Small animal fluorescence and bioluminescence tomography: a review of approaches, algorithms and technology update

Emerging fluorescence and bioluminescence tomography approaches have several common, yet several distinct features from established emission tomographies of PET and SPECT. Although both nuclear and optical imaging modalities involve counting of photons, nuclear imaging techniques collect the emitted high energy (100–511 keV) photons after radioactive decay of radionuclides while optical techniques count low-energy (1.5–4.1 eV) photons that are scattered and absorbed by tissues requiring models of light transport for quantitative image reconstruction. Fluorescence imaging has been recently translated into clinic demonstrating high sensitivity, modest tissue penetration depth, and fast, millisecond image acquisition times. As a consequence, the promise of quantitative optical tomography as a complement of small animal PET and SPECT remains high. In this review, we summarize the different instrumentation, methodological approaches and schema for inverse image reconstructions for optical tomography, including luminescence and fluorescence modalities, and comment on limitations and key technological advances needed for further discovery research and translation.