Can You See It? Optical Imaging in the OR

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MethBlue.jpg - Indocyanine
Indocyanine green and methylene blue are among some old dyes that have found new enthusiasts with the advance of near-infrared fluorescence imaging. They’re far less fluorescent than new optical molecular probes now in development, but they are FDA-approved—and their effectiveness at fine-targeting tissue for precise resection points to possible things to come in optical molecular imaging.
Source: Center for Molecular Imaging, Boston

What nuclear medicine is now to presurgical planning, optical molecular imaging may soon become to intraoperative tumor removal. Using near-infrared light to excite fluorescence in new contrast agents coming down the pike, and imaging the reactions in diseased tissue with specially sensitive imaging systems, surgeons would see tumor margins and molecular targets in real time. Tiny clusters of as few as 10 precancerous cells would give themselves up to the molecular searchlight. Fully formed tumors would be thoroughly resected. Across the board, healthy surrounding tissue would routinely remain untouched and unharmed.

The technology’s potential for improving care while reducing costs—early and thorough cancer treatments accomplish both—would explain why numerous attendees of June’s annual meeting of the Society of Nuclear Medicine and Molecular Imaging reported much buzz around optical imaging. It surely helped that the optical sessions were split into two tracks to showcase the field’s reach and scope. One dealt with the use of contrast agents (a.k.a. molecular probes), the other with basic optical properties inherent in all animal and human tissue. 

Meanwhile, to keep optical moving from the lab toward the OR, more than a few accomplished scientists are becoming energetic entrepreneurs. In the molecular-probe arena, where the hopes for the greatest advancements seem to be most concentrated, several researchers are working with old contrast agents that have relatively poor fluorescence but long histories of safe use in humans. 

Eva Sevick, PhD, is among them. Director of the Center for Molecular Imaging at the University of Texas Health Science Center in Houston, she is working with indocyanine green—a dye that’s been used in humans since the 1950s—and applying it to optical lymphatic imaging. 

“It’s a terrible fluorophore, but it works well with a device that we qualified under IND (Investigational New Drug) studies with NIH support,” says Sevick. “With a microdose of indocyanine green,” for example, “it takes only a couple of minutes to assess a patient’s lymph system. After cancer patients have been treated, you can quickly check to see if they have any phenotypes for lymphedema. It’s a great screening tool.” 

Sevick, who has launched a company to eventually commercialize the technology—she’s calling her firm NIRFImaging, for near-infrared fluorescence—adds that the application is not just for demonstration. “We are meeting an unmet clinical need and, at the same time, working with the National Institute of Standards and Technology to get these standards certified so that we can share with industry.”

Not incidentally, standardization is high on Sevick’s list of professional priorities. The FDA will only issue combinational approvals for optical advances, one particular contrast agent with one particular imaging device, which does little to fast-track a burgeoning technology as a broad category. So Sevick has become something of a standards evangelist, writing and speaking on the field’s need to progress from one-device, one-probe development to device platforms à la, for example, MRI scanners’ compatibility with any number of contrast agents regardless of scanner manufacturer. 

Sevick says that, absent such standardization, “the need for investment is going to be too great and we’re not going to be able to get this through to the clinic.” In the meantime, she adds, “There are things we can do to lower the translational barriers and show clinical utility. Clearly, resecting more disease is going to be a great thing to do. We’ll see where we go from there.” 

Adoptable options 

Among the attributes of light that make it uniquely promising for intraoperative imaging is its versatility, as every wavelength can be used to define a particular imaging parameter. Add in the variety of ways light interacts with tissues—whether “as is,” injected with contrast or both—and the means multiply for observing and measuring not only fluorescence but also scattering and absorption. That kind of versatility slows standardization and, thus, FDA approval, but it also drives innovation. 

At Stanford University School of Medicine, Christopher Contag, director of that institution’s Center for Innovation in In Vivo Imaging, is using micro-optics to develop miniaturized microscopes—3 millimeters by 5—that can work with a wide range of wavelengths and reach inside the body for point-of-care pathology. 

“The process of taking a tissue sample