Optical coherence tomography-guided confocal Raman microspectroscopy for rapid measurements in tissues

: We report a joint system with both confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) modules capable of quickly addressing the region of interest in a tissue for targeted Raman measurements from OCT. By using an electrically tunable lens in the Raman module, the focus of the module can be adjusted to address any specific depth indicated in an OCT image in a few milliseconds. We demonstrate the performance of the joint system in the depth dependent measurements of an ex vivo swine tissue and in vivo human skin. This system can be useful in measuring samples embedded with small targets, for example, to identify tumors in skin in vivo and assessment of tumor margins, in which OCT can be used to perform initial real-time screening with high throughput based on morphological features to identify suspicious targets then CRS is guided to address the targets in real time and fully characterize their biochemical fingerprints for confirmation.

[1]  Zhenan Bao,et al.  Multifunctional materials for implantable and wearable photonic healthcare devices , 2020, Nature Reviews Materials.

[2]  Lara M. Wurster,et al.  Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy. , 2019, The Analyst.

[3]  Quan Liu,et al.  Depth-sensitive Raman spectroscopy for skin wound evaluation in rodents. , 2019, Biomedical optics express.

[4]  Cilwyn S Braganza,et al.  Geometry-Dependent Spectroscopic Contrast in Deep Tissues , 2019, iScience.

[5]  Dayna E Every,et al.  Classification of burn injury using Raman spectroscopy and optical coherence tomography: An ex-vivo study on porcine skin. , 2019, Burns : journal of the International Society for Burn Injuries.

[6]  Robert R. Alfano,et al.  A pilot study for distinguishing basal cell carcinoma from normal human skin tissues using visible resonance Raman spectroscopy , 2019, Journal of Cancer Metastasis and Treatment.

[7]  Jürgen Popp,et al.  Combination of High-Resolution Optical Coherence Tomography and Raman Spectroscopy for Improved Staging and Grading in Bladder Cancer , 2018, Applied Sciences.

[8]  U. Morgner,et al.  Trimodal system for in vivo skin cancer screening with combined optical coherence tomography‐Raman and colocalized optoacoustic measurements , 2018, Journal of biophotonics.

[9]  Yao Zhang,et al.  Raman biophysical markers in skin cancer diagnosis , 2018, Journal of biomedical optics.

[10]  Wei Zheng,et al.  Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique , 2018, Journal of biophotonics.

[11]  G. Sriram,et al.  Physical and compositional analysis of differently cultured 3D human skin equivalents by confocal Raman spectroscopy. , 2018, The Analyst.

[12]  Jason R. Maher,et al.  Full depth measurement of tenofovir transport in rectal mucosa using confocal Raman spectroscopy and optical coherence tomography , 2018, Drug Delivery and Translational Research.

[13]  F. O'Brien,et al.  Raman spectroscopy predicts the link between claw keratin and bone collagen structure in a mouse model of oestrogen deficiency , 2017 .

[14]  Christian Matthäus,et al.  Detection and characterization of early plaque formations by Raman probe spectroscopy and optical coherence tomography: an in vivo study on a rabbit model , 2018, Journal of biomedical optics.

[15]  Kishan Dholakia,et al.  Depth‐resolved multimodal imaging: Wavelength modulated spatially offset Raman spectroscopy with optical coherence tomography , 2018, Journal of biophotonics.

[16]  A. Kotzianová,et al.  Non‐invasive diagnostic system and its opto‐mechanical probe for combining confocal Raman spectroscopy and optical coherence tomography , 2017, Journal of biophotonics.

[17]  U. Morgner,et al.  Development of a combined OCT-Raman probe for the prospective in vivo clinical melanoma skin cancer screening. , 2017, The Review of scientific instruments.

[18]  Jason R. Maher,et al.  Label-free analysis of tenofovir delivery to vaginal tissue using co-registered confocal Raman spectroscopy and optical coherence tomography , 2017, PloS one.

