Significance: The shortwave infrared (SWIR) optical window (∼900 to 2000 nm) has attracted interest for deep tissue imaging due to the lower scattering of light. SWIR spatial frequency domain imaging (SWIR SFDI) provides wide-field tissue optical property measurements in this wavelength band. Key design and performance characteristics, such as portability, wavelength selection, measurement resolution, and the effect of skin have not yet been addressed for SWIR SFDI.

Aim: To fabricate and characterize a SWIR SFDI system for clinical use.

Approach: The optimal choice of wavelengths was identified based on optical property uncertainty estimates and imaging depth. A compact light-emitting diode-based dual wavelength SWIR SFDI system was fabricated. A two-layer inverse model was developed to account for the layered structure of skin. Performance was validated using tissue-simulating phantoms and in-vivo measurements from three healthy subjects.

Results: The SWIR SFDI system had a μs′ resolution of at least 0.03  mm^−  1 at 880 nm and 0.02  mm^−  1 at 1100 nm. The two-layer inverse model reduced the error in deeper layer μs′ extractions by at least 24% in the phantom study. The two-layer model also increased the contrast between superficial vessels and the surrounding tissue for in-vivo measurements.

Conclusion: The clinic-ready SWIR SFDI device is sensitive to small optical property alterations in diffuse media, provides enhanced accuracy in quantifying optical properties in the deeper layers in phantoms, and provided enhanced contrast of subcutaneous blood vessels.