Imaging scope may lead to fewer biopsies

CORNELL (US) — A new imaging scope 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 multiphoton endoscopes that can be used in clinical settings to directly image tissues or tumors. The latest prototype—4 cm in length and 3 mm in diameter—is described in the Proceedings of the National Academy of Sciences.

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 into the tiny end of a thin endoscope to directly image tissues or tumors.

Researchers divert human tissue samples to the multiphoton microscopy lab to take images before sending the samples through normal pathology channels. (Credit: Jason Koski, Cornell University Photograph)


“The motivation all along was to look at human cells,” Webb says.

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.

The next-generation endoscope could minimize the need for biopsies altogether; doctors would image cancerous lesions in real time and remove only what’s necessary. The endoscope would also allow doctors to examine surgical margins at high resolution in real time, potentially improving surgical outcomes.

Webb and colleagues are collaborating with doctors at Weill Cornell Medical College, who will test the prototypes on human tissue samples. Eventually, with FDA approval, doctors 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 (who have signed releases) before the tissue is analyzed by traditional pathology methods.

“We not only have the corresponding histology, but also the clinical history of the person, so we know what is going on,” says Sushmita Mukherjee, director of multiphoton microscopy and assistant professor of biochemistry.

Developing an optical biopsy instrument has been called the “holy grail” for surgical endoscopy—the ability to get identical histologic information as one would obtain from a surgical biopsy without having to extract the tissue from the patient, says Douglas Scherr, urological surgeon and associate professor of urology.

Bladder cancers, in which Scherr specializes, have high rates of recurrence because it is difficult to pinpoint and remove every area of malignancy, he explains.

Even so, 70 percent of all bladder biopsies are benign, Scherr says, because with the naked eye, a surgeon cannot distinguish between an inflammatory and a malignant lesion, so they have to biopsy it all to be safe.

“Multiphoton endoscopy can act as an adjunct to our standard evaluation system and, hopefully, diminish the number of unnecessary biopsies we take,” Scherr adds.

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