Ultrasound Technique May Improve Renal Tumor Management

Ultrasound Technique May Improve Renal Tumor Management

Contrast-enhanced ultrasound (CEU) may improve doctors' ability to distinguish potentially dangerous renal tumors from relatively benign or indolent ones, according to a pilot study.

Used with other diagnostic criteria, the technique-which involves intravenous injection of a contrast medium consisting of gas-filled lipid microspheres-could help clinicians decide which tumors should be removed surgically and which can be managed conservatively.

The investigators, led by Scott Gerst, MD, Associate Attending Radiologist at Memorial Sloan-Kettering Cancer Center in New York, noted in a report in the American Journal of Roentgenology, that, to their knowledge, no established noninvasive way exists to differentiate-definitively and preoperatively-low-grade or benign malignant tumors from the more aggressive clear cell tumors, which has a higher risk of metastasis.

“Contrast-enhanced ultrasound of renal masses is a promising new tool which may provide added value over standard, noncontrast-enhanced ultrasound, and improves our ability to image and evaluate these lesions without radiation or the risk of either contrast-induced nephropathy or nephrogenic systemic fibrosis,” Dr. Gerst said.

By one set of enhancement criteria, the CEU technique had a 75% positive predictive value for determining whether a tumor was a non-clear-cell carcinoma. Using other criteria, the technique had an 85% positive predictive value for predicting whether a tumor was conventional clear-cell carcinoma or another kind of tumor.

“We therefore predict, although more data are needed, that in select patient populations such as those with contraindications to intravenous CT or MRI contrast, or patients with high surgical risk, contrast-enhanced ultrasound will have a role,” Dr. Gerst said.

Commenting on the new study, urologist Christopher G. Wood, MD, who has conducted extensive research on renal cancer, observed: “This and other studies highlight the true value of CEU, which is the capacity to image renal lesions and assess vascular flow, without the need for radiation or nephrotoxic contrast agents. This technology will greatly aid our ability to image patient lesions preoperatively, as well as follow patients post-operatively after non-extirpative therapies such as thermal ablation.”

Still, patient age, tumor size, presence or absence of symptoms related to the mass, and the presence of significant co-morbid conditions will play a much greater role than CEU in deciding how patients will be managed, said Dr. Wood, Professor of Urology at the University of Texas M.D. Anderson Cancer Center in Houston.

“In my opinion,” he said, “the use of CEU may add some small increment of information used to formulate a treatment plan for a given patient, be it active surveillance, energy ablation, or surgery, but it certainly will not be a decisive factor in predicting the biologic potential of a given tumor.
Ultrasound Tackles Radiation Therapy Guidance

The efficacy of radiotherapy is ultimately dependent upon the ability to accurately locate the target, particularly when treating organs with a tendency to move, such as the liver or prostate gland. As such, there's a real need for an imaging technique that can offer marker-free, soft-tissue visualization before -- and preferably also during -- beam delivery.
Ultrasound imaging could meet all of the above requirements, providing real-time tracking of target organ location without delivering any extra radiation dose to healthy tissue. Some of the latest work in this field was presented at the recent joint annual meeting of the American Association of Physicists in Medicine (AAPM) and the Canadian Organization of Medical Physicists (COMP) held in Vancouver, British Columbia.

One example is the development of a telerobotic ultrasound system for real-time detection of prostate and liver displacements, as described by Jeffrey Schlosser, a graduate student in bioengineering at Stanford University. The system uses a robotic manipulator to control the pressure and position of an ultrasound transducer on the patient and is operated via a remote interface located outside the treatment room.

Target position is monitored via continuous recording and processing of transabdominal ultrasound images, with 2D acquisition used to detect any displacements as quickly as possible. "For monitoring, we're interested in the fastest acquisition mode, which is single two-dimensional plane imaging," Schlosser explained.

During imaging, two tissue displacement parameters are extracted: the window position relative to its original position, and a coefficient of correlation with a reference image. Schlosser noted that processing time is less than 20 msec per image. The ultimate aim is to activate a beam gating signal when the displacement parameter(s) exceed a specified threshold, indicating a target shift.

The scheme was tested on a pelvic phantom and in vivo on five healthy volunteers. In the phantom, prostate translations of 1.5, 1.4, and 1.4 mm were detectable at 95% confidence in the anterior/posterior, superior/inferior, and medial/lateral directions, respectively; rotation of 1.3° was also detectable. The corresponding in vivo results were 2.3, 2.5, and 2.8 mm, and 4.7°.

