Small arteriole sign: an imaging feature for staging T4a colon cancer.

OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

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.

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 intermediate-stage 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.

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 clinical 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 receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA), respectively. Calibration 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.

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 computed 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 algorithm 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 statistically different between patients with or without tumor progression (P < 0.05). When clinical variables 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 ICAP (OR = 1.25, 95% CI: 1.01-1.62, P = 0.028) were associated 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.

Micro-positron emission tomography imaging of angiogenesis based on 18F-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 18F-AIF-NOTA-E[PEG4-c(RGDfk)]2 (denoted as 18F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential. METHODS: Twenty LoVo 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 18F-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 LoVo 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 LoVo and LS174T primary tumors (P < 0.05). The tumor-to-liver SUVmax or SUVmean ratio of 18F-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 18F-RGD SUVmean ratio, SUVmax ratio for differentiating LoVo from LS174T tumor were 0.801 and 0.759, respectively. CONCLUSIONS: The tumor-to-liver SUVmean ratio of 18F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.

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.

18F-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 18F-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. 18F-FMISO uptake in CRC cell lines was measured by cellular uptake assay. 18F-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 18F-FMISO SUVmax ratio, liver metastases number, hypoxia-induced factor 1α (HIF-1α) 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, 18F-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 18F-FMISO SUVmax ratio of CRLM mice and number of liver metastases larger than 0.5 cm, as well as between 18F-FMISO SUVmax ratio and HIF-1α or GLUT-1 expression in tumor-bearing tissues. CONCLUSIONS: 18F-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.

Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using 18F-FDG and 18F-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 of 18F-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 of 18F-FDG and 18F-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 of 18F-FDG in SW480 and SW620 cells was 6.07% ±â€¯1.19% and 2.82% ±â€¯0.15%, respectively (t = 4.69, P = 0.04); that of 18F-FLT was 24.81% ±â€¯0.45% and 15.57% ±â€¯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 and 18F-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 of 18F-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.

Accuracy of Multi-Slice Spiral Computed Tomography for Preoperative Tumor Node Metastasis (TNM) Staging of Colorectal Carcinoma.

BACKGROUND With the advances in imaging technologies, multi-slice spiral computed tomography (MSCT) has demonstrated superiority in the diagnosis and staging of colorectal carcinoma. In the current study, preoperative TNM staging of colorectal carcinoma by using MSCT was conducted and compared with the corresponding postoperative pathological examination findings, in order to evaluate the accuracy of preoperative MSCT for TNM staging. MATERIAL AND METHODS Combinations of biphasic or triphasic enhanced-phase MSCT scans were obtained for 76 patients with colorectal carcinoma, and the TNM stage was determined based on imaging reconstruction from various angles and perspectives to display the size, location, and affected range of tumors. The preoperative TNM stage was compared with the postoperative pathological stage, and the consistency between the 2 methods was tested by the k test using SPSS 17.0 software. RESULTS Among the different combinations of enhanced-phase MSCT scanning, triphasic MSCT imaging, comprising the arterial, portal venous, and delayed phases, showed the highest accuracy rates, at 81.6% (62/76), 82.89% (63/76), and 96.1% (73/76) for T, N, and M staging, respectively, with k values of 0.72, 0.65, and 0.56, respectively, indicating consistency with the postoperative pathological staging. CONCLUSIONS Combined MSCT scanning comprising the arterial phase, portal venous phase, and delayed phase showed satisfying consistency with the postoperative pathological analysis results for TNM staging of colorectal carcinoma. Thus, MSCT is an important clinical value for improving the accuracy of TNM staging and for planning the appropriate colorectal cancer treatment.

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 diagnosis of a small hepatocellular carcinoma (sHCC) on the background of liver cirrhosis possible. This study was to explore whether the combination of MSCT enhancement scan and alpha-fetoprotein (AFP) level could increase the diagnostic efficiency for sHCC. METHODS: This study included 35 sHCC patients and 52 cirrhotic patients without image evidence of HCC as a control group. The diagnoses were made by three radiologists employing a 5-point rating scale, with postoperative pathologic results as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic 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.

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 hepatocellular carcinoma (HCC). Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investigate 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.

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/mm2. Type II (blurry): the histology showed that the edges were clear with no capsules and an MVD>30/mm2. Type III (mixed): the pathology was similar to that of types I and II, and an MVD>30/mm2. 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.

