Abstract
Intraepithelial dysplasia of the oral mucosa typically originates in the proliferative cell layer at the basement membrane and extends to the upper epithelial layers as the disease progresses. Detection of malignancies typically occurs upon visual inspection by non-specialists at a late-stage. In this manuscript, we validate a quantitative hybrid imaging and spectroscopy microendoscope to monitor dysplastic progression within the oral cavity microenvironment in a phantom and pre-clinical study. We use an empirical model to quantify optical properties and sampling depth from sub-diffuse reflectance spectra (450–750 nm) at two source-detector separations (374 and 730 μm). Average errors in recovering reduced scattering (5–26 cm−1) and absorption coefficients (0–10 cm−1) in hemoglobin-based phantoms were approximately 2% and 6%, respectively. Next, a 300 μm-thick phantom tumor model was used to validate the probe’s ability to monitor progression of a proliferating optical heterogeneity. Finally, the technique was demonstrated on 13 healthy volunteers and volume-averaged optical coefficients, scattering exponent, hemoglobin concentration, oxygen saturation, and sampling depth are presented alongside a high-resolution microendoscopy image of oral mucosa from one volunteer. This multimodal microendoscopy approach encompasses both structural and spectroscopic reporters of perfusion within the tissue microenvironment and can potentially be used to monitor tumor response to therapy.
Highlights
Demonstrated in various body organs including the oral cavity[7,11], esophagus[12,13,14,15], lower gastrointestinal tract[16,17,18,19,20,21], cervix[22,23], ear[24,25,26], and liver and pancreas[27]
We have recently reported on a probe-based technique that combines high-resolution microendoscopy imaging, and a form of DRS called broadband sub-diffuse reflectance spectroscopy within a single fiber-bundle[29,53]
The high-resolution imaging modality may be beneficial in providing image data of later stage moderate and severe dysplasia while the sub-diffuse reflectance spectroscopy (sDRS) modality may be sensitive to tissue optical changes associated with early dysplasia arising at the basement membrane[29]
Summary
Demonstrated in various body organs including the oral cavity[7,11], esophagus[12,13,14,15], lower gastrointestinal tract[16,17,18,19,20,21], cervix[22,23], ear[24,25,26], and liver and pancreas[27]. The term “sub-diffuse reflectance” is used here to be distinguished from “diffuse reflectance” to describe the cases in which our source-detector separations (SDS) are less than one reduced mean-free path within a sample, which will vary based on a sample’s optical properties[40,54,55,56,57,58] This hybrid fiber-bundle spectroscopy and imaging probe is capable of co-registering qualitative high-resolution images of tissue surface microarchitecture with complimentary quantitative and depth-sensitive spectral data[29,53]. The extracted in vivo quantitative optical parameters were compared to an in vivo high-resolution image of healthy, non-keratinized oral tissue These studies validate our hybrid fiber-bundle imaging and spectroscopy technique and demonstrate the translational potential to a clinical setting. This technique can potentially be used to for diagnostic purposes as well as dynamically monitoring personalized tumor response to therapy
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