Cervical precancer identified by fluorescence, in a step toward bedside detection

May 19, 2020

MEDFORD/SOMERVILLE and BOSTON, Mass. (May 19, 2020) - A team of researchers at Tufts University's School of Engineering and its School of Medicine, and physicians at Tufts Medical Center have developed a method using fluorescence to detect precancerous metabolic and physical changes in epithelial cells lining the cervix. According to the researchers, the new imaging method opens the door to a non-invasive, early-stage bedside diagnostic. As described today in Cell Reports Medicine, the method can visualize both metabolic and structural changes within individual cells and at different depths of the epithelial tissue near the surface, while also being able to scan the surface in a completely non-destructive manner. The combined information provides a highly accurate assessment of metabolic states in tissues, often the first changes that occur in the transition to cancer.

The imaging method developed by the team looks at the intrinsic fluorescence of the cell, so it requires no contrast agents or radioactive tracers and can be observed using an optical microscope that shines light on the area examined and looks for a fluorescent "glow" at different wavelengths. Unlike biopsies, it requires no painful surgical incisions, and unlike PET imaging used for detecting metabolic signatures of cancer, the fluorescence imaging method provides much higher resolution for surface tissues, does not require intravenous injection of contrast agents, and could theoretically be applied at bedside as part of a routine regimen of monitoring.

Early detection is the most critical factor in the successful treatment and prevention of epithelial cancers, which include both skin and cervical cancers. Just as high risk individuals can reduce the risk of developing skin cancer with regular visits to the dermatologist to scan for precancerous lesions, cervical cancer could theoretically benefit from a similar strategy. However, the standard for diagnostics -- colposcopy followed by acetic acid application and selection of the worst appearing site for biopsy - is expensive, often requires multiple biopsies to obtain sufficient sensitivity in detection, and can be uncomfortable or even painful for patients. Previous studies have shown that the discomfort and inconvenience of the procedure has kept many women from keeping up with monitoring their condition.

"Although more work needs to be done to transition the method from the laboratory to the patient bedside, the technology enables us to gather more information on early cell states than is available by current diagnostic approaches, adding accuracy and precision to a convenient procedure," said Irene Georgakoudi, corresponding author of the study and a professor of biomedical engineering in the School of Engineering at Tufts.

Georgiakoudi added that even though metabolic transitions are an early hallmark of developing cancer, no current early detection methods examine metabolic states.

The method is based on the fluorescence of two important coenzymes -- biomolecules that work in concert with enzymes -- when excited by a laser beam. The coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are involved in a large number of metabolic pathways in every cell; for example, determining how they use up glucose or oxygen or how they find alternative sources of energy when glucose or oxygen are in short supply. An examination of the ratio of these coenzymes, a measure of the intensity of their fluorescent signals, and the arrangement of mitochondria (the energy producing "batteries" of the cell), can help reveal whether the cell is undergoing changes that would lead it to cancerous growth. The method can also track the size and shape of individual cells - often an indicator of disease transition - and can gather this information from different depths, which can be useful in identifying the hallmark invasion of precancerous cells through different layers of the epithelium, resulting in the loss of definition in epithelial tissue structure.

"Just looking at the metabolic readouts of the cells is useful, but adding a third dimension, looking at how the cells in the cervical epithelium change their metabolism and structure at different depths, significantly enhances our ability to accurately identify disease when it shows up," said Dimitra Pouli, researcher at Tufts University's School of Engineering, pathology resident physician at Beth Israel Deaconess Medical Center and Harvard Medical School, and lead author of the study. "We put all these quantitative parameters into an automated diagnostic algorithm, which makes it more convenient for the physician or technician using the method to interpret the results."

It is estimated that the annual costs of screening and treating for cervical cancer in the U.S. alone are at least $8 billion (according to a 2012 CDC study). Availability of a non-invasive imaging method has the potential to not only improve the accuracy of detecting early stage cancer or even pre-cancerous lesions, but also could transform monitoring of the disease into a routine and significantly less costly procedure for patients at high risk.
-end-
This research was supported by the American Cancer Society (RSG-09-174-01-CCE), the Alexander S. Onassis Public Benefit Foundation, the National Institutes of Health's National Cancer Institute (R03 CA235053), and Tufts University (Tufts Collaborates seed grant program). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Pouli, D., Thieu, H-T., Genega, E.M., Baecher-Lind, L., House, M., Bond, B., Roncari, D.M., Evans, M.L., Rius-Diaz, F., Munger, K. and Georgakoudi, I. "Label-free, high-resolution optical metabolic imaging of human cervical pre-cancers reveals potential for intraepithelial neoplasia diagnosis" Cell Reports Medicine. 2020 May 19

About Tufts University

Tufts University, located on campuses in Boston, Medford/Somerville and Grafton, Massachusetts, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.

Tufts University

Related Science Articles from Brightsurf:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.

Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.

Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.

Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.

World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.

PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.

Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.

Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.

Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.

Read More: Science News and Science Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.