Abstract
Non-contact and minimally invasive endoscopic optical imaging is an invaluable diagnostic tool for tissue examination and cancer screening. The point sampling techniques with high sensitivity to the tissue microenvironment are time consuming and often not affordable in clinics. There is a major clinical need for a large field-of-view (FOV) rapid screening method to highlight subtle tissue microstructural alterations. To address this unmet need, we have developed High Spatial Frequency Domain Imaging (HSFDI)-a non-contact imaging modality that spatially maps the tissue microscopic scattering structures over a large field of view (>1cm2). Based on an analytical reflectance model of sub-diffusive light from forward-peaked highly scattering media, HSFDI quantifies the spatially-resolved parameters of the light scattering phase function (i.e., the backscattering probability and the light spreading length) from the reflectance of structured light modulated at high spatial frequencies. Enhanced signal to noise ratio (SNR) is achieved at even ultra-high modulation frequencies with single snapshot multiple frequency demodulation (SSMD). The variations in tissue microstructures, including the strength of the background (pudding) refractive index fluctuation and the prominent scattering structure (plum) morphology, can then be inferred. After validation with optical phantoms, measurements of fresh ex vivo tissue samples revealed significant contrast and differentiation of the phase function parameters between different types and disease states (normal, inflammatory, and cancerous) of tissue whereas tissue absorption and reduced scattering coefficients only show modest changes. HSFDI may provide wide-field images of microscopic structural biomarkers unobtainable with either diffuse light imaging or point-based optical sampling. Potential clinical applications include the rapid screening of excised tissue and the noninvasive examination of suspicious lesions during operation.
Highlights
One central tenet in the application of light in biology and medicine is noninvasive diagnosis of the structure and function of tissue from tissue-light interaction [1]
Based on an analytical reflectance model of sub-diffusive light from forward-peaked highly scattering media [24], High Spatial Frequency Domain Imaging (HSFDI) quantifies the map of the backscattering probability pπ and the light spreading length lΘ governing sub-diffusive light from the reflectance of structured light modulated at high spatial frequencies (>1mm−1)
We have presented High Spatial Frequency Domain Imaging (HSFDI)–a non-contact imaging modality that spatially maps the tissue microscopic scattering structures over a large field of view (>1cm2)
Summary
One central tenet in the application of light in biology and medicine is noninvasive diagnosis of the structure and function of tissue from tissue-light interaction [1]. Non-contact and minimally invasive endoscopic optical imaging is an invaluable diagnostic tool for tissue examination and cancer screening. As tissue microstructure represents the refractive index variation which scatters light, scattered light by tissue has been used extensively to identify structural alterations or heterogeneities in tissue due to disease or physiological variations [2,3]. Fiber-optics based [4] and confocal [5] techniques have been successfully used to detect such changes in the superficial layer of tissue. The subwavelength features of microstructures at tens of nanometers have been quantified with scattered light as well with point spectroscopic detection [6,7]. A critical drawback of those approaches for clinical applications is that cumbersome and time consuming raster scanning is required for widefield imaging and often not affordable in clinics
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