Abstract

For decades, the incidence of esophageal adenocarcinoma (EAC) has risen, while the long-term survival rate remains poor. The progression of EAC is marked by superficial changes in cell and tissue microstructure. Early detection of EAC can reduce mortality, but current screening techniques require extensive biopsies because these tissue changes are invisible to conventional endoscopy. Optical coherence tomography (OCT) is being commercialized for screening and guiding biopsies, but is expensive and requires scanning a small beam across the entire surface of the esophagus. Spatial frequency domain imaging (SFDI) can capture microscopic tissue signatures over a wide field of view. However, conventional SFDI integrates signal from many millimeters deep into tissue, which is beyond the depth that OCT and histology observe abnormalities. We are developing a sub-diffuse SFDI system that measures the reflectance of tissues from spatial frequencies of 0 to 0.5 mm⁻¹. Optical property maps of absorption, reduced scattering, and qualitative scattering phase function differences are extracted using diffuse and Monte Carlo models. Scattering phase sensitivity was validated in agar phantoms containing polystyrene beads with a distribution of diameters. Varying the fractal dimensions from 3.50 to 4.25, our reflected measurements varied by 41% for a constant scattering coefficient of 0.6 mm⁻¹ at 851 nm and 0.5 mm⁻¹ spatial frequency. This approach was piloted in ex-vivo porcine tissue, where we observed strong scattering contrast between the esophagus, gastroesophageal junction, and stomach tissue. Future work will measure optical properties of ex-vivo human tissue to guide the design of an endoscope-compatible system.

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