A UCLA Health surgeon has created a revolutionary imaging device that potentially could transform the lives of patients diagnosed with cancer.
The Dynamic Optical Contrast Imaging (DOCI) device is a noninvasive, intraoperative imaging system that uses a high-speed camera and LED light to delineate margins between malignant and healthy tissue in real time intraoperatively, without the use of injectables or dyes.
The technology is being pioneered by a team led by head and neck surgeon Maie St. John, MD, PhD, professor and chair of the Department of Head and Neck Surgery at UCLA Health; professor of bioengineering; and Thomas C. Calcaterra chair in Head and Neck Surgery.
DOCI has demonstrated a high degree of accuracy in identifying tumor margins in animal studies and human trials. Over the past 18 months, it has been used with more than 150 patients in UCLA Health operating rooms to delineate cancer from surrounding normal tissue.
Although DOCI was developed for use on patients with head and neck squamous cell carcinoma (HNSCC), Dr. St. John emphasizes the technology shows promise for broader applications in cancer treatment and detection.
“We’re still in the process of rolling it out,” says Dr. St. John, executive director of cancer research and education at the UCLA Health Jonsson Comprehensive Cancer Center. “This is something that we’ve built through trying to understand some of the gaps in patient care and being able to work together across disciplines collaboratively at UCLA to help patients have better outcomes.”
A delicate balance
Each year, approximately 54,000 patients in the U.S. and 650,000 patients worldwide are diagnosed with head and neck cancer, according to the American Cancer Society. More than 90% of those are HNSCCs that begin in the cells lining the inside of the mouth, throat and voice box.
Several factors can diminish a patient’s overall prognosis, including positive surgical margins (in which cancer cells remain after the tumor is resected) and the presence of perineural invasion (cancer growing along surrounding nerves).
The dilemma for surgeons is how to remove all of the tumor without also resecting healthy tissue.
“It’s really a delicate balance,” says Dr. St. John, who notes that any remaining cancer cells can lead to a 90% increase in rates of cancer recurrence and mortality.
For example, Dr. St. John says, a surgeon can remove half of a patient’s tongue and if the tumor wasn’t removed completely, the patient could go on to have a poor outcome. Conversely, over-resection (removing healthy tissue) could affect their speech, their swallowing and their appearance, significantly affecting their quality of life.
Currently, margins are determined during surgery through a combination of surgeon experience, visual cues, palpation (use of fingers or hands) and frozen section, a laboratory procedure to perform rapid microscopic analysis of a tumor.
Surgeons also must determine whether important nerves harbor perineural invasion (PNI), which is diagnosed in about 50% of HNSCC and is associated with increased recurrence of the tumor and decreased survival.
“There is a gap and a need for this technology in the care of these cancer patients," Dr. St. John says. "We need precision surgery.”
Birth of DOCI
The inspiration for DOCI came to Dr. St. John almost by accident.
Several years ago, a young woman and her husband came to her office because the woman had been diagnosed with tongue cancer. During the visit, the patient’s husband asked Dr. St. John two questions: How much of my wife’s tongue are you going to take? And how will you know after surgery that you’ve removed all the cancer?
“Of course, I could give him standard-of-care answers to those questions,” Dr. St. John says. “But it was one of those moments when I thought, ‘How could I make things better for this young woman and all patients?’ ”
A few weeks later, Dr. St. John got her answer: As she was backing up in her Toyota Prius, she got too close to the hedges on her front lawn, setting off the car’s sensor.
“I thought, ‘How can we build a tool to do the same – to identify cancer cells while we’re operating to provide precision surgery?’” says Dr. St. John.
After performing surgery on the woman that morning, she went across the street to the UCLA Samueli School of Engineering and asked if she could talk to some of the engineers about her needs in the operating room.
“It was important for us to think about a detailed analysis of the system-side trade-offs: specificity – what is cancer versus non-cancer in that margin; and sensitivity – what is the lowest cancer cell concentration I could detect per unit volume of tissue,” Dr. St. John says.
The system also had to be easy to use in the operating room, allow a wide field of view and produce the images quickly.
After securing funding from the National Institutes of Health, work to design the imaging system began in earnest.
In addition to others on the engineering team, Dr. St. John credits the late Warren Grundfest, MD, professor of bioengineering, electrical engineering and surgery; the late Oscar Stafsudd, PhD, professor of electrical and computer engineering; Ramesh Shori, PhD; and Yazeed Alhiyari, PhD for helping bring DOCI to fruition.
“It is a beautiful collaboration that came together for the sake of helping others,” she says.
How it works
DOCI is a noninvasive imaging system that captures the natural fluorescence, or light energy, of a tumor using a high-speed camera and regular LED light.
The camera is mounted on an arm that can be swung over the tumor bed to allow the surgeon a wide view of the surgical field. A short pulse of light is pumped into the area surrounding the tumor, which generates two images just milliseconds apart. Images are then analyzed at multiple wavelengths to show the contrast between the tumor and healthy tissue.
Promising results
In the initial proof-of-concept study, mice were injected subcutaneously into the bilateral flanks with SCCVIISF, a murine head and neck cancer-cell line. DOCI imaging was performed before resection to determine the margins. Tumors that were difficult to distinguish from surrounding healthy tissue with white light were clearly identified with DOCI imaging.
The tumors and margins were then sent for histologic sectioning. The results were reviewed by UCLA Health Head and Neck pathologists and were consistent with DOCI imaging.
The researchers next investigated the ability of DOCI to identify perineural invasion. The results were extremely encouraging, Dr. St. John says: DOCI values distinguishing cancer from adjacent healthy tissue types were statistically significant. DOCI imaging also was able to detect perineural invasion with 100% accuracy compared to control.
Histology studies
Buoyed by the successful murine study, Dr. St. John and her team next began working with the tissue procurement lab through UCLA Health’s Department of Pathology. To date, they have studied the histology of more than 500 patients who have undergone surgery to remove tumors.
Once the tumor is removed, a slice is cut off and then imaged with the DOCI system. In the majority of the wavelengths tested, DOCI could delineate healthy tissue from cancer.
“This was very exciting to us,” Dr. St. John says. “You can inject a fluorescent agent into a patient and say, 'here’s the tumor,' but if you don’t have pathology to back it up, then, for me, that is not yet valid. We have to be able to ensure that what we’re doing is actually helping patients. The system has to be as good as histology: the gold standard.”
Future of DOCI
Dr. St. John and her team are working to put the DOCI system on an endoscope for use in robotic and endoscopic surgery. This would enable surgeons to see the limits of the tumor during throat surgery.
“We have begun discussions with colleagues around the country who are breast surgeons and colorectal surgeons, and we’re trying to move DOCI to other areas that operate on epithelial tumors as a manner of further validation,” Dr. St. John says.
Dr. St. John sees applications for DOCI beyond the operating room, including for early detection of cancer by dermatologists, primary care physicians, oral surgeons and dentists.
"Our team wants DOCI to be available to as many patients as possible to help have better outcomes and preserve their quality of life," she said.
