Evans blue (EB) dye has owned a long history as a biological dye and diagnostic agent since its first staining application by Herbert McLean Evans in 1914. Due to its high water solubility and slow excretion, as well as its tight binding to serum albumin, EB has been widely used in biomedicine, including its use in estimating blood volume and vascular permeability, detecting lymph nodes, and localizing the tumor lesions. Recently, a series of EB derivatives have been labeled with PET isotopes and can be used as theranostics with a broad potential due to their improved half-life in the blood and reduced release. Some of EB derivatives have even been used in translational applications in clinics. In addition, a novel necrosis-avid feature of EB has recently been reported in some preclinical animal studies. Given all these interesting and important advances in EB study, a comprehensive revisiting of EB has been made in its biomedical applications in the review.

Introduction: The emerging field of “radiomics” has considerable potential in disease diagnosis, pathologic grading, prognosis evaluation, and prediction of treatment response. We aimed to develop a novel radiomics nomogram based on radiomics features and clinical characteristics that could preoperatively predict early recurrence (ER) of intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy. Methods: A predictive model was developed from a training cohort comprising 139 ICC patients diagnosed between January 2010 and June 2014. Radiomics features were extracted from arterial-phase image of contrast-enhanced magnetic resonance imaging. Feature selection and construction of a “radiomics signature” were through Spearman's rank correlation and least absolute shrinkage and selection operator (LASSO) logistic regression. Combined with clinical characteristics, a radiomics nomogram was developed with multivariable logistic regression. Performance of the nomogram was evaluated with regard to discrimination, calibration, and clinical utility. An independent validation cohort involving 70 patients recruited from July 2014 to March 2016 was used to evaluate the utility of the nomogram developed. Results: The radiomics signature, consisting of nine features, differed significantly between ER patients and non-ER patients in training and validation cohorts. The area under the curve (AUC) of the radiomics signature in training and validation cohorts was 0.82 (confidence interval [CI], 0.74–0.88) and 0.77 (95% CI, 0.65–0.86), respectively. The AUC of the radiomics nomogram combining the radiomics signature and clinical stage in the two cohorts was 0.90 (95%CI, 0.83–0.94) and 0.86 (95% CI, 0.76–0.93), respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics nomogram. Conclusion: The non-invasive radiomics nomogram developed using the radiomics signature and clinical stage could be used to predict ER of ICC after partial hepatectomy.

Background: We aimed to develop and validate a nomogram combining bi-regional radiomics features from multimodal magnetic resonance imaging (MRI) and clinicoradiological characteristics to preoperatively predict microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods: A total of 267 HCC patients were divided into training (n=194) and validation (n=73) cohorts according to MRI data. Bi-regional features were extracted from whole tumors and peritumoral regions in multimodal MRI. The minimum redundancy maximum relevance (mRMR) algorithm was applied to select features and build signatures. The predictive performance of the optimal radiomics signature was further evaluated within subgroups defined by tumor size and alpha fetoprotein (AFP) level. Then, a radiomics nomogram including the optimal radiomics signature, radiographic descriptors, and clinical variables was developed using multivariable regression. The nomogram performance was evaluated based on its discrimination, calibration, and clinical utility. Results: The fusion radiomics signature derived from triphasic dynamic contrast-enhanced (DCE) MR images can effectively classify MVI and non-MVI HCC patients, with an AUC of 0.784 (95% CI: 0.719–0.840) in the training cohort and 0.820 (95% CI: 0.713–0.900) in the validation cohort. The fusion radiomics signature also performed well in the subgroups defined by the two risk factors, respectively. The nomogram, consisting of the fusion radiomics signature, arterial peritumoral enhancement, and AFP level, outperformed the clinicoradiological prediction model in the validation cohort (AUCs: 0.858 vs. 0.729; P=0.022), fitting well in the calibration curves (P>0.05). Decision curves confirmed the clinical utility of the nomogram. Conclusions: The radiomics nomogram can serve as a visual predictive tool for MVI in HCCs, and thus assist clinicians in selecting optimal treatment strategies to improve clinical outcomes.

Treatment decisions for an incidental renal mass are mostly made with pathologic uncertainty. Improving the diagnosis of benign renal masses and distinguishing aggressive cancers from indolent ones is key to better treatment selection. We analyze 13261 pre-operative computed computed tomography (CT) volumes of 4557 patients. Two multi-phase convolutional neural networks are developed to predict the malignancy and aggressiveness of renal masses. The first diagnostic model designed to predict the malignancy of renal masses achieves area under the curve (AUC) of 0.871 in the prospective test set. This model surpasses the average performance of seven seasoned radiologists. The second diagnostic model differentiating aggressive from indolent tumors has AUC of 0.783 in the prospective test set. Both models outperform corresponding radiomics models and the nephrometry score nomogram. Here we show that the deep learning models can non-invasively predict the likelihood of malignant and aggressive pathology of a renal mass based on preoperative multi-phase CT images.

Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions