Computed tomography radiomic features and clinical factors predicting the response to first transarterial chemoembolization in intermediate-stage hepatocellular carcinoma

Background:According to clinical practice guidelines,transarterial chemoembolization(TACE)is the standard treatment modality for patients with intermediate-stage hepatocellular carcinoma(HCC).Early prediction of treatment response can help patients choose a reasonable treatment plan.This study aimed to investigate the value of the radiomic-clinical model in predicting the efficacy of the first TACE treatment for HCC to prolong patient survival.Methods:A total of 164 patients with HCC who underwent the first TACE from January 2017 to September 2021 were analyzed.The tumor response was assessed by modified response evaluation criteria in solid tumors(mRECIST),and the response of the first TACE to each session and its correlation with overall survival were evaluated.The radiomic signatures associated with the treatment response were identified by the least absolute shrinkage and selection operator(LASSO),and four machine learning models were built with different types of regions of interest(ROIs)(tumor and corresponding tissues)and the model with the best performance was selected.The predictive performance was assessed with receiver operating characteristic(ROC)curves and calibration curves.Results:Of all the models,the random forest(RF)model with peritumor(+10 mm)radiomic signatures had the best performance[area under ROC curve(AUC)=0.964 in the training cohort,AUC=0.949 in the validation cohort].The RF model was used to calculate the radiomic score(Rad-score),and the optimal cutoff value(0.34)was calculated according to the Youden’s index.Patients were then divided into a high-risk group(Rad-score>0.34)and a low-risk group(Rad-score≤0.34),and a nomogram model was successfully established to predict treatment response.The predicted treatment response also allowed for significant discrimination of Kaplan-Meier curves.Multivariate Cox regression identified six independent prognostic factors for overall survival,including male[hazard ratio(HR)=0.500,95%confidence interval(CI):0.260–0.962,P=0.038],alpha-fetoprotein(HR=1.003,95%CI:1.002–1.004,P<0.001),alanine aminotransferase(HR=1.003,95%CI:1.001–1.005,P=0.025),performance status(HR=2.400,95%CI:1.200–4.800,P=0.013),the number of TACE sessions(HR=0.870,95%CI:0.780–0.970,P=0.012)and Rad-score(HR=3.480,95%CI:1.416–8.552,P=0.007).Conclusions:The radiomic signatures and clinical factors can be well-used to predict the response of HCC patients to the first TACE and may help identify the patients most likely to benefit from TACE.

Using receiver operating characteristic curves to evaluate the diagnostic value of the combination of multislice spiral CT and alpha-fetoprotein levels for small hepatocellular carcinoma in cirrhotic patients

BACKGROUND： The various combination of multiphase enhancement multislice spiral CT （MSCT） makes the diagno- sis of a small hepatocellular carcinoma （sHCC） on the back- ground of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein （AFP） level ficiency for sHCC. could increase the diagnostic ef- METHODS： This study included 35 sHCC patients and 52 cir- rhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists em- ploying a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic （ROC） curve analysis was performed to evaluate the diag- nostic value of the three MSCT combination modes （arterial phase＋portal-venous phase, arterial phase＋delayed phase, arterial phase＋portal-venous phase＋delayed phase） and AFP levels for sHCC on the background of liver cirrhosis. RESULTS： The area under ROC curve （AUC）, sensitivity, and specificity of the combination of arterial phase＋portal- venous phase＋delayed phase were 0.93, 93%, and 82%, respectively. The average AUC of the arterial phase＋portal- venous phase＋delayed phase combination was significantly greater than that of the arterial phase＋portal-venous phase （AUC=0.84, P=0.01） and arterial phase＋delayed phase （AUC=0.85, P=0.03）. Arterial phase＋portal-venous phase had a smaller AUC （0.84） than arterial phase＋delayed phase （0.85）, but the difference was insignificant （P=0.15）. After combining MSCT enhancement scan with AFP, the AUC, sensitivity, and specificity were 0.95, 94%, and 83%, respectively, indicating a greatly increased diagnostic efficiency for sHCC. CONCLUSIONS： The combination of AFP and 3 phases MSCT enhancement scan could increase the diagnostic efficiency for sHCC on the background of liver cirrhosis. The application of ROC curve analysis has provided a new method and reference in HCC diagnosis.

