Multiparametric MRI Evaluation of Liposomal Prostaglandins E1 Intervention on Hepatic Warm Ischemia-Reperfusion Injury in Rabbits.

BACKGROUND: Liposomal prostaglandin E1 (Lipo-PGE1) treatment should protect against hepatic warm ischemia-reperfusion injury (WIRI). Improved methods are needed for the noninvasive evaluation of hepatic responses to prophylactic Lipo-PGE1 pretreatment approaches. PURPOSE: To demonstrate that multiparametric MRI measurements permit noninvasive differentiation of Lipo-PGE1 treatment outcomes in a hepatic WIRI animal model. STUDY TYPE: Animal study. ANIMAL MODEL: Seventy rabbits were randomly divided into a sham-operated group (A0), warm ischemia groups experiencing increasing periods of ischemia (A1-A3), and corresponding intervention groups (I1-I3) (n = 10 for each group). FIELD STRENGTH/SEQUENCE: Imaging was performed at 3T using a multiecho gradient echo (GRE) sequence (repetition time / echo time [TR/TE], 75/2.57-24.25 msec) for R2* blood oxygenation level-dependent (BOLD) measurements, free-breathing single-shot echo-planar imaging (ss-EPI) sequence with two b-values (0 and 500 s/mm2 ) in 12 diffusion directions for diffusion tensor imaging (DTI), and a free-breathing ss-EPI sequence with eight b-values (0 to 800 s/mm2 ) for intravoxel incoherent motion (IVIM) measurements. ASSESSMENT: The BOLD-derived parameter (R2*), DTI-derived parameters (ADC, FA), and IVIM-derived parameters (Dslow, Dfast, and PF) were calculated for comparisons between treatment groups and correlation to ALT, AST, and LDH levels. STATISTICAL TESTS: One-way analysis of variance (ANOVA), independent sample t-test, Spearman correlation, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Histopathology confirmed the validity of the WIRI model and the efficacy of intervention with clear structure and morphology differences between the different ischemia times and between the Lipo-PGE1 treatment and control groups. Prolonged warm ischemia times resulted in higher R2* and FA values and gradually lower ADC, Dslow, Dfast, and PF values (all P < 0.05). The R2* and FA values were lower, and the ADC, Dslow, Dfast, and PF values were higher in the Lipo-PGE1 intervention groups compared with those in the warm ischemia group for each paired time. However, none of the parameters reached the levels of the A0 group (all P < 0.05). As the warm ischemia time increased, additional parameters demonstrated significant differences between warm ischemia time groups and corresponding intervention groups. At the shortest (30 min), middle (40 min), and longest (60 min) ischemia times, three, four, and five parameters were significantly different between the WIRI and intervention groups, respectively (all P < 0.05). ADC, Dslow, Dfast, and PF values were negatively correlated, while R2* and FA values were positively correlated with serum ALT (|r| = 0.312-0.606) and AST (|r| = 0.432-0.602) (all P < 0.05). ADC and Dfast values showed negative correlations, and R2* showed positive correlations with serum LDH (|r| = 0.323-0.542, all P < 0.05). ROC analysis showed that DTI yielded the strongest diagnostic performance for evaluating the improvement of WIRI. DATA CONCLUSION: Multiparametric MRI can serve as a noninvasive radiologic evaluation for monitoring the protective impact of Lipo-PGE1 therapy on hepatic WIRI. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;52:217-228.

Black titanium dioxide@manganese dioxide for glutathione-responsive MR imaging and enhanced photothermal therapy.

Multifunctional nanoprobes with tumor microenvironment response are playing important roles in highly efficient theranostics of cancers. Herein, a kind of theranostic nanoprobe was synthesized by coating manganese dioxide (MnO2) on the surface of black commercial P25 titanium dioxide (b-P25). The resultant nanoprobe (b-P25@MnO2) possessed glutathione (GSH)-responsive magnetic resonance (MR) imaging and enhanced photothermal therapy (PTT). In tumor microenvironments, the excessive GSH was consumed by reacting with MnO2 to generate Mn2+ for GSH-responsive MR imaging, in which the longitudinal relaxation rate of b-P25@MnO2 was up to 30.44 mM-1 s-1, showing excellent cellular and intratumoral MR imaging. Moreover, the prepared b-P25@MnO2 exhibited stable and strong photothermal conversion capability with a high photothermal conversion efficiency of 30.67%, by which the 4T1 tumors disappeared completely, indicating safe and highly efficient PTT performance. The current work developed GSH-responsive b-P25@MnO2 nanoprobes, demonstrated for MR imaging and enhanced PTT in cancers.

In vivo multiparametric magnetic resonance imaging study for differentiating the severity of hepatic warm ischemia-reperfusion injury in a rabbit model.

