1. Healio Rheumatology, Apr 20, 2016, Contrast-enhanced ultrasound may be effective in diagnosing large vessel vasculitis By Shirley Pulawski
2. Healio HCV Next, April 2016, The March Toward Elastography for Assessing Fibrosis in HCV
3. Medgadget.com, April 19, 2016, Key Factors Driving Pre-Clinical Imaging Market
Germanò G, et al. Arth Care Res. 2016;doi:10.1002/acr.22906.
Apr 20, 2016
Contrast-enhanced ultrasound may be effective in diagnosing large vessel vasculitis
By Shirley Pulawski
Carotid contrast-enhanced ultrasound vascularization grade and grade pf vascular inflammation shown on 18F-FDG positron emission tomography correlated well in patients with large vessel vasculitis, according to recently published research.
Researchers enrolled 31 patients with large vessel vasculitis (LVV), including four patients who were evaluated twice over a 12-month period. Standard color Doppler ultrasound (CDUS) evaluations of extra-cranial carotid arteries were administered to all patients and intima media thickness was measured at the far wall of both carotid arteries in proximity to the bifurcation. Vasculitis was determined in the presence of a hypoechoic, circumferential homogenous wall thickening, while inhomogenous, eccentric, thickening of the partly calcified arterial wall was deemed athermatosis. Criteria defined by Drielsma et al was used to define atherosclerotic
Within 5 to 10 seconds following the standard CDUS examination, an ultrasound contrast agent was infused to assess the right carotid artery with contrast-enhanced ultrasound (CEUS) and the degree of vascularization was classified.
Within 3 days of CEUS evaluation, patients underwent 18F-FDG PET/CT scans after fasting for 4 or more hours prior to injection.
Erythrocyte sedimentation rates and C-reactive protein were elevated during the testing point in 19 of the examinations. Abnormal vascular uptake was demonstrated in 10 examinations in the right carotid artery and in different vascular areas in nine examinations.
Patients with grade 2 vascularization at CEUS were more likely to have intima media thickness above 1 mm and FDG carotid uptake of 2 or greater and the maximum standardized uptake value (SUV) and the mean SUV in the right carotid artery and mean SUV in the superior vena cava were significantly higher in patients with severe vascularization on CEUS.
“In conclusion, CEUS is a cheap, non-invasive tool useful to examine large vessel wall vascularization in LVV,” the researchers wrote. “The correlation between CEUS and 18F-FDG uptake suggests an association between vascularization and inflammation and supports the use of CEUS as a noninvasive method able to detect disease activity in patients with LVV.”
The March Toward Elastography for Assessing Fibrosis in HCV
There are a number of ways to assess fibrosis in HCV, but none are perfect. The long-time mainstay of measuring fibrosis — liver biopsy — may eventually fall out of fashion in the wake of advances in noninvasive measures. The clinical community has been seeking its replacement for two decades, and has largely turned to imaging techniques. Magnetic resonance and transient ultrasound elastography have become the twin pillars of the field. HCV Next spoke with a handful of experts regarding elastography, and it became clear that addressing serum biomarkers and other scoring systems along with ongoing use of biopsy is necessary. Each method comes with drawbacks. The arguments against these various non-invasive ways of assessing fibrosis range from cost, to small sample size, to limited ability to view the liver in its entirety……..Clinicians in the U.S. rely heavily on magnetic resonance elastography (MRE), whereas various forms of ultrasound elastography are used abroad, according to SimonTaylor-Robinson, MD, PhD, clinical consul for the Faculty of Medicine at Imperial College of London. “Ultrasound contrast agents are the gold standard outside the U.S., largely because access to MR machines is less common in other parts of the world,” he said. “In the U.S., people tend not to use ultrasound.”
April 19, 2016
Key Factors Driving Pre-Clinical Imaging Market
Transparency Market Research Releases
The global pre-clinical imaging market has been exhibiting immense growth since the last few years and the trend is expected to continue in the coming years. The advancement in molecular imaging technologies and the increasing adoption of pre-clinical imaging technology as a reliable drug development tool are likely to propel this market in the nearing future.