Investigation on the optical scan condition for imaging of multi-slice spiral CT liver perfusion in rats.

BACKGROUND: Multi-slice CT liver perfusion has been widely used in experimental studies of hemodynamic changes in liver lesions, and is usually performed as an adjunct to a conventional CT examination because of its high temporal and spatial resolution, simple protocol, good reproducibility, and ability to measure hemodynamic changes of liver tissues at the capillary level. Experimental rat models, especially those of induced liver cancer, are often used in studies of hemodynamic changes in liver cancer. Carcinogenesis in rats has a similar pathological progression and characteristics resembling those in human liver cancer; as a result, rat models are often used as ideal animal models in the study of human liver cancer. However, liver perfusion imaging in rats is difficult to perform, because rats' livers are so small that different concentrations, flow rates, and dose of contrast agents during the CT perfusion scanning can influence the quality of liver perfusion images in rats. The purpose of this study, therefore, was to investigate the optimal scan protocol for the imaging of hepatic perfusion using a deconvolution mathematical method in rats by comparing the results of rats in different injection conditions of the contrast agent, including concentration, rate and time. METHODS: Plain CT scan conditions in eighty 2-month-old male Wistar rats were 5.0 mm slice thickness, 5.0 mm interval, 1.0 pitch, 120 kV tube voltage, 60 mA tube current, 512 × 512 matrix, and FOV 9.6 cm. Perfusion scanning was carried out with different concentrations of diatrizoate (19%, 38%, 57%, and 76%), different injection rates (0.3 and 0.5 ml/s), and different injection times (1, 2-3, 4-5, and 6 seconds). The above conditions were randomly matched and adjusted to determine the best perfusion scan protocol. Three-phase contrast-enhanced scanning was performed after CT perfusion. Histological examination of the liver tissues with hematoxylin and eosin stains was done after CT scanning. RESULTS: When the concentration of the contrast agent was 19% or 38%, no pseudo-color map was created. The viscosity increased when the concentration of the contrast agent was 76%; so it is difficult to inject the contrast agent at such a high concentration. Also no pseudo-color map was generated when the injection time was short (1, 2-3, and 4-5 seconds) or the injection rate was low (0.3 ml/s). The best perfusion images and perfusion parameters were obtained during 50 seconds scanning. Each rat was given an injection of 57% diatrizoate at 0.5 ml/s via the tail vein using a high-pressure syringe for 6 seconds. The perfusion parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT) of the contrast agent, capillary permeability-surface area product (PS), hepatic arterial index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). All these parameters reflected the perfusion status of liver parenchyma in normal rats. Three phases of enhancement were modified according to the time-density curves (TDCs) of the perfusion imaging: hepatic arterial phase (7 seconds), hepatic portal venous phase (15 seconds), and a delayed phase (23-31 seconds). On examination by microscopy, the liver tissues were pathologically normal. CONCLUSIONS: The appropriate protocol with multi-slice spiral CT liver perfusion reflected normal liver hemodynamics in rats. This study laid a solid foundation for further investigation of the physiological characteristics of liver cancer in a rat model, and was an important supplement to and reference for conventional contrast-enhanced CT scans.

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

BACKGROUND: Assessment of tumor response after argon-helium 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.

[Hemodynamic study of hepatocellular carcinoma nodules by multi-slice spiral computed tomographic perfusion].

