Objective
A new computer tool is proposed to distinguish between focal nodular hyperplasia (FNH) and an inflammatory hepatocellular adenoma (I-HCA) using contrast-enhanced ultrasound (CEUS). The new ...method was compared with the usual qualitative analysis.
Methods
The proposed tool embeds an “optical flow” algorithm, designed to mimic the human visual perception of object transport in image series, to quantitatively analyse apparent microbubble transport parameters visible on CEUS. Qualitative (visual) and quantitative (computer-assisted) CEUS data were compared in a cohort of adult patients with either FNH or I-HCA based on pathological and radiological results. For quantitative analysis, several computer-assisted classification models were tested and subjected to cross-validation. The accuracies, area under the receiver-operating characteristic curve (AUROC), sensitivity and specificity, positive predictive values (PPVs), negative predictive values (NPVs), false predictive rate (FPRs) and false negative rate (FNRs) were recorded.
Results
Forty-six patients with FNH (
n
= 29) or I-HCA (
n
= 17) with 47 tumours (one patient with 2 I-HCA) were analysed. The qualitative diagnostic parameters were accuracy = 93.6%, AUROC = 0.94, sensitivity = 94.4%, specificity = 93.1%, PPV = 89.5%, NPV = 96.4%, FPR = 6.9% and FNR = 5.6%. The quantitative diagnostic parameters were accuracy = 95.9%, AUROC = 0.97, sensitivity = 93.4%, specificity = 97.6%, PPV = 95.3%, NPV = 96.7%, FPR = 2.4% and FNR = 6.6%.
Conclusions
Microbubble transport patterns evident on CEUS are valuable diagnostic indicators. Machine-learning algorithms analysing such data facilitate the diagnosis of FNH and I-HCA tumours.
Key Points
• Distinguishing between focal nodular hyperplasia and an inflammatory hepatocellular adenoma using dynamic contrast-enhanced ultrasound is sometimes difficult.
• Microbubble transport patterns evident on contrast-enhanced sonography are valuable diagnostic indicators.
• Machine-learning algorithms analysing microbubble transport patterns facilitate the diagnosis of FNH and I-HCA.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
AIM： To evaluate in a multicenter study whether the sonographic characterization of focal liver lesions can be improved using SonoVue-enhancement; and to compare this method with computed tomography ...（CT） and magnetic resonance imaging （MRI）.
METHODS： One hundred and thirty four patients withone focal liver lesion detected in baseline ultrasound （US） were examined with conventional US, contrastenhanced US （n = 134）, contrast-enhanced CT （n = 115） and/or dynamic contrast-enhanced MRI （n = 70）. The lesions were classified as malignant, benign or indeterminate and the type of lesion was determined. The final diagnosis based on the combined information of all imaging examinations, clinical information and histology （n = 32） was used. Comparisons were made to see whether the addition of contrast-enhanced US led to the improvement of the characterization of doubtful focal liver lesions.
RESULTS： In comparison with unenhanced US, SonoVue markedly improves sensitivity and specificity for the characterization （malignant/benign） of focal liver lesions. In comparison with CT and/or dynamic MRI, SonoVue -enhanced sonography applied for characterization of focal liver lesions was 30.2% more sensitive in the recognition of malignancy and 16.1% more specific in the exclusion of malignancy and overall 22.9% more accurate. In the subgroup with confirmative histology available （n = 30）, sensitivity was 95.5% （CEUS）, 72.2% （CT） and 81.8% （MRI）, and specificity was 75.0% （CEUS）, 37.5% （CT） and 42.9% （MRI）. The sensitivity and specificity of CEUS for the identification of focal nodular hyperplasia （FNH） and hemangiomas was 100% and 87%, resulting in an accuracy of 94.5%.
CONCLUSION： SonoVue-enhanced sonography emerges as the most sensitive, ost specific and thus most accurate imaging modality for the characterization of focal liver lesions.
To compare treatment failure and survival associated with ultrasound-guided radiofrequency ablation (RFA) and trans-arterial chemoembolization (TACE) for early-stage HCC in Child-Pugh A cirrhosis ...patients.
122 cirrhotic patients (RFA: 61; TACE: 61) were well matched according to cirrhosis severity; tumor size and serum alpha-fetoprotein. TACE was performed in case of inconspicuous nodule on US or nodule with "at risk location". Treatment failure was defined as local tumor progression (LTP) and primary treatment failure (failing to obtain complete response after two treatment session). Treatment failure and overall survival (OS) were compared after coarsened exact matching. Cox proportional model to assess independent predictive factors was performed.
