New imaging technology is introduced every year at the Radiology Society of North America (RSNA). Yet for every new device on the convention room floor, there are more waiting in the wings while they're being developed in the laboratory.

Duke University's Multi-Modality Imaging Laboratory (MMIL) in Durham, NC, is one of those laboratories that hopes to have not just one, but three unique 3D breast imaging technology inventions on the RSNA show floor someday. Yet even with its Duke pedigree, National Institutes of Health (NIH) funding, and recent national attention on Good Morning America, MMIL scientists recognize that it is a long road to Chicago.

Three Big Ideas

Martin Tornai, PhD, associate professor of radiology and biomedical engineering, is MMIL's founder and the laboratory's team leader. Randolph McKinley, PhD, is Tornai's former Duke PhD student, and is CEO of their Duke spinout, ZumaTek Inc.

It was Tornai who first conceptualized the three modalities (in addition to others) for which MMIL is gaining national recognition. He had worked with early versions of miniaturized breast nuclear medicine gamma cameras as a graduate student at the University of California, Los Angeles, but those were 2D imaging devices.

Arriving at Duke in 1997, Tornai remembered these cameras and believed he could go several steps further: He could create several 3D breast imaging systems with off-the-shelf parts. Two years later, he received a small grant that enabled him to begin work on the first of these systems, a single photon emission computed tomography (SPECT) 3D breast imaging system. However, his intention was to produce a computed mammotomography (ie, 3D breast CT) scanner, followed by a hybrid SPECT-CmT device that would allow radiologists to image a breast with both greater sensitivity and specificity.

But it was not until 2002, after receiving a generous grant from the NIH, that Tornai officially opened the doors of MMIL in a 1,500-square-foot facility.

Reconstructed, volume rendered views of a breast phantom scanned simultaneously on MMIL’s ZumaTek system.

ZumaTek-CT Image

ZumaTek-SPECT Image

ZumaTek-Hybrid Image is a registered and fused image of both CT and SPECT data sets.

Since then, with the help of graduate students, Duke faculty, and various grants, Tornai and McKinley have constructed three prototypes based on Tornai's original concepts, and they are now awaiting patent confirmation. Once that is approved, the team will be a step closer to commercializing the inventions through Zumatek and reserving a spot at a future RSNA.

3D SPECT: High Specificity, Flexibility

According to Tornai, the SPECT system that MMIL has developed is the smallest clinical SPECT in existence that can image breasts in 3D. The patient is injected with a radiolabeled tracer designed to enhance tumors. Currently, Tornai is using Tc-99m-Miraluma (aka Tc-99m Sestamibi) from Bristol-Meyers Squibb Medical Imaging, Billerica, Mass.

The dedicated technique is similar to imaging with larger conventional nuclear medicine gamma cameras, but the process changes when the patient lies face-down on a specially designed table with an opening for her breast. There is no breast compression. Instead, with the breast hanging down, the gamma camera moves around the breast three-dimensionally, collecting many images, and then creating a 3D image in a computer offline.

Aside from patient-friendly image acquisition, the MMIL's 3D SPECT system has several advantages over a larger nonbreast-dedicated SPECT or digital mammography.

First, the camera's imaging system is agile enough for close-up shots of a section of the breast, or even to tilt up and image beyond the breast into the chest wall.

Tornai adds, "Another advantage from a physics and engineering point of view is that by moving around three-dimensionally, you more completely sample the volume. In other words, for every picture you take, you take a better picture than if the camera was just stationary or moving in a simple circle."¹

In terms of markets, Tornai sees the SPECT being used both for lesion diagnostics and also for therapeutic monitoring of treatment response.

Computed Mammotomography (CmT): 3D Imaging with Less Radiation

After successfully constructing the SPECT prototype, MMIL tackled fabricating the 3D CmT system. With fresh funding from the NIH, Tornai and McKinley started buying and gathering off-the-shelf components. These included an x-ray tube and a digital flat-panel detector the size of a laptop, and a similar system that would enable the 3D movement. After putting it all together, McKinley wrote and refined the software needed for the various parts to synchronize and create a 3D scan.

McKinley admits that the team was quite amazed when they did their first scan and it worked. He said, "We were initially hand-turning things, and the scan took about 6½ hours to complete. Now with everything fully automated and synchronized, we're down to anywhere from 3 to 6 minutes." He added that the team is working on reducing the time to around 30 seconds.

The result of their work is a CT imaging modality that can provide anatomical or structural information with 0.5-mm isotropic resolution.

Tornai readily points out that MMIL's CmT system is not the only breast CT system in existence. He mentions a project at University of California, Davis, under the direction of John Boone and another at the University of Rochester under Ruola Ning, who are each developing a cone beam breast CT system.

However, Tornai believes that his system has several advantages over the others. "We've really taken advantage of the physics and done a lot of engineering to change the quality of the x-rays that are actually getting to the breast. For example, in our cone beam x-ray CT, the x-rays are modulated to be quasi-monochromatic,² and so you can acquire the data with about 5 times less radiation dose than a current screening mammogram," Tornai said. "Of course, the other difference with our system is that it moves three-dimensionally, just like our SPECT system does."

