Taking multiphoton microscopy into a new dimension, a new imaging device under development that can be inserted safely into a patient’s body could minimize the need for unnecessary biopsies. Researchers at Cornell University are developing prototypes of the multiphoton endoscope, which can be used in clinical settings to directly image tissues or tumors. The latest prototype, which is 4 cm long and 3 mm in diameter, is described in a recent edition of Proceedings of the National Academy of Sciences. Engineer Watt W. Webb, co-inventor of multiphoton microscopy, holds his lab’s latest multiphoton endoscope prototype. (Photos: Jason Koski, Cornell University Photograph) For more than two decades, Watt W. Webb, a professor of applied and engineering physics, has dreamed of making multiphoton microscopy — which he invented with colleagues in 1990 — available in clinical settings to quickly image inside a person’s liver, bladder, lung or any other organ. The same technology that uses two-photon excitation to harness cells’ intrinsic fluorescence could be housed in the tiny end of a thin endoscope to directly image tissues or tumors, he thought. “The motivation all along was to look at human cells,” Webb said. Multiphoton microscopy acquires high-resolution images deep below the surface of a tissue sample. This allows visualization of cellular details within unstained tissues that would be useful for pathologists to make diagnostic predictions. Researchers divert human tissue samples to the multiphoton microscopy lab to take images before sending the samples through normal pathology channels. The next-generation endoscope could minimize the need for biopsies altogether; doctors would image cancerous lesions in real time and remove only what is necessary. The endoscope also could allow doctors to examine surgical margins at high resolution in real time, potentially improving surgical outcomes. Webb and his colleagues are collaborating with doctors at Weill Cornell Medical College in New York City, who will test the prototypes on human tissue samples. Eventually, with approval from the US Food and Drug Administration, the investigators hope the multiphoton endoscope can be used in lieu of, or in tandem with, a traditional low-magnification optical endoscope in the operating room. Equipped with two benchtop multiphoton microscopes, Weill researchers are testing multiphoton capabilities with tissue from patients before the tissue is analyzed by traditional pathology methods. For more information, visit: www.cornell.edu