In a collaboration between Vanderbilt University Medical Center’s Department of Otolaryngology-Head and Neck Surgery and the Vanderbilt University School of Engineering, investigators have received a $2.5 million grant to develop a head-mounted augmented reality system that can guide surgeons in ensuring complete tumor removal in head and neck cancer surgery and potentially reduce the recurrence rate of tumors. 

The National Institutes of Health grant was awarded to primary investigator Jie Ying Wu, PhD, assistant professor of Computer Science, with secondary appointments in Biomedical Engineering, Electrical and Computer Engineering, and Mechanical Engineering at Vanderbilt University. Wu also has an appointment in the Department of Surgery at Vanderbilt University Medical Center. 

Co-investigators include Michael Miga, PhD, director of the Vanderbilt Institute for Surgery and Engineering and the Harvie Branscomb Professor and chair of the Department of Biomedical Engineering, as well as Michael Topf, MD, associate professor of Otolaryngology-Head and Neck Surgery, and Matthew Weinger, MD, professor of Anesthesiology and Biomedical Informatics. 

“I am delighted to receive this award to transform surgical care for head and neck cancer,” said Wu. “This funding will allow us to build novel deformation models for heterogeneous tissue shrinkage and ensure the augmented reality software design is intuitive for surgeons and fits within the clinical workflow.” 

The development of the technology stems from a deficit Topf noticed in surgical oncology. While three-dimensional scanning has become part of the norm for other aspects of patient care, from same-day dental crowns to prosthetic limbs, Topf was troubled by the lack of application for 3D scanning in oncologic surgery. Topf implemented a protocol to create 3D models of resected cancers for surgeons, pathologists and oncologists to reference. 

“We came up with a way to 3D scan a surgical specimen in real time in less than 10 minutes prior to processing and not interfere with all the other important things that are going on in the pathology lab,” said Topf. “Encouragingly, this is a widely transferable practice and would be applicable to most cancer surgeries, from orthopaedic oncology to breast cancer.” 

Weinger, who is a faculty member of the Center for Research and Innovation in Systems Safety (CRISS) at VUMC, expressed the organization’s eagerness to support the research. 

“CRISS is excited to contribute to this important project, applying advanced engineering to ensure the user interface of this technology guides surgeons to safely and effectively treat cancer patients,” said Weinger, who holds the Norman Ty Smith Chair in Patient Safety and Medical Simulation. 

Safety and effectiveness are at the core of the research. As Miga explained, the 3D mapping technology will allow surgeons to rely less on a fallible mental construction of the resection plane, thereby reducing the risk of human error affecting the procedure. 

“When it comes to cancer surgery, surgeons often say, ‘We think we got it all,’” said Miga. “What many don’t realize is that every operation requires the surgeon to construct a mental spatial map, linking the visible surgical field to their internal understanding of the tumor’s extent. It’s an incredibly complex task, and sometimes, despite best efforts, reoperations are necessary. 

“Now imagine if, while the patient is still on the table, we could detect the margin in real time, and then, using a holographic overlay, highlight the precise region that needs further attention. Through our collaboration, that’s the kind of transformation we’re seeking to make commonplace with this research.” 

Collaboration has been consistent over the last few years between the Medical Center and the University, said Wu. She hopes research into the technology will eventually support a clinical trial, a sentiment shared by Eben Rosenthal, MD, Barry and Amy Baker Professor and chair of the Department of Otolaryngology-Head and Neck Surgery. 

“Improving surgical outcomes is of the utmost importance, especially when it comes to ensuring total tumor removal and reduced risk of recurrence for cancer patients,” said Rosenthal. “The research supported by this grant will help us perfect this technology as we seek practical applications for patient care, including clinical trials and, eventually, everyday use in the operating room.” 

This study is supported by NIH grant R01EB037685. 

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A study published in the journal JAMA Surgery demonstrated the benefits of using fluorescence-guided imaging to assess margins in head and neck cancer. Researchers at Vanderbilt University Medical Center found that leveraging data collected both during surgery (in vivo) and after the tumor’s removal (ex vivo) can help guide surgeons in achieving a negative margin in cancer resection. 

A margin refers to the areas around the tumor being removed. The desirable outcome is to complete surgery with a negative margin, indicating that no cancer was found at the edge of the resection. A positive margin indicates that cancer cells remain in the tissue, which increases the risk of recurrence and reduces the chance of survival. 

