A method for inverting measurements made on the surfaces of tissues for recovery of interior optical property maps is demonstrated for sparse near-infrared (NIR) fluorescence measurement sets on large tissue-simulating volumes with highly variable signal-to-noise ratio. A Bayesian minimum-variance reconstruction algorithm compensates for the spatial variability in signal-to-noise ratio that must be expected to occur in actual NIR contrast-enhanced diagnostic medical imaging. Image reconstruction is demonstrated by using frequency-domain photon migration measurements on 256-cm(3) tissue-mimicking phantoms containing none, one, or two 1-cm(3) heterogeneities with 50- to 100-fold greater concentration of Indocyanine Green dye over background levels. The spatial parameter estimate of absorption owing to the dye was reconstructed from only 160 to 296 surface measurements of emission light at 830 nm in response to incident 785-nm excitation light modulated at 100 MHz. Measurement error of acquired fluence at fluorescent emission wavelengths is shown to be highly variable. Convergence and quality of image reconstructions are improved by Bayesian conditioning incorporating (i) experimentally determined measurement error variance, (ii) recursively updated estimates of parameter uncertainty, and (iii) dynamic zonation. The results demonstrate that, to employ NIR fluorescence-enhanced optical imaging for large volumes, reconstruction approaches must account for the large range of signal-to-noise ratio associated with the measurements.