August 6, 2010

Headlines in the News:

Contrast Ultrasound Processing Tool Shows Malignant Liver Lesions

Two Studies Find Carotid Ultrasound Bests Framingham Risk Scores

Portable Ultrasound System to Provide Vital Obstetric Scanning Support in Southern Sudan

Cryolipolysis Focused Ultrasound for Body-Contouring Make Waves in Europe

Contrast Ultrasound Processing Tool Shows Malignant Liver Lesions

Swiss researchers have developed a real-time parametric imaging technique for distinguishing benign from malignant liver lesions easily and noninvasively using contrast-enhanced ultrasound. In its first clinical run, the method delivered high sensitivity and specificity in a patient cohort.

Distinguishing benign from malignant focal liver lesions noninvasively using ultrasound is a key research goal, and is considered the most promising potential use of contrast-enhanced ultrasound.

"It may be possible to characterize a lesion by looking at its contrast uptake compared to its surrounding normal parenchyma," said Nicolas Rognin, PhD, from Bracco Research in Lausanne, Switzerland. Rognin spoke in a presentation at the June 2010 Computer Assisted Radiology and Surgery (CARS) meeting in Geneva.

After a bolus contrast injection, the characterization of liver lesions can be guided by the known dynamic vascular patterns (DVP) of the lesions with respect to the surrounding healthy parenchyma. Following linearization of video signals that record contrast uptake in the liver, contrast uptake kinetics can be expressed in echo-power units as a function of time, he said.

"There are two type of lesions, benign or malignant, each one separated into two classes," Rognin said. "In the example of hepatocellular carcinoma, its DVP shows strong enhancement in the arterial phase compared to the surrounding healthy parenchyma, followed by a washout in the portal phase, and it becomes strongly hypoenhanced in the late phase."

To render these grayscale differences more conspicuous, the researchers previously developed an image processing technique to enhance these DVP sequences in postprocessed images, Rognin said. Their method "demonstrated usefulness in aiding lesion characterization," he said, but it was limited to characterizing a single image at a single moment in time.

In the current study, "the objective is to provide all the relevant clinical information in a single image," a feat accomplished by "applying pixel classification to map dynamic vascular signatures into a parametric image," he said.

The dynamic parametric mapping technique consists of four main steps:

1. Preprocessing: Video data are spatially transformed to compensate for any in-plane motion, and then linearized to derive echo-power signals at the pixel level.
2. Signal smoothing: Echo-power signals are then smoothed using a curve-fitting technique with a bolus perfusion model function.
3. Signal subtraction: The "difference" signals are calculated by subtracting the reference signal from the smoothed echo-power signals.
4. Pixel classification: Pixels are categorized into four classes according to the polarity of their difference signals over time.

Using contrast-enhanced ultrasound, benign "hemangiomas are typically hyperenhanced at all times, while [malignant] hypervascular metastases usually present hyperenhancement during the arterial phase followed by a hypoenhancement in the portal-venous phase," Rognin said. "The 'difference' signal in the hemangioma exhibits a unipolar vascular signature, whereas the hypervascular metastasis difference signal has a bipolar vascular signature."

The pixel classification scheme used green hues to represent unipolar positives (permanent hyperenhanced signature). Blue hues depicted unipolar negatives (permanent hypoenhanced signature), while red hues represented bipolar positives (hyperenhancement, followed by hypoenhancement signature) and yellow hues depicted bipolar negatives (hypoenhancement, followed by hyperenhancement signature).

Thus, malignant lesions appear as red areas, leaving benign lesions colored green or yellow. Once analyzed, the contrast sequence analyses can then be synthesized as spatial maps of vascular signatures that can be used to determine the lesion type, Rognin said.

For this, the researchers subjected their DVP parametric imaging technique to clinical assessment that included 146 focal liver lesions (113 malignant and 33 benign), imaged with real-time low-mechanical index (MI) contrast-specific ultrasound after a bolus injection of 2.4 mL of a microbubble contrast agent (SonoVue, Bracco, Milan).

To verify the findings, a reference diagnosis was provided in each case by CT, MRI, or biopsy. The lesions were scanned using low-MI real-time contrast ultrasound on one of several scanners, including HDI 5000 and iU22 (Philips Healthcare, Andover, MA), SSD-5500 (Aloka, Tokyo), or Sequoia 512 (Siemens Healthcare, Erlangen, Germany).

The DVP parametric images were read by a clinician blinded to the results using the presence of red coloration as a criterion of malignancy. The method yielded 97% sensitivity and 91% specificity for malignancy.