Another advantage of their CmT system is its ability to see soft tissue objects. In a comparative study with a breast phantom with lesions, six human readers saw as small as 4-mm-diameter-sized lesions in images with MMIL's CmT system. When the same phantom was imaged with digital x-ray mammography, the readers were statistically half as accurate with digital mammography compared with the CmT system.³

In terms of markets, Tornai sees the CmT being used not only for screening, but diagnosis and biopsy guidance, and also for the planning of breast-reconstruction surgery, as well as for evaluating implant integrity.

The MMIL team has constructed three prototype breast imaging devices that are awaiting patent confirmation.

Hybrid SPECT-CmT: High Sensitivity with High Specificity

Tornai's original goal was to create a Hybrid SPECT-CmT system, but of course, the first two modalities needed to be developed first. Because the hybrid and the SPECT system involve injecting nuclear compounds, he does not see these modalities being used for screening, except for high-risk patients with a history of breast cancer.

"Generally speaking, the main use of the combined hybrid would be for better diagnostic accuracy, but also therapeutic treatment monitoring," Tornai said.

The hybrid system marries the high sensitivity of a dedicated CT scanner with the high specificity of the SPECT system. After the two images are acquired, registered, and fused together by MMIL's software, the resulting data could give radiologists enough information to substantially minimize the need for unnecessary biopsies.

"In a CT image, if you have a system with high sensitivity, you can't biopsy all suspicious things. That would make for lots of unnecessary biopsies, scar tissue, etc. So you want to hone in on the most suspicious regions," Tornai said. "So, what we do [with the SPECT] is we inject the radioactivity into the patient and those lesions that are more active or that are active, period, would take up the radioactivity due to the specificity of that compound to whatever cancer is there. And if it in fact overlaps with something that you see in the anatomical image from the CT, those are the ones that you would go and biopsy."

Despite the hybrid technology's improved diagnostic image quality, Tornai cautions that there will always be a chance for false positives.

"There are false positives from SPECT because it just happens," he said. "Non-cancerous tissue may also take up that particular compound. That's something we can't control. Our objective was just to build a better imaging device; others are working to improve the chemical imaging compound(s)."

Tornai has thus far used Tc-99m-miraluma for his patient studies. This compound is very general, being approved for cardiac imaging as well as for the breast. He is wary that in the initial studies other SPECT compounds may be too specific to any particular cancer; by their very nature, a more specific compound would highlight the targeted cancers but miss others.

For now, Tornai is satisfied with the results they have achieved with the Tc-99m-miraluma because of its FDA approval and long, documented history. At the same time, he is hopeful that more specific targeted compounds will become available so that he can evaluate them.

The Hybrid SPECT-CmT device is intended to image a breast with greater sensitivity and specificity.

Next Steps to Debut

Thus far, the SPECT and CmT modalities have only been tested on a limited number of patients. Tornai said that MMIL's next task, aside from the usual grant hurdles, is to collect more patient data and perform more hybrid studies with different-sized patients, different-sized breasts, as well as different nuclear tracers.

They also are working on getting their technology installed in a women's clinic, rather than in the laboratory. Being in a woman's clinic will more easily provide subjects.

McKinley said, "It is much easier if you can get one of these [modalities] into a clinic. Our lab is a building outside of the hospital, so scheduling has been difficult because you have to get a physician out of their office. Also, in a clinic, patients will be more comfortable because it's more like a hospital setting and not a lab."

McKinley added that with every test, the team goes back to make refinements to the systems. Ultimately, their goal is to have the systems not only be clinically accurate, but also easy enough for an imaging center's technician to operate simply.

ZumaTek, the Duke spin-off founded by Tornai and McKinley, recently received NIH SBIR Phase I and North Carolina matching grants to fund investigations associated with the commercialization of these systems. The clinical data that they hope to gain over the next year will also help Tornai and McKinley to obtain more grants, as well as financing from early-stage venture capital firms.

Once that is in place and more prototypes are built, the next major hurdle will be gaining approval by the FDA.

Ironically, though the CmT device has the potential to compete with or perhaps replace traditional digital mammography screening, applying for that use may not be the quickest road to FDA approval and a future display at RSNA.

"If you say to the FDA, 'we think this commercial device will eventually replace screening,' the bar that you've set for yourself is that you need to screen tens of thousands of women and prove that it's going to be better than the standard screening methodology," Tornai said.

Instead, Tornai believes that the devices will more likely be approved for a more narrow market segment, such as breast reconstruction. Then, when physicians begin to use the devices and realize their other capabilities, there will be that much more data; it will then be easier to receive a second FDA approval for a different application, such as screening.

Asked which of their devices is closest to taking center stage at the big show in Chicago, both scientists agree that it would most likely be the CmT—hopefully—within the next 5 years.

Tor Valenza is a staff writer for Medical Imaging. For more information, contact .

References

1. Brzymialkiewicz CN, Tornai MP, McKinley RL, Bowsher JE. Evaluation of fully 3D emission mammotomography with a compact cadmium zinc telluride detector. IEEE Trans Med Imaging. 2005:MI-24(7):868-877.
2. McKinley RL, Tornai MP, Samei E, Bradshaw ML. Initial study of a quasi-monochromatic beam performance for x-ray computed mammotomography. IEEE Trans Nucl Sci. 2005:NS-52(5):1243-1250.
3. McKinley RL, Tornai MP, Floyd CE, Samei E. Contrast-detail comparison of computed mammotomography and digital mammography. Proc SPIE 2007: Physics of Medical Imaging. 6150:(1D-1)-(1D-10).