The advent of microbubble contrast agents has enhanced the capabilities of ultrasound as a medical imaging modality and stimulated innovative strategies for ultrasound-mediated drug and gene delivery. While the utilization of microbubbles as carrier vehicles has shown encouraging results in cancer therapy, their applicability has been limited by a large size which typically confines them to the vasculature. To enhance their multifunctional contrast and delivery capacity, it is critical to reduce bubble size to the nanometer range without reducing echogenicity. In this work, we present a novel strategy for formulation of nanosized, echogenic lipid bubbles by incorporating the surfactant Pluronic, a triblock copolymer of ethylene oxide copropylene oxide coethylene oxide into the formulation. Five Pluronics (L31, L61, L81, L64 and P85) with a range of molecular weights (Mw: 1100 to 4600 Da) were incorporated into the lipid shell either before or after lipid film hydration and before addition of perfluorocarbon gas. Results demonstrate that Pluronic–lipid interactions lead to a significantly reduced bubble size. Among the tested formulations, bubbles made with Pluronic L61 were the smallest with a mean hydrodynamic diameter of 207.9 ± 74.7 nm compared to the 880.9 ± 127.6 nm control bubbles. Pluronic L81 also significantly reduced bubble size to 406.8 ± 21.0 nm. We conclude that Pluronic is effective in lipid bubble size control, and Pluronic Mw, hydrophilic–lipophilic balance (HLB), and Pluronic/ lipid ratio are critical determinants of the bubble size. Most importantly, our results have shown that although the bubbles are nanosized, their stability and in vitro and in vivo echogenicity are not compromised. The resulting nanobubbles may be better suited for contrast enhanced tumor imaging and subsequent therapeutic delivery.

In situ forming drug delivery systems provide a means by which a controlled release depot can be physically inserted into a target site without the use of surgery. The release rate of drugs from these systems is often related to the rate of implant formation. Currently, only a limited number of techniques are available to monitor phase inversion, and none of these methods can be used to visualize the process directly and noninvasively. In this study, diagnostic ultrasound was used to visualize and quantify the process of implant formation in a phase inversion based system both in vitro and in vivo. Concurrently, sodium fluorescein was used as a mock drug to evaluate the drug release profiles and correlate drug release and implant formation processes. Implants comprised of three different molecular weight poly(lactic-co-glycolic acid) (PLGA) polymers dissolved in 1-methyl-2-pyrrolidinone (NMP) were studied in vitro and a 29 kDa PLGA solution was evaluated in vivo. The implants were encapsulated in a 1% agarose tissue phantom for five days, or injected into a rat subcutaneously and evaluated for 48 hrs. Quantitative measurements of the gray-scale value (corresponding to the rate of implant formation), swelling, and precipitation were evaluated using Correspondence to: Agata A. Exner, agata.exner@case.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

We describe a 91-year-old woman with a clinical history of invasive ductal carcinoma of the breast diagnosed in 1991 who was admitted because of dizziness, poor appetite, and some swelling and tenderness over her cheeks. The patient's initial work up revealed a 5-cm well-demarcated hypodense solid lesion in her spleen with abnormally intense uptake on PET/CT scan raising suspicion for malignancy i.e. breast metastasis versus lymphoma. Further review demonstrated the presence of this splenic lesion, though slightly smaller, on a CT scan from ten years earlier (2000). An ultrasonographic guided core needle splenic biopsy was performed and the pathology result revealed histological findings compatible with inflammatory pseudotumor of the spleen. As a result, unnecessary splenectomy was avoided.

Rapid on-site evaluation/adequacy assessment (ROSE) is considered an essential component of thyroid fine needle aspiration (FNA) and many reported that it significantly decreases the nondiagnostic (ND) rate. The average reported ND rate without ROSE is about 20% and is improved by 12% when ROSE is implemented. However, the data also suggest that the improvement in ND rate after implementation of ROSE is directly related to the ND rate prior to ROSE and that it is mostly beneficial to aspirators with less experience. Several studies have also raised concerns regarding the impact of ROSE as it prolongs the procedure time, requires additional resources and increases the cost incurred by the additional fees. This resulted in a wide variation in the methodology applied to acquire the sample and implement ROSE across the globe with variation in the number of passes performed, stain utilized and the personnel reviewing the slides, e.g., cytotechnologists versus pathologist. This review summarized the literature reporting the impact of ROSE including its pros and cons, its accuracy and reproducibility, concordance between cytotechnologists and pathologists based on final diagnosis and highlights the different ways laboratories attempted to circumvent the challenges. In particular, the review highlights a unique approach practiced in

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pulmonary cytology including indications for bronchial brushings, washings and endobronchial ultrasound-guided fine needle aspiration, technical recommendations for cytologic sampling, recommended terminology and classification scheme, recommendations for ancillary testing and recommendations for postcytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of the authors, extensive literature review and feedback from presentations at national and international conferences. This document selectively presents the results of these discussions. The present document summarizes the recommendations for clinical and imaging evaluation of pulmonary lesions along with the indications for cytologic studies regarding these abnormalities. Preprocedural requirements regarding brushing, washing and needle aspiration procedures are discussed also. Diagn. Cytopathol. 2016;44:1010-1023. © 2016 Wiley Periodicals, Inc.