OBJECTIVE: To analyze the 64-slice computed tomographic (CT) perfusion parameters of hepatocellular carcinoma (HCC) nodule so as to assess the diagnostic value of hemodynamic changes of HCC nodule by this perfusion technique. METHODS: Forty volunteers without liver disease (control subjects) and 37 HCC patients (experimental group) were selected. After informed consents, all of them underwent plain, perfusion and contrast CT examinations. Perfusion CT scan was performed at 120 kV, 60 mA and a thickness of up to 40 mm. The injection rate of contrast medium was 4 - 5 ml/sec at a dose of 1.0 ml/kg body weight. And 50 seconds of continuous scanning time was set at 5 seconds post-injection. The indices were 1 second per 360° revolution, 5 mm slice thickness image reconstruction and a matrix size of 512×512 pixels. Perfusion parameters associated with changes in hepatic blood flow included blood flow (HBF), hepatic blood volume (HBV), hepatic arterial perfusion index (HAI), hepatic artery perfusion (HAP) and portal venous perfusion (HPP). Perfusion parameters were measured thrice at each time point for each different region of interest (ROI): hepatic parenchyma surrounding HCC nodule, HCC nodule and normal liver parenchyma(control group). RESULTS: For HCC nodule, the increased levels of HBF, HAP and HAI were significantly differentiated from normal liver parenchyma of control group (P < 0.01). Increased HBV and decreased HPP had no difference from control group (P > 0.05). Higher levels of HAP, HPP and HAI in HCC nodules were differentiated from hepatic parenchyma surrounding HCC nodules (P < 0.05). HBV decreased and HBF increased in HCC nodule. But it had no differences from hepatic parenchyma surrounding HCC nodule (P > 0.05). CONCLUSION: Perfusion CT may visualize the status of liver blood flow caused by HCC nodule so as to serve as a new tool of studying the hemodynamic changes of HCC nodules.

Optimization of the scanning technique and diagnosis of pulmonary nodules with first-pass 64-detector-row perfusion VCT.

OBJECTIVE: The aims of this study were to optimize the scanning technique of first-pass 64-detector-row perfusion volume computed tomography imaging, to evaluate the effectiveness and stability of this scan protocol, and lastly to evaluate the differential diagnosis ability of perfusion imaging in solitary pulmonary nodules (SPNs). METHODS: A total of 144 patients with SPNs underwent perfusion scan with 64-slice spiral CT scanner. The CT perfusion imaging was analyzed for time-density curve, perfusion parametric maps, and the respective perfusion parameters. We then analyzed the main factors concerning the imaging quality and evaluated the effectiveness of scan protocol by determining the receiver operating characteristic (ROC) curve, diagnostic efficacy, and odds ratio as well as the stability of scan protocol by consistency analysis. Immunohistochemical findings of microvessel density measurement and vascular endothelial growth factor expression were evaluated. RESULTS: The total sensitivity, specificity, accuracy, positive predictive value, negative predictive value, likelihood ratio, and the area under ROC curve during 5-45-s scan period were 78.95%, 82.4%, 80.6%, 83.3%, 77.8%, 4.620, 0.280, and 0.840, respectively, and Kappa value was 0.894. The diagnostic efficacy of CT pulmonary perfusion was significantly higher than during 0-40-s scan period. The parameter values in different nodules were different. CONCLUSION: The optimized 5-45-s scan period of CT pulmonary perfusion imaging is effective in pathologic diagnosis and has good stability, worthy of being popularized. Lung perfusion CT could be a promising and feasible method for differentiation of SPNs.

Early changes of hepatic hemodynamics measured by functional CT perfusion in a rabbit model of liver tumor.

BACKGROUND: Early detection and treatment of hepatocellular carcinoma is crucial to improving the patients' survival. The hemodynamic changes caused by tumors can be serially measured using CT perfusion. In this study, we used a CT perfusion technique to demonstrate the changes of hepatic hemodynamics in early tumor growth, as a proof-of-concept study for human early hepatocellular carcinoma. METHODS: VX2 tumors were implanted in the liver of ten New Zealand rabbits. CT perfusion scans were made 1 week (early) and 2 weeks (late) after tumor implantation. Ten normal rabbits served as controls. CT perfusion parameters were obtained at the tumor rim, normal tissue surrounding the tumor, and control liver; the parameters were hepatic blood flow, hepatic blood volume, mean transit time, permeability of capillary vessel surface, hepatic arterial index, hepatic arterial perfusion and hepatic portal perfusion. Microvessel density and vascular endothelial growth factor were correlated. RESULTS: At the tumor rim, compared to the controls, hepatic blood flow, hepatic blood volume, permeability of capillary vessel surface, hepatic arterial index, and hepatic arterial perfusion increased, while mean transit time and hepatic portal perfusion decreased on both early and late scans (P<0.05). Hepatic arterial index increased (135%, P<0.05), combined with a sharp increase in hepatic arterial perfusion (182%, P<0.05) and a marked decrease in hepatic portal perfusion (-76%, P<0.05) at 2 weeks rather than at 1 week (P<0.05). Microvessel density and vascular endothelial growth factor showed significant linear correlations with hepatic blood flow, permeability of capillary vessel surface and hepatic arterial index, but not with hepatic blood volume or mean transit time. CONCLUSION: The CT perfusion technique demonstrated early changes of hepatic hemodynamics in this tumor model as proof-of-concept for early hepatocellular carcinoma detection in humans.

Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor in China, and early diagnosis is critical for patient outcome. In patients with HCC, it is mostly based on liver cirrhosis, developing from benign regenerative nodules and dysplastic nodules to HCC lesions, and a better understanding of its vascular supply and the hemodynamic changes may lead to early tumor detection. Angiogenesis is essential for the growth of primary and metastatic tumors due to changes in vascular perfusion, blood volume and permeability. These hemodynamic and physiological properties can be measured serially using functional computed tomography perfusion (CTP) imaging and can be used to assess the growth of HCC. This study aimed to clarify the physiological characteristics of tumor angiogenesis in cirrhotic liver disease by this fast imaging method. METHODS: CTP was performed in 30 volunteers without liver disease (control subjects) and 49 patients with liver disease (experimental subjects: 27 with HCC and 22 with cirrhosis). All subjects were also evaluated by physical examination, laboratory screening and Doppler ultrasonography of the liver. The diagnosis of HCC was made according to the EASL criteria. All patients underwent contrast-enhanced ultrasonography, pre- and post-contrast triple-phase CT and CTP study. A mathematical deconvolution model was applied to provide hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic arterial index (HAI), hepatic arterial perfusion (HAP) and hepatic portal perfusion (HPP) data. The Mann-Whitney U test was used to determine differences in perfusion parameters between the background cirrhotic liver parenchyma and HCC and between the cirrhotic liver parenchyma with HCC and that without HCC. RESULTS: In normal liver, the HAP/HVP ratio was about 1/4. HCC had significantly higher HAP and HAI and lower HPP than background liver parenchyma adjacent to the HCC. The value of HBF at the tumor rim was significantly higher than that in the controls. HBF, HBV, HAI, HAP and HPP, but not MTT and PS, were significantly higher in the cirrhotic liver parenchyma involved with HCC than those of the controls. Perfusion parameters were not significantly different between the controls and the cirrhotic liver parenchyma not involved with HCC. CONCLUSIONS: CTP can clearly distinguish tumor from cirrhotic liver parenchyma and controls and can provide quantitative information about tumor-related angiogenesis, which can be used to assess tumor vascularization in cirrhotic liver disease.

Quantification of angiogenesis by CT perfusion imaging in liver tumor of rabbit.

BACKGROUND: Tumor angiogenesis is essential for primary and metastatic tumor growth. Computed tomography perfusion (CTP) is a new imaging method, made possible by the recent development of fast CT scanners and improved data analysis techniques, which allows measurement of the physiologic and hemodynamic properties of tissue vasculature. This study aimed to evaluate CTP in the quantification of angiogenesis and to assess the relationship between tissue perfusion parameters and microvascular density (MVD) and vascular endothelial growth factor (VEGF), attempting to detect the physiologic properties of angiogenesis. METHODS: Sixteen rabbits with VX2 liver tumors underwent multi-slice CT perfusion (MSCTP) on day 14 after tumor inoculation. CTP parameters included hepatic blood flow (HBF), hepatic blood volume (HBV), mean transit time (MTT), permeability of capillary vessel surface (PS), hepatic artery index (HAI), hepatic artery perfusion (HAP), and hepatic portal perfusion (HPP). The border of the tumor was stained with CD34 and VEGF immunohistochemical stains, and MVD was measured by anti-CD34. Then, CTP parameters were determined whether they were correlated with MVD and VEGF using Pearsonos correlation coefficient. RESULTS: The positive expression of MVD was different in the center and border of the tumor (P<0.01). There was a positive correlation between MVD and VEGF in the border (P<0.05). As more VEGF was expressed, the number of microvessels increased. Correlation analyses were also made between the perfusion parameters and MVD and VEGF in the border of the tumor. HBF, PS, HAI, and HAP values were positively correlated with MVD and VEGF (P<0.05), HPP was negatively correlated with MVD and VEGF (P<0.01), and HBV and MTT values were not correlated with MVD and VEGF (P>0.05). CONCLUSIONS: Significant correlations were found between perfusion parameters and MVD and VEGF. Therefore, MSCTP can be used to evaluate tumor angiogenesis in vivo.