Incidence and risk factors of pancreatitis in obstructive jaundice patients after percutaneous placement of self-expandable metallic stents

Background:Percutaneous transhepatic biliary drainage is an alternative treatment for patients with malignant distal biliary obstruction.The aim of this study was to investigate the occurrence of pancreatitis in patients who had undergone percutaneous placement of a biliary stent and to assess the risk factors for pancreatitis and the treatment outcomes.Methods:From January 2010 to October 2016,980 patients in our hospital who underwent percutaneous placements of self-expandable metallic stents for obstructive jaundice were retrospectively analyzed.The incidence of pancreatitis and risk factors were assessed by univariate and multivariate logistic regression analysis.Therapeutics,such as somatostatin,which were also adminstrated to release the symptom and promote the restoration of normal function of pancreas,were also analyzed.Results:Pancreatitis occurred in 45(4.6%)patients.One patient died from severe acute pancreatitis.Multivariate logistic regression analysis showed that common bile duct stent placement was the only independent risk factor that related to pancreatitis(odds ratio=2.096,95%CI:1.248–5.379;P=0.002).By using somatostatin,the concentrations of serum amylase and lipase were decreased in 44 patients with pancreatitis.No major complications were found during the treatment.Conclusions:Pancreatitis is a relatively low complication of percutaneous placement of biliary stents.The common bile duct stent placement is the only independent risk factor that related to pancreatitis.In this case,the percutaneous transhepatic biliary drainage is a preferred method for treatment.Furthermore,somatostatin is a secure and efficacious method to release the symptom and promote the restoration of pancreatic function.

CT assessment of liver hemodynamics in patients with hepatocellular carcinoma after argon-helium cryoablation

BACKGROUND:Assessment of tumor response after argonhelium cryoablation is critical in guiding future therapy for unresectable hepatocellular carcinoma.This study aimed to evaluate liver hemodynamics in hepatocellular carcinoma after argon-helium cryoablation with computed tomography perfusion.METHODS:The control group comprised 40 volunteers without liver disease.The experimental group was composed of 15 patients with hepatocellular carcinoma treated with argon-helium cryoablation.Computed tomography perfusion parameters were measured:hepatic blood flow,hepatic blood volume,mean transit time,permeability of capillary vessel surface,hepatic arterial fraction,hepatic arterial perfusion,and hepatic portal perfusion.RESULTS:After treatment,in the tumor foci,permeability of capillary vessel surface was higher,and hepatic blood flow,hepatic blood volume,hepatic arterial fraction,and hepatic arterial perfusion values were lower(P【0.05).In the liver parenchyma surrounding the tumor,hepatic arterial perfusion was significantly lower(P【0.05);however,there was no significant difference in hepatic blood flow,hepatic blood volume,mean transit time,permeability of capillary vessel surface,hepatic arterial fraction,or hepatic portal perfusion(P】0.05).CONCLUSION:Computed tomography perfusion can evaluate tumor response after argon-helium cryoablation.

Detection and differentiation of early hepatocellular carcinoma from cirrhosis using CT perfusion in a rat liver model

BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.

Clinical-radiomics predictors to identify the suitability of transarterial chemoembolization treatment in intermediate-stage hepatocellular carcinoma:A multicenter study

Background: Although transarterial chemoembolization(TACE) is the first-line therapy for intermediatestage hepatocellular carcinoma(HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. Methods: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator(LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting(XGBoost) with 5-fold cross-validation. The Shapley additive explanations(SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model’s performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. Results: A third of the patients(81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve(AUC) of 0.759, 0.885, 0.906 [95% confidence interval(CI): 0.859-0.953] in the training cohort and 0.826, 0.776, and 0.894(95% CI: 0.815-0.972) in the testing cohort, respectively. Conclusions: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.

^(18)F-fluoromisonidazole positron emission tomography may be applicable in the evaluation of colorectal cancer liver metastasis

Background: Positron emission tomography(PET) imaging is a non-invasive functional imaging method used to reflect tumor spatial information, and to provide biological characteristics of tumor progression. The aim of this study was to focus on the application of 18 F-fluoromisonidazole(FMISO) PET quantitative parameter of maximum standardized uptake value(SUVmax) ratio to detect the liver metastatic potential of human colorectal cancer(CRC) in mice. Methods: Colorectal liver metastases(CRLM) xenograft models were established by injecting tumor cells(LoVo, HT29 and HCT116) into spleen of mice, tumor-bearing xenograft models were established by subcutaneously injecting tumor cells in the right left flank of mice. Wound healing assays were performed to examine the ability of cell migration in vitro. ^(18)F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. ^(18)F-FMISO-based micro-PET imaging of CRLM and tumor-bearing mice was performed and quantified by tumor-to-liver SUVmax ratio. The correlation between the ^(18)F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1 α(HIF-1 α) and serum starvation-induced glucose transporter 1(GLUT-1) was evaluated using Pearson correlation analysis. Results: Compared with HT29 and HCT116, LoVo-CRLM mice had significantly higher liver metastases ratio and shorter median survival time. LoVo cells exhibited stronger migration capacity and higher radiotracer uptake compared with HT29 and HCT116 in in vitro. Moreover, ^(18)F-FMISO SUVmax ratio was significantly higher in both LoVo-CRLM model and LoVo-bearing tumor model compared to models established using HT29 and HCT116. In addition, Pearson correlation analysis revealed a significant correlation between ^(18)F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between ^(18)F-FMISO SUVmax ratio and HIF-1 α or GLUT-1 expression in tumor-bearing tissues. Conclusions: ^(18)F-FMISO parameter of SUVmax ratio may provide useful tumor biological information in mice with CRLM, thus allowing for better prediction of CRLM and yielding useful radioactive markers for predicting liver metastasis potential in CRC.