OBJECTIVES: To assess the value of multiparametric magnetic resonance imaging including intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI in differentiating the severity of hepatic warm ischemia-reperfusion injury (WIRI) in a rabbit model. METHODS: Fifty rabbits were randomly divided into a sham-operation group and four test groups (n = 10 for each group) according to different hepatic warm ischemia times. IVIM, DTI and BOLD MRI were performed on a 3 T MR scanner with 11 b values (0 to 800 s/mm2), 2 b values (0 and 500 s/mm2) on 12 diffusion directions, multiple-echo gradient echo (GRE) sequences (TR/TE, 75/2.57-24.25 ms), respectively. IVIM, DTI and BOLD MRI parameters, hepatic biochemical and histopathological parameters were compared. Pearson and Spearman correlation methods were performed to assess the correlation between these MRI parameters and laboratory parameters. Furthermore, receiver operating characteristic (ROC) curves were compiled to determine diagnostic efficacies. RESULTS: True diffusion (Dslow), pseudodiffusion (Dfast), perfusion fraction (PF), mean diffusivity (MD) significantly decreased, while R2* significantly increased with prolonged warm ischemia times, and significant differences were found in all of biochemical and histopathological parameters (all P < 0.05). Dslow, PF, and R2* correlated significantly with all of biochemical and histopathological parameters (all |r| = 0.381-0.746, all P < 0.05). ROC analysis showed that the area under the ROC curve (AUC) of IVIM across hepatic WIRI groups was the largest among IVIM, DTI and BOLD. CONCLUSIONS: Multiparametric MRI may be helpful with characterization of early changes and determination of severity of hepatic WIRI in a rabbit model.

Radiomics analysis enables recurrence prediction for hepatocellular carcinoma after liver transplantation.

OBJECTIVES: To assess whether radiomics signature can identify aggressive behavior and predict recurrence of hepatocellular carcinoma (HCC) after liver transplantation. METHODS: Our study consisted of a training dataset (n = 93) and a validation dataset (40) with clinically confirmed HCC after liver transplantation from October 2011 to December 2016. Radiomics features were extracted by delineating regions-of-interest (ROIs) around the lesion in four phases of CT images. A radiomics signature was generated using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The association between radiomics signature and recurrence-free survival (RFS) was assessed. Preoperative clinical characteristics potentially associated with RFS were evaluated to develop a clinical model. A combined model incorporating clinical risk factors and radiomics signature was built. RESULTS: The stable radiomics features associated with the recurrence of HCC were simply found in arterial phase and portal phase. The prediction model based on the radiomics features extracted from the arterial phase showed better prediction performance than the portal vein phase or the fusion signature combining both of arterial and portal vein phase. A radiomics nomogram based on combined model consisting of the radiomics signature and clinical risk factors showed good predictive performance for RFS with a C-index of 0.785 (95% confidence interval [CI]: 0.674-0.895) in the training dataset and 0.789 (95% CI: 0.620-0.957) in the validation dataset. The calibration curves showed agreement in both training (p = 0.121) and validation cohorts (p = 0.164). CONCLUSIONS: Radiomics signature extracted from CT images may be a potential imaging biomarker for liver cancer invasion and enable accurate prediction of HCC recurrence after liver transplantation.

A novel hydroquinidine imprinted microsphere using a chirality-matching N-acryloyl-L-phenylalanine monomer for recognition of cinchona alkaloids.

Using a combination of molecular imprinting technology and traditional chiral stationary phases, the synergistic effect between chiral monomer and chiral cavity of molecularly imprinted polymers in stereoselective recognition was investigated. We designed and synthesized an amino acid derivative to be used as a novel chiral functional monomer. Monodisperse molecularly imprinted core-shell microspheres using surface imprinting method on silica gel were prepared with hydroquinidine as the pseudo-template molecule for the resolution of cinchona alkaloids. The results showed a significant synergistic effect in stereoselective recognition, confirming our initial hypothesis. Furthermore, our computational simulation and experiments intensively support the hypothetical chiral recognition mechanism for the imprinted microspheres.

Novel molecularly imprinted microsphere using a single chiral monomer and chirality-matching (S)-ketoprofen template.

We designed and synthesized a cinchonine derivative to be used as a novel chiral monomer. It was employed in a dual role of functional monomer and cross-linking monomer, displaying multi-binding sites for the template (S)-ketoprofen. Monodisperse molecularly imprinted core-shell microspheres were prepared using surface imprinting method on silica gel. The results show a substantial synergistic effect in the enantioselective recognition, confirming our initial hypothesis. Computational simulation of the monomer and template pre-arrangement strongly supports our proposed chiral recognition mechanism for the imprinted microspheres.