Comparing radiomics models with different inputs for accurate diagnosis of significant fibrosis in chronic liver disease.

OBJECTIVE: The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. METHODS: This was a retrospective multicenter study with 807 CLD patients and 4842 images from three hospitals. All of these patients have liver biopsy results as referenced standard. Multichannel deep learning radiomics models were developed. Elastography images, gray-scale images of the liver capsule, gray-scale images of the liver parenchyma, and serological results were gradually integrated to establish different diagnosis models, and the optimal model was selected for assessing ≥ F2. Its accuracy was thoroughly investigated by applying different F0-1 prevalence cohorts and independent external test cohorts. Analysis of receiver operating characteristic (ROC) curves was performed to calculate the area under the ROC curve (AUC) for significance of fibrosis (≥ F2) and cirrhosis (F4). RESULTS: The AUC of the DLRE2.0 model significantly increased to 0.91 compared with the DLRE model (AUC 0.83) when evaluating ≥ F2 (p = 0.0167). However, it did not show statistically significant differences as integrating gray-scale images and serological data into the DLRE2.0 model. AUCs of DLRE and DLRE2.0 increased, when there was higher F0-1 prevalence. All radiomics models had good robustness in the independent external test cohort. CONCLUSIONS: DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability. KEY POINTS: • The non-invasive discrimination of significant fibrosis (≥ F2) in patients with chronic liver disease (CLD) is clinically critical but technically challenging. • We aimed to develop an updated deep learning radiomics model of elastography (DLRE2.0) based on our previous DLRE model to achieve significantly improved performance in ≥ F2 evaluation. • Our study based on 807 CLD patients and 4842 images with liver biopsy found that DLRE2.0 was the most suitable model for staging significant fibrosis while considering the balance of diagnostic accuracy and clinical practicability.

Liver Stiffness Measured with Two-dimensional Shear-Wave Elastography Is Predictive of Liver-related Events in Patients with Chronic Liver Disease Due to Hepatis B Viral Infection.

Background Liver stiffness measurement has been proposed as a noninvasive marker for predicting liver-related complications of cirrhosis. Purpose To evaluate the predictive value of liver stiffness measurement by using two-dimensional (2D) shear-wave elastography (SWE) for liver-related events among patients with chronic hepatitis B. Materials and Methods This retrospective study recruited consecutive patients with chronic hepatitis B who were referred for liver biopsy between May 2011 and May 2015. All patients underwent 2D SWE before biopsy, and a subset of patients underwent transient elastography. Patients were followed up for 4 years through the electronic medical records or telephone interviews. Univariable and multivariable logistic regression analyses were used to determine prognostic factors. Accuracy of prognostic parameters was evaluated by using the area under the receiver operating characteristic curve (AUC). Results Among 430 patients (mean age, 38 years; range, 18-67 years) including 328 men and 102 women, 29 patients developed liver-related events. Multivariable analysis demonstrated that liver stiffness measured with 2D SWE, spleen longitudinal diameter at US, age, and albumin level were predictive factors of liver-related events. The AUC of the multivariable model was higher (0.89; 95% confidence interval [CI]: 0.86, 0.92) but not significantly different from that of 2D SWE (0.86; 95% CI: 0.82, 0.89; P = .23) and was significantly higher than that of the fibrosis stage (0.72; 95% CI: 0.68, 0.76; P < .001), the aspartate aminotransferase-to-platelet ratio index (0.80; 95% CI: 0.76, 0.84; P < .001), and the fibrosis-4 index (0.84; 95% CI: 0.80, 0.87; P = .02). In a subset of patients with available transient elastography (n = 188), the multivariable model, 2D SWE, and transient elastography showed comparable performance (AUC: 0.91 vs 0.86 vs 0.88, respectively). When inflammatory activity was considered, the multivariable model was highly accurate in patients with low-grade inflammation and normal levels of alanine aminotransferase (AUC: 0.97 and 0.94, respectively). Conclusion The multivariable model and two-dimensional shear-wave elastography are more accurate in predicting liver-related events than are the fibrosis stage and serum markers of liver fibrosis tests. © RSNA, 2020 Online supplemental material is available for this article.

How intrahepatic cholestasis affects liver stiffness in patients with chronic hepatitis B: a study of 1197 patients with liver biopsy.

