1. Atherosclerosis, July, 2015, Therapeutic ultrasound: Increased HDL-Cholesterol following
infusions of acoustic microspheres and apolipoprotein A-I plasmids
Authors: Jason W. Castle et al.
2. Echo Research and Practice, Feb 1, 2016, Echo Research and Practice is now indexed in PubMed!
Atherosclerosis 241 (2015) 92e99
Therapeutic ultrasound: Increased HDL-Cholesterol following
infusions of acoustic microspheres and apolipoprotein A-I plasmids
Authors: Jason W. Castle a, *, Kevin P. Kent b, Ying Fan a, Kirk D. Wallace a, Cynthia E.L. Davis a,
Jeannette C. Roberts a, Michael E. Marino a, Kai E. Thomenius a, Hae W. Lim b, Eric Coles c,
Michael H. Davidson c, d, Steven B. Feinstein c, e, Anthony DeMaria f
a General Electric Global Research, Niskayuna, NY, USA
b Formerly GE Global Research, Niskayuna, NY, USA
c SonoGene LLC, Glen Ellyn, IL, USA
d University of Chicago, Pritzker School of Medicine, Chicago, IL, USA
e Rush University Medical Center, Chicago, IL, USA
f Sulpizio Cardiovascular Center, University of California, San Diego, CA, USA
Background: Low levels of HDL-C are an independent cardiovascular risk factor associated with increased premature cardiovascular death. However, HDL-C therapies historically have been limited by issues relating to immunogenicity, hepatotoxicity and scalability, and have been ineffective in clinical trials.
Objective: We examined the feasibility of using injectable acoustic microspheres to locally deliver human ApoA-I DNA plasmids in a pre-clinical model and quantify increased production of HDL-C in vivo.
Methods: Our novel site-specific gene delivery system was examined in naïve rat model and comprised the following steps: (1) intravenous co-administration of a solution containing acoustically active microspheres (Optison™, GE Healthcare, Princeton, New Jersey) and human ApoA-I plasmids; (2) ultrasound verification of the presence of the microspheres within the liver vasculature; (3) External application of locally-directed acoustic energy, (4) induction of microsphere disruption and in situ sonoporation; (4) ApoA-I plasmid hepatic uptake; (5) transcription and expression of human ApoA-I protein; and (6) elevation of serum HDL-C.
Results: Co-administration of ApoA-I plasmids and acoustic microspheres, activated by external ultrasound energy, resulted in transcription and production of human ApoA-I protein and elevated serum HDL-C in rats (up to 61%; p-value < 0.05).
Conclusions: HDL-C was increased in rats following ultrasound directed delivery of human ApoA-I plasmids by microsphere sonoporation. The present method provides a novel approach to promote ApoA-I synthesis and nascent HDL-C elevation, potentially permitting the use of a minimally-invasive ultrasound-based, gene delivery system for treating individuals with low HDL-C.
Echo Research and Practice
Feb 1, 2016
Echo Research and Practice is now indexed in PubMed!
Echo Research and Practice, the open-access journal endorsed by the International Contrast Ultrasound Society (ICUS), is now indexed in PubMed. In addition, the journal has been selected for indexing in the Web of Science’s Emerging Sources Citation Index. Authors submitting their work to the journal can expect to receive an initial response in an average of 25 days, and accepted work will be published in 2 months average. Members of ICUS receive a 10% discount on the article publication charge. Authors receive suggestions for increasing post-publication impact, the results of which are visible with article-level metrics. To submit your work in Echo Research and Practice go to: http://www.echorespract.com
1. Ultrasound in Medicine and Biology, Jan 28, 2016, Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics
Authors: Andrew John Healey, et al
2. Ultrasound in Medicine and Biology, Jan 21, 2016, Contrast-Enhanced Ultrasonography of Pancreatic Carcinoma: Correlation with Pathologic Findings Authors: Yanjie Wang, et al
Ultrasound in Medicine and Biology
Acoustic Cluster Therapy: In Vitro and Ex Vivo Measurement of Activated Bubble Size Distribution and Temporal Dynamics
Authors: Andrew John Healey; Per Christian Sontum; Svein Kvåle; Morten Eriksen; Ragnar Bendiksen; Audun Tornes; Jonny Østensen
Address correspondence to: Andrew John Healey, CSO, Phoenix Solutions AS, PO Box 4741, N-0421 Oslo, Norway.
