Concurrent Osteosarcoma Theranostic Strategy Using Contrast-Enhanced Ultrasound and Drug-Loaded Bubbles.

Osteosarcoma (OS) is the most common bone tumor in children and teenagers. The multidrug resistant property of OS produces a major obstacle to chemotherapy, since the effective drug dose cannot be achieved via conventional drug delivery routes without serious systemic cytotoxicity. Microbubbles in conjunction with ultrasound (US) has recently been shown to spatially and temporally permeabilize the cellular membrane, promoting drug penetration into tumors. Here, we investigated whether drug (doxorubicin, DOX)-loaded bubbles (DOX-bubbles) can serve as drug-loaded carriers in combination with US in order to facilitate tumor drug delivery. The proposed bubbles have a high payload capacity (efficiency of 69.4 ± 9.1%, payload of 1.4 mg/mL) for DOX. In vitro data revealed that when used in combination with US (1-MHz), these DOX-bubbles facilitate DOX entering into tumor cells. In tumor-bearing animals, DOX-bubbles + US could provide 3.7-fold suppression of tumor growth compared with the group without insonation (1.8 ± 0.9 cm3 vs. 8.5 ± 2.2 cm3) because of the acceleration of DOX-induced tumor necrosis. In the meantime, the tumor perfusion and volume can be monitored by DOX-bubbles with contrast-enhanced ultrasound imaging. Our data provide useful information in support of translating the use of theranostic US-responsive bubbles for regulated tumor drug delivery into clinical use.

Assessment of Median Nerve Mobility by Ultrasound Dynamic Imaging for Diagnosing Carpal Tunnel Syndrome.

Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy and is characterized by median nerve entrapment at the wrist and the resulting median nerve dysfunction. CTS is diagnosed clinically as the gold standard and confirmed with nerve conduction studies (NCS). Complementing NCS, ultrasound imaging could provide additional anatomical information on pathological and motion changes of the median nerve. The purpose of this study was to estimate the transverse sliding patterns of the median nerve during finger movements by analyzing ultrasound dynamic images to distinguish between normal subjects and CTS patients. Transverse ultrasound images were acquired, and a speckle-tracking algorithm was used to determine the lateral displacements of the median nerve in radial-ulnar plane in B-mode images utilizing the multilevel block-sum pyramid algorithm and averaging. All of the averaged lateral displacements at separate acquisition times within a single flexion-extension cycle were accumulated to obtain the cumulative lateral displacements, which were curve-fitted with a second-order polynomial function. The fitted curve was regarded as the transverse sliding pattern of the median nerve. The R2 value, curvature, and amplitude of the fitted curves were computed to evaluate the goodness, variation and maximum value of the fit, respectively. Box plots, the receiver operating characteristic (ROC) curve, and a fuzzy c-means clustering algorithm were utilized for statistical analysis. The transverse sliding of the median nerve during finger movements was greater and had a steeper fitted curve in the normal subjects than in the patients with mild or severe CTS. The temporal changes in transverse sliding of the median nerve within the carpal tunnel were found to be correlated with the presence of CTS and its severity. The representative transverse sliding patterns of the median nerve during finger movements were demonstrated to be useful for quantitatively estimating median nerve dysfunction in CTS patients.

Carpal tunnel syndrome: US strain imaging for diagnosis.

PURPOSE: To determine the feasibility of two-dimensional (2D) ultrasonographic (US) strain imaging for quantifying and mapping mechanical behaviors of the median nerve, flexor retinaculum, and flexor tendons within the carpal tunnel in normal and carpal tunnel syndrome (CTS) disease states during active finger motion. MATERIALS AND METHODS: This prospective study was approved by the institutional review board; all subjects gave written informed consent and had both of their hands examined. Ten wrists in 10 healthy volunteers (age range, 35-51 years) and 16 wrists in 12 patients with CTS (age range, 37-55 years) were examined. In the patients, CTS had been confirmed on the basis of clinical symptoms and results of electrophysiologic studies. Raw US signals were acquired and were cross correlated to enable estimation of 2D incremental displacements, from which 2D strains were computed. The median nerve was characterized by the axial normal strain, while the flexor tendons and the flexor retinaculum were characterized by the shear strain. Temporal mean values (mean cumulative strain [MCS] values) and standard deviations (standard deviations of the cumulative strain [SDCS]) of the spatially averaged cumulative strains in each tissue region over the entire cycle of finger motion were compared by using an unpaired two-tailed Student t test. RESULTS: MCS for patients with CTS and volunteers was similar. The SDCS for the shear strain of the flexor retinaculum was significantly lower (P < .001) in patients with CTS than in healthy volunteers, while that for the axial strain of the median nerve was higher in healthy volunteers than in patients with CTS (P = .0065). CONCLUSION: US strain imaging can be used to quantify and map tissue kinematics in the carpal tunnel and to differentiate abnormal from normal median nerves in the wrist.

Carpal tunnel syndrome diagnosis by a self-normalization process and ultrasound compound imaging.

PURPOSE: Carpal tunnel syndrome (CTS) is the common entrapment neuropathy that occurs due to compression of the median nerve at the wrist. Ultrasound images have been used to highlight anatomical variants of the median nerve, and CTS is thought to be associated to enlargement of the cross-sectional area (CSA) of the median nerve. However, there remains controversy regarding the most appropriate cutoff values of the computer measurements including the CSA, flattening ratio, and palmar bowing of median nerve, especially given that they can be influenced by image artifacts and factors that differ between individual patients. This study proposed a modified ultrasound compound imaging technique by moving fingers to reduce image artifacts, and the estimates of the normalized CSA [i.e., CSA at the wrist (CSAw) to CSA at the midforearm] with the aim of reducing discrepancies in CSA estimates and improving the ability of CTS discrimination. METHODS: The subjects were examined with their arms supine and while they were making repetitive movements of their fingers (from an open palm into a clenched fist) within 3 s. By a commercial ultrasound scanner with a 10-MHz linear array transducer, a total of 70 images were acquired in each subject. The frame rate of ultrasound system was 25 fps. Nine frames in the acquisition sequence that had produced partial speckle decorrelation were incoherently added to form a compound image, and the inplane motion of them was corrected using the multilevel block-sum pyramid algorithm. The manual contours outlined by ten experimenters and three physicians were used to test the performance in determining the boundary of the median nerve. The receiver operating characteristic (ROC) curve was used to evaluate the usefulness of the estimates in distinguishing healthy volunteers from CTS patients. RESULTS: The manual contours of the median nerve in the compound images had an average area overlap exceeding 90% and relatively small area errors. The areas under the ROC curve obtained using the CSAw estimates for the original and compound images were 0.60 ± 0.09 (mean ± standard error) and 0.80 ± 0.05, respectively; that using normalized CSA estimates for the original and compound images were 0.76 ± 0.04 and 0.89 ± 0.04, respectively. The results show that variations in the CSAw values of compound images for healthy overweight and obese subjects can adversely influence CTS diagnosis, but that this can be overcome using the normalized CSA estimate of compound images. CONCLUSIONS: Compound imaging provides images of superior quality for determining the location of the median nerve boundary. Using the normalized CSA estimate would assist in eliminating problems associated with variability between populations, since the subject becomes his or her own internal control, thereby improving the ultrasound-based diagnosis of CTS.