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Researchers have developed an extremely thin, flexible imager that could be useful for noninvasively acquiring images from inside the body. The new technology could one day enable early and precise disease detection, providing critical insights to guide timely and effective treatment.

"As opposed to existing prohibitively large endoscopes made of cameras and optical lenses or bulky fiber optic bundles, our microimager is very compact," said research team leader Maysam Chamanzar from Carnegie Mellon University. "Much thinner than a typical eyelash, our device is ideal for reaching deep regions of the body without causing significant damage to the tissue."

In the journal Biomedical Optics Express, the that the microimager, which is only 7 microns thick—a tenth of an eyelash diameter—and about 10 mm long, can be used in a mouse brain for structural and functional imaging of brain activity. The width of the thin film imager can be customized based on the desired field of view and resolution.

"With further development, the microimager could be implanted for short- or long-term imaging or attached to catheters to image internal body parts like the gastrointestinal tract or inside of blood vessels," said Chamanzar. "It could also be used with surgical tools to provide real-time visual feedback to surgeons to improve the surgical outcome and reduce the chance of adverse effects."

Leveraging a biocompatible polymer

The miniaturized endoscope is based on a flexible photonic platform that uses the biocompatible transparent polymer Parylene to create photonic components such as waveguides. The researchers originally developed Parylene photonics to create miniaturized implantable devices that provide targeted light delivery in tissue.

In the new work, the researchers used the bidirectional capability of Parylene waveguides, which can both deliver and detect light, to create an array of waveguides designed for imaging tissue structure and function. They designed a microimager with waveguides that each have a micromirror at both ends.

One or more of the waveguides deliver light to illuminate the tissue while backscattered light is collected by the micromirrors, coupled to other individual waveguides and transmitted to the back end. There, the light is projected onto an image sensor array. With this design, each waveguide effectively relays a pixel of the tissue image.

"We made the miniaturized endoscope using microscale fabrication techniques similar to those used in microelectronics and microelectromechanical systems (MEMS)," said M. Hassan Malekoshoaraie, the doctoral student who designed and demonstrated these endoscopic imagers. "This allows the waveguides and micromirrors to be easily customized for imaging various tissues with the desired resolution."

Imaging inside the brain

To demonstrate the miniaturized endoscope, the researchers first showed that it can image fluorescent microspheres embedded within a scattering medium, enabling 3D localization of the microspheres. They then used the microimager to capture a fluorescent image of mouse brain tissue expressing green fluorescent protein. Finally, they demonstrated functional neural imaging from mouse brain tissue that expresses genetically encoded calcium indicators, demonstrating that the microimager can capture neural function.

"We validated the functional optical images obtained using our endoscopes by comparing them with ground truth electrophysiology recordings," said Vishal Jain, a neuroscientist on the research team. "Observing such a strong correspondence between the imaging data and electrophysiology was encouraging."

The researchers say that this work is one step toward their overarching goal of imaging neural tissue in action. "We eventually want to be able to correlate neural activity to the transcriptional profile of specific cell types involved in the population activity," said Chamanzar.

Next, the researchers want to integrate light sources, image sensor arrays and filters into the device's back end to implement a fully integrated standalone microimager for in vivo applications. This could allow the microimager to be surgically implanted in tissue for applications such as imaging remnant cancer cells after tumor removal or monitoring disease progression after treatment.