Highly Sensitive MoS_2–Indocyanine Green Hybrid for Photoacoustic Imaging of Orthotopic Brain Glioma at Deep Site

Photoacoustic technology in combination with molecular imaging is a highly effective method for accurately diagnosing brain glioma. For glioma detection at a deeper site, contrast agents with higher photoacoustic imaging sensitivity are needed. Herein, we report a MoS_2–ICG hybrid with indocyanine green(ICG) conjugated to the surface of MoS_2 nanosheets. The hybrid significantly enhanced photoacoustic imaging sensitivity compared to MoS_2 nanosheets. This conjugation results in remarkably high optical absorbance across a broad near-infrared spectrum, redshifting of the ICG absorption peak and photothermal/photoacoustic conversion efficiency enhancement of ICG. A tumor mass of 3.5 mm beneath the mouse scalp was clearly visualized by using MoS_2–ICG as a contrast agent for the in vivo photoacoustic imaging of orthotopic glioma, which is nearly twofold deeper than the tumors imaged in our previous report using MoS_2 nanosheet. Thus, combined with its good stability and high biocompatibility, the MoS_2–ICG hybrid developed in this study has a great potential for high-efficiency tumor molecular imaging in translational medicine.

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.

Highly uniform ultrasound-sensitive nanospheres produced by a pH-induced micelle-to-vesicle transition for tumor-targeted drug delivery

Although gas-filled microbubbles with high echogenicity are widely applied in clinical ultrasonography, the micron scale particle size impedes their use in the treatment of solid tumors, which are accessible to objects less than several hundred nanometers. We herein propose an unusual approach involving a pH-induced core-shell micelle-to-vesicle transition to prepare ultrasound-sensitive polymeric nanospheres （polymersomes in structure） possessing multiple features, including nanosize, monodispersity, and incorporation of a phase- transitional imaging agent into the aqueous lumen. These features are not achievable via the conventional double-emulsion method for polymersome preparation. The nanospheres were constructed based on a novel triblock copolymer with dual pH sensitivity. The liquid-to-gas phase transition of the imaging agent induced by external low-frequency ultrasound may destroy the nanospheres for a rapid drug release, with simultaneous tissue-penetrating drug delivery inside a tumor. These effects may provide new opportunities for the development of an effective cancer therapy with few adverse effects.

A Prognostic Nomogram with High Accuracy Based on 2D-SWE in Patients with Acute-on-chronic Liver Failure

Background and Aims:Acute-on-chronic liver failure(ACLF)is associated with very high mortality.Accurate prediction of prognosis is critical in navigating optimal treatment decisions to improve patient survival.This study was aimed to develop a new nomogram integrating two-dimensional shear wave elastography(2D-SWE)values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes.Methods:A total of 449 consecutive patients with ACLF were recruited and randomly allocated to a training cohort(n=315)or a test cohort(n=134).2D-SWE values,conventional ultrasound features,laboratory tests,and other clinical characteristics were included in univariate and multivariate analysis.Factors with prognostic value were then used to construct a novel prognostic nomogram.Receiver operating curves(ROCs)were generated to evaluate and compare the performance of the novel and published models including the Model for EndStage Liver Disease(MELD),MELD combined with sodium(MELD-Na),and Jin’s model.The model was validated in a prospective cohort(n=102).Results:A ACLF prognostic nomogram was developed with independent prognostic factors,including 2D-SWE,age,total bilirubin(TB),neutrophils(Neu),and the international normalized ratio(INR).The area under the ROC curve(AUC)was 0.849 for the new model in the training cohort and 0.861 in the prospective validation cohort,which were significantly greater than those for MELD(0.758),MELD-Na(0.750),and Jin’s model(0.777,all p<0.05).Calibration curve analysis revealed good agreement between the predicted and observed probabilities.The new nomogram had superior overall net benefit and clinical utility.Conclusions:We established and validated a 2D-SWE-based noninvasive nomogram to predict the prognosis of ACLF patients that was more accurate than other prognostic models.