With the goal of making it easier for
surgeons to detect malignant tissue during surgery and hopefully reduce the
rate of cancer recurrence, scientists have invented a new imaging system that
causes tumors to “light up” when a hand-held laser is directed at them.
“A surgeon’s goal during
cancer surgery is to remove the tumor, as well as enough surrounding tissue to
ensure that malignant cells are not left behind,” said Aaron Mohs, Ph.D., assistant
professor of regenerative
medicine at Wake
Forest Baptist Medical Center and a co-inventor of the
system. “But how do they know when they’ve removed enough tissue? Our goal is
to provide better real-time information to guide the surgery.”
Published online ahead of print in IEEE Transactions
on Biomedical Engineering (TBME), Mohs and co-authors report on
their prototype system that combines a fluorescent dye that localizes in tumors
with a real-time imaging system that allows the surgeon to simply view a screen
to distinguish between normal tissue and the “lighted” malignant tissue.
In both mice and companion dogs with tumors, the
scientists found that the fluorescent dye accumulated at higher levels in tumors
than in the surrounding tissue and the system was able to detect a distinct
boundary between normal and tumor tissue. Canine tumors are known to be similar
to human tumors in architecture and canines get the same types of tumors as
The scientists are working to further develop the system
so it can be evaluated in human patients.
Current technology allows cancer surgeons to scan tumors
prior to surgery with magnetic resonance imaging and other systems. However, to
scan the tumor during surgery involves moving the patient from the operating
table and into the machinery –which prolongs the surgery.
“Being able to quickly scan a tumor during surgery to
visualize tumor tissue from non-tumor tissue is an unmet clinical need,” said
Mohs. “Pathology techniques that examine tumor tissue during surgery can take
up to 20 minutes and they focus on the tissue removed during surgery, not the tissue
that remains in the body.”
In TBME, the authors noted that the ideal system would
find tumor boundaries with high sensitivity, have minimal impact on operative
time and surgical technique, present findings in an intuitive manner and avoid
the use of ionizing radiation or a specialized imaging environment, such as MRI
The system, invented by Mohs, Michael C. Mancini at
Spectropath Inc., and Shuming Nie with Emory University and Georgia Institute
of Technology, combines two types of imaging. A surgeon-controlled laser can be
directed at any area of interest. In addition, an imaging system with three
cameras sits above the surgical field. The
images recorded by both systems are processed to display a composite image.
Using this system, a surgeon would scan the tumor prior
to surgery to determine its boundaries. The tumor would then be surgically removed
and the area would be re-scanned to assess for any remaining malignant tissue.
If diseased tissue is found, it would be removed, and the process would be
repeated until diseased tissue could no longer be detected.
In the prototype system reported in TBME, the scientists
used indocyanine green dye as the source of fluorescence. They noted that
future studies will focus on higher performance fluorescent dyes and
nanoparticles that can be targeted to specific tumors.
Recently, Mohs was awarded a $1.37 million research grant
from the National Institute of Biomedical Imaging and Bioengineering for a
project to optimize the system and to test it in rodents.
Under the four-year project, Mohs’ team will develop nanoparticles
based on hyaluronic acid, a substance naturally present in the human body.
These nanoparticles will have the ability to entrap near infrared fluorescent
dyes. The research will investigate invasive ductal carcinoma, the most common
type of breast cancer.
Under the project, the researchers will focus on
optimizing the loading of the dye, determining how fluorescence can be
activated and performing studies in rodents to evaluate safety and whether
disease recurrence is reduced.
Members of the research team, all from Wake Forest
Baptist, are: Edward Levine, M.D., Surgical Sciences – Oncology; Frank Marini,
Ph.D., and Graca Almeida Porada, M.D., Ph.D., Institute for Regenerative
Medicine; Ralph D'Agostino, Ph.D., Biostatistics; and King Li, M.D., Division
of Radiologic Science. (Grant Number: 1R01EB019449-01)
Co-authors on the TBME paper, in addition to the inventors,
were James M. Provenzale, M.D., Duke University Medical Center and Emory
University; and Corey F. Saba, D.V.M., Karen K. Cornell, D.V.M., Ph.D., and
Elizabeth W. Howerth, D.V.M., Ph.D., University of Georgia.