A correlation of computed tomography perfusion and histopathology in tumor edges of hepatocellular carcinoma

BACKGROUND： The peripheral morphologic characteristics of hepatocellular carcinoma （HCC） reflect tumor growth patterns. Computed tomography （CT） perfusion is a new method to analyze hemodynamic changes in tissues. We assessed the relationship between CT perfusion and histopathologic findings in the periphery of HCC lesions. METHODS： Non-contrast CT, enhanced dual-phase CT, and CT perfusion were performed on 77 subjects （47 patients and 30 controls）. Based on the imaging findings of enhanced dual- phase CT, the tumor edges were classified into three types： type Ⅰ （sharp）; type Ⅱ （blurry）; and type Ⅲ （mixed）. The CT perfusion parameters included hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion. The tissue sections from resected specimens were subjected to routine hematoxylin and eosin staining and immunohistochemical staining for CD34. The correlations between microvessel density （MVD） and the CT perfusion parameters were analyzed using Pearson＇s product-moment correlation coefficient. Changes in the perfusion parameters in tumor edges of different tumor types were evaluated. RESULTS： Type Ⅰ （sharp）： the pathologic findings showed fibrous connective tissue capsules in the tumor edges, and an MVD 〈30/ram2. Type Ⅱ （blurry）： the histology showed that the edges were clear with no capsules and an MVD 〉30/ram2. Type Ⅲ （mixed）： the pathology was similar to that of types I and II, and an MVD 〉30/mm~. Hepatic blood flow, hepatic arterial fraction, hepatic arterial perfusion, and hepatic portal perfusion were significantly increased in the tumor edges of HCC patients compared to those of the controls （P〈0.05）. The correlation between CT perfusion parameters and MVD was higher in blurry tumor edges of type II than in those of types Ⅰ or Ⅲ. CONCLUSION： CT perfusion imaging of tumor edges may be helpful in revealing histopathological features, and indirectly reflect angiogenic changes of HCCs.

Prediction of early recurrence of hepatocellular carcinoma after liver transplantation based on computed tomography radiomics nomogram

Background:Early recurrence results in poor prognosis of patients with hepatocellular carcinoma(HCC)after liver transplantation(LT).This study aimed to explore the value of computed tomography(CT)-based radiomics nomogram in predicting early recurrence of patients with HCC after LT.Methods:A cohort of 151 patients with HCC who underwent LT between December 2013 and July 2019 were retrospectively enrolled.A total of 1218 features were extracted from enhanced CT images.The least absolute shrinkage and selection operator algorithm(LASSO)logistic regression was used for dimension reduction and radiomics signature building.The clinical model was constructed after the analysis of clin-ical factors,and the nomogram was constructed by introducing the radiomics signature into the clinical model.The predictive performance and clinical usefulness of the three models were evaluated using re-ceiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.Cali-bration curves were plotted to assess the calibration of the nomogram.Results:There were significant differences in radiomics signature among early recurrence patients and non-early recurrence patients in the training cohort(P<0.001)and validation cohort(P<0.001).The nomogram showed the best predictive performance,with the largest area under the ROC curve in the training(0.882)and validation(0.917)cohorts.Hosmer-Lemeshow testing confirmed that the nomogram showed good calibration in the training(P=0.138)and validation(P=0.396)cohorts.DCA showed if the threshold probability is within 0.06-1,the nomogram had better clinical usefulness than the clinical model.Conclusions:Our CT-based radiomics nomogram can preoperatively predict the risk of early recurrence in patients with HCC after LT.