OBJECTIVES: To evaluate the impact of intrahepatic cholestasis on liver fibrosis staging using liver stiffness measurements (LSM). METHODS: Between July 2011 and September 2016, a total of 1197 patients with chronic hepatitis B (CHB) infection were enrolled to collect clinical, biological, 2D shear wave elastography (SWE), and histological (METAVIR scoring system) data. LSM was compared in patients with normal total bilirubin (TB) versus abnormal TB for each group of fibrosis stage, alanine aminotransferase (ALT) levels, and inflammation grade. Logistic regression and ROC analyses were performed to assess the benefit of adding TB and to LSM for fibrosis staging. RESULTS: Nine hundred and seventy-three patients were analyzed. Within the same fibrosis stage, LSMs showed significantly higher value in patients with abnormal TB than those with normal TB. Increased LSM for abnormal TB was generally found within different sub-groups of patients (≤ F2 or ≥ F3; ALT < 2 × upper limit of normal (ULN) or ALT ≥ 2 × ULN; METAVIR activity grade ≤ 1 or ≥ 2). Patients with abnormal TB level showed higher optimal cutoff values: 10.46 kPa for ≥ F2, 10.94 kPa for ≥ F3, and 15.88 kPa for F4, than those with normal TB (7.62 kPa, 8.26 kPa, and 11.01 kPa, respectively). LSM assessed fibrosis stage (≥ F2, ≥ F3, F4) showed higher false positive rate in patients with abnormal TB level (44.6%, 45.1%, 39.6%) than those with normal TB (20.7%, 17.1%, 14.4%). However, the area under the ROC curve did not change appreciably when adding TB to LSM for fibrosis stage. CONCLUSION: Intrahepatic cholestasis showed slight effect on LSM in patients with CHB, also leading to overestimation of liver fibrosis stages. But adding TB level to LSM did not improve the overall diagnostic performance of liver fibrosis stage. KEY POINTS: • Intrahepatic cholestasis showed slight effect on liver stiffness measurements (LSMs) in chronic HBV patients. • Patients with abnormal total bilirubin (TB) level showed higher optimal cutoff values and false positive rate. • When taking into account intrahepatic cholestasis, the diagnostic performance of LSM for liver fibrosis staging in patients with chronic HBV infection will not improve.

Partial deficiency of CTRP12 alters hepatic lipid metabolism.

Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/-) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/-) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/-) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/-) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes.

Comparison of Two-Dimensional Shear Wave Elastography and Real-Time Tissue Elastography for Assessing Liver Fibrosis in Chronic Hepatitis B.

BACKGROUND: Noninvasive assessment of liver fibrosis has important clinical significance. Different techniques including two-dimensional shear-wave elastography (2D SWE) and real-time tissue elastography (RTE) are reported to be useful for the noninvasive diagnosis of hepatic fibrosis. All these techniques are affected by many factors. How to choose a reasonable method needs further studies. PURPOSE: This study was conducted to comparatively assess the diagnostic performance of 2D SWE and RTE in patients with Chronic Hepatitis B (CHB) and influence of inflammation on the stiffness values obtained by both techniques, so as to objectively assess the reasonable choice between these 2 elastography techniques for noninvasive assessment of hepatic fibrosis in clinical practice. MATERIALS AND METHODS: Four-hundred and thirty-seven patients with CHB meeting the inclusion criteria were enrolled in the study. All patients underwent liver stiffness measurements by using 2D SWE and RTE on the same day. Histologic fibrosis was staged and inflammation activity was graded based on the METAVIR scoring system on liver biopsy specimens. RESULTS: The liver stiffness values by using 2D SWE and RTE both increased in parallel with the degree of liver fibrosis and the grade of inflammation. However, the diagnostic efficacy of significant fibrosis and cirrhosis using 2D SWE was significantly higher than that of RTE. The 2D SWE measurement values were statistically different in different alanine aminotransferase (ALT) levels and METAVIR activity grades; however, no statistically significant differences were observed by using RTE. The diagnostic efficacy of 2D SWE significantly varied with elevated ALT levels compared with RTE. CONCLUSION: 2D SWE was more accurate than RTE in the assessment of significant fibrosis and cirrhosis in patients with CHB. Compared with RTE, the measurement values and diagnostic performance obtained by 2D SWE were prone to be more easily affected by the inflammation fluctuations.

Discovery of perfluoroalkyl sulfonyl quaternary ammonium substances in the environment and their environmental behaviors.

A variety of per- and polyfluoroalkyl substances (PFASs) have been released into the environment via wastewater treatment plant (WWTP) effluent, with current target and nontarget analytical methods typically focusing on negatively ionized PFASs while largely overlooking positively ionized ones. In this study, five cationic PFASs, perfluoroalkyl sulfonyl quaternary ammonium substances (PFAQASs), were first identified in surface water impacted by the WWTP effluent, applying a metabolomics-based nontarget analysis method. Environmental behaviors of identified novel PFAQASs were further investigated. In surface water, sediment, and fish (Coilia mystus) samples collected from the Yangtze River, 8:3 PFAQA was consistently the predominant PFAQASs, with the mean concentrations of 90 ng/L (< LOD-558 ng/L), 92 ng/g dw (< LOD-421 ng/g dw), and 2.3 ng/g ww (< LOD-4.6 ng/g ww), respectively. This study highlights the necessity to discover other cationic PFASs in the environment. Among PFAQASs, 8:4 PFAQA (4.2, range 3.4 - 4.6) had the highest mean sediment-water partitioning coefficient (log Koc), followed by 8:3 PFAQA (3.9, 2.8 - 4.5) and 6:3 PFAQA (3.7, 3.3 - 4.1). The log Koc of PFAQASs showed a general increase trend with the increasing carbon chain length. Mean bioaccumulation factor (BAF) values of PFAQASs calculated in the collected fish from the Yangtze River ranged from 1.9 ± 0.32 (4:3 PFAQA) to 2.9 ± 0.34 (8:4 PFAQA). The mean BAF values of PFAQASs generally increased with the carbon chain length. Further studies are warranted to elucidate the environmental fate, potential toxicity, and human exposure implications for these identified novel PFASs.

