On the rigidity of four hundred Pickering-stabilised microbubbles

This study explores the rigidity of Pickering-stabilised microbubbles subjected to low-amplitude ultrasound. Such microbubbles might be suitable ultrasound contrast agents. Using an adapted Rayleigh-Plesset equation, we modelled the dynamics of microbubbles with a 7.6-N m−1 shell stiffness under 1-MHz, 0.2-MPa sonication. Such dynamics were observed experimentally, too, using high-speed photography. The maximum expansions were agreeing with those predicted for Pickering-stabilised microbubbles. Subjecting microbubbles to multiple time- delayed pulses yielded the same result. We conclude that Pickering-stabilised microbubbles remain very stable at low acoustic amplitudes.

SonoVue® vs. Sonazoid™ vs. Optison™: Which Bubble Is Best for Low-Intensity Sonoporation of Pancreatic Ductal Adenocarcinoma?

The use of ultrasound and microbubbles to enhance therapeutic efficacy (sonoporation) has shown great promise in cancer therapy from in vitro to ongoing clinical studies. The fastest bench-to-bedside translation involves the use of ultrasound contrast agents (microbubbles) and clinical diagnostic scanners. Despite substantial research in this field, it is currently not known which of these microbubbles result in the greatest enhancement of therapy within the applied conditions. Three microbubble formulations—SonoVue®, Sonazoid™, and Optison™—were physiochemically and acoustically characterized. The microbubble response to the ultrasound pulses used in vivo was simulated via a Rayleigh–Plesset type equation. The three formulations were compared in vitro for permeabilization efficacy in three different pancreatic cancer cell lines, and in vivo, using an orthotopic pancreatic cancer (PDAC) murine model. The mice were treated using one of the three formulations exposed to ultrasound from a GE Logiq E9 and C1-5 ultrasound transducer. Characterisation of the microbubbles showed a rapid degradation in concentration, shape, and/or size for both SonoVue® and Optison™ within 30 min of reconstitution/opening. Sonazoid™ showed no degradation after 1 h. Attenuation measurements indicated that SonoVue® was the softest bubble followed by Sonazoid™ then Optison™. Sonazoid™ emitted nonlinear ultrasound at the lowest MIs followed by Optison™, then SonoVue®. Simulations indicated that SonoVue® would be the most effective bubble using the evaluated ultrasound conditions. This was verified in the pre-clinical PDAC model demonstrated by improved survival and largest tumor growth inhibition. In vitro results indicated that the best microbubble formulation depends on the ultrasound parameters and concentration used, with SonoVue® being best at lower intensities and Sonazoid™ at higher intensities.

Nanosized Contrast Agents in Ultrasound Molecular Imaging

Applying nanosized ultrasound contrast agents (nUCAs) in molecular imaging has received considerable attention. nUCAs have been instrumental in ultrasound molecular imaging to enhance sensitivity, identification, and quantification. nUCAs can achieve high performance in molecular imaging, which was influenced by synthetic formulations and size. This review presents an overview of nUCAs from different synthetic formulations with a discussion on imaging and detection technology. Then we also review the progress of nUCAs in preclinical application and highlight the recent challenges of nUCAs.

A Novel Endoscopic Ultrasonography Imaging Technique for Depicting Microcirculation in Pancreatobiliary Lesions without the Need for Contrast-Enhancement: A Prospective Exploratory Study

Detective flow imaging endoscopic ultrasonography (DFI-EUS) provides a new method to image and detect fine vessels and low-velocity blood flow without using ultrasound contrast agents. The aim of this study was to evaluate the utility of DFI-EUS for pancreatobiliary lesions and lymph nodes. Between January 2019 and January 2020, 53 patients who underwent DFI-EUS, e-FLOW EUS, and contrast-enhanced EUS were enrolled. The ability of DFI-EUS and e-FLOW EUS to detect vessels was compared with that of contrast-enhanced EUS. This article describes the DFI technique along with our first experience of its use for vascular assessment of pancreatobiliary lesions. Vessels were imaged in 34 pancreatic solid lesions, eight intraductal papillary mucinous neoplasms (IPMNs), seven gall bladder lesions, and four swollen lymph nodes. DFI-EUS (91%) was significantly superior to e-FLOW EUS (53%) with respect to detection of vessels (p < 0.001) and for discrimination of mural nodules from mucous clots in IPMN and gallbladder lesions from sludge (p = 0.046). Thus, DFI-EUS has the potential to become an essential tool for diagnosis and vascular assessment of various diseases.