In comparison, a multicenter study of contrast-enhanced ultrasound that did not employ a mapping method delivered 91% sensitivity and 86% specificity, Rognin said (American Journal of Roentgenology, June 2006, Vol. 186:6, pp. 1551-1559).

"The high efficacy scores obtained with DVP parametric imaging demonstrate the potential of the method for increasing confidence in characterizing focal liver lesions," Rognin said, noting that the results compared favorably with the literature.

In addition to providing an interpretation method that was as simple as looking for red areas as an indicator of malignancy, the technique has the advantage of being less time-consuming than the usual method of reviewing entire sequences of contrast images, Rognin said. It can be performed in about two minutes per case.

The researchers plan to study automated segmentation of normal parenchyma as a way to reduce operator-dependent variability in the resulting parametric maps, thus approaching true computer-aided diagnosis of focal liver lesions on contrast ultrasound, Rognin said.

"In the future, 4D contrast imaging is likely to become more prevalent," he said. "The review of such sequences could become rather tedious, so the extension of DVP parametric imaging to volumetric data may represent a very valuable tool for clinicians."
The researchers also plan to evaluate their technique more broadly in the clinical setting using a larger group of patients.

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Article written by staff at auntminnie.com and adapted for the purposes of this newsletter.

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Two Studies Find Carotid Ultrasound Bests Framingham Risk Scores

Screening young to middle-aged patients with ultrasound for carotid plaque or carotid intima-media thickness (CIMT) is likely to uncover cardiovascular risk in patients with a low Framingham risk score (FRS). In addition, carotid ultrasound proved better than a coronary artery calcium (CAC) score via CT to predict risk, according to two studies in the August issue of the Journal of the American Society of Echocardiography.

In one study, Mackram Eleid, MD, and colleagues from the department of internal medicine at the Mayo Clinic College of Medicine in Scottsdale, Ariz., retrospectively reviewed records of 441 subjects younger than 65 years old (mean age 49), with no history of coronary artery disease or diabetes. They found 42 percent had high-risk carotid ultrasound findings (either CIMT greater than the 75th percentile or findings of plaque greater than 1.5 mm).

Of the 336 patients with the lowest FRS (less than 5 percent), 38 percent had high-risk carotid ultrasound findings (17 percent plaque, 21 percent CIMT). Of this 38 percent, 61 percent were recommended for lipid-lowering therapy, primarily in an internal medicine and family medicine practice.

"The lack of radiation exposure, relatively low cost and ability to detect early-stage atherosclerosis suggest that carotid ultrasound for CIMT and plaque detection should continue to be explored as a primary tool for cardiovascular risk stratification in young to middle-aged adults with low FRS," the researchers concluded.

Eleid and colleagues noted that atherosclerosis begins early in life and can progress silently over decades and that the FRS does not incorporate variables such as family history of premature coronary artery disease, remote smoking history, waist circumference, impaired fasting glucose and triglyceride levels.

While the FRS is useful in the "epidemiology of large populations, it has limitations in predicting cardiovascular risk in individuals," they wrote.

They also found that women had similar prevalence of high-risk carotid ultrasound findings, plaque and abnormally thickened CIMT as men despite having lower body mass indexes, significantly higher HDL and much lower FRS. "This finding suggests a role for carotid ultrasound in identifying women at higher risk for adverse cardiovascular events with minimal traditional cardiovascular risk factors," they said.

In an interview, Eleid said that he anticipated more insurers paying for a CIMT screening in the future. "Once the internal medicine organizations, such as the American College of Physicians, embrace it, which has not happened yet, then we will see more widespread use and reimbursement."

In the second study, Tasneem Z. Naqvi, MD, from the University of Southern California, Los Angeles, and colleagues from Cedars Sinai Heart Institute in Los Angeles, evaluated 136 asymptomatic subjects with no history of cardiovascular events.

Of the 103 subjects with low-risk FRS (less than 10 percent):

• 41 percent had CAC scores greater than zero;
• 50 percent had CIMT greater than the 75th percentile;
• 59 percent had plaque; and
• 66 percent had CIMT or plaque.

Of the 33 subjects with intermediate (14) or high (19) FRS:

• 70 percent had CAC scores greater than zero;
• 81 percent had CIMT greater than the 75th percentile;
• 87 percent had plaque; and
• 87 percent had CIMT or plaque.

Overall, 52 percent of subjects with CAC scores of zero had carotid plaque. Body mass index was an independent predictor of abnormal CIMT in the low-FRS group, but not of an abnormal CAC score. Also, CIMT upgraded more patients to intermediate and high risk than CAC.