The global market for pre-clinical imaging is broadly analyzed on the basis of the imaging system, the imaging reagent, technology, and the regional spread of this market. Based on the imaging system, the market is classified into standalone imaging systems and multimodal imaging systems.
Based on the imaging reagent, the market is categorized into optical imaging agents, MRI contrasting reagents, CT contrast reagents, nuclear imaging agents, and ultrasound contrast reagents. Technology wise, the market includes PET + SPECT + CT, PET + MRI, and SPECT + MRI as the major segments.
On the regional basis, the worldwide pre-clinical imaging market is segmented into North America, Asia Pacific, Europe, and the Rest of the World.
This report on the global pre-clinical imaging market attempts to provide a comprehensive overview of this market on the basis of its current and historical performance as well as its future prospects. Driving forces, limitations, latest and upcoming trends, and opportunities of this market have also been discussed at length in this research study.
Overview of the Global Pre-Clinical Imaging Market
The global pre-clinical imaging market has experienced a surge in its valuation in the recent times. Various macro-environmental factors such as technical innovation and government grants and funding have boosted this market significantly over the past few years.
The standalone imaging systems market includes micro-MRI, micro-CT, micro-ultrasound, nuclear imaging, and optical imaging. Multimodal nuclear imaging devices and multimodal optical imaging devices are the major segments of the multimodal imaging systems market.
North America leads the worldwide pre-clinical imaging systems and is closely followed by Europe. Asia Pacific and the Rest of the World are also projected to emerge as lucrative markets for pre-clinical imaging in the near future.
Overall, the global market is witnessing a steady rise in demand. However, the increasing prices of imaging systems and the lack of awareness regarding technology in developing economies are hampering the market’s growth. The consolidation in the worldwide pharmaceutical industry is also expected to restrict this market from rising steadily in the forthcoming years.
Companies mentioned in the research report:
Bioscan Inc., PerkinElmer Inc., Siemens AG, Aspect Imaging, Life Technologies Corp., and Gamma Medica Inc. are leading the worldwide pre-clinical imaging market.
1. Auntminnie.com, Apr 12, 2016, Fans of contrast ultrasound celebrate FDA approval
By Erik Ridley
2. Ultrasonography 2016, International guidelines for contrast-enhanced ultrasonography: ultrasound imaging in the new millennium
Authors: Christian Pállson Nolsøe, Torben Lorentzen
Apr 12, 2016
Fans of contrast ultrasound celebrate FDA approval
By Erik Ridley
For advocates of ultrasound contrast, the recent U.S. Food and Drug Administration (FDA) approval of Lumason from Bracco Diagnostics for characterizing liver lesions was a long overdue moment that will likely serve as a catalyst for broad adoption of these agents -- and not just in the liver.
First of all, the FDA approval offers incredible potential for patient care, patient safety, and optimal management of liver tumors, especially in those patients at risk for hepatocellular carcinoma (HCC), said Dr. Stephanie Wilson, co-chair of the International Contrast Ultrasound Society (ICUS) and a clinical professor of radiology and gastroenterology at the University of Calgary.
"Microbubble contrast agents, including Lumason, are easy to use, are cost-effective, and provide a brand new arena in which the investigation of liver masses may now expand," she said. The approval paves the way for employing contrast-enhanced ultrasound (CEUS) in liver indications that are typically being imaged now in the U.S. by CT or MRI, according to Wilson.
A logical choice
Because characterizing liver masses is the most important indication for CEUS, it was a logical choice for the first approved indication in radiology, said Dr. Edward Grant, an ICUS board member and chairman of radiology at the University of Southern California (USC) Keck School of Medicine.
"CEUS performs well in this area, and there is a huge body of existing literature outside of the USA supporting it," Grant said.
Liver masses are common -- 5% to 10% of the population is believed to have one -- and most are incidentally discovered and benign. Until now, patients in the U.S. were typically referred for a contrast-enhanced CT or MR, Grant said.
"However, most liver masses can be characterized definitively on the spot with CEUS -- end of workup," he said.
