ICUS Weekly News Monitor 8-11-17

Business Journal News Network

Crouse Health unveils new ultrasound-imaging test to detect liver, kidney cancer

Aug 4, 2017

Author:  Eric Reinhardt

SYRACUSE, N.Y. — Crouse Health has introduced a new imaging test to detect liver and kidney cancers that it says “up until now has only been available in larger markets such as Boston, New York City, and Philadelphia.”

It’s called contrast-enhanced ultrasound (CEUS).

The procedure uses contrast agents called “microbubbles,” Dr. Thomas Green, chief of radiology at Crouse Health, said in a news release.

Green recently took special training in CEUS at Thomas Jefferson University in Philadelphia, Crouse Health said.

The microbubbles are “dramatically improving” the precision of diagnostic sonograms and expanding the clinical scope of a widely used, imaging modality.

Once injected in the patient’s arm, the microbubbles go directly to the suspected area of the liver or kidney, improving visualization of blood flow, the cardiovascular system and the movement of blood into vital organs, particularly the liver and kidney.

“Liver and renal lesions are very common,” Green said. “Differentiating benign from malignant can be difficult and expensive. Traditionally, this has been done with enhanced CT scanning, enhanced MRI or sometimes nuclear medicine.”

CEUS has advantages over all three methods, according to Green.

For example, CEUS doesn’t involve radiation, as CT and nuclear medicine do. It also doesn’t generate concerns about renal function or iodine contrast allergy.

It also doesn’t result in “issues” with metallic implants, internal pacemakers or claustrophobia, as an MRI (magnetic resonance imaging) procedure would produce.

And, according to Green, the test is “significantly less expensive” than other options, which is “important, especially with today’s high-deductible insurance plans.”

Crouse is expecting the number of cases using the new ultrasound-imaging test will increase once providers learn of its availability, Green adds.


Dove Medical Press

Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-co-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer

Jul 26, 2017

Authors:   Meng Wu,1,2 Ying Wang,3 Yiru Wang,2 Mingbo Zhang,2 Yukun Luo,2 Jie Tang,2 Zhigang Wang,4 Dong Wang,5 Lan Hao,4 Zhibiao Wang6

1School of Medicine, Nankai University, Tianjin, 2Department of Ultrasound, Chinese PLA General Hospital, Beijing, 3Wuhan Textile University, Wuhan, 4Chongqing Key Laboratory of Ultrasound Molecular Imaging, The Second Affiliated Hospital of Chongqing Medical University, 5Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 6College of Biomedical Engineering, Chongqing Medical University, Chongqing, People’s Republic of China

Published 26 July 2017 Volume 2017:12 Pages 5313—5330



In the current study, we synthesized prostate cancer-targeting poly(lactide-co-glycolic acid) (PLGA) nanobubbles (NBs) modified using A10-3.2 aptamers targeted to prostate-specific membrane antigen (PSMA) and encapsulated paclitaxel (PTX). We also investigated their impact on ultrasound (US) imaging and therapy of prostate cancer. PTX-A10-3.2-PLGA NBs were developed using water-in-oil-in-water (water/oil/water) double emulsion and carbodiimide chemistry approaches. Fluorescence imaging together with flow cytometry verified that the PTX-A10-3.2-PLGA NBs were successfully fabricated and could specifically bond to PSMA-positive LNCaP cells. We speculated that, in vivo, the PTX-A10-3.2-PLGA NBs would travel for a long time, efficiently aim at prostate cancer cells, and sustainably release the loaded PTX due to the improved permeability together with the retention impact and US-triggered drug delivery. The results demonstrated that the combination of PTX-A10-3.2-PLGA NBs with low-frequency US achieved high drug release, a low 50% inhibition concentration, and significant cell apoptosis in vitro. For mouse prostate tumor xenografts, the use of PTX-A10-3.2-PLGA NBs along with low-frequency US achieved the highest tumor inhibition rate, prolonging the survival of tumor-bearing nude mice without obvious systemic toxicity. Moreover, LNCaP xenografts in mice were utilized to observe modifications in the parameters of PTX-A10-3.2-PLGA and PTX-PLGA NBs in the contrast mode and the allocation of fluorescence-labeled PTX-A10-3.2-PLGA and PTX-PLGA NBs in live small animals and laser confocal scanning microscopy fluorescence imaging. These results demonstrated that PTX-A10-3.2-PLGA NBs showed high gray-scale intensity and aggregation ability and showed a notable signal intensity in contrast mode as well as aggregation ability in fluorescence imaging. In conclusion, we successfully developed an A10-3.2 aptamer and loaded PTX-PLGA multifunctional theranostic agent for the purpose of obtaining US images of prostate cancer and providing low-frequency US-triggered therapy of prostate cancer that was likely to constitute a strategy for both prostate cancer imaging and chemotherapy.

