Fluorescent, optoacoustic imaging could guide interventional cancer procedures

Optical and optoacoustic imaging techniques have been emerging in research and have been slowly translating into clinical practice with humans, and research indicates that these techniques could be expanded further into interventional image guidance in the search for tumors, with both advantages and limitations, according to a review published in the April issue of the Journal of Nuclear Medicine.

P. Beatriz Garcia-Allende, PhD, from the Institute for Biological and Medical Imaging, Technische Universitat at Munchen and Helmholtz Zentrum Munchen, Munich, Germany, and colleagues, explored a variety of optical and other imaging techniques including fluorescent molecular imaging (FMI) and optoacoustic imaging, as well as narrow-band imaging, autofluorescent imaging and cross-sectional optical imaging methods for their potential benefits in an intraoperative setting. 

Narrow-band imaging works by illuminating tissue in the blue at 415 nm to capture superficial mucosal vessels and green at 540 nm of the light spectrum for deep mucosal and submucosal vessels. Intrinsic fluorescent or autofluorescent variations between tissues, from malignant to dysplastic, have been considered for tumor detection, but the technique has not performed well enough to expand significantly as a surgical or endoscopic device in clinical practice. It was noted that there was room for the technique in a context where diversified imaging techniques are being used.

Another method reviewed was cross-sectional optical imaging. Optical coherence tomography provides images with cross-sectional information due to high resolution (10 microns or greater) representations of differences in scattering light in tissue elements through 1-2 mm of tissue depth. Endoscopic microscopy using fiber-bundle-based confocal technology was presented as a potential imaging method, but both of these techniques appear to be hampered by a small field of view, making it difficult to translate the technology into widespread clinical practice.

A more promising modality is fluorescent molecular imaging, which could potentially be utilized in interventional oncology procedures.

“FMI, that is, imaging of fluorescent agents targeting specific tissue biomarkers, is an emerging modality with significant promise for enhancing endoscopic and surgical vision,” wrote the authors. “Similarly to autofluorescent imaging or narrow-band imaging, FMI offers a large field of view that matches the surgeon’s or endoscopist’s view.”

FMI may improve present clinical standards by utilizing near-infrared technologies that allow multiple-millimeter depths of visualization with a range of agents that go above and beyond the usefulness of general contrast and reach into the realm of targeted biomarkers. The only remarkable limitations to this method were camera limitations, according to the researchers. Conventional photographic or video means may not accurately portray actual emission intensity or agent uptake and distribution. The modality’s two-dimensional and surface-weighted operation may counteract its ability to provide useful information at impressive depths.

Still, FMI has opened the door to research on humans. One such study recorded the results of imaging with tumor-specific fluorescent agents and FMI technology for image guidance during an ovarian cancer procedure. A real-time multispectral imaging system was applied using intravenous fluorescein isothiocyanate as an agent targeting folate receptor-a. Results showed that fluorescent contrast revealed up to five times more malignant lesions than visual inspection. Other studies have replicated this effect.

Perhaps the most promising modality reviewed was an investigational technique called multispectral optoacoustic tomography, otherwise known as photoacoustic imaging.

“For many years, FMI has been heralded as a potent tool for improving the endoscopic identification of cancer, reducing the number of incomplete surgeries by more sensitive identification of tumor margins, and enabling inspection of locoregional or lymph node metastasis,” explained Garcia-Allende et al. “Recently, pilot clinical translation has confirmed the potential of FMI to enhance visual inspection, and advanced multispectral fluorescent and optoacoustic techniques are emerging for real-time guidance of interventional procedures. Similar to nuclear imaging, successful FMI translation would depend on the identification of potent biomarkers and targeting agents addressing unmet clinical needs, especially since promising results in animal studies do not necessarily imply clinical success.”

Optoacoustic imaging enables cross-sectional optical imaging of tissues at tens to a few hundreds of microns of resolution. The modality operates by irradiating tissue with nanosecond photon pulses and documents responding temperature changes and ultrasonic waves inside tissues.

“The technique sequentially illuminates tissue at multiple wavelengths and tomographically images intrinsic contrast (oxy- or deoxyhemoglobin, blood vessels) and exogenous photo-absorbing agents including fluorochromes and nanoparticles based on their distinct spectral signatures,” the researchers added. “Therefore, it offers a larger field of view, a higher penetration depth, and a wider ability to image intrinsic contrast and exogenous agents than does optical coherence tomography or confocal microscopy. Although the fluorochrome detection sensitivity of multispectral optoacoustic tomography is currently lower than that of FMI in detecting superficial fluorescence, the clinical application of optoacoustic imaging is expected to grow over the next few years to enable high-resolution cross-sectional imaging at depths ranging up to a few centimeters.”