A large number of cirrhosis patients are screened for HCC using noncontrast ultrasound every six months or even more frequently, Grant said. In the U.S., these masses identified on ultrasound would also typically be sent for a contrast-enhanced CT or MR.
"However, most can be definitively characterized using CEUS, avoiding CT/MR in cases of benign tumors and, thus, decreasing cost and radiation exposure," he said.
Access to ultrasound contrast agents for characterizing masses in patients with renal failure also represents a huge leap forward, Grant said.
"As with CEUS for the liver, CEUS for the kidney can be a problem-solver since it can be used to characterize masses seen on CT or MR that are indeterminate, or, as we use it, as a first-line agent to characterize masses seen on noncontrast [ultrasound]," he said. "This helps avoid many costly CT/MRIs and also avoids radiation in the case of CT."
Triggering broad expansion
In the absence of FDA approval for ultrasound contrast in radiology applications, many ultrasound contrast advocates had been recommending the off-label use of ultrasound contrast agents for noncardiac indications. Despite those efforts, off-label adoption has remained largely limited to academic medical centers.
The FDA approval of Lumason for characterizing liver lesions, however, is a game-changing moment for the use of ultrasound contrast agents, Grant said.
Prior to approval, many radiologists hesitated to use ultrasound contrast agents off-label for a variety for reasons, including the mistaken belief that they could not get reimbursed for off-label use. In addition, some in leadership positions simply refused to allow off-label contrast use in their departments, citing the lack of approval.
As an added complication, representatives from ultrasound contrast vendors could not speak to radiologists about contrast for legal reasons, Grant said.
"And most people in the major ultrasound companies in the radiology market have had little or no experience with ultrasound contrast agents, making it doubly difficult for practitioners to get started," he said.
The approval should also go a long way toward easing the minds of referring physicians.
"Now that we have an FDA approval for liver, I think our oncologists will feel more comfortable referring patients for contrast-enhanced ultrasound," said Dr. Richard Barr, PhD, from Northeast Ohio Medical University. "I think they were a little concerned before when it was off-label use, especially if they weren't doing studies."
Indeed, clinicians may soon expect the availability of CEUS, according to Grant.
"As the benefits of contrast [ultrasound] become more well-known in the USA, clinicians will eventually expect radiologists to step up, or risk having nonradiologists provide the service," Grant told AuntMinnie.com. "A perfect example would be a patient with renal failure who cannot have contrast-enhanced CT or MR. Once it becomes known that contrast-enhanced ultrasound studies are available, urologists will demand them for their patients' sake."
The approval also marks a major shift toward acceptance of CEUS in children and will herald its introduction as a diagnostic option, said Dr. Kassa Darge, PhD, an ICUS board member and chief of body imaging at the Children's Hospital of Philadelphia (CHOP).
"It goes from something more like a 'research' application to routine clinical use," Darge said. "In addition, it opens up the possibility of reimbursement. It is amazing to see the increase in requests for information regarding pediatric CEUS applications just in the first week of the approval."
CEUS has been used routinely in pediatrics in Europe since the late 1990s, and since then to a lesser extent in Asia, Australia, and South America. The main pediatric application for CEUS is actually intravesical injection for detecting vesicoureteric reflux, Darge said.
"The patients for this indication are many more than the patients having the indications for intravenous contrast administration of the [ultrasound] contrast agents," he said.
Intravenous CEUS in children does provide major improvements, however, including the ability to perform an ultrasound study instead of exposing patients to radiation with CT or fluoroscopy.
"Furthermore, with CEUS it is possible to do a study without sedation, unlike MRI in small children," Darge said. "Thus, with pediatric CEUS we are able to avoid radiation and sedation in children for selected indications. Other advantages include the ability to do CEUS as a bedside study and the possibility to administer [ultrasound] contrast agents in patients with reduced renal function."
In the liver, the most important applications for pediatric CEUS are the detection and characterization of focal liver lesions, assessment for blunt trauma, and evaluation for disseminated infections, according to Darge.
