Optimization of diffuse Raman spectroscopy for in-vivo quantification of foreign body response in a small animal model

Dooley, Max; Luckett, Jeni; Alexander, Morgan R.; Matousek, Pavel; Dehghani, Hamid; Ghaemmaghami, Amir M.; Notingher, Ioan

Abstract

Diffuse Raman spectroscopy (DRS) allows subsurface molecular analysis of optically turbid samples. Numerical modeling of light propagation was used as a method for improving the design of an DRS instrument to maximize the signal to noise ratio (SNR) while ensuring safe laser exposure parameters required for in-vivo measurements. Experimental validation of the model was performed on both phantom samples and disks implanted postmortem to mimic the typical response to foreign bodies (formation of a fibrotic capsule around an implant). A reduction of laser exposure of over 1500-fold was achieved over previous studies whilst maintaining the same Raman collection rates and reaching the safe power density of 3 mW/mm2. The validation of this approach in a subcutaneous implant in a mouse cadaver showed a further improvement of 1.5-fold SNR, with a thickness limit of detection for the fibrotic layer of 23 µm, under the same acquisition times. In the animal body, a thickness limit of detection of 16 µm was achieved. These results demonstrate the feasibility of numerical model-based optimization for DRS, and that the technique can be improved sufficiently to be used for in-vivo measurement of collagenous capsule formation as a result of the foreign body response in murine models.

Citation

Dooley, M., Luckett, J., Alexander, M. R., Matousek, P., Dehghani, H., Ghaemmaghami, A. M., & Notingher, I. (2023). Optimization of diffuse Raman spectroscopy for in-vivo quantification of foreign body response in a small animal model. Biomedical Optics Express, 14(12), 6592-6606. https://doi.org/10.1364/boe.512118

• Journal Article Type: Article
• Acceptance Date: Nov 13, 2023
• Online Publication Date: Nov 29, 2023
• Publication Date: Dec 1, 2023
• Deposit Date: Dec 2, 2023
• Publicly Available Date: Dec 6, 2023
• Journal: Biomedical Optics Express
• Electronic ISSN: 2156-7085
• Publisher: Optical Society of America
• Peer Reviewed: Peer Reviewed
• Volume: 14
• Issue: 12
• Pages: 6592-6606
• DOI: https://doi.org/10.1364/boe.512118
• Keywords: Atomic and Molecular Physics, and Optics; Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/27874306
• Publisher URL: https://opg.optica.org/boe/fulltext.cfm?uri=boe-14-12-6592&id=542942
• Additional Information: Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.