A fluorescence molecular tomography imaging system comprising: an excitation light source; an optical imaging apparatus configured to direct light from the excitation light source into a subject at a plurality of locations; a detector configured to detect at multiple locations fluorescent light emanating from a region within the subject; and a processor configured to process data corresponding to the detected fluorescent light emanating from the region of the subject to produce a tomographic representation of the region of the subject, wherein the processor is configured to execute instructions to: a) establish a forward model of excitation light propagation from the excitation light source to the region of the subject and of fluorescent light propagation from the region to the detector using the data corresponding to the detected fluorescent light, wherein one or more virtual-matching transformation(s) is/are applied to the data corresponding to the detected fluorescent light to account for a refractive index discontinuity at the surface of the subject, and the forward model is established as a weight matrix of elements using one or more functions that do not take into account the presence of the boundary at the surface of the subject such that light propagation is modeled as if the subject is surrounded by an infinite and homogeneous diffusive medium and there is no discontinuity in refractive index at the surface of the subject, wherein the virtual-matching transformation is a transformation that converts fluorescent data obtained from a diffusive object surrounded by free space into data that would be obtained if the same object were surrounded by an optically matching diffusive medium; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject. an excitation light source; an optical imaging apparatus configured to direct light from the excitation light source into a subject at a plurality of locations; a detector configured to detect at multiple locations fluorescent light emanating from a region within the subject; and a processor configured to process data corresponding to the detected fluorescent light emanating from the region of the subject to produce a tomographic representation of the region of the subject, wherein the processor is configured to execute instructions to: a) establish a forward model of excitation light propagation from the excitation light source to the region of the subject and of fluorescent light propagation from the region to the detector using the data corresponding to the detected fluorescent light, wherein one or more virtual-matching transformation(s) is/are applied to the data corresponding to the detected fluorescent light to account for a refractive index discontinuity at the surface of the subject, and the forward model is established as a weight matrix of elements using one or more functions that do not take into account the presence of the boundary at the surface of the subject such that light propagation is modeled as if the subject is surrounded by an infinite and homogeneous diffusive medium and there is no discontinuity in refractive index at the surface of the subject, wherein the virtual-matching transformation is a transformation that converts fluorescent data obtained from a diffusive object surrounded by free space into data that would be obtained if the same object were surrounded by an optically matching diffusive medium; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject. a) establish a forward model of excitation light propagation from the excitation light source to the region of the subject and of fluorescent light propagation from the region to the detector using the data corresponding to the detected fluorescent light, wherein one or more virtual-matching transformation(s) is/are applied to the data corresponding to the detected fluorescent light to account for a refractive index discontinuity at the surface of the subject, and the forward model is established as a weight matrix of elements using one or more functions that do not take into account the presence of the boundary at the surface of the subject such that light propagation is modeled as if the subject is surrounded by an infinite and homogeneous diffusive medium and there is no discontinuity in refractive index at the surface of the subject, wherein the virtual-matching transformation is a transformation that converts fluorescent data obtained from a diffusive object surrounded by free space into data that would be obtained if the same object were surrounded by an optically matching diffusive medium; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject.