Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

Hepatocellular carcinoma(HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging(MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines.

Hepatocellular carcinoma: Can LI-RADS v2017 with gadoxetic-acid enhancement magnetic resonance and diffusion-weighted imaging improve diagnostic accuracy?

BACKGROUND The Liver Imaging Reporting and Data System(LI-RADS), supported by the American College of Radiology(ACR), has been developed for standardizing the acquisition, interpretation, reporting, and data collection of liver imaging examinations in patients at risk for hepatocellular carcinoma(HCC). Diffusionweighted imaging(DWI), which is described as an ancillary imaging feature of LI-RADS, can improve the diagnostic efficiency of LI-RADS v2017 with gadoxetic acid-enhanced magnetic resonance imaging(MRI) for HCC.AIM To determine whether the use of DWI can improve the diagnostic efficiency of LIRADS v2017 with gadoxetic acid-enhanced magnetic resonance MRI for HCC.METHODS In this institutional review board-approved study, 245 observations of high risk of HCC were retrospectively acquired from 203 patients who underwent gadoxetic acid-enhanced MRI from October 2013 to April 2018. Two readers independently measured the maximum diameter and recorded the presence of each lesion and assigned scores according to LI-RADS v2017. The test was used to determine the agreement between the two readers with or without DWI. In addition, the sensitivity(SE), specificity(SP), accuracy(AC), positive predictive value(PPV), and negative predictive value(NPV) of LI-RADS were calculated.Youden index values were used to compare the diagnostic performance of LIRADS with or without DWI.RESULTS Almost perfect interobserver agreement was obtained for the categorization of observations with LI-RADS(kappa value: 0.813 without DWI and 0.882 with DWI). For LR-5, the diagnostic SE, SP, and AC values were 61.2%, 92.5%, and71.4%, respectively, with or without DWI; for LR-4/5, they were 73.9%, 80%, and75.9% without DWI and 87.9%, 80%, and 85.3% with DWI; for LR-4/5/M, they were 75.8%, 58.8%, and 70.2% without DWI and 87.9%, 58.8%, and 78.4% with DWI; for LR-4/5/TIV, they were 75.8%, 75%, and 75.5% without DWI and 89.7%,75%, and 84.9% with DWI. The Youden index values of the LI-RADS classification without or with DWI were as follows: LR-4/5: 0.539 vs 0.679; LR-4/5/M: 0.346 vs 0.467; and LR-4/5/TIV: 0.508 vs 0.647.CONCLUSION LI-RADS v2017 has been successfully applied with gadoxetate-enhanced MRI for patients at high risk for HCC. The addition of DWI significantly increases the diagnostic efficiency for HCC.

Radiomics in hepatocellular carcinoma:A state-of-the-art review

Hepatocellular carcinoma(HCC)is the most common cancer and the second major contributor to cancer-related mortality.Radiomics,a burgeoning technology that can provide invisible high-dimensional quantitative and mineable data derived from routine-acquired images,has enormous potential for HCC management from diagnosis to prognosis as well as providing contributions to the rapidly developing deep learning methodology.This article aims to review the radiomics approach and its current state-of-the-art clinical application scenario in HCC.The limitations,challenges,and thoughts on future directions are also summarized.

Sinusoidal obstruction syndrome: A systematic review of etiologies,clinical symptoms, and magnetic resonance imaging features

BACKGROUND Sinusoidal obstruction syndrome (SOS) is a kind of rare liver disease which is characterized by damage to small hepatic vessels, affecting particularly the sinusoidal endothelium. Due to the special etiology and high mortality, early diagnosis of SOS is significant for clinical survival and prognosis. AIM To generalize the common etiologies and clinical symptoms of SOS and summarize the characteristic magnetic resonance imaging (MRI) features so as to provide more valuable information for early diagnosis of SOS. METHOD We searched PubMed, Web of science, Wanfang Data, China Knowledge Resource Integrated, VIP, and Cochrane Library databases without a limiting period and the types of articles. The search process mainly revolved around the etiologies, common clinical symptoms, and MRI imaging features of SOS. Ultimately, 29 full articles were included in this review and 222 articles were excluded. RESULTS Eleven case reports included 13 patients. The etiologies of these patients including chemotherapy (5/13), medicinal herbs containing pyrrolidine alkaloids (PAs, e.g. Tusanqi)(4/13), hematopoietic stem cell transplantation (HSCT)(2/13), drug toxicity (6-thioguanine)(1/13), and “poppers”, a recreational drug used during anal intercourse (1/13). Eighteen case series including 497 patients, and SOS in 465 (93.6%) patients was caused by PAs. Ascites, abdominal pain and swelling, jaundice were the most common clinical symptoms. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), direct bilirubin (DBil), and prothrombin time (PT) had varying degrees of elevation.Heterogeneous signals on T1 weighted imaging/T2 weighted imaging (T1WI/T2WI), heterogeneous enhancement of liver parenchyma, ascites, hepatomegaly, narrowing and blurring of intrahepatic inferior vena cava and three main hepatic veins, edema around the portal vein, and gallbladder wall edema were the most common MRI imaging features of SOS. CONCLUSION In the West, SOS was mostly secondary to HSCT. Some SOS developed in the process of chemotherapy for hepatic metastatic tumor. A few SOS were caused by toxicity of certain drugs. In the East, Tusanqi was a major cause of SOS. Ascites, abdominal pain and swelling, jaundice were the common clinical symptoms. Elevations of ALT, AST, GGT, ALP, TBil, and DBil could be used as predictors of liver function damage. Numerous characteristic MRI imaging features could provide more valuable information for early diagnosis of SOS.

