Noninvasive, label-free imaging method can penetrate deeper into living tissue to visualize cellular activities

Good news!

"Metabolic imaging is a noninvasive method that enables clinicians and scientists to study living cells using laser light, which can help them assess disease progression and treatment responses.

But light scatters when it shines into biological tissue, limiting how deep it can penetrate and hampering the resolution of captured images.

Now, MIT researchers have developed a new technique that more than doubles the usual depth limit of metabolic imaging. Their method also boosts imaging speeds, yielding richer and more detailed images. ...

They use a multimode fiber, a type of optical fiber which can carry a significant amount of power, and couple it with a compact device called a “fiber shaper.” This shaper allows them to precisely modulate the light propagation by adaptively changing the shape of the fiber. Bending the fiber changes the color and intensity of the laser. ..."

From the abstract:

"Label-free imaging through two-photon autofluorescence of NAD(P)H allows for nondestructive, high-resolution visualization of cellular activities in living systems. However, its application to thick tissues has been restricted by its limited penetration depth within 300 μm, largely due to light scattering. Here, we demonstrate that the imaging depth for NAD(P)H can be extended to more than 700 μm in living engineered human multicellular microtissues by adopting multimode fiber-based, low repetition rate, high peak power, three-photon excitation of NAD(P)H at 1100 nm. This is achieved by having more than 0.5 megawatts peak power at the band of 1100 ± 25 nm through adaptively modulating multimodal nonlinear pulse propagation with a compact fiber shaper. Moreover, the eightfold increase in pulse energy enables faster imaging of monocyte behaviors in the living multicellular models. These results represent a substantial advance for deep and dynamic imaging of intact living biosystems. The modular design is anticipated to allow wide adoption for demanding imaging applications, including cancer research, immune responses, and tissue engineering."

Noninvasive imaging method can penetrate deeper into living tissue | MIT News | Massachusetts Institute of Technology "Using high-powered lasers, this new method could help biologists study the body’s immune responses and develop new medicines."

Deep and dynamic metabolic and structural imaging in living tissues (open access)

Fig. 1. SI MMF as a compact, accessible, and high-quality label-free imaging source.