To assess those margins, surgeons may use fluorescent agents administered to the patient’s tissue. Systemically infused agents have been shown to differentiate cancerous and healthy tissue with high accuracy. 

“Our research found that the use of fluorescence imaging both internally and externally can improve surgeons’ ability to precisely and safely excise tumors,” said Shravan Gowrishankar, MD, a research fellow in the Department of Otolaryngology-Head and Neck Surgery and the study’s first author. “This research seeks to illuminate methods of leveraging fluorescence imaging to achieve negative margins, particularly for deep resections, which often prove difficult.” 

The researchers defined two classifications of margins: the superficial or mucosal margin refers to the area uninvolved with the tumor but surrounding its surface, while the deep margin refers to the 4 to 5 millimeters of healthy tissue beyond the tumor’s most invasive points, or the depth of normal tissue between the tumor edge and the cut surface of the specimen. 

“Currently, it’s easier to achieve negative mucosal margins than deep margins,” said corresponding author Eben Rosenthal, MD, chair of the Department of Otolaryngology-Head and Neck Surgery and Barry and Amy Baker Professor of Laryngeal, Head and Neck Research. “Deep margins aren’t able to be assessed as easily because surgeons must rely on estimation of the distance from the tumor to guide the resection. 

“We sought to improve methods of achieving negative margins across the board because estimation isn’t good enough where patient safety is concerned.” 

The assessment of deeper margins is further confounded during surgery by tissue retraction and the presence of blood, which can obscure the view of the surgeon. And while autofluorescence — a process by which naturally occurring chemicals in the tissue can absorb light of a particular wavelength and reemit it at a different wavelength — can help surgeons assess mucosal margins, deeper margins are impossible to assess via this process because the light does not penetrate beyond a millimeter. 

To assist in ensuring a negative margin in a deep resection, surgeons can use fluorescence imaging techniques. Mapping tumors after resection can provide data on how close the margins are to the surface of the deep resection, and intraoperative in vivo fluorescence imaging can reveal areas of residual disease in the tumor bed. In combination, the information provided by both methods of fluorescence imaging can guide further examination and sampling to help achieve fuller resection of the deep margin. 

While both methods in combination are critical to achieving better outcomes in surgery, said Gowrishankar, ex vivo imaging devices have certain advantages over in vivo hardware. 

“While the data we get from in vivo imaging is valuable, it’s largely qualitative because of variance in ambient light in the operating room,” said Gowrishankar. “Ex vivo imaging is more precise because we can seal out external light in a controlled environment to measure fluorescence intensity and guide our assessment of deep margins.” 

In ex vivo imaging, fluorescence intensity increases the closer the tumor tissue approaches the cut surface of the tumor specimen, and data from this measurement can be used to create a sort of “heat map” measuring the relative depth of the tumor across the entire specimen. By using this imaging technique, surgeons can more precisely detect the reach of cancer cells in the tissue and perform precise resections. 

“Mucosal margins are easy enough to detect during surgery without fluorescent agents, but those agents are critical in helping us close the gap with deep margins,” said Rosenthal. “Missed deep margins contribute to the majority of positive margins after resection, which in turn contribute to negative health outcomes for patients. Large-scale adoption of these techniques will have a meaningful impact on the health of patients who undergo surgery to remove cancerous tumors.” 

Additional authors from Vanderbilt University Medical Center include: 

• Jennifer Choe, MD, PhD, assistant professor of Medicine in the Division of Hematology Oncology 

• Alexander Langerman, MD, SM, FACS, associate professor of Otolaryngology-Head and Neck Surgery 

• Kyle Mannion, MD, FACS, associate professor of Otolaryngology-Head and Neck Surgery 

• Aviva S. Mattingly, MD, MS, VTOPS/R25 Research Resident 

• Sarah L. Rohde, MD, MMHC, associate professor of Otolaryngology-Head and Neck Surgery and division director of Head and Neck Oncologic Surgery 

• Robert Sinard, MD, FACS, professor of Otolaryngology-Head and Neck Surgery 

• Hidenori Tanaka, MD, PhD, visiting assistant professor of Otolaryngology-Head and Neck Surgery 

• Michael Topf, MD, MSCI, assistant professor of Otolaryngology-Head and Neck Surgery. 

This research was supported by the National Cancer Institute, part of the National Institutes of Health (grants R01CA279249, R01CA239257, R01CA266233 and R01CA238686). 

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