While CAC measurement is less operator dependent and more reproducible than CIMT or carotid plaque assessment, it is associated with ionizing radiation. Also, CAC scans may produce false negatives in younger subjects whose soft plaque has not fully calcified, according to researchers.

Naqvi and colleagues noted that CIMT measurement is more standardized than plaque assessment, but CIMT measurement is more labor intensive.

Another finding was that the mean vascular CIMT age was significantly higher than coronary calcium age (61.6 vs. 58.3 years), and both were significantly higher than chronologic age (56.9 years).

"In low-risk subjects, initial screening by CIMT and plaque assessment is likely to provide the highest yield to detect subclinical atherosclerosis," they concluded.

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Article written by staff at cardiovascularbusiness.com and adapted for the purposes of this newsletter.

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Portable Ultrasound System to Provide Vital Obstetric Scanning Support in Southern Sudan

An ACUSON P10™ handheld ultrasound system from Siemens Healthcare has been selected to perform obstetric scanning in a newly renovated healthcare facility in the town of Yei in Southern Sudan. The P10 will be used in The Martha Primary Healthcare Centre, which currently sees 900 antenatal patients each month. The system was selected by representatives from Winchester based charity The Brickworks who are running several health initiatives in the region. 

Southern Sudan has a population of approximately ten million people but only ten qualified midwives, meaning there is extremely limited access to clinical care and that it currently has the highest maternal mortality rate in the world. The P10 will help local staff at the clinic to identify any problems during pregnancy as soon as possible along with any other obstetric problems. Further down the line it may also be used for other procedures. 

The P10 is a handheld ultrasound system, small enough to fit into a coat pocket and lightweight for easy carrying in remote terrain. It is suitable for application in a variety of environments including obstetrics as it enables clinicians to evaluate fetal presentation, heartbeat, fluid levels and placenta location. With instant power-up capabilities, superior image quality and a simple user interface, the system aids with diagnostic confidence in remote settings and on wards. 

"In Southern Sudan a girl is more likely to die in childbirth than complete her primary education and so we are committed to exploring all avenues that can protect women during pregnancy and their newborn babies," said Poppy Spens, International Health Coordinator for the Episcopal Church of Sudan Diocese of Yei. "We chose the P10 because upon research we found it to be a lightweight and extremely portable system. Scans can also be printed onto normal paper, which is a big plus and made it stand out from similar systems that require special paper to print on that would be damaged by the heat." 

"The use of the ACUSON P10 in Southern Sudan illustrates the flexibility that portable ultrasound can deliver in more remote communities and outside of what may be considered a traditional hospital environment," said Andrew Pattison, North West Europe Business Manger for Ultrasound at Siemens Healthcare. "We are very pleased to have been able to help in such an important project and will be monitoring the developments in Yei closely." 

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Article written by staff at medicalnewstoday.com and adapted for the purposes of this newsletter.

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Cryolipolysis Focused Ultrasound for Body-Contouring Make Waves in Europe

Although medicine is a global community, specific protocols tend to be local. Most countries boast their own regulatory agencies that, in turn, impose their own guidelines regarding safety, efficacy, evidence and approval of medical devices, drugs and applications.

As a result, many products debut in stages, first entering foreign markets where requirements are not necessarily more relaxed, but possibly less complicated, comprehensive or confining. Companies often launch their products in European markets after obtaining a CE mark of approval, all the while completing trials for submission to the Food and Drug Administration (FDA). Subsequently, new protocols, including those in cosmetic surgery, frequently enter the mainstream overseas.

Protocols currently making a splash across the pond include two noninvasive body-contouring techniques — cryolipolysis (CoolSculpting, Zeltiq Aesthetics), which uses cold, and UltraShape (UltraShape), which employs focused ultrasound technology.

CRYOLIPOLYSIS Ironically, the principles upon which cryolipolysis are founded were discovered by two dermatologists working at Massachusetts General Hospital, Boston; all commercial development rights are held by Zeltiq, a medical device company headquartered in Pleasanton, Calif., that is marketing the product as CoolSculpting.

"Cryolipolysis is based on the principle that fat cells are more vulnerable to energy extraction than surrounding tissues. Cooled fat cells undergo apoptosis and are gradually eliminated, reducing the thickness of the fat layer," said Gerhard Sattler, M.D., a founder of Rosenpark Clinic, Darmstadt, Germany.

Precisely controlled cooling is applied through the skin to the fat layer using a noninvasive applicator that protects the skin, nerves, muscles and other tissue. Cooling is maintained for a predetermined time to damage the fat cells.

