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    Combination of high-resolution optical coherence tomography and raman spectroscopy for improved staging and grading in bladder cancer
    (Basel : MDPI, 2018) Bovenkamp, Daniela; Sentosa, Ryan; Rank, Elisabet; Erkkilä, Mikael T.; Placzek, Fabian; Püls, Jeremias; Drexler, Wolfgang; Leitgeb, Rainer Andreas; Garstka, Nathalie; Shariat, Shahrokh F.; Stiebing, Clara; Schie, Iwan W.; Popp, Jürgen; Andreana, Marco; Unterhuber, Angelika
    We present a combination of optical coherence tomography (OCT) and Raman spectroscopy (RS) for improved diagnosis and discrimination of different stages and grades of bladder cancer ex vivo by linking the complementary information provided by these two techniques. Bladder samples were obtained from biopsies dissected via transurethral resection of the bladder tumor (TURBT). As OCT provides structural information rapidly, it was used as a red-flag technology to scan the bladder wall for suspicious lesions with the ability to discriminate malignant tissue from healthy urothelium. Upon identification of degenerated tissue via OCT, RS was implemented to determine the molecular characteristics via point measurements at suspicious sites. Combining the complementary information of both modalities allows not only for staging, but also for differentiation of low-grade and high-grade cancer based on a multivariate statistical analysis. OCT was able to clearly differentiate between healthy and malignant tissue by tomogram inspection and achieved an accuracy of 71% in the staging of the tumor, from pTa to pT2, through texture analysis followed by k-nearest neighbor classification. RS yielded an accuracy of 93% in discriminating low-grade from high-grade lesions via principal component analysis followed by k-nearest neighbor classification. In this study, we show the potential of a multi-modal approach with OCT for fast pre-screening and staging of cancerous lesions followed by RS for enhanced discrimination of low-grade and high-grade bladder cancer in a non-destructive, label-free and non-invasive way.
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    Looking for a perfect match: multimodal combinations of Raman spectroscopy for biomedical applications
    (Bellingham, Wash. : SPIE, 2021) Schie, Iwan; Stiebing, Clara; Popp, Jürgen
    Raman spectroscopy has shown very promising results in medical diagnostics by providing label-free and highly specific molecular information of pathological tissue ex vivo and in vivo. Nevertheless, the high specificity of Raman spectroscopy comes at a price, i.e., low acquisition rate, no direct access to depth information, and limited sampling areas. However, a similar case regarding advantages and disadvantages can also be made for other highly regarded optical modalities, such as optical coherence tomography, autofluorescence imaging and fluorescence spectroscopy, fluorescence lifetime microscopy, second-harmonic generation, and others. While in these modalities the acquisition speed is significantly higher, they have no or only limited molecular specificity and are only sensitive to a small group of molecules. It can be safely stated that a single modality provides only a limited view on a specific aspect of a biological specimen and cannot assess the entire complexity of a sample. To solve this issue, multimodal optical systems, which combine different optical modalities tailored to a particular need, become more and more common in translational research and will be indispensable diagnostic tools in clinical pathology in the near future. These systems can assess different and partially complementary aspects of a sample and provide a distinct set of independent biomarkers. Here, we want to give an overview on the development of multimodal systems that use RS in combination with other optical modalities to improve the diagnostic performance.