CHOP has been using ultrasound contrast agents off-label for routine clinical indications for almost two years; these indications go beyond the liver to include assessment for blunt abdominal trauma (including spleen, kidneys, and pancreas); detection and characterization of focal lesions also in the spleen, kidneys, and pancreas; and evaluation of the bowel in children with inflammatory bowel disease.
"We have [also] expanded the use beyond contrast-enhanced voiding urosonography with intravesical administration to applications for pediatric interventional radiology in the setting of renal angioplasty or pleural drainage procedures," he said.
Should companies feel that additional approvals are warranted, USC's Grant recommends evaluating the use of CEUS in kidney imaging.
"In our practice, we probably use ultrasound contrast in the kidney almost as frequently as we do for the liver," Grant said. "We routinely use it to characterize indeterminate masses on CT/MR, or complex masses seen on noncontrast [ultrasound]. It is also an excellent method to follow up patients who have undergone partial nephrectomy for renal cell carcinomas, since many of these patients will experience some form of renal failure after the surgery."
Barr said that characterizing renal masses is the biggest use for CEUS at Northeast Ohio Medical University.
"We get much better results [with CEUS] in characterizing renal masses than CT and MR," he said.
While characterizing liver lesions has been the most popular and also the most successful pursuit worldwide for CEUS in radiology, nonhepatic indications are equally exciting and many of them are "incredibly successful," Wilson said.
"Renal mass evaluation [with CEUS], where performed, becomes an essential tool for urologists," Wilson noted. "My own great interest in the use of microbubble contrast agents for assessing inflammatory activity in [inflammatory bowel disease] is an exciting and expanding arena that shows the great value of quantification of blood flow, which can be done with CEUS related to the purely intravascular location of the microbubbles. This objective biomarker of disease will hopefully be standard care in the future."
The use of CEUS to monitor chemotherapy treatment response will also likely be a very important application in the future, Barr said. Performing that task with multiple CT and MR exams is not very efficient, and in the case of CT, it exposes patients to a lot of radiation.
"There are a lot of groups working on how to apply [CEUS] now in monitoring chemotherapy treatment," he said.
What remains to be seen is whether or not other ultrasound contrast firms will pursue FDA approval for these and/or other radiology applications.
A GE Healthcare spokesperson declined to comment on the company's plans for submitting its Optison agent for FDA approval in radiology indications. However, the firm "sees the approval of contrast imaging for ultrasound in the liver as a positive and pivotal moment in the history of ultrasound in the U.S."
"As an industry leader in both ultrasound and contrast, we have worked closely with clinicians globally to ensure that our products excel in this important clinical application, and we are excited about the potential to improve healthcare with this important new clinical capability," the spokesperson told AuntMinnie.com.
Mary Anne Heino, president and CEO of Lantheus Medical Imaging, said it's the company's policy not to comment on ongoing regulatory discussions with the FDA. However, she noted that Definity has been approved in 40 countries worldwide, with approvals for abdominal imaging of the liver and kidneys in five of those markets.
What's more, Lantheus is teaming with its partner Double Crane in China to seek approval for both cardiac and abdominal imaging, and it's also in the process of obtaining approval for cardiac and abdominal imaging in Taiwan, she said.
"Definity has been used in more than 6.7 million patients worldwide since commercial approval," she said. "Lantheus has an extensive database of clinical data and publications for Definity."
In commenting on the new FDA approval for Bracco's Lumason agent, Heino said that Lantheus welcomes additional clinical work that demonstrates the safety and value of contrast agents.
"Demonstration of the clinical benefit of contrast use helps healthcare practitioners and the patients they serve," Heino said. "Lantheus welcomes and supports all industry efforts to better characterize the value of contrast use."
As for Bracco, the company is pursuing additional noncardiac and cardiac indications in the U.S. for Lumason, focusing on areas the firm believes Lumason-enhanced ultrasound would bring the most clinical value, said Dr. Alberto Spinazzi, senior vice president of global medical and regulatory affairs for the Bracco Group.
"We are in advanced stages of development, either phase III of clinical testing or preparing the application," he told AuntMinnie.com.
A bright future in pediatrics
Thanks to the new approval of Lumason, ultrasound contrast use in pediatrics has a much brighter future in the U.S., Darge said.
