Imaging systems featuring waveguiding compensation

A fluorescence molecular tomography imaging system comprising:

• an excitation light source;
• an optical imaging chamber configured to direct excitation light from said excitation light source into an object disposed within said chamber at multiple locations;
• a detector configured to detect at multiple locations excitation light emanating from said object, thereby acquiring an intrinsic image, and fluorescent light emitted from one or more probes within or on a surface of said object, thereby acquiring a detected emission image;
• and
• a processor configured to process data from said intrinsic image and said detected emission image to provide a representation of said region within said object, said representation compensated for waveguiding effects, wherein said processor is configured to perform the following:
• (i) create an estimated emission image using at least said intrinsic image and alter said detected emission image using at least said estimated emission image;
• and
• (ii) determine a coincidence mask from said intrinsic image and said detected emission image and alter said detected emission image using at least said coincidence mask.