"Procedure time can take up to two hours or more depending on the size of the area to be treated," Dr. Sattler said. During the final phase, the fat cells are removed in a natural process that continues for several months and results in gradual fat-layer reduction.

"Clinical studies demonstrate the CoolSculpting procedure provides noticeable, measurable fat reduction in properly selected patients over the course of two to four months following the procedure. Additional procedures may be administered [then] to achieve greater fat reduction," Dr. Sattler said.

Long-term studies have not been completed, but available data presented as a poster at the 2009 annual meeting of the American Society for Dermatologic Surgery indicates patients show persistent results at least six months after the procedure. Results are expected to last as long as those from more invasive protocols (such as liposuction), although the actual effect is often less dramatic in comparison.

Ideal candidates are relatively fit and want to target stubborn, modest-sized fat bulges noninvasively "The CoolSculpting procedure is not intended for weight loss or obesity, and it is not a substitute for invasive methods, such as liposuction," Dr. Sattler said. It is currently most commonly used to treat "muffin tops," love handles and back fat, though other areas may also be addressed.

Contraindications for cryolipolysis treatment include two rare conditions — cryoglobulinemia and paroxysmal cold hemoglobinuria. Otherwise, risks are low, side effects rare and recovery immediate.

"Some patients experience redness, tingling, minor bruising or numbness in the treated areas, but this is temporary," Dr. Sattler said.

Before use, physicians need to be trained on the device, committing to specific patient selection criteria, case management responsibilities and protocol requirements. Zeltiq CoolSculpting has been cleared for use in the United States for applications related to skin cooling during dermatologic treatments, and it holds a pending application with the FDA for use in noninvasive fat-layer reduction.

UltraShape, available from a company of the same name with a U.S. office in San Ramon, Calif., will be entirely new to the U.S. market. It has not yet been approved by the FDA for domestic use in any capacity. UltraShape has, however, undertaken a large clinical study through six U.S. clinics to collect data needed for an FDA submission.

Research to date has been positive. "In a multicenter controlled clinical trial, an average 2 cm reduction in circumference was achieved after a single treatment of the abdomen, outer thighs or flanks. In independent studies and commercial use, multiple treatments have shown incremental circumference reduction and high patient satisfaction," said Dr. med. Markus Steinert, with Laserklinik, Biberach an der Ri , Germany (Brown SA, Greenbaum L, Shtukmaster S, et al. Plast Reconstr Surg. 2009 Jul;124(1):92-101).

The treatment breaks down unwanted fat using ultrasound technology. Focused energy selectively targets fat cells in the specific body area without harming surrounding tissues, such as nerves or blood vessels. The procedure typically takes one hour, but can vary depending on the area targeted.

"During the UltraShape treatment, the membranes of the fat cells are disrupted. Their contents, primarily comprised of triglycerides, are dispersed into the fluid between the cells and then transported through the vascular and lymphatic systems to the liver," Dr. Steinert said.

Because the liver does not differentiate between fat coming from the UltraShape treatment and that originating from consumed food, both are processed by the body's natural mechanisms.

The procedure is noninvasive, requiring no anesthesia, no surgery, no recovery and no risks. Follow-up, however, may be necessary. In some cases, patients are advised to undergo three treatments, and in all cases, recommendations are made regarding diet and exercise.

"Following treatment, patients need to maintain a negative calorie intake for four days to ensure fat energy released as a result of the UltraShape treatment is utilized by the body," Dr. Steinert said.

Patients report no post-treatment pain or discomfort. Contraindications are few and preclude using UltraShape over tattoos, nevi and depressed scars, as well as in pregnant women. "There are virtually no disadvantages other than a commitment to the three-treatment protocol and the guidelines for a healthy lifestyle," Dr. Steinert said, adding that skin surface remains smooth and fat texture homogeneous.

Patient expectations do need to be managed, however. "Similar to literature recommendations for liposuction, patients should be aware the treatment is not 'magic,' and they should maintain a healthy lifestyle to preserve the effect," Dr. Steinert said.

Incorporating UltraShape into a practice is not difficult. The physician determines whether the treatment is appropriate, and assistants who have completed the two-day training perform the procedure. "Both technique and treatment speed have a short learning curve," Dr. Steinert said. He estimates the typical return on investment at one year.

Both procedures — the Zeltiq system and UltraShape — offer body contouring to European patients not eligible for or interested in liposuction. In time (and if the technologies win FDA approval), U.S. patients may benefit, as well.

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Article written by staff at modernmedicine.com and adapted for the purposes of this newsletter.

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