ICUS Weekly News Monitor 7-11-17

Science Daily

Tiny bubbles offer sound solution for drug delivery

Noninvasive approach to drug delivery for next generation brain therapies uses ultrasound and bubbles

June 26, 2017

Source: Acoustical Society of America

Cavitation microstreaming generated by a SonoVue microbubble and marked by fluorescent beads. Under ultrasound exposure, microbubbles can produce streaming flows which may contribute to blood-brain barrier opening and will be investigated directly using our in vitro platform.

Credit: Miles M. Aron, courtesy of BUBBL, University of Oxford, England

Your brain is armored. It lives in a box made of bones with a security system of vessels. These vessels protect the brain and central nervous system from harmful chemicals circulating in the blood. Yet this protection system -- known as the blood-brain barrier -- also prevents delivery of drugs that could help treat patients with brain cancers and brain diseases such as Alzheimer's disease. The heavily guarded brain has long frustrated physicians tending patients in need of brain treatments without surgery.

With recent advances in technology, the blood-brain barrier can now be opened safely, noninvasively and in a targeted manner using ultrasound. One of the newest approaches aiming to advance this research will be presented during Acoustics '17 Boston, the third joint meeting of the Acoustical Society of America and the European Acoustics Association being held June 25-29, in Boston, Massachusetts.

Investigators at the University of Oxford in the United Kingdom, collaborating with colleagues at the University of Twente in the Netherlands, have produced a promising in vitro experimental platform to investigate relationships between the way the blood-brain barrier opens, how long it takes to recover, and the sounds emitted during blood-brain barrier opening. Think of it as a blood-brain barrier on-a-chip using cultured cells rather than animal or human models.

"The key advantage of our system is that it uses three modalities -- involving light, sound, and electrical fields -- to simultaneously monitor acoustic emissions, blood-brain barrier disruption and recovery, and the biological response of blood-brain barrier cells in real-time," said Miles M. Aron at the University of Oxford.

Researchers have tried to open the blood-brain barrier using ultrasound since the 1950s. The breakthrough for safely opening the blood-brain barrier was to use tiny bubbles that interact with the ultrasound field known as "cavitation agents." Several cavitation agents are already approved for enhancing contrast in ultrasound imaging by the U.S. Food and Drug Administration. Cavitation agents work by oscillating rapidly or "singing" when exposed to ultrasound.

"The treatment can be monitored externally by 'listening' to the re-radiated sound from the cavitation agents interacting with the ultrasound field. These acoustic emissions provide information regarding the energy of cavitation within the blood vessels and are already being used to adjust ultrasound parameters in real-time to reduce the likelihood of damaging healthy cells during treatment," Aron said.

The team monitors acoustic emissions and the integrity of the blood-brain barrier in real-time throughout the treatment, an improvement compared to other approaches that generally involve blood-brain barrier assessment only after the treatment is completed, Aron said.

In addition, the team uses fluorescent probes to monitor either changes in the cells during treatment, or mechanical and chemical effects from the cavitation agents as they are exposed to ultrasound in real-time.

"By analyzing multiple sources of data during ultrasound exposure and throughout BBB recovery, we aim to better understand this promising new treatment," Aron said. "With the Oxford Centre for Drug Delivery Devices, OxCD3, we are currently working on a non-invasive method to detect and treat brain metastases before they become deadly. Our in vitro system will play a critical role in the development of this and other next-generation approaches to ultrasound-mediated blood brain barrier opening."


Uro Today

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine. Contrast-Enhanced Ultrasound Differentiation Between Low and High-Grade Bladder Urothelial Carcinoma and Correlation With Tumor Microvessel Density.

May 27, 2017

By Suping Guo, Pan Xu, Aiyun Zhou, Gongxian Wang, Weimin Chen, Jinhong Mei, Fan Xiao, Juan Liu, Cheng Zhang

Department of Ultrasonography, First Affiliated Hospital of Nanchang University, Nanchang, China., Department of Urology Surgery, First Affiliated Hospital of Nanchang University, Nanchang, China., Department of Pathology, First Affiliated Hospital of Nanchang University, Nanchang, China.

  1. PubMed

Time-intensity curves (TICs) of contrast-enhanced ultrasound (CEUS) were analyzed retrospectively to differentiate between low-grade and high-grade bladder urothelial carcinoma, and to investigate correlation with tumor microvessel density (MVD).

The data of 105 patients with pathologically confirmed bladder urothelial carcinoma (55 low-grade and 50 high-grade) were reviewed. Lesions were examined before surgery using conventional ultrasound and CEUS with TIC analysis. The TIC parameters time from peak to one-half the signal intensity (TPH) and the corresponding descending slope (DS) of the low-grade and high-grade groups were compared, and receiver operating characteristic curves constructed. The MVDs of the resectioned tissue specimens were quantified via immunohistochemistry for CD34.