With a suitable threshold selected, the rate of false positives was less than 1.5 per 10 minutes of continuous in vivo imaging. Schlosser noted that the planar tissue displacement was detected more accurately than out-of-plane displacement. "In the future, we're looking to combine this with dual-plane imaging to equalize monitoring performance in all directions," he said.

Respiratory tracking

Reliable tracking of respiratory motion can help enhance the accuracy of radiotherapy, by enabling gated delivery, for example. Ping Yan, PhD, a research scientist at Columbia University, discussed how ultrasound images of the diaphragm can be used to determine respiratory motion. She also examined the correlation between diaphragm motion and abdominal surface motion measured using the real-time position management (RPM) system.

Yan and colleagues recorded ultrasonic videos of the diaphragms of volunteers during uncontrolled breathing cycles. The ultrasound probe was held next to the RPM marker block and the two signals acquired simultaneously. An automatic tracking method was then used to extract the diaphragm motion from the ultrasound images.

Evaluating the phase shifts between diaphragm motion and the RPM-measured respiratory signal revealed a delay of between 0.2 sec and 0.4 sec. The results also demonstrated a wide range of phase shifts between different people, as well as significant differences between different breathing cycles for the same people.

Yan concluded that ultrasound can be a more reliable method than the RPM system for respiratory gating in radiation therapy. "In [the] future, we'd like to use the respiratory signal from the ultrasound video of the diaphragm to reconstruct 4D CT images," she said. "Later, we'd like to develop an ultrasound gating system for lung radiotherapy."

Operator uncertainties

Professor Frank Verhaegen, PhD, head of physics research at the Maastro Clinic in Maastricht, the Netherlands, took a look at the Clarity system -- a 3D ultrasound system from Resonant Medical. Clarity is used for patient alignment in both planning and treatment rooms, enabling comparison between the two images. Reflective markers track the position of a 2D ultrasound probe, allowing volumetric images to be recorded as the probe is moved over the patient.

Verhaegen described a study looking at intra- and interoperator variability in image acquisition and matching. The study examined 13 prostate cancer patients, who received a total of 383 ultrasound scans that were used in 842 matches to reference scans. Overall, the mean intraoperator variability was 0.2, 0.0, and 0.4 mm in the x, y, and z directions, respectively, with standard deviations of 1.8, 2.2, and 2.7 mm. The mean interoperator variability was -0.2, -0.3, and -0.2 mm, with standard deviations of 2.6, 2.2, and 2.9 mm.

The researchers also examined the effect of probe pressure on prostate position. "The probe pressure effect is real," said Verhaegen. He noted, however, that as Clarity uses an intramodality approach (i.e., comparison of two ultrasound images), the prostate displacement should be the same in both scans.

Finally, the team compared ultrasound images with portal images of fiducial markers in eight patients. In the left-right direction, no correlation was seen between ultrasound and portal images. However, good (although not perfect) correlation was observed in the superior-inferior and anterior-posterior directions.

Overall, the total uncertainty of this 3D ultrasound approach to prostate localization was conservatively estimated to be 4 mm. This uncertainty is comparable to that of electronic portal imaging of fiducial markers -- the current standard for image-guided prostate radiotherapy.

Martin Lachaine, PhD, director of research at Elekta's Resonant Medical facility, described the development of a mechanically sweeping autoscan probe based on the Clarity system. Here, the freehand scanning is replaced with an autoscan technique, which could allow motion tracking during radiation treatment while the therapist remains in the console room.

Automated (user-independent) scanning.

The autoscan probe's accuracy was assessed by comparing CT and 3D ultrasound images of a phantom. Results showed submillimeter accuracy in all directions, which Lachaine noted is accurate enough for intrafraction motion tracking. Tests also demonstrated that radiation dose -- from CT scans or treatment beam -- does not affect the probe's performance.

While transabdominal ultrasound imaging is suitable for monitoring prostate position during planning or patient setup, this probe placement geometry can restrict the treatment beam direction used during radiotherapy. Thus the researchers investigated the use of transperineal ultrasound, which also benefits from a shorter skin-to-prostate distance and doesn't require bladder filling.

