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Significance : Spatial frequency domain imaging (SFDI) is a diffuse optical measurement technique that can quantify tissue optical absorption (μ a ) and reduced scattering (&lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt;) on a pixel-by-pixel basis. Measurements of μ a at different wavelengths enable the extraction of molar concentrations of tissue chromophores over a wide field, providing a noncontact and label-free means to assess tissue viability, oxygenation, microarchitecture, and molecular content. We present here openSFDI: an open-source guide for building a low-cost, small-footprint, three-wavelength SFDI system capable of quantifying μ a and &lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt; as well as oxyhemoglobin and deoxyhemoglobin concentrations in biological tissue. The companion website provides a complete parts list along with detailed instructions for assembling the openSFDI system.&lt;p&gt; Aim : We describe the design of openSFDI and report on the accuracy and precision of optical property extractions for three different systems fabricated according to the instructions on the openSFDI website.&lt;/p&gt; &lt;p&gt; Approach : Accuracy was assessed by measuring nine tissue-simulating optical phantoms with a physiologically relevant range of μ a and &lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt; with the openSFDI systems and a commercial SFDI device. Precision was assessed by repeatedly measuring the same phantom over 1 h.&lt;/p&gt; &lt;p&gt; Results : The openSFDI systems had an error of 0  ±  6  %   in μ a and -2  ±  3  %   in &lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt;, compared to a commercial SFDI system. Bland-Altman analysis revealed the limits of agreement between the two systems to be   ±  0.004  mm   -  1 for μ a and -0.06 to 0.1  mm   -  1 for &lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt;. The openSFDI system had low drift with an average standard deviation of 0.0007  mm   -  1 and 0.05  mm   -  1 in μ a and &lt;inline-formula&gt;μ    s    '&lt;/inline-formula&gt;, respectively.&lt;/p&gt;,&lt;p&gt; Conclusion : The openSFDI provides a customizable hardware platform for research groups seeking to utilize SFDI for quantitative diffuse optical imaging.&lt;/p&gt;

OpenSFDI: an open-source guide for constructing a spatial frequency domain imaging system