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 of 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: (i) the excitation light source is represented in real space; (ii) the detected fluorescent light is represented in frequency space; (iii) in the forward model, boundary removal equations are used to convert data corresponding to the surface of the subject into a simulated infinite homogeneous medium; and (iv) the forward model is established as a discretized weight matrix of normalized elements; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject in real space. 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 of 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: (i) the excitation light source is represented in real space; (ii) the detected fluorescent light is represented in frequency space; (iii) in the forward model, boundary removal equations are used to convert data corresponding to the surface of the subject into a simulated infinite homogeneous medium; and (iv) the forward model is established as a discretized weight matrix of normalized elements; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject in real space. 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: (i) the excitation light source is represented in real space; (ii) the detected fluorescent light is represented in frequency space; (iii) in the forward model, boundary removal equations are used to convert data corresponding to the surface of the subject into a simulated infinite homogeneous medium; and (iv) the forward model is established as a discretized weight matrix of normalized elements; and (i) the excitation light source is represented in real space; (ii) the detected fluorescent light is represented in frequency space; (iii) in the forward model, boundary removal equations are used to convert data corresponding to the surface of the subject into a simulated infinite homogeneous medium; and (iv) the forward model is established as a discretized weight matrix of normalized elements; and b) invert the weight matrix to obtain the tomographic representation of the region of the subject in real space. <EOS>