Frequency-domain diffuse optical spectroscopy (FD-DOS) is a powerful non-invasive technique for assessing tissue optical properties, with applications ranging from basic research to clinical diagnosis. In this study, we introduce and validate a novel approach termed the cross-wavelength calibrating (CWC) method within the framework of TrackDOSI, a real-time FD-DOS imaging system for tissue characterization. The CWC method aims to mitigate the effects of changing optical coupling and motion artifacts encountered during probe scanning, thus enhancing the accuracy and reliability of optical property measurements. Notably, the CWC method also allows for a simpler geometry with fewer sources than traditional self-calibrating (SC) methods, reducing instrumental complexity and cost while maintaining robustness in estimating optical properties. We first validate the CWC method on solid silicone phantoms, demonstrating strong agreement with the gold standard SC method with an error of -10% and 1% for absorption and reduced scattering coefficients, respectively. Furthermore, experiments on phantom and human tissue reveal the CWC approach's ability to suppress motion artifacts and optical coupling variations, thereby improving measurement repeatability, signal fidelity, and artifact correction in dynamic imaging scenarios. Our findings underscore the potential of the CWC method to enhance the clinical utility of DOSI techniques by enabling real-time artifact correction and improving the accuracy of tissue optical property measurements.
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