Micro-positron emission tomography imaging of angiogenesis based on ^(18)F-RGD for assessing liver metastasis of colorectal cancer

Background:Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment.This study aimed to explore the feasibility of ^(18)F-AIF-NOTA-E[PEG_(4-c)(RGDfk)]_(2) (denoted as ^(18)F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential.Methods:Twenty Lo Vo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection.Radiotracer-based micro-PET imaging of animal model was performed and the uptake of ^(18)F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio.Pearson correlation was used to analyze the relationship between radioactive parameters and tumor markers.Results:The SUVmax and SUVmean ratios of Lo Vo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions (P<0.05).A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between Lo Vo and LS174T primary tumors (P<0.05).The tumor-to-liver SUVmax or SUVmean ratio of ^(18)F-RGD showed a moderate correlation with VEGF expression (r=0.5700,P=0.001 and r=0.6657,P<0.001,respectively),but the SUVmean ration showed a weak correlation with Ki67 expression (r=0.3706,P<0.05).The areas under the receiver operating characteristic (ROC) curves of ^(18)F-RGD SUVmean ratio,SUVmax ratio for differentiating Lo Vo from LS174T tumor were 0.801 and 0.759,respectively.Conclusions:The tumor-to-liver SUVmean ratio of ^(18)F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.

Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using^(18)F-FDG and^(18)F-FLT

Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of18F-fludeoxyglucose(18F-FDG) and 3’-deoxy-3’-18F-fluorothymidine(18F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of18F-FDG and18F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of18F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of18F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P < 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and18F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).18F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of18F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.18F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.

Quantitative dual-energy computed tomography texture analysis predicts the response of primary small hepatocellular carcinoma to radiofrequency ablation

Background:Radiofrequency ablation(RFA)is one of the effective therapeutic modalities in patients with hepatocellular carcinoma(HCC).However,there is no proper method to evaluate the HCC response to RFA.This study aimed to establish and validate a clinical prediction model based on dual-energy com-puted tomography(DECT)quantitative-imaging parameters,clinical variables,and CT texture parameters.Methods:We enrolled 63 patients with small HCC.Two to four weeks after RFA,we performed DECT scanning to obtain DECT-quantitative parameters and to record the patients’clinical baseline variables.DECT images were manually segmented,and 56 CT texture features were extracted.We used LASSO al-gorithm for feature selection and data dimensionality reduction;logistic regression analysis was used to build a clinical model with clinical variables and DECT-quantitative parameters;we then added texture features to build a clinical-texture model based on clinical model.Results:A total of six optimal CT texture analysis(CTTA)features were selected,which were statis-tically different between patients with or without tumor progression(P<0.05).When clinical vari-ables and DECT-quantitative parameters were included,the clinical models showed that albumin-bilirubin grade(ALBI)[odds ratio(OR)=2.77,95%confidence interval(CI):1.35-6.65,P=0.010],λAP(40-100 keV)(OR=3.21,95%CI:3.16-5.65,P=0.045)and IC AP(OR=1.25,95%CI:1.01-1.62,P=0.028)were asso-ciated with tumor progression,while the clinical-texture models showed that ALBI(OR=2.40,95%CI:1.19-5.68,P=0.024),λAP(40-100 keV)(OR=1.43,95%CI:1.10-2.07,P=0.019),and CTTA-score(OR=2.98,95%CI:1.68-6.66,P=0.001)were independent risk factors for tumor progression.The clinical model,clinical-texture model,and CTTA-score all performed well in predicting tumor progression within 12 months after RFA(AUC=0.917,0.962,and 0.906,respectively),and the C-indexes of the clinical and clinical-texture models were 0.917 and 0.957,respectively.Conclusions:DECT-quantitative parameters,CTTA,and clinical variables were helpful in predicting HCC progression after RFA.The constructed clinical prediction model can provide early warning of potential tumor progression risk for patients after RFA.

The Role of Multimodality Imaging Techniques on Differential Diagnosis of Precancerous Nodules and Hepatocellular Carcinoma

In recent years, the incidence of hepatocellular carcinoma (HCC) has been increasing worldwide, and its high mortality seriously threatens public health. Early detection and treatment are crucial to improving the survival rate. Imaging examination widely used for the diagnosis of HCC and provides a non-invasive means of tumor visualization. The rapid development of medical imaging technology is expected to improve early-stage diagnosis rates for HCC. This article summarizes the methods for the differential diagnosis of premalignant dysplastic nodule (DN) and small hepatocellular carcinoma during the carcinogenesis of cirrhosis and reviews their application. In addition, a discussion on some recently patented medical imaging development was also presented.

Single-Component MLCT-Active Photodetecting Material Based on a Two-Dimensional Coordination Polymer

Conductive coordination polymers(CCPs)have shown great potential for electronic purposes.However,their applications in photodetection have been limited by poor sensitivity,low on/off current ratio,and slow response owing to the low charge generation and/or separation efficiency.In this work,metal-to-ligand chargetransfer(MLCT)in PhSeAg was used to fabricate a single-component MLCT photodetecting material for the first time to solve the above challenges.The material obtained possesses ultrahigh sensitivity to weak-light intensity(0.03 mW cm^(−2)),the highest on/off ratio,and the fastest response speed than other wellknown CCPs materials tested.Our work might provide a simple but common strategy for designing high-performance CCPs composites for optoelectrical applications.