Estimating Tumor Boundaries with Fluorescence Lifetime Imaging Cancer is the second leading cause of death in the United States, with an estimated 1,762,450 new cases diagnosed and 606,880 deaths in 2019 alone. While important advances have been made in the development of treatments for cancer, including surgery, a number of challenges remain. Not least: surgeons still lack tools that can clearly delineate tumors from normal tissue during tumor resection. In current practice, surgeons estimate tumor boundaries using palpation and visual inspection, but this approach often results in incomplete removal, leading to disease recurrence and repeat surgeries. Now, the Martinos Center’s Rahul Pal and Anand T.N. Kumar and colleagues have developed an optical imaging method that can address this challenge using fluorescence lifetime-based tumor contrast enhancement. They reported the method in late 2019 in Clinical Cancer Research. Establishing tumor boundaries during resection is a major area of interest. In recent years, researchers have been exploring ways to label tumors with fluorescent molecules so they can better highlight the boundaries. One of the approaches they have devised capitalizes on clinically approved antibodies that target specific ‘receptors’—called EGFR
84
receptors—that are overexpressed on the cancer cells. Because they are overexpressed, the receptors offer a means to distinguish between tumors and surrounding healthy tissue using fluorescence imaging techniques. But any gains with this approach are mitigated by the fact that EGFR is also expressed in the healthy tissue, creating background fluorescence and thereby reducing the overall contrast between the two. The Martinos-based team tackled this problem by visualizing the fluorescence lifetimes of the molecules: that is, the average time it takes for the molecules to return to a normal state (typically in the range of nanoseconds) following excitation with pulses of laser light. The conventional optical imaging methods used in previous studies rely on continuous-wave excitation—essentially a beam of light with constant amplitude and frequency—and consequently do not have access to this information. The advantages of using fluorescence lifetimes for better delineation of tumor boundaries were made evident in the Clinical Cancer Research study. Not only did the researchers demonstrate, for the first time, that EGFR-overexpressing tumors exhibit a unique fluorescence lifetime, they also showed
