ICUS Weekly News Monitor 6-5-2018

ICUS Weekly News Monitor

05 June 2018 - 9 am Eastern

  1. Dovepress,  Perfluorooctylbromide nanoparticles for ultrasound imaging and drug delivery,  May 25, 2018   Authors:  Xiao Li, et al
  2. EuroIntervention,  Association between fractional flow reserve, instantaneous wave-free ratio and dobutamine stress echocardiography in patients with stable coronary artery disease,   March 20, 2018     Authors:  Vasileios F. Panoulas


Volume 2018:13 Pages 3053—3067; DOI

Perfluorooctylbromide nanoparticles for ultrasound imaging and drug delivery

May 25, 2018

Authors: Xiao Li, Zhongguo Sui, Xin Li, Wen Xu, Qie Guo, Jialin Sun, Fanbo Jing

Department of Clinical Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China


Perfluorooctylbromide nanoparticles (PFOB NPs) are a type of multifunctional nanotechnology that has been studied for various medical applications. Commercial ultrasound contrast agents (UCAs) suffer from the following limitations: short half-lives in vivo, high background signal and restricted distribution in the vascular circulation due to their micrometer dimensions. PFOB NPs are new potential UCAs that persist for long periods in the circulatory system, possess a relatively stable echogenic response without increasing the background signal and exhibit lower acoustic attenuation than commercial UCAs. Furthermore, PFOB NPs may also serve as drug delivery vehicles in which drugs are dissolved in the outer lipid or polymer layer for subsequent delivery to target sites in site-targeted therapy. The use of PFOB NPs as carriers has the potential advantage of selectively delivering payloads to the target site while improving visualization of the site using ultrasound (US) imaging. Unfortunately, the application of PFOB NPs to the field of ultrasonography has been limited because of the low intensity of US reflection. Numerous researchers have realized the potential use of PFOB NPs as UCAs and thus have developed alternative approaches to apply PFOB NPs in ultrasonography. In this article, we review the latest approaches for using PFOB NPs to enhance US imaging in vivo. In addition, this article emphasizes the application of PFOB NPs as promising drug delivery carriers for cancer and atherosclerosis treatments, as PFOB NPs can transport different drug payloads for various applications with good efficacy. We also note the challenges and future study directions for the application of PFOB NPs as both a delivery system for therapeutic agents and a diagnostic agent for ultrasonography.



Association between fractional flow reserve, instantaneous wave-free ratio and dobutamine stress echocardiography in patients with stable coronary artery disease.

March 20, 2018

Authors: Vasileios F. Panoulas1,2,3*, MD, PhD; Kalliopi Keramida1, MD; Olga Boletti1, MD; Michail I. Papafaklis1, MD, PhD; Dimitris Flessas1, MD; Maria Petropoulou1, MD; Petros Nihoyannopoulos1,2, MD

1. Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; 2. Division of Cardiovascular Sciences, National Heart and Lung Institute, Imperial College London, London, United Kingdom; 3. Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom

This paper also includes supplementary data published online at:



The association between fractional flow reserve (FFR) and dobutamine stress echocardiography(DSE) in real-world stable angina patients is scant and controversial whereas no such comparison exists with instantaneous wave-free ratio (iFR). The current retrospective study aimed to investigate the associations among these modalities in patients with stable coronary artery disease (CAD) and intermediate coronary lesions.

Methods and results

We studied 62 consecutive stable angina patients who underwent DSE and subsequently coronary angiography with FFR (in all 62) and iFR (in 46/62 patients) assessment of intermediate single-vessel lesions between 2014 and 2015. Using receiver operating characteristic (ROC) curves we sought to identify the optimal FFR and iFR cut-off points with the highest discriminative power to predict

the DSE result. The kappa coefficient was used to assess the agreement between FFR, iFR and DSE. Themean age of the study cohort was 63.5±12 years and 35 (56.5%) were males. Thirteen (21%) lesions were adjudicated as causing reversible ischaemia on DSE. Using ROC (FFR predicting DSE result), the area under the curve was 0.952 (95% CI: 0.902 to 1), whereas for iFR it was 0.743 (95% CI: 0.560 to 0.927), pAUC comparison=0.03. The optimal FFR cut-off point predicting positive DSE was 0.80. There was strong agreement between DSE and FFR (kappa 0.682, p<0.001). There was only modest agreement between iFR and DSE (kappa 0.258, p=0.068) using a cut-off value of 0.9.