No significant difference was seen for baseline characteristics between the two groups. Mean tumor size was 3cm in both group with 41% HCC>3cm. Treatment failure rates after TACE was 42.6% (14 primary treatment failures and 12 LTP) and 9.8% after RFA (no primary treatment failure and 6 LTP) P < 0.001. TACE was the only predictive factor of treatment failure (Hazard ratio: 5.573). The 4-years OS after RFA and TACE were 54.1% and 31.5% (P = 0.042), respectively.
For Child-Pugh A patients with early-stage HCC, alternative treatment as supra-selective TACE to RFA regarded as too challenging using common US guidance decrease significantly the local tumor control and overall survival. Efforts to improve feasibility of RFA especially for inconspicuous target have to be made.
Highlights • Non severe VUA have spontaneous favorable outcome without recurrence. • Fertility is conserved after VUA even if embolization was performed. • Recurrences are more often observed for ...severe VUA. • Embolization must be proposed for anaemic patients or severe VUA on angiography. • Recurrence occurs more often when a history of curettage is found.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hepatocellular adenomas (HCA) are rare benign hepatocellular tumors occurring mainly in women taking oral contraceptives with 2 major complications: severe bleeding and malignant transformation that ...can be avoided if nodules exceeding 5 cm are resected. This simple attitude has been challenged in the recent years with HCA in men, in young adolescent, in aged persons, and complications in hepatocellular adenomas below 5 cm. The discovery of specific mutations leading to specific phenotypes has modified the clinical spectrum of the disease. The phenotypic immune classification of HCA based on the molecular classification is being widely used in liver referral centers. The aim of this snapshot is to briefly present for each subtype the clinical, pathological, immuno-pathological criteria as well as the risk of complications and guidelines for treatment and management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin ...beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the clinical relevance of ASS1 overexpression for diagnosis. Molecular, proteomic, and immunohistochemical analyses were performed in UHCA cases of the Bordeaux series. The clinico‐pathological features, including ASS1 immunohistochemical labeling, were analyzed on a large international series of 67 cases. ASS1 overexpression and the shHCA subgroup were superimposed in 15 cases studied by molecular analysis, establishing ASS1 overexpression as a hallmark of shHCA. Moreover, the ASS1 immunomarker was better than prostaglandin D2 synthase and only found positive in 7 of 22 shHCAs. Of the 67 UHCA cases, 58 (85.3%) overexpressed ASS1, four cases were ASS1 negative, and in five cases ASS1 was noncontributory. Proteomic analysis performed in the case of doubtful interpretation of ASS1 overexpression, especially on biopsies, can be a support to interpret such cases. ASS1 overexpression is a specific hallmark of shHCA known to be at high risk of bleeding. Therefore, ASS1 is an additional tool for HCA classification and clinical diagnosis.
ShHCA is a new HCA subgroup with a high risk of bleeding with PTGDS and ASS1 proposed as immunomarkers, with conflicting results and interpretations in the literature. By molecular, proteomic, and immunohistochemistry analyses, we established that ASS1 overexpression was a specific hallmark of shHCA. Having shown that PTGDS was not a good marker, we demonstrated, using a large cohort of UHCAs, the sensitivity of ASS1 immunomarker and its clinical relevance. Therefore, ASS1 is an additional tool for HCA classification, clinical diagnosis of shHCA, and appropriate management.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Bubble-enhanced heating (BEH) can be exploited to increase heating efficiency in treatment of liver tumors with non-invasive high-intensity focused ultrasound (HIFU). The objectives of this study ...were: (i) to demonstrate the feasibility of increasing the heating efficiency of sonication exploiting BEH in pig liver in vivo using a clinical platform; (ii) to determine the acoustic threshold for such effects with real-time, motion-compensated magnetic resonance-guided thermometry; and (iii) to compare the heating patterns and thermal lesion characteristics resulting from continuous sonication and sonication including a burst pulse. The threshold acoustic power for generation of BEH in pig liver in vivo was determined using sonication of 0.5-s duration ("burst pulse") under real-time magnetic resonance thermometry. In a second step, experimental sonication composed of a burst pulse followed by continuous sonication (14.5 s) was compared with conventional sonication (15 s) of identical energy (1.8 kJ). Modification of the heating pattern at the targeted region located at a liver depth between 20 and 25 mm required 600-800 acoustic watts. The experimental group exhibited near-spherical heating with 40% mean enhancement of the maximal temperature rise as compared with the conventional sonication group, a mean shift of 7 ± 3.3 mm toward the transducer and reduction of the post-focal temperature increase. Magnetic resonance thermometry can be exploited to control acoustic BEH in vivo in the liver. By use of experimental sonication, more efficient heating can be achieved while protecting tissues located beyond the focal point.