Based on conventional ultrasound, the low-grade and high-grade groups were similar in tumor shape, number, topography, internal echo, height, width, and vascularity. The TPH of the high-grade group was significantly longer than that of the low-grade group, and the DS was lower. The cutoff points of TPH and DS for differentiating low-grade and high-grade bladder urothelial carcinoma were 48.06 seconds and 0.15 dB/seconds, respectively (area under the receiver operating characteristic curve = 0.79 for both). The mean MVDs per high-power field of the low-grade and high-grade groups were 41.39 16.65 and 51.03 20.16, respectively (P = .009). The TPH correlated linearly with MVD (P < .01), as did the DS (P < .01).

Contrast-enhanced ultrasound can be used to differentiate low from high-grade bladder urothelial carcinoma. The TIC parameters of CEUS reflect the MVD of bladder urothelial tumors and may be helpful for evaluating tumor angiogenesis, with implications for clinical diagnosis, treatment, and prognosis.

ICUS Weekly News Monitor 6-29-17

European Medicines Agency

Committee for Medicinal Products for Human Use (CHMP)

Summary of opinion (post authorisation)

22 June 2017


SonoVue (sulphur hexafluoride)

On 22 June 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product SonoVue. The marketing authorisation holder for this medicinal product is Bracco International B.V.

The CHMP adopted a new indication associated with a new route of administration for intravesical use as follows:

“Ultrasonography of excretory urinary tract

SonoVue is indicated for use in ultrasonography of the excretory tract in paediatric patients from newborn to 18 years to detect vesicoureteral reflux. For the limitation in the interpretation of a negative urosonography, see section 4.4 and 5.1.”

For information, the full indications for SonoVue will be as follows:

Intravenous use:

“This medicinal product is for diagnostic use only.

SonoVue is for use with ultrasound imaging to enhance the echogenicity of the blood, or of fluids in the urinary tract which results in an improved signal to noise ratio.

SonoVue should only be used in patients where study without contrast enhancement is inconclusive.


SonoVue is a transpulmonary echocardiographic contrast agent for use in adult patients with suspected or established cardiovascular disease to provide opacification of cardiac chambers and enhance left ventricular endocardial border delineation.

Doppler of macrovasculature

SonoVue increases the accuracy in detection or exclusion of abnormalities in cerebral arteries and extracranial carotid or peripheral arteries in adult patients by improving the Doppler signal to noise ratio.

SonoVue increases the quality of the Doppler flow image and the duration of clinically-useful signal enhancement in portal vein assessment in adult patients.

Doppler of microvasculature

SonoVue improves display of the vascularity of liver and breast lesions during Doppler sonography in adult patients leading to more specific lesion characterisation.

Intravesical use:

Ultrasonography of excretory urinary tract

SonoVue is indicated for use in ultrasonography of the excretory tract in paediatric patients from newborn to 18 years to detect vesicoureteral reflux. For the limitation in the interpretation of a negative urosonography, see section 4.4 and 5.1.”

Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.


Health Imaging

Brain ultrasound during tumor surgery matches pre-op MRI guidance and then some

Jun 05, 2017

By Dave Pearson

Italian researchers have shown how surgeons resecting glioblastomas, the most common and aggressive brain tumors, can use contrast-enhanced ultrasound to guide their view of tumor location, morphologic features, margins and dimensions in real time and for the duration of the entire surgery.

Radiology has published their findings online, ahead of print.

Francesco Prada, MD, of the Carlo Besta Neurological Institute in Milan and colleagues reviewed the cases of 10 patients who had glioblastoma multiforme and underwent tumor resection surgery with fusion guidance, which allowed the team to combine and then compare intraoperative ultrasound imaging against gadolinium-enhanced T1-weighted MR images obtained preoperatively.

The researchers found that, in all cases, the two sets of images were superimposable with correct scaling and a positional discrepancy of less than two millimeters.

In one patient, the imaging did differ meaningfully between the two modalities: The ultrasound showed the full bulk of the tumor while the MRI supplied peripheral contrast enhancement.

The authors conclude that intraoperative contrast-enhanced ultrasound enables surgeons to access, in real time, key tumor information that compares favorably with targeting information from preoperative gadolinium MRI—and therefore “can be used as an intraoperative guidance tool.”

They note that, compared with neuro navigation guided by static pre-op images, the ultrasound technique is “dynamic, economic and repeatable” throughout the surgery.

“Future studies should investigate the role of intraoperative ultrasound in the evaluation of residual tumor, usually a great challenge for neurosurgeons,” Prada et al. write. “The synergistic use of contrast-enhanced ultrasound with navigation systems and other imaging modalities, such as intraoperative MR imaging, fluorescence imaging and optical imaging, might help maximize resection of glioblastoma multiforme, thereby minimizing the risks for our patients.”

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