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    Nonresonant Raman spectroscopy of isolated human retina samples complying with laser safety regulations for in vivo measurements
    (Bellingham, Wash. : SPIE, 2019) Stiebing, Clara; Schie, Iwan W.; Knorr, Florian; Schmitt, Michael; Keijzer, Nanda; Kleemann, Robert; Jahn, Izabella J.; Jahn, Martin; Kiliaan, Amanda J.; Ginner, Laurin; Lichtenegger, Antonia; Drexler, Wolfgang; Leitgeb, Rainer A.; Popp, Jürgen
    Retinal diseases, such as age-related macular degeneration, are leading causes of vision impairment, increasing in incidence worldwide due to an aging society. If diagnosed early, most cases could be prevented. In contrast to standard ophthalmic diagnostic tools, Raman spectroscopy can provide a comprehensive overview of the biochemical composition of the retina in a label-free manner. A proof of concept study of the applicability of nonresonant Raman spectroscopy for retinal investigations is presented. Raman imaging provides valuable insights into the molecular composition of an isolated ex vivo human retina sample by probing the entire molecular fingerprint, i.e., the lipid, protein, carotenoid, and nucleic acid content. The results are compared to morphological information obtained by optical coherence tomography of the sample. The challenges of in vivo Raman studies due to laser safety limitations and predefined optical parameters given by the eye itself are explored. An in-house built setup simulating the optical pathway in the human eye was developed and used to demonstrate that even under laser safety regulations and the above-mentioned optical restrictions, Raman spectra of isolated ex vivo human retinas can be recorded. The results strongly support that in vivo studies using nonresonant Raman spectroscopy are feasible and that these studies provide comprehensive molecular information of the human retina. © The Authors. Published by SPIE.
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    Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis
    ([London] : Macmillan Publishers Limited, part of Springer Nature, 2021) Schie, Iwan W.; Placzek, Fabian; Knorr, Florian; Cordero, Eliana; Wurster, Lara M.; Hermann, Gregers G.; Mogensen, Karin; Hasselager, Thomas; Drexler, Wolfgang; Popp, Jürgen; Leitgeb, Rainer A.
    The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future.