Dynamic Contrast-Enhanced Ultrasound Radiomics for Hepatocellular Carcinoma Recurrence Prediction After Thermal Ablation.

PURPOSE: To develop a radiomics model based on dynamic contrast-enhanced ultrasound (CEUS) to predict early and late recurrence in patients with a single HCC lesion ≤ 5 cm in diameter after thermal ablation. PROCEDURES: We enrolled patients who underwent thermal ablation for HCC in our hospital from April 2004 to April 2017. Radiomics based on two branch convolution recurrent network was utilized to analyze preoperative dynamic CEUS image of HCC lesions to establish CEUS model, in comparison to the conventional ultrasound (US), clinical, and combined models. Clinical follow-up of HCC recurrence after ablation were taken as reference standard to evaluate the predicted performance of CEUS model and other models. RESULTS: We finally analyzed 318 patients (training cohort: test cohort = 255:63). The combined model showed better performance for early recurrence than CUES (in training cohort, AUC, 0.89 vs. 0.84, P < 0.001; in test cohort, AUC, 0.84 vs. 0.83, P = 0.272), US (P < 0.001), or clinical model (P < 0.001). For late recurrence prediction, the combined model showed the best performance than the CEUS (C-index, in training cohort, 0.77 vs. 0.76, P = 0.009; in test cohort, 0.77 vs. 0.68, P < 0.001), US (P < 0.001), or clinical model (P < 0.001). CONCLUSIONS: The CEUS model based on dynamic CEUS radiomics performed well in predicting early HCC recurrence after ablation. The combined model combining CEUS, US radiomics, and clinical factors could stratify the high risk of late recurrence.

A novel identification system combining diffusion kurtosis imaging with conventional magnetic resonance imaging to assess intestinal strictures in patients with Crohn's disease.

PURPOSE: To determine the utility of diffusion kurtosis imaging (DKI) for assessing bowel fibrosis and to establish a new magnetic resonance imaging (MRI)-based classification based on DKI and conventional MRI parameters for characterizing intestinal strictures in Crohn's disease (CD) using the histological evaluation of resected intestine samples as the reference standard. METHODS: Thirty-one patients with CD undergoing preoperative conventional MRI and diffusion-weighted imaging (DWI) (b values = 0-2000 s/mm2) were consecutively enrolled. We classified the mural T2-weighted signal intensity and arterial-phase enhancement patterns on conventional MRI. We also measured DWI-derived apparent diffusion coefficients (ADCs) and DKI-derived apparent diffusion for non-Gaussian distribution (Dapp) and apparent diffusional kurtosis (Kapp). A new MRI-based classification was established to characterize intestinal strictures in CD. Its performance was validated in nine additional patients with CD. RESULTS: Histological inflammation grades were significantly correlated to T2-weighted signal intensity (r = 0.477; P < 0.001) and ADC (r = - 0.226; P = 0.044). Histological fibrosis grades were moderately correlated to Kapp (r = 0.604, P < 0.001); they were also correlated to Dapp (r = - 0.491; P < 0.001) and ADC (r = - 0.270; P = 0.015). T2-weighted signal intensity could differentiate between no-to-mild and moderate-to-severe bowel inflammation (sensitivity, 0.970; specificity, 0.479). Kapp could differentiate between no-to-mild and moderate-to-severe bowel fibrosis (sensitivity, 0.959; specificity, 0.781). The agreement between the new MRI-based classification and the histological classification was moderate in the test (κ = 0.507; P < 0.001) and validation (κ = 0.530; P < 0.001) sets. CONCLUSIONS: DKI can be used to assess bowel fibrosis. The new MRI-based classification can help to distinguish between fibrotic and inflammatory intestinal strictures in patients with CD.

[Feasibility of integrating tumor therapy with therapeutic effect evaluation using siRNA-loaded microbubbles].

OBJECTIVE: To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs). METHODS: siRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3-labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography. RESULTS: The siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of +8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy. CONCLUSIONS: As a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.