Learned end-to-end high-resolution lensless fiber imaging toward intraoperative real-time cancer diagnosis

Endomicroscopy is indispensable for minimally invasive diagnostics in clinical practice. For optical keyhole monitoring of surgical interventions, high-resolution fiber endoscopic imaging is considered to be very promising, especially in combination with label-free imaging techniques to realize in vivo diagnosis. However, the inherent honeycomb-artifacts of coherent fiber bundles (CFB) reduce the resolution and limit the clinical applications. We propose an end-to-end lensless fiber imaging scheme toward intraoperative real-time cancer diagnosis. The framework includes resolution enhancement and classification networks that use single-shot fiber bundle images to provide both high-resolution images and tumor diagnosis result. The well-trained resolution enhancement network not only recovers high-resolution features beyond the physical limitations of CFB, but also helps improving tumor recognition rate. Especially for glioblastoma, the resolution enhancement network helps increasing the classification accuracy from 90.8% to 95.6%. The novel technique can enable histological real-time imaging through lensless fiber endoscopy and is promising for rapid and minimal-invasive intraoperative diagnosis in clinics.

Quantitative phase imaging through an ultra-thin lensless fiber endoscope

Quantitative phase imaging (QPI) is a label-free technique providing both morphology and quantitative biophysical information in biomedicine. However, applying such a powerful technique to in vivo pathological diagnosis remains challenging. Multi-core fiber bundles (MCFs) enable ultra-thin probes for in vivo imaging, but current MCF imaging techniques are limited to amplitude imaging modalities. We demonstrate a computational lensless microendoscope that uses an ultra-thin bare MCF to perform quantitative phase imaging of biomedical samples with up to 1 {\mu}m lateral resolution and nanoscale axial resolution. The incident complex light field at the measurement side is precisely reconstructed from a single-shot far-field speckle pattern at the detection side, enabling digital focusing and 3D volumetric reconstruction without any mechanical movement. The accuracy of the quantitative phase reconstruction is validated by imaging the phase target and hydrogel beads through the MCF. With the proposed imaging modality, 3D imaging of human cancer cells is achieved through the ultra-thin fiber endoscope, promising widespread clinical applications.

Lensless multicore-fiber microendoscope for real-time tailored light field generation with phase encoder neural network (CoreNet)

The generation of tailored light with multi-core fiber (MCF) lensless microendoscopes is widely used in biomedicine. However, the computer-generated holograms (CGHs) used for such applications are typically generated by iterative algorithms, which demand high computation effort, limiting advanced applications like in vivo optogenetic stimulation and fiber-optic cell manipulation. The random and discrete distribution of the fiber cores induces strong spatial aliasing to the CGHs, hence, an approach that can rapidly generate tailored CGHs for MCFs is highly demanded. We demonstrate a novel phase encoder deep neural network (CoreNet), which can generate accurate tailored CGHs for MCFs at a near video-rate. Simulations show that CoreNet can speed up the computation time by two magnitudes and increase the fidelity of the generated light field compared to the conventional CGH techniques. For the first time, real-time generated tailored CGHs are on-the-fly loaded to the phase-only SLM for dynamic light fields generation through the MCF microendoscope in experiments. This paves the avenue for real-time cell rotation and several further applications that require real-time high-fidelity light delivery in biomedicine.