Acoustic cluster technology (ACT) is a two-component, microparticle formulation platform being developed for ultrasound-mediated drug delivery. Sonazoid microbubbles, which have a negative surface charge, are mixed with micron-sized perfluoromethylcyclopentane droplets stabilized with a positively charged surface membrane to form microbubble/microdroplet clusters. On exposure to ultrasound, the oil undergoes a phase change to the gaseous state, generating 20- to 40-μm ACT bubbles. An acoustic transmission technique is used to measure absorption and velocity dispersion of the ACT bubbles. An inversion technique computes bubble size population with temporal resolution of seconds. Bubble populations are measured both in vitro and in vivo after activation within the cardiac chambers of a dog model, with catheter-based flow through an extracorporeal measurement flow chamber. Volume-weighted mean diameter in arterial blood after activation in the left ventricle was 22 μm, with no bubbles >44 μm in diameter. After intravenous administration, 24.4% of the oil is activated in the cardiac chambers.
Ultrasound in Medicine and Biology
Jan 21, 2016
Contrast-Enhanced Ultrasonography of Pancreatic Carcinoma: Correlation with Pathologic Findings
Authors: Yanjie Wang; Kun Yan; Zhihui Fan; Li Sun; Wei Wu; Wei Yang
Address correspondence to: Kun Yan, Fucheng Road Number 52, District of Haidian, Beijing, China.
We concluded that contrast-enhanced ultrasound (CEUS) has clinical value in identifying the pathologic changes of pancreatic carcinomas. Forty-three patients diagnosed with pancreatic carcinoma through surgery were retrospectively investigated. CEUS examinations were performed on all patients before surgery. Enhancement patterns on CEUS were observed. Time–intensity curves of CEUS were generated for the regions of interest in the pancreas, and quantitative parameters were obtained. Resected cancer specimens were stained with hematoxylin and eosin for histologic analysis, and the microvascular density (MVD) of the specimens was determined by CD34 immunohistochemical staining. Enhancement patterns of CEUS were compared with histopathologic findings in pancreatic carcinomas. Correlations between time–intensity curve parameters and microvascular density were analyzed. Twenty cases manifested centripetal enhancement, and 23 cases, global enhancement. The amount of tumor necrosis or mucus in the centripetally enhanced pancreatic carcinomas was greater than that in the globally enhanced pancreatic carcinomas (p = 0.027). Thirty-eight of 43 (88.4%) pancreatic carcinomas manifested hypo-enhancement with a maximum intensity (IMAX) <90%. Contrast arrival time in pancreatic carcinoma was longer than that in adjacent pancreatic tissue (p < 0.05). IMAX was positively correlated with microvascular density (r = 0.577, p < 0.05). We concluded that CEUS manifestations could reflect the histologic changes of pancreatic carcinomas and CEUS can be used to evaluate blood perfusion of tumors, as IMAX is positively correlated with microvascular density.
1. Journal of Ultrasound in Medicine, Feb 1, 2016, Kupffer Imaging by Contrast-Enhanced Sonography With Perfluorobutane Microbubbles Is Associated With Outcomes After Radiofrequency Ablation of Hepatocellular Carcinoma Authors: Junya Nuta, MD, et al
2. Nanowerk News, Jan 28,2016, Trapping microbubbles with lasers and sound
Journal of Ultrasound in Medicine
Published January 18, 2016, doi: 10.7863/ultra.15.04067
JUM February 1, 2016 vol. 35 no. 2 359-371
Feb 1, 2016
Kupffer Imaging by Contrast-Enhanced Sonography With Perfluorobutane Microbubbles Is Associated With Outcomes After Radiofrequency Ablation of Hepatocellular Carcinoma
Authors: Junya Nuta, MD, Hideyuki Tamai, MD, PhD⇑, Yoshiyuki Mori, MD, Naoki Shingaki, MD, Shuya Maeshima, MD, Ryo Shimizu, MD, Yoshimasa Maeda, MD, Kosaku Moribata, MD, PhD,
Toru Niwa, MD, PhD, Hisanobu Deguchi, MD, Izumi Inoue, MD, PhD, Takao Maekita, MD, PhD,
Mikitaka Iguchi, MD, PhD, Jun Kato, MD, PhD and Masao Ichinose, MD, PhD
+ Author Affiliations
Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Objectives—An ultrasound contrast agent consisting of perfluorobutane microbubbles (Sonazoid; Daiichi Sankyo, Tokyo, Japan) accumulates in Kupffer cells, which thus enables Kupffer imaging. This study aimed to elucidate the association of defect patterns of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography with outcomes after radiofrequency ablation (RFA).
