Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue

Maher, Jason R.; Chuchuen, Oranat; Henderson, Marcus H.; Kim, Sang-Hoon; Rinehart, Matthew T.; Kashuba, Angela D. M.; Wax, Adam; Katz, David F.

doi:10.1364/boe.6.002022

Cited by 30 publications

(43 citation statements)

References 39 publications

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“…A custom built CRS-OCT (confocal Raman spectroscopy and optical coherence tomography) instrument integrated with a white-light camera was used to acquire data in this study. 19 The axial and lateral resolutions of the CRS subsystem are 19 and 3 μm, respectively. The OCT subsystem has an axial resolution of 8 μm and a lateral resolution of 40 μm, and the white-light camera offers a lateral resolution of 2 μm.…”

Section: Methodsmentioning

confidence: 99%

“…A custom Matlab script was used to process raw spectral data, as outlined previously. 19 The contributions of tenofovir to each Raman spectrum were established by ordinary least squares fitting. A representative fit with the Raman spectral contributions of Tenofovir, gel, and vaginal fluid simulant is displayed in Figure 2.…”

Section: Methodsmentioning

confidence: 99%

“…13 Recently, our group applied high-resolution confocal RS (CRS) to measure concentrations of microbicide drugs in liquids and their concentration distributions in porcine tissues, using a Transwell configuration. 18,19 Here, we constructed a custom horizontal diffusion cell enabling measurements of spatiotemporal concentration distributions of the microbicide drug tenofovir in its clinical vaginal gel. 2,20,21 These data were fit with a time-dependent diffusion model to obtain diffusion coefficients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy

Chuchuen

Maher

Simons

et al. 2017

Journal of Pharmaceutical Sciences

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Confocal Raman spectroscopy was implemented in a new label-free technique to quantify molecular diffusion coefficients within gels. A leading anti-HIV drug, tenofovir, was analyzed in a clinical microbicide gel. The gel was tested undiluted, and in 10 – 50%w/w dilutions with vaginal fluid simulant to capture the range of conditions likely occurring in vivo. The concentration distributions of tenofovir in gel over time and space were measured and input to a mathematical diffusion model to deduce diffusion coefficients. These were 3.16 ± 0.11 × 10-6 cm2/s in undiluted gel, and increased by 11 – 46% depending upon the extent of dilution. Results were interpreted with respect to traditional release rate measurements in devices such as Franz cells. This comparison highlighted an advantage of our assay in that it characterizes the diffusive barrier within the gel material itself; in contrast, release rate in the traditional assay is affected by external conditions, such as drug partitioning at the gel/liquid sink interface. This new assay is relevant to diffusion in polymeric hydrogels over pharmacologically relevant length scales, e.g. those characteristic of topical drug delivery. Resulting transport parameters are salient measures of drug delivery potential, and serve as inputs to computational models of drug delivery performance.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy

Chuchuen

Maher

Simons

et al. 2017

Journal of Pharmaceutical Sciences

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“…Various illumination and detection schemes have been combined with RS providing different trade‐offs in resolution, penetration depth, and contrast. Confocal detection, for example, provides high spatial resolution up to approximately one transport length below the sample surface . When measuring bone, confocal RS is primarily sensitive to the cortex, as the transport length of near‐infrared light in bone is only about 500 microns .…”

Section: Introductionmentioning

confidence: 99%

Sensitivity of spatially offset Raman spectroscopy (SORS) to subcortical bone tissue

et al. 2017

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The development of spatially offset Raman spectroscopy (SORS) has enabled deep, non-invasive chemical characterization of turbid media. Here, we use SORS to measure subcortical bone tissue and depth-resolved biochemical variability in intact, exposed murine bones. We also apply the technique to study a mouse model of the genetic bone disorder osteogenesis imperfecta. The results suggest that SORS is more sensitive to disease-related biochemical differences in subcortical trabecular bone and marrow than conventional Raman measurements.

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“…It is highly desirable to combine the RS and OCT techniques for simultaneously acquiring both tissue morphology and biochemical information on the same tissue in real‐time. Previous studies on the combined RS and OCT are largely limited to the bench‐top optics , and the 2 optical techniques are conducted sequentially with lengthy acquisition time , unsuited for rapid in vivo tissue measurements in clinical settings. Since the biochemical and morphological profiles of distinctive anatomical regions in the oral cavity can be highly functionally specialized and exhibit significant variations in architectural properties and cell types (eg, tissue thickness, distinct epithelium types, vascularity, papillae, bone, etc.)…”

Section: Introductionmentioning

confidence: 99%

Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique

Wang

Zheng

Lin

et al. 2017

Journal of Biophotonics

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This study aims to characterize biochemical and morphological variations of the clinically relevant anatomical locations of in vivo oral tissue (ie, alveolar process, lateral tongue and floor of the mouth) by using hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) technique. A total of 1049 in vivo fingerprint (FP: 800-1800 cm ) and high wavenumber (HW: 2800-3600 cm ) Raman spectra were acquired from different oral tissue (alveolar process = 331, lateral tongue = 339 and floor of mouth = 379) of 26 normal subjects in the oral cavity under the OCT imaging guidance. The total Raman dataset were split into 2 parts: 80% for training and 20% for testing. Tissue optical attenuation coefficients of alveolar process, lateral tongue and the floor of the mouth were derived from OCT images, revealing the inter-anatomical morphological differences; while RS uncovers subtle FP/HW Raman spectral differences among different oral tissues that can be attributed to the differences in inter- and intra-cellular proteins, lipids, DNA and water structures and conformations, enlightening biochemical variability of different oral tissues at the molecular level. Partial least squares-discriminant analysis implemented on the training dataset show that the integrated tissue optical attenuation coefficients and FP/HW Raman spectra provide diagnostic sensitivities of 99.6%, 82.3%, 50.2%, and specificities of 97.0%, 75.1%, 92.1%, respectively, which are superior to using either RS (sensitivities of 90.2%, 77.5%, 48.8%, and specificities of 95.8%, 72.1%, 88.8%) or optical attenuation coefficients derived from OCT (sensitivities of 75.0%, 78.2%, 47.2%, and specificities of 96.2%, 67.7%, 85.0%) for the differentiation among alveolar process, lateral tongue and the floor of the mouth. Furthermore, the diagnostic algorithms applied to the independent testing dataset based on hybrid RS-OCT technique gives predictive diagnostic sensitivities of 100%, 76.5%, 51.3%, and specificities of 95.1%, 77.6%, 89.6%, respectively, for the classifications among alveolar process, lateral tongue and the floor of the mouth, which performs much better than either RS or optical attenuation coefficient derived from OCT imaging. This work suggests that inter-anatomical morphological and biochemical variability are significant which should be considered as an important parameter in the interpretation and rendering of hybrid RS-OCT technique for oral tissue diagnosis and characterization.

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Co-localized confocal Raman spectroscopy and optical coherence tomography (CRS-OCT) for depth-resolved analyte detection in tissue

Cited by 30 publications

References 39 publications

Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy

Label-Free Measurements of Tenofovir Diffusion Coefficients in a Microbicide Gel Using Raman Spectroscopy

Sensitivity of spatially offset Raman spectroscopy (SORS) to subcortical bone tissue

Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique

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