The first clinical study of transperineal prostate imaging has now been performed, in collaboration with researchers at the University of Vermont. The study involved 20 patients, the first 15 of whom were used to optimize image quality and patient positioning. The remaining five patients took part in a feasibility test for transperineal ultrasound imaging.

Lachaine reported that the process was well tolerated by all patients, and that the prostate and surrounding anatomy were visualized well. The next step will be to develop automated, continuous imaging for monitoring prostate motion during treatment, enabling interruption of the beam if too much motion is detected.

"The autoscan probe can be used to obtain high-quality images of prostate and surrounding soft tissue," Lachaine concluded. "Extension to 4D intrafractional prostate imaging for conventional and stereotactic body radiotherapy is feasible, and is under development."

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

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Intravascular Ultrasound (IVUS) Imaging Reveals Hidden Heart Attack Culprit in Women

A heart attack can occur in a coronary artery that looks completely normal on angiography, long considered the "gold standard" of coronary imaging. But newer techniques, such as intravascular ultrasound (IVUS) and cardiac magnetic resonance (CMR) imaging, were able to reveal the cause of the incident: plaque disruption.
Such is the conclusion of a new study by researchers at the Cardiac & Vascular Institute at NYU Langone Medical Center. And this type of non-obstructive myocardial infarction seems to happen more frequently in women than in men.

A coronary artery may look completely normal using the standard two-dimensional "shadow" image of coronary angiography. But when the same arterial segment is viewed cross-sectionally using intravascular ultrasound, a "flap" of plaque can be seen hanging in the arterial lumen. This plaque disruption, a rupture or ulceration of cholesterol plaque, was shown to be the mechanism behind myocardial infarction (heart attack) in some women who were classified as having no significant coronary artery disease (CAD). The study, "Obstructive Coronary Artery Disease Mechanisms of Myocardial Infarction in Women Without Angiographically Obstructive Coronary Artery Disease" was published in the journal Circulation.
The research team, led by Dr. Harmony Reynolds of NYU Langone, investigated the origin of heart attacks in fifty women with "normal" coronary arteries, as seen on angiography. Using intravascular ultrasound (IVUS), they found that almost 40% of the women showed evidence of plaque disruption -- something that cannot be seen on an angiogram. When the results of cardiac magnetic resonance (CMR) imaging were added, 70% of the women were found to have abnormalities not detectable during angiography.

As shown by the PROSPECT study of over 700 patients, published in the New England Journal of Medicine, IVUS was been able to identify so-called "vulnerable plaques" that are invisible on angiograms. Dr. Reynolds opined that her study "knitted together" some of the PROSPECT results she commented.

"We know from PROSPECT that lesions that are ultimately going to be culprits were non-obstructive and looked vulnerable on IVUS.... Angiography unfortunately doesn't tell the whole story and I think IVUS is a fantastic tool to be able to learn more about the artery wall in all kind of conditions. And this MI with non-obstructive disease is definitely one of them."

Dr. Reynolds' thoughts are that it is possible that these plaque disruptions may cause a thrombosis, especially in women, because of hormonal and other gender-specific differences, but that the body then lyses this thrombotic blockage naturally and, by the time the patient is in the cath lab, the blockage is gone...but the heart attack is very real.

“Women who have had a heart attack and have normal or near-normal angiogram results may be told they didn’t have a heart attack at all because of the angiogram result,” said Reynolds. “Our study shows the benefit of additional imaging to find a plaque disruption when it occurs and correctly diagnose the reason for heart attack in these women.”
The clinical and treatment implications of this study are significant because many heart attack patients without angiographically obstructive coronary artery disease may go undiagnosed and not receive the necessary heart medications like antiplatelet drugs and statins -- lifesaving tools against future cardiac events.

Dr. Reynolds continued: "I think, if plaque rupture is the culprit in a substantial portion of them which we've shown, then if it's the same cause it should be the same medicine. We can do a lot better -- there's a big way to go from telling people that they didn't have a heart attack at all towards treating everybody with proven medications. And that's what I would like to see this do...definitely aspirin and statins, maybe beta-blockers, maybe even thienopyridines.

"Myocardial infarction without CAD that appears to be significant on an angiogram is more common than many people think. Patients and doctors both need to know there is a form of heart attack that can occur in which the arteries are not blocked on an angiogram. This is in fact a heart attack and steps need to be taken to prevent another cardiac event.”

View the article online.

Article written by staff at angioplasty.org and adapted for the purposes of this newsletter.

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