Noninvasive imaging of hepatic dysfunction: A state-of-the-art review

Hepatic dysfunction represents a wide spectrum of pathological changes,which can be frequently found in hepatitis,cholestasis,metabolic diseases,and focal liver lesions.As hepatic dysfunction is often clinically silent until advanced stages,there remains an unmet need to identify affected patients at early stages to enable individualized intervention which can improve prognosis.Passive liver function tests include biochemical parameters and clinical grading systems(e.g.,the Child-Pugh score and Model for End-Stage Liver Disease score).Despite widely used and readily available,these approaches provide indirect and limited information regarding hepatic function.Dynamic quantitative tests of liver function are based on clearance capacity tests such as the indocyanine green(ICG)clearance test.However,controversial results have been reported for the ICG clearance test in relation with clinical outcome and the accuracy is easily affected by various factors.Imaging techniques,including ultrasound,computed tomography,and magnetic resonance imaging,allow morphological and functional assessment of the entire hepatobiliary system,hence demonstrating great potential in evaluating hepatic dysfunction noninvasively.In this article,we provide a state-of-the-art summary of noninvasive imaging modalities for hepatic dysfunction assessment along the pathophysiological track,with special emphasis on the imaging modality comparison and selection for each clinical scenario.

Nonlinear signal transduction network with multistate

Signal transduction is an important and basic mechanism to cell life activities.The stochastic state transition of receptor induces the release of signaling molecular,which triggers the state transition of other receptors.It constructs a nonlinear sigaling network,and leads to robust switchlike properties which are critical to biological function.Network architectures and state transitions of receptor affect the performance of this biological network.In this work,we perform a study of nonlinear signaling on biological polymorphic network by analyzing network dynamics of the Ca^(2+)-induced Ca^(2+)release(CICR)mechanism,where fast and slow processes are involved and the receptor has four conformational states.Three types of networks,Erdos–R´enyi(ER)network,Watts–Strogatz(WS)network,and BaraB´asi–Albert(BA)network,are considered with different parameters.The dynamics of the biological networks exhibit different patterns at different time scales.At short time scale,the second open state is essential to reproduce the quasi-bistable regime,which emerges at a critical strength of connection for all three states involved in the fast processes and disappears at another critical point.The pattern at short time scale is not sensitive to the network architecture.At long time scale,only monostable regime is observed,and difference of network architectures affects the results more seriously.Our finding identifies features of nonlinear signaling networks with multistate that may underlie their biological function.

Three-dimensional cytoplasmic calcium propagation with boundaries

Ca^(2+)plays an important role in cell signal transduction.Its intracellular propagation is the most basic process of Ca^(2+)signaling,such as calcium wave and double messenger system.In this work,with both numerical simulation and mean field ansatz,the three-dimensional probability distribution of Ca^(2+),which is read out by phosphorylation,is studied in two scenarios with boundaries.The coverage of distribution of Ca^(2+)is found at an order of magnitude ofμm,which is consistent with experimental observed calcium spike and wave.Our results suggest that the double messenger system may occur in the ER-PM junction to acquire great efficiency.The buffer effect of kinase is also discussed by calculating the average position of phosphorylations and free Ca^(2+).The results are helpful to understand the mechanism of Ca^(2+)signaling.

Imaging biomarkers for predicting poor prognosis of hepatocellular carcinoma: a review

Hepatocellular carcinoma(HCC)is a primary malignancy of the liver with a high mortality rate.Heterogeneity is the main biological characteristic of HCC,which manifests through the different biological behaviors of each phenotype and ultimately,affects patient prognosis and treatment efficacy.Various aggressive biological behaviors are considered to be associated with the poor prognosis of HCC patients including poor differentiation,microvascular invasion,intracellular fat accumulation,invasive growth,bile duct invasion or tumor thrombosis,and tumor spread and metastasis,and have been reported as prognostic biomarkers.In addition,HCC results from multifactor synergistic damage,and various factors related to genetics,molecular pathology and immunohistochemistry such asβ-catenin,Ki67,cytokeratin-19,and epithelial cell adhesion molecule have an impact on HCC differentiation and prognosis.This article is an overview of the biological behaviors that lead to poor prognosis of HCC,and the roles of morphological and quantitative noninvasive imaging biomarkers in the evaluation and prediction of these behaviors.Some common biomarkers related to genetics,molecular pathology and immunohistochemistry are also briefly summarized.It is hoped that this review will provide clinicians and radiologists with an update on the development of liver imaging,and provide directions for the combination of radiology,genetics,molecular pathology and histopathology to better predict the prognosis of HCC patients.