Sensitization of nerve cells to ultrasound stimulation through Piezo1-targeted microbubbles.

Neuromodulation by ultrasound (US) has recently drawn considerable attention due to its great advantages in noninvasiveness, high penetrability across the skull and highly focusable acoustic energy. However, the mechanisms and safety from US irradiation still remain less understood. Recently, documents revealed Piezo1, a mechanosensitive cation channel, plays key role in converting mechanical stimuli from US through its trimeric propeller-like structure. Here, we developed a Piezo1-targeted microbubble (PTMB) which can bind to the extracellular domains of Piezo1 channel. Due to the higher responsiveness of bubbles to mechanical stimuli from US, significantly lower US energy for these PTMB-binding cells may be needed to open these mechanosensitive channels. Our results showed US energy at 0.03 MPa of peak negative pressure can achieve an equivalent level of cytoplasmic Ca2+ transients which generally needs 0.17 MPa US intensity for the control cells. Cytoplasmic Ca2+ elevations were greatly reduced by chelating extracellular calcium ions or using the cationic ion channel inhibitors, confirming that US-mediated calcium influx are dependent on the Piezo1 channels. No bubble destruction and obvious temperature increase were observed during the US exposure, indicating cavitation and heating effects hardly participate in the process of Ca2+ transients. In conclusion, our study provides a novel strategy to sensitize the response of nerve cells to US stimulation, which makes it safer application for US-mediated neuromodulation in the future.

Dynamic Contrast-Enhanced Ultrasound Radiomics for Hepatocellular Carcinoma Recurrence Prediction After Thermal Ablation.

PURPOSE: To develop a radiomics model based on dynamic contrast-enhanced ultrasound (CEUS) to predict early and late recurrence in patients with a single HCC lesion ≤ 5 cm in diameter after thermal ablation. PROCEDURES: We enrolled patients who underwent thermal ablation for HCC in our hospital from April 2004 to April 2017. Radiomics based on two branch convolution recurrent network was utilized to analyze preoperative dynamic CEUS image of HCC lesions to establish CEUS model, in comparison to the conventional ultrasound (US), clinical, and combined models. Clinical follow-up of HCC recurrence after ablation were taken as reference standard to evaluate the predicted performance of CEUS model and other models. RESULTS: We finally analyzed 318 patients (training cohort: test cohort = 255:63). The combined model showed better performance for early recurrence than CUES (in training cohort, AUC, 0.89 vs. 0.84, P < 0.001; in test cohort, AUC, 0.84 vs. 0.83, P = 0.272), US (P < 0.001), or clinical model (P < 0.001). For late recurrence prediction, the combined model showed the best performance than the CEUS (C-index, in training cohort, 0.77 vs. 0.76, P = 0.009; in test cohort, 0.77 vs. 0.68, P < 0.001), US (P < 0.001), or clinical model (P < 0.001). CONCLUSIONS: The CEUS model based on dynamic CEUS radiomics performed well in predicting early HCC recurrence after ablation. The combined model combining CEUS, US radiomics, and clinical factors could stratify the high risk of late recurrence.

Risk factors of intrahepatic biloma and secondary infection after thermal ablation for malignant hepatic tumors.

Objective: This study aimed to evaluate the risk factors of biloma formation and secondary infection after thermal ablation for malignant hepatic tumors. Patients and methods: A total of 58 patients with 68 bilomas after thermal ablation were recruited as the complication group, and 61 patients with 72 lesions without major complications were selected randomly as the control group. The potential risk factors for biloma formation were analyzed with the chi-square test and multivariate logistic regression analysis. To determine the optimum management method for biloma, patients with secondary infection were included for the subgroup analysis of risk factors. Results: A history of transcatheter arterial chemoembolization (TACE) treatment (odds ratio [OR]: 3.606, 95% confidence interval [CI]: 1.165-11.156, p = .026) and tumor location (OR: 37.734, 95% CI: 13.058-109.034, p = .000) were independent predictors of biloma formation. Among the 58 patients with biloma, 49 (84.5%) showed no symptoms (i.e., the asymptomatic group), while the remaining 9 (15.5%) developed symptoms related to secondary infections (i.e., the symptomatic group). There were significant differences in the history of biliary manipulation (p = .031) between the symptomatic and asymptomatic groups. Conclusion: A history of TACE treatment and the distance from the biliary tract were independent predictors of biloma formation after thermal ablation. Therefore, protecting the bile duct (i.e., cooling of the bile duct and combing thermal ablation with chemical ablation) should be considered for high-risk patients. Moreover, active monitoring and management should be performed for patients with bilomas who underwent biliary surgery before.