In patients referred for evaluation of stable CAD, there was good agreement between DSE and FFR (87%) but less so with iFR (71.7%).

ICUS Weekly News Monitor 4-27-2018

1.ICUS, CEUS Basic Training - Calgary - Jun 22-23, 2018, Registration Now Open!, New ultrasound imaging technique better detects prostate cancer, April 23, 2018 by Lauren Dubinsky


CEUS Basic Training - Calgary - Jun 22-23, 2018

Registration Now Open!

Abdominal CEUS (with live patient demonstrations) - Host: Stephanie Wilson, MD

ICUS is proud to expand its educational programs in 2018 to include practical training for successful use of contrast enhanced ultrasound (CEUS) of the cardiovascular system and abdomen.

We are excited to announce the upcoming abdominal CEUS program sponsored by the International Contrast Ultrasound Society (ICUS) and hosted by Dr. Stephanie R. Wilson, Professor of Medicine, University of Calgary.

Click here for Registration and to learn more about the Program:

For any questions, contact Heather Baylis at: This email address is being protected from spambots. You need JavaScript enabled to view it. This email address is being protected from spambots. You need JavaScript enabled to view it. or call (403) 220-6166


New ultrasound imaging technique better detects prostate cancer

April 23, 2018

By Lauren Dubinsky , Senior Reporter

A team of researchers at Thomas Jefferson University in Philadelphia has discovered a way to better diagnose prostate cancer with ultrasound imaging.

“Unfortunately, conventional ultrasound does not do a very good job at finding prostate cancer,” Venkata Masarapu of Jefferson Medical College at Thomas Jefferson University, told HCB News. “Our experience suggests that by using contrast-enhanced imaging, we can improve the ability of ultrasound.”

Masarapu and his team have been working on contrast-enhanced imaging of the prostate with conventional harmonic imaging (HI) for over a decade and have had some success with it. But then a newer technique called subharmonic imaging (SHI) was introduced that provides better contrast signal and tissue suppression than HI.

They hypothesized that SHI could improve the detection of the vascularity that is associated with prostate cancer. When they tested it, they found out that they were right.

“Some of our recent studies suggest that the diagnostic accuracy of contrast-enhanced ultrasound may be similar to that of MR,” said Masarapu.

The first in-vivo application of SHI found that it may improve the performance of contrast-enhanced ultrasound for detecting prostate cancer. The team demonstrated that it improves conspicuity of microbubble contrast enhancement and spotted cancer in five patients that MR missed.

“If we can match the diagnostic accuracy, and also provide advantages of portability, availability and lower cost, then we believe that ultrasound will supplant MR for evaluation of the prostate,” said Masarapu.

He will present these findings at the American Roentgen Ray Society Annual Meeting later this month in Washington, D.C.

ICUS Weekly News Monitor 4-20-2018

1.Science Daily, Detailed images of tumor vasculature - Medical engineering, April 18,2018, By tracking individual microbubbles, high-resolution images can be taken with conventional ultrasound scanners, April 18, 2018

2.Journal of the American Society of Echocardiography, Clinical Use of Ultrasound Enhancing Agents; Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions, March, 2018 Authors: Hang Zhao MD, et al

Science Daily

Detailed images of tumor vasculature - Medical engineering

By tracking individual microbubbles, high-resolution images can be taken with conventional ultrasound scanners.

April 18, 2018

Ruhr-University Bochum. "Detailed images of tumor vasculature: Medical engineering." ScienceDaily, 18 April 2018. <>.


Thanks to a new method of analyzing ultrasound images, conventional scanners can be used for generating high-res images of blood vessels in tumors. This approach makes it easier to distinguish between different types of tumors, and it facilitates the tracking of the progress and success of chemotherapy.

The new technology has been developed jointly by teams headed by Prof Dr Georg Schmitz at the Chair for Medical Engineering at Ruhr-Universität Bochum and by Prof Dr Fabian Kiessling at the Institute for Experimental Molecular Imaging at the University Hospital Aachen. They published their report in the journal Nature Communications from April 18, 2018.

Monitoring microbubbles on their path through the body

The new technology called "Motion Model Ultrasound Localization Microscopy" is based on contrast medium-enhanced ultrasound images. Microbubbles are administered to patients as contrast agents: gas bubbles no larger than one micrometre that travel through the body in the bloodstream. In ultrasound images, they appear as shapeless white blobs. "Once the centre of each of these blobs has been identified, it's possible to determine the location of individual bubbles," explains Georg Schmitz.

