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  • Biophotonics Pushes the Boundaries of Radiology

    Radiologists are playing a key role in biophotonics -- an emerging area of research that uses light and other forms of radiant energy to understand the inner workings of cells and tissues in living organisms. By Richard Dargan

    August 4, 2016

    Biophotonics — the development and application of optical techniques for the study of biological molecules, cells and tissue — is expanding the scope of radiology by bringing clinicians and researchers new tools for noninvasive imaging of cancer and other diseases.

    While the x-rays and gamma rays commonly used in imaging represent high-energy light sources, biophotonics typically relies on sources at the lower end of the energy spectrum like infrared, near infrared, visible and ultraviolet light. This lower energy light helps preserve the biological cells examined even as the optical equipment visualizes structures too small to be seen with x-ray, CT and MRI.

    “With biophotonics, we can image very small-scale physiology at high-speed resolution,” said Michael A. Choma, MD, PhD, principal investigator at the Yale Biophotonics Laboratory in New Haven, Conn., and assistant professor of radiology & biomedical imaging, pediatrics, biomedical engineering and applied physics at Yale University. “It’s highly complementary to MRI and CT and the technology continues to develop with advances in computing, light sources and cameras.”

    While biophotonics is a highly interdisciplinary field encompassing medicine, biology, physics, engineering and technology, among others, it is moving radiology in exciting new directions, Dr. Choma said.

    “Biophotonics is pushing the boundaries of what is meant by radiology,” he said.

    Biophotonics Impacts Cancer Care

    While optical techniques such as pulse oximetry and Lasik surgery are already well established in everyday practice, more and more applications for biophotonics are emerging in a variety of settings.

    In cancer care, optical biopsy systems provide real-time detection of abnormal tissue. During conventional biopsies, the tissue sample is removed and sent to the lab, which can be a lengthy process. Optical biopsies allow the sample to be studied in the operating room, improving the process and helping to avoid the sampling errors common to conventional methods.

    “In conventional biopsy, we take the tissue to the microscope, but with optical biopsy, we’re taking the microscope to the tissue,” said Arthur F. Gmitro, PhD, professor and head of the Department of Biomedical Engineering and professor of medical imaging and optical sciences at the University of Arizona in Tucson.

    For example, conventional biopsy of Barrett’s esophagus, a potential precursor to esophageal cancer, involves periodic four-quadrant biopsies. Even with as many as 20 samples removed, surgeons still may miss areas with abnormal cells.

    “With optical biopsy, you scan across the tissue in real time and make a less invasive and potentially more accurate diagnosis,” Dr. Gmitro said.

    Dr. Gmitro’s lab pioneered the development of the confocal microendoscope, an imaging system that joins a confocal microscope to a fiber optic imaging bundle with a lens and a focusing mechanism. The setup allows for remote use of the microscope outside of the surgical field. Fluorescent dyes can be delivered to tissue surface to label molecules and look for abnormalities.

    “It’s basically an endoscopic use of a microscope,” Dr. Gmitro said. “Anywhere you can do an endoscopy — the colon, esophagus, bladder, ovary — you can use this type of system.”

    Dr. Gmitro and colleagues recently used the imaging system to study ovarian cancer, an often deadly cancer that usually does not present until it is at an advanced stage. Evaluation of a laparoscopic system on patients showed a clear distinction between normal and abnormal regions within the ovarian surface, suggesting a role for early detection in patients with ovarian cancer risk factors like BRCA genes.

    The researchers are also developing a system to help distinguish lung cancer from Valley fever, a fungal infection of the lung that is endemic to people who live in the arid climates of the American Southwest. Since Valley fever mimics lung cancer on CT, optical scanning could help spare patients from much more invasive conventional lung biopsies.

    OCT Expands Beyond the Eye

    Optical coherence tomography (OCT), a high-speed, cross-sectional microscopic imaging modality, is another well-established area of biophotonics. Like ultrasound, OCT operates on an echo-based paradigm except that in OCT the ultrasonic waves are replaced by light waves. OCT is commonly used in the eye to study the retina and diagnose glaucoma, macular degeneration and other conditions.

    “OCT is now used for image-guided surgery in the retina and has potential importance for interventional and vascular radiology,” Dr. Choma said.

    Dr. Choma used OCT to image ciliary physiology. Cilia are minute hair-like organelles that extend from cells on respiratory epithelial surfaces and beat rhythmically to move mucus out of the lungs. This mucus contains bacteria, viruses, allergens and pollution; as such, defects in flow can have significant health ramifications. The small size makes ciliary physiology difficult to image and quantify using conventional radiologic modalities, but Dr. Choma has been able to study them with OCT.

    “It started off as a curiosity five or six years ago and now with collaborators, we are looking at human specimens,” he said.

    Recent research from Dr. Choma's lab and several others suggests that OCT has promise in better understanding and diagnosing lung disease ranging from asthma to cystic fibrosis to lung failure in the ICU. For example, “lungs require speed to image and the ability to look at microscale processes like air exchange in the alveoli,” Dr. Choma said. “We started our research with tadpoles, which have skin ciliated like human lungs, and we’ve developed better imaging systems and image processing software to improve the information we get from looking at specimens."

    Biophotonics also has potential applications in evaluating the effectiveness of radiation therapy by optically examining the treatment site.

    “Some blue light is generated by radiation interacting with tissues,” Dr. Choma said, discussing the work of Brian W. Pogue, PhD, professor of engineering and science and adjunct professor of physics at Dartmouth College. “This tells you where the radiation actually went and if the treatment was able to match the plans.”

    Biophotonics Pushes the Boundaries

    Diffuse optical tomography (DOT) is another promising biophotonics approach that uses light in the near-infrared spectrum for imaging soft tissues like the breast and brain.

    Other emerging possibilities for biophotonics include intravascular imaging, tumor margin assessment in the operating room, chemotherapy treatment response and image-guided
    cardiovascular interventions.

    “Biophotonics is somewhat like magnetic resonance: a rich technology that can measure many different things,” Dr. Gmitro said. “There are a host of parameters, such as phase, polarization and fluorescence that we can use to detect disease.”

    “The possibilities are expanding as the people who develop the technology work with the people who use it to improve screening and treatment,” Dr. Choma added.



    A scanning electron micrograph of a multi-ciliated cell. Advances in biophotonics are opening up new ways to image and study respiratory ciliary physiology, an important but incompletely understood aspect of diseases ranging from cystic fibrosis to primary ciliary dyskinesia to asthma. (Biomedical Optics Express 2011;2;7:2022-2034) ©OSA 2011. Printed with permission.

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