Raman Spectroscopy can give a biochemical fingerprint of tissue and therefore could detect malignant changes in bladder tissue. In the introduction the basics of bladder cancer diagnosis and Raman... Show moreRaman Spectroscopy can give a biochemical fingerprint of tissue and therefore could detect malignant changes in bladder tissue. In the introduction the basics of bladder cancer diagnosis and Raman Spectroscopy and the current status of research in this field is described. In chapter 2 we performed phantom measurements using a superficial probe which showed to measure more superficial and has a higher signal to noise ratio than a nonsuperfical probe. In chapter 3 this probe was tested in during cystoscopie. Thesignal to noise ratio, sensitivity and specificity of detecting urothelial carcinoma was higher for the superficial probe compared to the nonsuperficial probe. In chapter 4 we used this probe for 2D spatial measurements of a cystectomy specimen. In this chapter we found more uncertainty surrounding the tumor which could be explained by the fact that tissue surrounding the tumor is in transition into malignancy or that there is tissue heterogeniety. In chapter 5 we describe a bladder lesion registration and navigation tool. We tested it in a phantom model. Show less
Understanding the biochemical changes in irradiated human mandible after radiotherapy of cancer patients is critical for oral rehabilitation. The underlying mechanism for radiation-associated... Show moreUnderstanding the biochemical changes in irradiated human mandible after radiotherapy of cancer patients is critical for oral rehabilitation. The underlying mechanism for radiation-associated changes in the bone at the molecular level could lead to implant failure and osteoradionecrosis. The study aimed to assess the chemical composition and bone quality in irradiated human mandibular bone using Raman spectroscopy. A total of 33 bone biopsies from 16 control and 17 irradiated patients were included to quantify different biochemical parameters from the Raman spectra. The differences in bone mineral and matrix band intensities between control and irradiated groups were analyzed using unpaired Student's t-test with statistical significance at p < 0.05. Findings suggest that the intensity of the phosphate band is significantly decreased and the carbonate band is significantly increased in the irradiated group. Further, the mineral crystallinity and carbonate to phosphate ratio are increased. The mineral to matrix ratio is decreased in the irradiated group. Principal component analysis (PCA) based on the local radiation dose and biopsy time interval of irradiated samples did not show any specific classification between irradiation sub-groups. Irradiation disrupted the interaction and bonding between the organic matrix and hydroxyapatite minerals affecting the bone biochemical properties. However, the normal clinical appearance of irradiated bone would have been accompanied by underlying biochemical and microscopical changes which might result in radiation-induced delayed complications. Show less
A clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown... Show moreA clear margin is an important prognostic factor for most solid tumours treated by surgery. Intraoperative fluorescence imaging using exogenous tumour-specific fluorescent agents has shown particular benefit in improving complete resection of tumour tissue. However, signal processing for fluorescence imaging is complex, and fluorescence signal intensity does not always perfectly correlate with tumour location. Raman spectroscopy has the capacity to accurately differentiate between malignant and healthy tissue based on their molecular composition. In Raman spectroscopy, specificity is uniquely high, but signal intensity is weak and Raman measurements are mainly performed in a point-wise manner on microscopic tissue volumes, making whole-field assessment temporally unfeasible. In this review, we describe the state-of-the-art of both optical techniques, paying special attention to the combined intraoperative application of fluorescence imaging and Raman spectroscopy in current clinical research. We demonstrate how these techniques are complementary and address the technical challenges that have traditionally led them to be considered mutually exclusive for clinical implementation. Finally, we present a novel strategy that exploits the optimal characteristics of both modalities to facilitate resection with clear surgical margins. Show less
Hsu, C.C.; Xu, J.B.; Brinkhof, B.; Wang, H.; Cui, Z.F.; Huang, W.E.; Ye, H. 2020
Stem cells with the capability to self-renew and differentiate into multiple cell derivatives provide platforms for drug screening and promising treatment options for a wide variety of neural... Show moreStem cells with the capability to self-renew and differentiate into multiple cell derivatives provide platforms for drug screening and promising treatment options for a wide variety of neural diseases. Nevertheless, clinical applications of stem cells have been hindered partly owing to a lack of standardized techniques to characterize cell molecular profiles noninvasively and comprehensively. Here, we demonstrate that a label-free and noninvasive single-cell Raman microspectroscopy (SCRM) platform was able to identify neural cell lineages derived from clinically relevant human induced pluripotent stem cells (hiPSCs). By analyzing the intrinsic biochemical profiles of single cells at a large scale (8,774 Raman spectra in total), iPSCs and iPSC-derived neural cells can be distinguished by their intrinsic phenotypic Raman spectra. We identified a Raman biomarker from glycogen to distinguish iPSCs from their neural derivatives, and the result was verified by the conventional glycogen detection assays. Further analysis with a machine learning classification model, utilizing t-distributed stochastic neighbor embedding (t-SNE)-enhanced ensemble stacking, clearly categorized hiPSCs in different develop- mental stages with 97.5% accuracy. The present study demon-strates the capability of the SCRM-based platform to monitor cell development using high content screening with a noninvasive and label-free approach. This platform as well as our identified bio- marker could be extensible to other cell types and can potentially have a high impact on neural stem cell therapy. Show less
Gaio, N.; Silvestri, C.; Meer, B. van; Vollebregt, S.; Mummery, C.L.; Dekker, R. 2016