Each bubble is given a name

Using algorithms originally developed for radar technology, the research team successfully monitored the motion of individual microbubbles. "We are currently attempting to teach the computer something that our eyes are able to do: namely read movement in a sequence of images in which a dot appears in different locations," says Schmitz. To this end, the researchers gave each bubble a name. Thus, they were able to track their paths through the vascular system and count them in the process.

Resolution much higher than mere image resolution

Subsequently, fine vascular networks can be reconstructed based on the motion of the bubbles. The direction and speed of the blood flow can likewise be recorded. The resolution of the images is greatly enhanced: experts refer to the technique as super-resolution imaging.

"In the publication, we demonstrated that the synthesis of morphological and functional parameters considerably facilitates the differentiation between tumour types," explains Fabian Kiessling. In the course of their project, they tested the technique in three model cases, including in human subjects. In collaboration with Prof Dr Elmar Stickeler from the Clinic for Gynaecology and Obstetrics at the University Hospital Aachen, the researchers successfully identified how tumour vessels responded to chemotherapy in breast cancer patients.

Monitoring therapy effects

"One reason why this is important is because new therapy approaches aim at manipulating the vascular system of tumours, in order to enhance the therapeutic effect by increasing the concentration of drugs in the tumours," says Fabian Kiessling. One of these approaches is so-called sonoporation. Here, tumours are treated with ultrasound in order to render the vascular walls more permeable to active substances.

"The advantage of our approach is that it can be performed with conventional ultrasound scanners, which have a low frame frequency, with sometimes as few as 15 images per second," points out Georg Schmitz. The research teams have already filed an application for a follow-up project, in the course of which they intend to test the method in large-scale clinical studies.


Journal of the American Society of Echocardiography

Volume 31, Issue 3, March 2018, Pages 289-296

Clinical Use of Ultrasound Enhancing Agents; Contrast-Enhanced Echocardiography Has the Greatest Impact in Patients with Reduced Ejection Fractions

Authors: Hang Zhao MD a, b, Rupal O'Quinn MD a, Marietta Ambrose MD a, Dinesh Jagasia MD a, Bonnie Ky MD a, Joyce Wald DO a, Victor A. Ferrari MD a, James N. Kirkpatrick MD, FASE c, Yuchi Han MD, MMSc, FASE a

aCardiovascular Division, Department of Medicine, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, bDepartment of Cardiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,  cCardiovascular Division, Department of Medicine, University of Washington School of Medicine, Seattle, Washington


•Contrast use in patients with suboptimal images affects patient care, especially in patients who have reduced precontrast estimated LVEF.

•The impact of contrast use is seen more significantly in patients with HF, cardiomyopathy, and arrhythmias.

•The impact of contrast is not influenced by the results of prior studies, whether outpatient or inpatient, or whether the patient has a defibrillator or a pacemaker.


Contrast-enhanced echocardiography (CE) helps to improve image quality in patients with suboptimal acoustic windows. Despite current recommendations, contrast use remains low. The aim of this study was to identify populations that would benefit more from contrast use.


A total of 176 subjects (137 men; mean age, 60.8 ± 13.7 years) with technically difficult transthoracic echocardiographic studies who received clinically indicated intravenous contrast were prospectively studied. The impact on clinical decision making (including alterations in medical therapy, referral, imaging, or clinical procedures) was evaluated.


The use of CE enabled biplane left ventricular (LV) ejection fraction measurement in 97.2% of studies and the interpretation of regional wall motion in 95% of studies. CE allowed definitive assessment of the presence or absence of LV thrombus in 99% of the cases. In the 174 patients whose ordering physicians could be reached at the time of image interpretation, changes in management occurred in 51% of subjects. There was no difference in the proportion of management changes between inpatients and outpatients (60.0% vs 48.1%, P = .225). Subjects with heart failure, cardiomyopathy, and arrhythmia had a higher proportion of changes (61.4% vs 44.2% [P = .031], 62.5% vs 45.0% [P = .028], and 72.0% vs 47.7% [P = .030], respectively). The proportion of management change after CE increased as pre-CE estimated ejection fraction decreased. Logistic regression showed that pre-CE estimated LV ejection fraction < 50% was the only significant predictor of change of management after contrast (P = .004).


The use of CE has a significant impact on clinical decision making in patients with suboptimal acoustic windows, especially in those with depressed pre-CE LV ejection fractions.

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