.2% (95% CI 83.6–95.5) and CTA [91.6% (95% CI 83.6–95.9)] were similar. Eight new HCCs from 7 patients, which accounted for 9.4% (8/85) of the total HCCs, were correctly detected and diagnosed by CEIOUS, and we performed an additional partial hepatectomy in 3 of these 7 patients.

Conclusions

CEIOUS with Sonazoid provided increased sensitivity of detection of small HCCs compared with preoperative CTA, thereby leading to a more appropriate surgical procedure and contributing to complete tumor removal.     

超声造影对诊断早期肝硬化合并小肝癌的价值

目的：了解超声造影对肝硬化合并小肝癌的诊断价值。方法选取2010年5月至2013年6月收治的患者96例,进行超声造影检查,从而评价小肝癌的增强变化,并与动态增强 MRI 以及动态增强CT 进行对比。结果超声造影下的小肝癌表现出动脉期增强,静脉期降低,以增强期或者低增强为标准,最终诊断的正确率为85．4％（82/96）,进一步结合延迟期肝癌的低增强的指标,诊断的正确率达到94．8％（91/96）,假阳性率为5．2％（5/96）。结论超声造影在诊断早期肝硬化合并小肝癌方面有着较为理想的价值。     

Contrast-enhanced gray-scale harmonic ultrasound in the efficacy assessment of ablation treatments for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to compare contrast-enhanced gray-scale harmonic ultrasound with multiphasic spiral computed tomography in the assessment of treatment efficacy of non-surgically treated HCC. METHODS: We studied 56 HCCs treated by percutaneous ethanol injection (31 cases), radiofrequency ablation (three cases), trans-arterial chemoembolization (12 cases), and combined treatment (10 cases). The efficacy of therapies was blindly assessed by multiphasic computed tomography and gray-scale harmonic ultrasound with a second-generation contrast agent (sulfur hexafluoride). RESULTS: On computed tomography 30 tumors (53.6%) showed complete necrosis, while 26 lesions (45.4%) were still viable. On contrast-enhanced ultrasound examination 33/56 nodules (58.9%) had no contrast enhancement in the arterial phase, while 23/56 lesions (41.1%) were still vascularized. All the nodules assessed as completely necrotic on computed tomography did not show arterial enhancement on contrast-enhanced ultrasound and diagnostic agreement was found in 53/56 cases (94.6%) (P<0.001). Contrast-enhanced ultrasound demonstrated relative sensitivity and specificity of 87.0% and 98.4%. CONCLUSIONS: Contrast-enhanced harmonic ultrasound is promising in the efficacy evaluation of ablation treatments for HCC. Nodules vascularized in the arterial phase on contrast harmonic ultrasound should be considered still viable and addressed to additional treatment without further evaluation.     

Computer‐aided grading system for endoscopic severity in patients with ulcerative colitis

The degree of mucosal redness can be quantified as an index of hemoglobin (IHB) that changes with photographic conditions. The first aim of the present study was to stress the exclusion of γ correction as a critical procedure for reliable measurements of IHB. The second aim was to characterize Matts grade by pictorial parameters in the gray scale picture of IHB and to establish a computer‐aided grading system of endoscopic severity in ulcerative colitis. A total of 130 digital endoscopic pictures of 55 patients with ulcerative colitis (30 Matts 1, 70 Matts 2, 20 Matts 3 and 10 Matts 4) were used. The pictures without γ correction were processed for the mean IHB, SD of IHB, kurtosis of IHB and contrast feature. A computer‐aided grading system was constructed on the basis of Bayes decision theory. Significant increase in the mean IHB was seen when comparing Matts 1 to Matts 2. The SD of IHB or contrast feature significantly increased from Matts 2 to Matts 3 or from Matts 3 to Matts 4. Kurtosis of IHB was significantly larger in Matts 3 than in Matts 1 or Matts 4. Sensitivity and specificity when discriminating Matts 1 from Matts 2, Matts 2 from Matts 3 and Matts 3 from Matts 4 by the grading system were found to be 84 and 96%, 94 and 70%, and 100 and 85%, respectively. The computer‐aided grading system may permit quantitative evaluation of effects of treatments in ulcerative colitis with minimal interobserver variation.     