"This will not only spur the routine clinical use, but also will be instrumental in advancing innovative research projects in pediatric CEUS," he said. "This will also open the door for future approval expansion of the indication for intravesical use. It may also motivate other [ultrasound] contrast agent manufacturers to follow suit and seek pediatric approvals."
The advantage of not using ionizing radiation will be a key selling point for CEUS, particularly for pediatric radiologists, Barr said.
"I think the pediatric radiologists will accept it much more rapidly than the adults," he added.
The long-awaited approval is a very exciting development that opens new doors for the use of ultrasound, according to Grant.
"Radiologists in the USA will finally be on a par with those practicing in the rest of the world," he said. "However, we cannot underestimate the need for education as well as further research and development leading to improved agents and equipment."
While it's a very exciting time for ultrasound contrast, widespread adoption of CEUS won't happen overnight, Barr noted.
"There is a fair learning curve in getting the sonographers, the radiologists, and everybody onboard to use the agent," he said.
The long delay in getting approval for radiology applications has had a negative effect on U.S. radiologists, and the practice standards are firmly established, Wilson said. On the bright side, she noted, the American College of Radiology's Liver Imaging Reporting and Data System (LI-RADS) Committee recently added CEUS along with CT and MR for liver imaging in patients at risk for HCC.
"I hope very much that the role of CEUS for so many important capabilities will grow in the years ahead," Wilson said.
pISSN: 2288-5919 • eISSN: 2288-5943
International guidelines for
ultrasound imaging in the new millennium
Authors: Christian Pállson Nolsøe, Torben Lorentzen
Ultrasound Section, Department of Gastric Surgery, Herlev Hospital, University of
Copenhagen, Herlev, Denmark http://dx.doi.org/10.14366/usg.15057
The intent of this review is to discuss and comment on common clinical scenarios in which
contrast-enhanced ultrasonography (CEUS) may play a decisive role and to illustrate important
points with typical cases. With the advent of CEUS, the scope of indications for ultrasonography
has been dramatically extended, and now includes functional imaging and tissue characterization, which in many cases enable tumor diagnosis without a biopsy. It is virtually impossible to imagine the practice of modern medicine as we know it in high-income countries without the use of imaging, and yet, an estimated two thirds of the global population may receive no such care. Ultrasound imaging with CEUS has the potential to correct this inequity.
(To read the full article go to: http://dx.doi.org/10.14366/usg.15057)
1. Healio, Apr 5, 2016, FDA approves Lumason for hepatic lesions in adults, children
2. DOTmed.com, April 04, 2016, FDA clears LUMASON, Bracco contrast agent, for liver ultrasound By Gus Iversen
3. AuntMinnie.com, Mar 30, 2016, Ultrasound Insider By Erik Ridley
Apr 5, 2016
FDA approves Lumason for hepatic lesions in adults, children
The FDA has approved Lumason for use in ultrasonography of the liver to differentiate between hepatic lesions in adult and pediatric patients, according to a press release from the manufacturer.
Lumason (sulfur hexafluoride lipid-type A microspheres, Bracco Diagnostics), a contrast agent comprised of gas-filled microspheres that reflect sound waves to enhance an image, will improve the sensitivity and specificity of ultrasonography to better differentiate between malignant and benign focal hepatic lesions. It is the first approved ultrasound contrast agent for children, according to the release.
“Bracco is delighted to obtain FDA approval for the use of Lumason in liver imaging for both adult and pediatric patients,” Fulvio Renoldi Bracco, head of global business unit imaging at
Bracco Imaging, said in the release. “The use of contrast-enhanced ultrasound for characterization of focal liver lesions is already established in several countries in Europe and Asia, and Bracco is glad to offer this diagnostic option to U.S. patients.”
The FDA first approved Lumason in 2014 for use in echocardiograms of patients whose ultrasound image of the heart were too difficult to see with ultrasound waves.
Lumason should only be used for ultrasonography of the liver for liver lesions and in echocardiography to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border in adult patients with suboptimal echocardiograms, according to the release.