[19]  Christian Matthäus,et al.  Combination of OCT and Raman spectroscopy for improved characterization of atherosclerotic plaque depositions , 2017 .

[20]  C. Perlaki,et al.  Snapshot depth sensitive Raman spectroscopy in layered tissues. , 2016, Optics express.

[21]  Guillermo L. Monroy,et al.  Rapid diagnosis and differentiation of microbial pathogens in otitis media with a combined Raman spectroscopy and low-coherence interferometry probe: toward in vivo implementation , 2016, Journal of biomedical optics.

[22]  Wei Zheng,et al.  Development of a hybrid Raman spectroscopy and optical coherence tomography technique for real-time in vivo tissue measurements. , 2016, Optics letters.

[23]  Lutz Franzen,et al.  Applications of Raman spectroscopy in skin research--From skin physiology and diagnosis up to risk assessment and dermal drug delivery. , 2015, Advanced drug delivery reviews.

[24]  M. Schmitt,et al.  The combination of optical coherence tomography and Raman spectroscopy for tissue characterization , 2015 .

[25]  Adam Wax,et al.  Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue. , 2015, Biomedical optics express.

[26]  Werner Gellermann,et al.  Optical detection methods for carotenoids in human skin. , 2015, Archives of biochemistry and biophysics.

[27]  Valery P Zakharov,et al.  Comparative analysis of combined spectral and optical tomography methods for detection of skin and lung cancers , 2015, Journal of biomedical optics.

[28]  Kirill V. Larin,et al.  Line-scan Raman microscopy complements optical coherence tomography for tumor boundary detection , 2014 .

[29]  Y. Silberberg,et al.  Hybrid single-source online Fourier transform coherent anti-Stokes Raman scattering/optical coherence tomography. , 2014, Optics letters.

[30]  Kirill V. Larin,et al.  Improvement of tissue analysis and classification using optical coherence tomography combined with Raman spectroscopy , 2014, Photonics West - Biomedical Optics.

[31]  Kishan Dholakia,et al.  Multi-modal approach using Raman spectroscopy and optical coherence tomography for the discrimination of colonic adenocarcinoma from normal colon. , 2013, Biomedical optics express.

[32]  Michel Manfait,et al.  Confocal Raman microspectroscopy for skin characterization: a comparative study between human skin and pig skin. , 2012, The Analyst.

[33]  Maxim E. Darvin,et al.  The Role of Carotenoids in Human Skin , 2011, Molecules.

[34]  Anita Mahadevan-Jansen,et al.  A clinical instrument for combined raman spectroscopy‐optical coherence tomography of skin cancers , 2011, Lasers in surgery and medicine.

[35]  Wei Zheng,et al.  Fiber-optic Raman probe couples ball lens for depth-selected Raman measurements of epithelial tissue , 2010, Biomedical optics express.

[36]  Rui Liu,et al.  Optical coherence tomography and Raman spectroscopy of the ex‐vivo retina , 2009, Journal of biophotonics.

[37]  Matthew D. Keller,et al.  Combined Raman spectroscopy and optical coherence tomography device for tissue characterization. , 2008, Optics letters.

[38]  Effendi Widjaja,et al.  A novel method for human gender classification using Raman spectroscopy of fingernail clippings. , 2008, The Analyst.

[39]  D. McLean,et al.  Automated Autofluorescence Background Subtraction Algorithm for Biomedical Raman Spectroscopy , 2007, Applied spectroscopy.

[40]  Juergen Lademann,et al.  Porcine ear skin: an in vitro model for human skin , 2007, Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging.

[41]  S. Lieberman,et al.  Fluorescence Rejection in Raman Spectroscopy by Shifted-Spectra, Edge Detection, and FFT Filtering Techniques , 1995 .

[42]  Anita Mahadevan-Jansen,et al.  Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography. , 2011, Journal of biomedical optics.