Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

Nomogram Incorporating Contrast-Enhanced Ultrasonography Predicting Time to the Development of Castration-Resistant Prostate Cancer.

BACKGROUND: It is valuable to predict the time to the development of castration-resistant prostate cancer (CRPC) in patients with advanced prostate cancer (PCa). This study aimed to build and validate a nomogram incorporating the clinicopathologic characteristics and the parameters of contrast-enhanced ultrasonography (CEUS) to predict the time to CRPC after androgen deprivation therapy (ADT). METHODS: Patients with PCa were divided into the training (n = 183) and validation cohorts (n = 37) for nomogram construction and validation. The clinicopathologic characteristics and CEUS parameters were analyzed to determine the independent prognosis factors and serve as the basis of the nomogram to estimate the risk of 1-, 2-, and 3-year progress to CRPC. RESULTS: T stage, distant metastasis, Gleason score, area under the curve (AUC), prostate-specific antigen (PSA) nadir, and time to PSA nadir were the independent predictors of CRPC (all P < 0.05). Three nomograms were built to predict the time to CRPC. Owing to the inclusion of CEUS parameter, the discrimination of the established nomogram (C-index: 0.825 and 0.797 for training and validation datasets) was improved compared with the traditional prediction model (C-index: 0.825 and 0.797), and when it excluded posttreatment PSA, it still obtained an acceptable discrimination (C-index: 0.825 and 0.797). CONCLUSIONS: The established nomogram including regular prognostic indicators and CEUS obtained an improved accuracy for the prediction of the time to CRPC. It was also applicable for early prediction of CRPC when it excluded posttreatment PSA, which might be helpful for individualized diagnosis and treatment.

Association Between Contrast-Enhanced Ultrasound Indicators and Prostate Cancer Biochemical Recurrence After Treatment.

BACKGROUND: Some patients with prostate cancer (PCa) will experience biochemical recurrence (BCR) after treatment. Current researches have identified the influencing factors of BCR, but these factors are difficult to quantify and hence unable to accurately predict the BCR in PCa patients. OBJECTIVE: To explore the value of contrast-enhanced ultrasound (CEUS) indicators in predicting the BCR after treatment by evaluating the association between them. PATIENTS AND METHODS: In a retrospective cohort study, 157 PCa patients were recruited and received prostate specific antigen (PSA) measurement, CEUS, pathological classification, and immunohistochemistry after puncture biopsy. PCa patients with BCR were included in the recurrence group, while the remaining patients were included in the non-recurrence group after a 5-year follow-up. The clinical characteristics and CEUS indicators were compared between the two groups, and the multivariable COX regression was used for screening the influencing factors of BCR. Receiver operating characteristic (ROC) curves were used to analyze the value of potential factors in predicting BCR. The effect of the combined prediction model was explored to improve the accuracy of the prediction. RESULTS: Twelve patients are lost during the follow-up period and the final analysis included 145 patients. The 5-year BCR rate of PCa patients was 27%, with 43 patients in the recurrence group and 102 patients in the non-recurrence group. Multivariate analysis showed that lymph node metastasis (P<0.001), distant metastasis (P<0.001), Gleason score (P<0.001), pretreatment PSA (P<0.001), treatment method (P<0.001), peak intensity (PI) (P=0.001), and time to peak (TTP) (P=0.003) were independent influencing factors for BCR after treatment. ROC analysis showed that the AUCs of all indicators in predicting BCR were not high (all <0.9). The combination of lymph node metastasis, Gleason score, pretreatment PSA, and treatment method can improve the predictive accuracy (AUC = 0.85), but the AUC was still under 0.9. The combined prediction model including CEUS time-intensity curve (TIC) indicators (PI and TTP) could accurately predict the BCR after treatment (AUC=0.953). The sensitivity and specificity were 93.02% and 88.24%, respectively. CONCLUSION: The prediction model including TIC indicators and common influencing factors can more accurately predict the BCR in PCa patients.