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Research & Development

Vrije Universiteit images evidence of Alzheimer's disease

06 Jul 2022

Multimode optical fiber and compressive imaging approach could assist neuroimaging.

Microendoscopes able to view tissues within a living brain have recently made use of advanced optical fibers and gradient-index (GRIN) lenses to allow in vivo imaging, although the image quality has remained a challenge.

Multimode (MM) fibers offer a more flexible and potentially smaller optical fiber for deeper brain imaging, but to date MM fiber endoscopes have tended to lose image information due to scrambling of the light within the fiber.

A project at Vrije Universiteit Amsterdam has now investigated epi-fluorescence imaging of the human brain through a MM fiber, tackling the inherent losses to achieve faster acquisition times and expanded fields of view. The work was published in APL Photonics.

"We propose to use the scrambling of the light to our advantage," commented the project in its published paper. "Coherent light entering at one point at the proximal side of the MM fiber creates a random speckle pattern at the distal end. By altering the entry position at the input side, multiple and uncorrelated random speckle patterns can be created."

The scrambled data can then be recovered via the computational approach termed compressive imaging, a technique already being investigated for other microscopy modalities and thought to hold promise for imaging objects completely embedded in a scattering medium. The Vrije project's termed their application of this approach speckle-based compressive imaging (SBCI).

The project also investigated the use of raster-scan imaging by active wavefront shaping, whereby the incident wavefront is matched to the scattering properties of the fiber. Once correctly calibrated, diffraction limited spots of around 1.1 microns were sequentially scanned across the sample, with the obtained fluorescence intensity recorded in epi-direction for computational analysis.

Deep-tissue imaging in real time

In trials, the two techniques were used to image lipofuscin, an age-related fluorescent pigment that accumulates over time as metabolic waste in a neuron's core cell body, or soma. Abnormal accumulation of lipofuscin may be associated with Alzheimer’s disease progression although to date there is little understanding of this mechanism.

In what the team believes to be the first imaging of unlabelled Alzheimer human brain tissues through a MM-based endoscopic probe, the SBCI approach successfully visualized age-related lipofuscin. The imaging compression rates showed a considerable improvement over previous methods, according to the team's paper, so acquisition times at video frame rates may be possible in the future.

Future work will involve tackling the stability of the speckle patterns, since small variations after the device has been calibrated can introduce artefacts into the reconstructed image. Using a bundle of stable single mode fibers with a fused MM fiber part may be one solution.

"SBCI can produce high-resolution images up to 11 times faster, for a space three times as big, than the traditional raster-scan approach," commented the project, which anticipates its MM approach also being employed during other medical procedures where imaging endoscopy will be valuable.

"The ultrathin multimode fiber would easily fit into an acupuncture needle, and we know these needles can be inserted into anyone's body with almost no pain, potentially enabling deep-tissue imaging in real time," said Benjamin Lochocki, from Vrije Universiteit Amsterdam.

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