Cheaper Bioimaging of In-Vivo Interactions

A new method quickly, economically, and accurately tracks multiple in vivo interactions. (Source: RPI)

A new approach to optical imaging makes it possible to quickly and econo­mically monitor multiple molecular inter­actions in a large area of living tissue such as an organ or a small animal; technology that could have appli­cations in medical diagnosis, guided surgery, or pre-clinical drug testing. The method is capable of simul­taneously tracking 16 colors of spa­tially linked infor­mation over an area spanning several centi­meters, and can capture inter­actions that occur in mere billionths of a second.

“We have developed a smart way to acquire a massive amount of infor­mation in a short period of time,” said Xavier Intes, a professor of bio­medical engi­neering at Rensse­laer Poly­technic Insti­tute. “Our approach is faster and less expensive than existing tech­nology without any compromise in the precision of the data we acquire.” In bio­medical appli­cations, optical imaging has many advan­tages over techniques such as MRI and PET, which use magne­tism and posi­tron emissions to acquire images inside of living tissue.

The method the Intes lab developed makes use of advanced optical imaging techniques – fluores­cence lifetime imaging paired with foster resonance energy transfer – to reveal the molecular state of tissues. In fluores­cence lifetime imaging (FLIM), molecules of interest are tagged with fluores­cent “reporter” molecules which, when excited by a beam of light, emit a light signal with a certain color over time that is indi­cative of their immediate environ­ment. Reporter molecules can be tuned to offer infor­mation on environ­mental factors such as viscosity, pH, or the presence of oxygen.

FLIM is ideal for the thick tissues of a body because it relies on time information, rather than light inten­sity, which degrades signi­ficantly as it travels through tissue. Researchers also used Forster resonance energy transfer (FRET), which determines close proximity between two similarly tagged molecules such as a drug and its target based on an energy transfer that occurs only when the tagged molecules are delivered into the diseased cells for maximal thera­peutically efficacy.

However, while the FLIM-FRET method generates a signal rich in infor­mation, collecting that signal quickly and economi­cally is proble­matic. Current methods rely on expensive cameras, which can image only one reporter at a time, and scanning the subject can take hours as the camera collects infor­mation from its full field of vision. To overcome this obstacle, the researchers dispensed with cameras and instead used a single-pixel detection method combined with a mathe­matical sampling technique (based on a Hadamard transform) that allowed them to collect suffi­cient relevant infor­mation in 10 minutes to construct a precise image.

The detection method can collect infor­mation on 16 spectral channels simul­taneously, and three detection devices positioned around the sample provided spatial infor­mation used to construct a three-dimen­sional image. “This is a new platform, a new option in macro­scopy, and we think it will have traction in multiple appli­cations in the biome­dical arena,” said Intes. (Source: RPI)

Reference: Q. Pian et al.: Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging, Nat. Phot. 11, 411 (2017); DOI: 10.1038/nphoton.2017.82

Link: Biomedical Engineering Dept., Rensselaer Polytechnic Institute, Troy, USA

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