A new noninvasive microscopy technique that could lead to optical biopsies without removal of tissue is being reported by biophysical scientists at Cornell and Harvard universities.

The researchers have demonstrated the new imaging technique by making live-tissue intrinsic fluorescence scans of autopsy samples from the brains of patients with Alzheimer’s disease and by imaging mammary gland tumors in mice that serve as models of human cancer.

Scans can be made through the surface of intact organs or body systems. Side-by-side comparison with conventional medical biopsy images of thin embalmed sections of the same organs reveals that the new method provides at least equal information, and in some cases contains additional diagnostic details not found in the conventional biopsies, which require invasive surgery.

The techique uses multiphoton microscopy, which produces high-resolution, three-dimensional pictures of tissues with minimal damage to living cells,” Watt W. Webb, Cornell Professor of engineering and applied physics, explains. “Using a laser that produces a stream of extremely short, intense pulses, the probability that two or three interact with an individual biological molecule at the same time is greatly increased. When this occurs, their individual energies can combine.” This energy stimulates the natural fluorescence of certain constituents in living tissue.

The scanning laser microscope moves the focused beam of pulsed photons across a sample at a precise depth (plane of focus) so that cells above or below the plane are not affected, according to Webb. When repeated scans at different focal planes are “stacked,” a three-dimensional picture emerges.