Multiparametric MRI-based whole-liver radiomics for predicting early-stage liver fibrosis in rabbits.

OBJECTIVES: To develop and validate a whole-liver radiomic model using multiparametric MRI for predicting early-stage liver fibrosis (LF) in rabbits. METHODS: A total of 134 rabbits (early-stage LF, n = 91; advanced-stage LF, n = 43) who underwent liver magnetic resonance elastography (MRE), hepatobiliary phase, dynamic contrast enhanced (DCE), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging, and T2* scanning were enrolled and randomly allocated to either the training or validation cohort. Whole-liver radiomic features were extracted and selected to develop a radiomic model and generate quantitative Rad-scores. Then, multivariable logistic regression was utilized to determine the Rad-scores associated with early-stage LF, and effective features were integrated to establish a combined model. The predictive performance was assessed by the area under the curve (AUC). RESULTS: The MRE model achieved superior AUCs of 0.95 in the training cohort and 0.86 in the validation cohort, followed by the DCE-MRI model (0.93 and 0.82), while the IVIM model had lower AUC values of 0.91 and 0.82, respectively. The Rad-scores of MRE, DCE-MRI and IVIM were identified as independent predictors associated with early-stage LF. The combined model demonstrated AUC values of 0.96 and 0.88 for predicting early-stage LF in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the remarkable performance of a multiparametric MRI-based radiomic model for the individualized diagnosis of early-stage LF. ADVANCES IN KNOWLEDGE: This is the first study to develop a combined model by integrating multiparametric radiomic features to improve the accuracy of LF staging.

Enhancing Oral Performance of Paclitaxel Lipid-Mimic Prodrug via Modulating Type of Fatty Acids.

Owing to the serious clinical side effects of intravenous Taxol, an oral chemotherapeutic strategy is expected to be promising for paclitaxel (PTX) delivery. However, its poor solubility and permeability, high first-pass metabolism, and gastrointestinal toxicity need to be overcome. A triglyceride (TG)-like prodrug strategy facilitates oral drug delivery by bypassing liver metabolism. However, the effect of fatty acids (FAs) in sn-1,3 on the oral absorption of prodrugs remains unclear. Herein, a series of TG-mimetic prodrugs of PTX is explored with different carbon chain lengths and degrees of unsaturation of FAs at the sn-1,3 position in an attempt to enhance oral antitumor effect and to guide the design of TG-like prodrugs. Interestingly, the different FA lengths exhibit great influence on in vitro intestinal digestion behavior, lymph transport efficiency, and up to fourfold differences in plasma pharmacokinetics. The prodrug with long-chain FAs shows a more effective antitumor effect, whereas the degree of unsaturation has a negligible impact. The findings illustrate how FAs structures affect the oral delivery efficiency of TG-like PTX prodrugs and thus provide a theoretical basis for their rational design.