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    Liquid-Core Microstructured Polymer Optical Fiber as Fiber-Enhanced Raman Spectroscopy Probe for Glucose Sensing
    (Washington, DC : OSA, 2020) Azkune, Mikel; Frosch, Timea; Arrospide, Eneko; Aldabaldetreku, Gotzon; Bikandi, Iñaki; Zubia, Joseba; Popp, Jürgen; Frosch, Torsten
    This work reports the development and application of two liquid-core microstructured polymer optical fibers (LC-mPOF) with different microstructure sizes. They are used in a fiber-enhanced Raman spectroscopy sensing platform, with the aim of detecting glucose in aqueous solutions in the clinically relevant range for sodium-glucose cotransporter 2 inhibitor therapy. The sensing platform is tested for low-concentration glucose solutions using each LC-mPOF. Results confirm that a significant enhancement of the Raman signal is achieved in comparison to conventional Raman spectroscopy. Additional measurements are carried out to obtain the valid measurement range, the resolution, and the limit of detection, showing that the LC-mPOF with 66-µm-diameter central hollow core has the highest potential for future clinical applications. Finally, preliminary tests successfully demonstrate glucose identification in urine. © 1983-2012 IEEE.
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    Computational tissue staining of non-linear multimodal imaging using supervised and unsupervised deep learning
    (Washington, DC : OSA, 2021) Pradhan, Pranita; Meyer, Tobias; Vieth, Michael; Stallmach, Andreas; Waldner, Maximilian; Schmitt, Michael; Popp, Juergen; Bocklitz, Thomas
    Hematoxylin and Eosin (H&E) staining is the 'gold-standard' method in histopathology. However, standard H&E staining of high-quality tissue sections requires long sample preparation times including sample embedding, which restricts its application for 'real-time' disease diagnosis. Due to this reason, a label-free alternative technique like non-linear multimodal (NLM) imaging, which is the combination of three non-linear optical modalities including coherent anti-Stokes Raman scattering, two-photon excitation fluorescence and second-harmonic generation, is proposed in this work. To correlate the information of the NLM images with H&E images, this work proposes computational staining of NLM images using deep learning models in a supervised and an unsupervised approach. In the supervised and the unsupervised approach, conditional generative adversarial networks (CGANs) and cycle conditional generative adversarial networks (cycle CGANs) are used, respectively. Both CGAN and cycle CGAN models generate pseudo H&E images, which are quantitatively analyzed based on mean squared error, structure similarity index and color shading similarity index. The mean of the three metrics calculated for the computationally generated H&E images indicate significant performance. Thus, utilizing CGAN and cycle CGAN models for computational staining is beneficial for diagnostic applications without performing a laboratory-based staining procedure. To the author's best knowledge, it is the first time that NLM images are computationally stained to H&E images using GANs in an unsupervised manner.
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    Polarization-resolved second-harmonic generation imaging through a multimode fiber
    (Washington, DC : OSA, 2021) Cifuentes, Angel; Pikálek, Tomáš; Ondráčková, Petra; Amezcua-Correa, Rodrigo; Antonio-Lopez, José Enrique; Čižmár, Tomáš; Trägårdh, Johanna
    Multimode fiber-based endoscopes have recently emerged as a tool for minimally invasive endoscopy in tissue, at depths well beyond the reach of multiphoton imaging. Here, we demonstrate label-free second-harmonic generation (SHG) microscopy through such a fiber endoscope. We simultaneously fully control the excitation polarization state and the spatial distribution of the light at the fiber tip, and we use this to implement polarization-resolved SHG imaging, which allows imaging and identification of structural proteins such as collagen and myosin. We image mouse tail tendon and heart tissue, employing the endoscope at depths up to 1 mm, demonstrating that we can differentiate these structural proteins. This method has the potential for enabling instant and in situ diagnosis of tumors and fibrotic conditions in sensitive tissue with minimal damage.