Ultrasound News: Small Step Promises Big Gain
By Dan Harvey
Vol. 21 No. 8 P. 8
Next-generation ultrasound technology gives MRI a run for its money.
Until recently, clinicians considered multiparametric MRI (mpMRI) the gold-standard diagnostic technology for prostate cancer diagnosis. However, that label is curling at the edges due to the emergence of high-resolution microultrasound (microUS).
A multicenter study is, in sizeable part, responsible for this sudden shift. The comparison study—microUS measured against MRI—underscores how developments have moved swiftly in the prostate imaging precinct, observes urologist Laurence Klotz, MD, FRCSC. “Microultrasound and mpMRI were both developed fairly recently,” he says.
Initially, mpMRI caused a dramatic alteration to the prostate cancer diagnosis approach. “The targeted biopsies resulted in diagnoses of more significant and less insignificant cancer,” says Klotz, a professor in the department of surgery at the Sunnybrook Health Sciences Center in Toronto, Canada.
But the modality had significant limitations for potential users: the expense, the expertise requirement, a notable learning curve, and a necessary additional visit for the fusion-targeted biopsy. The study revealed that microUS eliminated these constraints and, more significantly, its metrics compared quite favorably to mpMRI.
MicroUS was first developed for use in prostate research involving small animal models (mice), which, obviously, requires higher resolution. It proved to be a relatively inexpensive and effective technique for studying cancer in the mouse. Its success led researchers to wonder whether it could be applied to human prostate patients. Further research led to the development of ExactVu technology.
“It came out of my institution at Sunnybrook,” Klotz says. “I have had a research center all my career, and 10 years ago I was studying prostate cancer in mice. One of the Sunnybrook research engineers developed a small system that allowed for imaging 1-mm tumors in the mouse prostate. We used it to track tumor growth. At the time, it didn’t occur to me that it could have clinical application, but the engineering team developed a human-sized system that had extremely high resolution, about three or four times higher than conventional ultrasound.”
That led to further development by Exact Imaging, a developer of ultrahigh-resolution microUS technologies, which led to development of ExactVu, the only microUS-based imaging tool for the prostate. As such, it was used in the multicenter study conducted by Klotz and a group of international researchers. The study indicates that ExactVu provides higher resolution within the same form factor as a traditional ultrasound system, reports Brian Wodlinger PhD, vice president of engineering and clinical research at Exact Imaging.
“The images are about three times higher in resolution, taking them about down to 70 microns,” Wodlinger says. “This makes it unique, especially when used for prostate cancer, because the 70-micron resolution is about the same size as prostatic ducts. The increased sensitivity allows us to see the disruptions to the prostate tissue structure that indicate cancer.”
ExactVu is the first microUS application for humans. The system improves visualization of suspicious areas, enables better guidance for biopsies, and provides increased certainty about the grade and stage of detected cancer, streamlining a treatment pathway. It provides physicians with a 300% improvement in resolution over conventional ultrasound, and it enables imaging at 29 MHz during biopsies.
“I had been doing conventional US on the prostate all throughout my career,” Klotz says. “And we used it to image the whole prostate. We never looked at the images to identify cancer. It wasn’t sensitive. The only thing that would show up with US was a huge cancer. So, I didn’t even look for abnormalities in the image [previously], but now we can see patterns. And that was novel, and it was exciting. We had never been able to do that before.”
The study Klotz performed, recently published in the Canadian Urological Association Journal, was the first large-scale analysis of multicenter use of microUS, specifically comparing microUS and mpMRI for prostate cancer. It included centers in Canada, Europe, and the United States and involved 1,040 subjects at 11 sites in seven countries who had prior mpMRI and underwent microUS-guided biopsy. Results revealed metrics comparable to mpMRI.
The researchers compared the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of mpMRI with high-resolution microUS imaging for the detection of clinically significant prostate cancer. Subjects included patients referred for biopsy who had a prior MRI. MicroUS had comparable or higher sensitivity for clinically significant prostate cancer compared with mpMRI, with similar specificity. In their paper, the researchers write that, overall, 39.5% of subjects were positive for clinically significant prostate cancer. MicroUS and mpMRI sensitivity were 94% vs 90%, respectively (p=0.03), and NPV was 85% vs 77%, respectively. Specificities of microUS and mpMRI were both 22%, with similar PPV (44% vs 43%).
The researchers also looked at the potential of high-resolution microUS related to costs, simplicity, and accessibility. These are important considerations, as the National Comprehensive Cancer Network recommends MRI-assisted biopsy for patients with a prior negative systematic biopsy and clinical suspicion of cancer. The researchers included in their report that “this poses many challenges in terms of access, cost, and expertise.”
The economics factor proved to be a considerable advantage. “With its portability, microUS is relatively inexpensive compared to MRI,” Klotz says. “MicroUS itself is rather simple, whereas, with MRI, you have a huge, complex, and expensive magnet. The urologist or radiologist can use microUS in the clinic, just as with traditional ultrasound. The space the device requires is the same, too. This makes it a much more accessible tool.”
MicroUS is much more time-efficient as well, given it is a one-stop procedure. In addition, MRI requires significantly more expertise. “It’s read by the radiologist, which requires another whole set of expertise, and such expertise doesn’t come easy,” Klotz says. “It’s a hard area. Also, for a biopsy, a patient comes back for a second visit where the images from MRI and ultrasound are put through a fusion process. This requires another person, and there can be many sources of error somewhere in the two visits. So, there is a lot involved.”
He says microUS is far simpler in comparison. There is “evidence that the learning curve for microUS is quite short. It is fairly easy to learn how to recognize these abnormalities—maybe 15 or 20 cases,” Klotz says. “You see the lesion and, for the biopsy, you put the needle in the lesion, and you can tell, at the time, if the needle is going accurately into the abnormality, because you can see it. So, microUS can be very practical as, in many parts of the world, MRI fusion is not at all practical due to costs and availability.”
“All of this makes microUS much less expensive in terms of patient care,” Wodlinger says. “MicroUS is faster for the patient and physician, it’s cheaper for the health care system, and it appears to be more accurate than MRI.”
“It turned out that it could give MRI a run for its money,” Klotz says. “It won’t replace MRI, but it serves as an adjunct and as a more accessible, less expensive device.” He adds that further, larger-scale studies are required for more validation of all findings.
— Dan Harvey is a freelance writer based in Wilmington, Delaware.