•Non-invasive subtyping of HCA remains challenging for several subtypes, thus carrying different levels of risks and management; to date, ß-HCA and sh-HCA are not detected and no discrimination ...between I-HCA and ß-I-HCA is achieved in daily practice.•Multiple HCA subtyping can be improved using clinical features, i.e., age and sex, combined with MRI-radiomics features.•Machine-learning algorithms including basic clinical features and MRI-radiomics could help discrimination between I-HCA and ß-I-HCA.
Non-invasive subtyping of hepatocellular adenomas (HCA) remains challenging for several subtypes, thus carrying different levels of risks and management. The goal of this study is to devise a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics and to evaluate its diagnostic performance.
This single-center retrospective case-control study included all consecutive patients with HCA identified within the pathological database from our institution from January 2003 to April 2018 with MRI examination (T2, T1-no injection/injection-arterial-portal); volumes of interest were manually delineated in adenomas and 38 textural features were extracted (LIFEx, v5.10). Qualitative (i.e., visual on MRI) and automatic (computer-assisted) analysis were compared. The prognostic scores of a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics (tumor volume and texture features) were assessed using a cross-validated Random Forest algorithm.
Via visual MR-analysis, HCA subgroups could be classified with balanced accuracies of 80.8 % (I-HCA or ß-I-HCA, the two being indistinguishable), 81.8 % (H-HCA) and 74.4 % (sh-HCA or ß-HCA also indistinguishable). Using a model including age, sex, volume and texture variables, HCA subgroups were predicted (multivariate classification) with an averaged balanced accuracy of 58.6 %, best=73.8 % (sh-HCA) and 71.9 % (ß-HCA). I-HCA and ß-I-HCA could be also distinguished (binary classification) with a balanced accuracy of 73 %.
Multiple HCA subtyping could be improved using machine-learning algorithms including two clinical features, i.e., age and sex, combined with MRI-radiomics. Future HCA studies enrolling more patients will further test the validity of the model.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Transient elastography (TE) is widely used for non-invasive assessment of liver fibrosis in HIV-HCV co-infected patients. TE, however, cannot determine liver morphology. Acoustic radiation force ...impulse (ARFI) imaging is a novel procedure enabling assessment of liver fibrosis during a conventional ultrasonographic examination. This study evaluated the correlation between liver fibrosis measurements by TE and ARFI.
Each of 46 HIV-HCV patients underwent both ARFI and TE within 6 months. Patients were evaluated by the "equivalent METAVIR" scoring system, using previously established cut-off values. Agreements between the ARFI and TE scores were estimated by Kappa coefficients, with Kappa values ≥0.40, ≥0.60, and ≥0.80 defined as moderate, good and very good agreement, respectively.
ARFI and TE yielded "Equivalent Metavir" fibrosis scores of F1 in 26 and 31 patients, respectively; F2 in nine and seven, respectively; F3 in three and two, respectively; and F4 in eight and six, respectively. The two methods showed very good agreement in predicting overall stages Kappa = 0.82 and for F ≥3 Kappa = 0.80 and moderate agreement in predicting significant fibrosis F ≥2 Kappa = 0.50. Morphologic ultrasound analysis concomitant to ARFI detected two hepatocarcinomas.
ARFI showed promising results in the non-invasive assessment of liver fibrosis in HIV-HCV patients, with liver fibrosis staging similar to that of TE. Moreover, ARFI can assess morphology and fibrosis during the same session.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess the practical feasibility and effectiveness of real-time magnetic resonance (MR) temperature monitoring for the radiofrequency (RF) ablation of liver tumours in a clinical setting, nine ...patients (aged 49–87 years, five men and four women) with one malignant tumour (14–50 mm, eight hepatocellular carcinomas and one colorectal metastasis), were treated by 12-min RF ablation using a 1.5-T closed magnet for real-time temperature monitoring. The clinical monopolar RF device was filtered at 64 MHz to avoid electromagnetic interference. Real-time computation of thermal-dose (TD) maps, based on Sapareto and Dewey’s equation, was studied to determine its ability to provide a clear end-point of the RF procedure. Absence of local recurrence on follow-up MR images obtained 45 days after the RF ablation was used to assess the apoptotic and necrotic prediction obtained by real-time TD maps. Seven out of nine tumours were completely ablated according to the real-time TD maps. Compared with 45-day follow-up MR images, TD maps accurately predicted two primary treatment failures, but were not relevant in the later progression of one case of secondary local tumour. The real-time TD concept is a feasible and promising monitoring method for the RF ablation of liver tumours.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
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