There is a major drive in Tissue Engineering towards creating functional tissues or organs in vitro in 3D thick scaffolds. Such scaffolds are generally thick (few mm) and constructed using biomaterials that are highly-scattering (such as elastin or collagen). Hence, laser scanning microscopy techniques (e.g., confocal and two-photon) cannot image entirely these scaffolds as the depth penetration of such techniques is still limited by the scattering properties of the sample. Thus, there is a critical need to develop new imaging techniques that can image well beyond the penetration limits of conventional microscopy. We develop novel multispectral mesoscopic fluorescence molecular imaging platform to this end.