Validation of an extension of the international non-invasive criteria for the diagnosis of hepatocellular carcinoma to the characterization of macroscopic portal vein thrombosis

Background and Aim: We aimed to validate the non‐invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non‐invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria). Methods: A total of 96 cases of PVT detected using ultrasonography in patients with cirrhosis and HCC were included in the study. When coincidental arterial hypervascularity was detected by contrast perfusional ultrasonography and helical computed tomography, the thrombus was considered malignant according to our EASL/AASLD extension criteria. In all cases, an ultrasound‐guided biopsy examination of the thrombus was performed. Results: Coincidental hypervascularity was found in 54 of 96 nodules (56.2%), and all were malignant upon biopsy (100% positive predictive value). Twenty‐four (25%) had negative results with both techniques (non‐vascular thrombus). Biopsies showed HCC in five non‐vascular thrombi (5.3% of all thrombi) and in 13 of 18 thrombi with a hypervascularity result from only one technique. Conclusions: The EASL/AASLD extension criteria for non‐invasive diagnosis of malignant thrombosis were satisfied in 75.2% of malignant thrombi; thus, a biopsy is frequently required in this setting. However, in the presence of coincidental hypervascularity of a thrombus with both techniques, a biopsy is not required (absolute positive predictive value for malignancy). Relying on imaging techniques in thrombi could miss the diagnosis of malignant portal invasion in up to 24.9% of cases.     

Recent advances in the diagnosis of hepatocellular carcinoma

In the last decade, new imaging techniques have become available, offering the possibility of investigating contrast perfusion of liver nodules in cirrhosis. It is now accepted that a non-invasive diagnosis of hepatocellular carcinoma (HCC) can be established based on the vascular pattern, obtained with pure blood pool contrast agents. The diagnostic pattern includes: hypervascularity in the arterial phase (15–35 s after contrast injection), consisting in a contrast signal in the nodule greater than in the surrounding parenchyma, followed by contrast wash out, which leads the nodule to show the same, or, more specifically, a lower contrast signal, than the surrounding parenchyma in the portal and late phases (>40 s after injection). Such a pattern can be obtained not only by computed tomography or magnetic resonance imaging, but also by contrast-enhanced ultrasonography, most simply with real-time low mechanical index harmonic imaging ultrasound equipment with second-generation ultrasound contrast agents. The risk of false-positive diagnosis of malignancy isnearly abolished when the functional vascular pattern is not the only feature, but is superimposed on a nodule visible also without contrast. One single contrast imaging technique may suffice to make a diagnosis of HCC if the nodule is >1 cm in diameter and has developed during a surveillance program. Other types of contrast agents, such as those taken up by the reticular-endothelial system cells, may offer additional diagnostic clues, but definitive evidence of their efficacy is still to be produced. In conclusion, contrast-enhanced imaging techniques now offer the possibility of a non-invasive diagnosis of HCC in a large number of cases, reducing the need of invasive investigations, such as ultrasound-guided biopsy or angiography.     

Contrast‐enhanced ultrasound for quantification of tissue perfusion in humans

Contrast‐enhanced ultrasound is an imaging technique that can be used to quantify microvascular blood volume and blood flow of vital organs in humans. It relies on the use of microbubble contrast agents and ultrasound‐based imaging of microbubbles. Over the past decades, both ultrasound contrast agents and experimental techniques to image them have rapidly improved, as did experience among investigators and clinicians. However, these improvements have not yet resulted in uniform guidelines for CEUS when it comes to quantification of tissue perfusion in humans, preventing its uniform and widespread use in research settings. The objective of this review is to provide a methodological overview of CEUS and its development, the influences of hardware and software settings, type and dosage of ultrasound contrast agent, and method of analysis on CEUS‐derived perfusion data. Furthermore, we will discuss organ‐specific imaging challenges, advantages, and limitations of CEUS.