Applications of Ultrasound-Mediated Drug Delivery and Gene Therapy

Gene therapy has continuously evolved throughout the years since its first proposal to develop more specific and effective transfection, capable of treating a myriad of health conditions. Viral vectors are some of the most common and most efficient vehicles for gene transfer. However, the safe and effective delivery of gene therapy remains a major obstacle. Ultrasound contrast agents in the form of microbubbles have provided a unique solution to fulfill the need to shield the vectors from the host immune system and the need for site specific targeted therapy. Since the discovery of the biophysical and biological effects of microbubble sonification, multiple developments have been made to enhance its applicability in targeted drug delivery. The concurrent development of viral vectors and recent research on dual vector strategies have shown promising results. This review will explore the mechanisms and recent advancements in the knowledge of ultrasound-mediated microbubbles in targeting gene and drug therapy.

Incidental nonfunctioning pancreatic neuroendocrine tumors: Contrast enhanced ultrasound features in diagnosis

AIM: Preoperative suspicion of malignancy in nonfunctioning pancreatic neuroendocrine tumors (pNETs) is mostly based on tumor size. We retrospectively analyzed the contrast enhanced ultrasound (CEUS) features of a series of histopathologically proved nonfunctioning pNETs. METHODS: In this retrospective study, 37 surgery and histologically proved nonfunctioning pNETs were included. All pNETs lesions were incidentally detected by transabdominal ultrasound. B mode ultrasound (BMUS) and CEUS features were reviewed and analyzed. 52 histopathologically proved pancreatic ductal adenocarcinoma (PDACs) lesions were included as a control group. RESULTS: All nonfunctioning pNETs patients showed no typical clinical symptoms. No significant differences were observed in size, echogenicity or internal color flow imaging signal between pNETs and PDAC patients (P > 0.05). Most of nonfunctioning pNETs showed a well-defined tumor margin. The presence of pancreatic duct dilatation was less frequently observed in nonfunctioning pNETs patients (P < 0.05). After injection of ultrasound contrast agents, homogeneous enhancement was more commonly observed in nonfunctioning pNETs group (P < 0.05). During arterial phase of CEUS, most of nonfunctioning pNETs were hyper- or isoenhanced (32/37, 86.5%), whereas most of PDACs were hypoenhanced (34/52, 65.4%) (P < 0.05). Nonenhanced necrosis area was more commonly detected in PDACs (P = 0.012). CONCLUSIONS: CEUS features are helpful for preoperative non-invasive differential diagnosis of nonfunctioning pNETs, assisting further clinical decision-making process.

Safety and parents´ acceptance of ultrasound contrast agents in children and adolescents – contrast enhanced voiding urosonography and contrast enhanced ultrasound

Aims: To evaluate the safety of the contrast enhanced voiding urosonography (ceVUS) and contrast enhanced ultrasound (CEUS) in children and adolescence and to receive data about parents’ acceptance of intravesical and intravenous application of sulfur hexafluoride.Material and methods: In this prospective, single centre study conducted over a 1 year study period, parents of 56 children (f/m=32/24; mean age 3.1 years; range 3 weeks - 15.9 years) with ceVUS and of 30 children (f/m=15/15; mean age 10.5 years; range 2 months - 17.7 years) with CEUS agreed to be included. A standardized telephone survey about the acceptance of the parents during and after the procedure as well as the adverse events (AE) were conducted within three days of the examination.Results: The parents would agree with the use of both ceVUS and CEUS as a diagnostic tool again in 96% (54/56) or 100% (30/30) of the cases, respectively and 92.9% (52/56) would prefer ceVUS to voiding cystourethrography (VCUG). In addition, 83.3% (25/30) would prefer CEUS to CT and 73.3% (22/30) would prefer CEUS to MRI. AE were reported in 3.6% after ceVUS (2/56; skin rash, mild fever) and in 3.3% after CEUS (1/30; vomiting). AE were subacute and self‑limited.Conclusions: The vast majority of parents prefer ceVUS and CEUS to VCUG, CT or MRI because of the safety profile of the contrast agent and diagnostic accuracy.