Methods—For this study, 226 patients with initial hypervascular hepatocellular carcinoma, who could be evaluated by contrast-enhanced sonography with Sonazoid before RFA, were analyzed. Patients were divided into 2 groups according to the tumor defect pattern during the Kupffer phase. The irregular-defect group was defined as patients with hepatocellular carcinoma that had a defect with an irregular margin, and the no-irregular-defect group was defined as patients with hepatocellular carcinoma that had either a defect with a smooth margin or no defect. Critical recurrence was defined as more than 3 intrahepatic recurrences, vascular invasion, dissemination, or metastasis.
Results—The irregular-defect and no-irregular-defect groups included 86 and 140 patients, respectively, and had cumulative 5-year critical recurrence rates of 49% and 17% (P < .01). Multivariate analysis indicated that the tumor diameter, lens culinaris agglutinin– reactive α-fetoprotein level, and defect pattern were independent factors related to critical recurrence. The cumulative 5-year overall survival rates for the irregular-defect and no-irregular-defect groups were 46% and 61% (P< .01). Multivariate analysis indicated that the Child-Pugh class, tumor diameter, lens culinaris agglutinin–reactive α-fetoprotein level, and defect pattern were independent factors related to survival.
Conclusions—The defect pattern of hepatocellular carcinoma during the Kupffer phase of Sonazoid contrast-enhanced sonography is associated with critical recurrence and survival after RFA.
Trapping microbubbles with lasers and sound
(Nanowerk News) The National Physical Laboratory (NPL) has worked with University College London (UCL) and the University of Oxford to develop an innovative system that can trap microbubbles. This enables scientists to study the bubbles' properties and develop safer, more effective medical products.
Microbubbles are gas bubbles that are smaller than 1 mm in size - their radius is typically between 1 and 10 microns for medical applications. In the past 10 years, the use of microbubbles to enhance contrast in ultrasound images has become an everyday practice in hospitals in UK and across the world. Microbubbles now sit at the forefront of techniques used for the diagnosis of heart diseases and certain types of cancer.
Video frames of acoustically trapped bubbles and one optically trapped bubble (centre in all images) which is manipulated away from the cloud
New technological advances, and recent successes in treatment have shown that the addition of certain molecules to the shell of these bubbles could make them ideal vehicles for targeted medicine delivery and microsurgery.
As the potential applications increase, it becomes more important to characterise how microbubbles interact with sound and how different manufacturing techniques impact on their performance. Information about the microbubble properties can be used to engineer bubbles for specific medical uses, and in a more cost-effective way.
Scientists from NPL have worked with UCL and the University of Oxford to develop a controlled setting in which to study microbubbles. The unique device, which was designed and constructed at NPL, traps the microbubbles using optical tweezers in combination with acoustic tweezers, which control the movement of objects using sound waves.
While these two techniques are commonly used for solid particles, they both present challenges when used with bubbles. Optical tweezers, for instance, are often used to trap and study biological samples using highly-focused laser beams to hold and move items. However, objects with a low refractive index, such as microbubbles, are difficult to optically trap due to strong repulsive forces experienced in proximity to high intensity light.
Bubbles also present a peculiar response to acoustical tweezing, behaving in different ways depending on the selected manipulation frequency. If the acoustic field is higher than the bubbles natural frequency they will move to where the field is strongest in pressure, but if the field is lower than the natural frequency the bubbles will collect at the weakest point.
This method will allow researchers to perform characterization at the single bubble level and support the development of medical microbubbles. Fully characterised bubbles may even act as stand-alone sensors, for stratified medicine purposes.
Source: National Physical Laboratory