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 highenergy
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.
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
“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.
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
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
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
“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
“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.
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