Contraindications for use mentioned in the release include: known or suspected right-to-left, bi-directional or transient right-to-left cardiac shunts, and history of hypersensitivity reactions to sulfur hexafluoride lipid microsphere components or to any of the inactive ingredients.
April 04, 2016
FDA clears LUMASON, Bracco contrast agent, for liver ultrasound
by Gus Iversen , DOTmed News Online Editor
Bracco announced today that the FDA has given clearance to the contrast agent LUMASON for use in liver ultrasound for characterization of focal liver lesions. The agent — known globally as SonoVue — is also now the first ultrasound contrast agent approved in the U.S. for use in pediatric patients.
"The use of contrast-enhanced ultrasound for characterization of focal liver lesions is already established in several countries in Europe and Asia, and Bracco is glad to offer this diagnostic option to U.S. patients," said Fulvio Renoldi Bracco, Head of Global Business Unit Imaging at Bracco Imaging, in a statement.
LUMASON had already been cleared by the FDA for use in adults with suboptimal echocardiograms, to opacify the left ventricular chamber and to improve the delineation of the left ventricular endocardial border in adult patients. That approval took place in October 2014.
The agent has been marketed for over 14 years in more than 40 countries. It is made up of gas-filled microspheres that reflect sound waves to enhance ultrasound images.
"The expanded indication for LUMASON now offers health care professionals and their patients further benefits of our ultrasound contrast agent," said Vittorio Puppo, CEO and president of Bracco Diagnostics, in the release. "This approval demonstrates Bracco's leadership and commitment to the imaging community, across imaging modality and service lines. We are proud to be a leader in contrast imaging and delivery systems, and of our continuous investment in imaging activities to help improve patient care in the U.S."
Mar 30, 2016
By Erik Ridley
Contrast-enhanced ultrasound (CEUS) is employed routinely -- and to substantial clinical benefit -- around the world for radiology applications. However, in the U.S., regulatory clearance has remained limited to cardiology indications.
The seemingly interminable delay has long stuck in the craw of ultrasound contrast experts, many of whom now advocate that this valuable problem-solving tool be used off-label in the U.S. There's never been a better time: CEUS seems well-positioned to benefit from growing questions over radiation exposure and the risk of contrast-induced nephrotoxicity from contrast-enhanced CT, as well as concerns about the safety of gadolinium-based MR contrast agents.
In a presentation at the American Institute of Ultrasound in Medicine (AIUM) annual meeting in New York City, Dr. Michelle Robbin from the University of Alabama at Birmingham shared some tips for integrating CEUS into your practice now. Our coverage of her presentation is this newsletter's Insider Exclusive, which you have access to before our regular members.
Speaking of CEUS, another presentation at AIUM 2016 reported that the combination of contrast-enhanced transrectal ultrasound-guided biopsy and medially directed sextant biopsy was the best biopsy approach for the vital task of detecting high-grade prostate cancers.
Also at AIUM 2016, researchers shared how a focused cardiac ultrasound exam yielded a faster and more accurate diagnosis for thoracic aortic dissection, also known as the "Great Masquerader."
Meanwhile, Dr. Stamatia Destounis of Elizabeth Wende Breast Care in Rochester, NY, reported that ultrasound screening in women with dense breasts can identify invasive cancers not seen on mammography, and that performance improves with experience. What else did the outpatient breast center learn during its second year of providing breast ultrasound screening for women with dense breasts?
If widely adopted, prenatal ultrasound could significantly affect half of maternal deaths in the developing world, according to Dr. Alfred Abuhamad of Eastern Virginia Medical School. Click here for our coverage of the plenary session at AIUM 2016.
In big industry news this month, Canon completed a $5.9 billion acquisition of Toshiba Medical Systems. Click here to get all of the details in our report by Editor-in-Chief Brian Casey.
Also, a quantitative ultrasound computer-aided detection algorithm is showing promise for diagnosing several diseases at once. International Editor Eric Barnes has our coverage.
Finally, Italian researchers found that CEUS is useful for characterizing small renal masses that are indeterminate on contrast-enhanced CT or MRI.