Historically, optical imaging as the first imaging device uses visible light as source of imaging but with very limited tissue penetration. The most common optical imaging modalities used for in vivo small animal imaging are the fluorescence and bioluminescence imaging systems. Fluorescence imaging gets its source for imaging from fluorochromes injected inside the subject that are excited by an external light source and emitting light of a different wavelength in response. Traditional fluorochromes include GFP, RFP, and their many other mutants. Recently, near-infrared dyes and infrared fluorescent proteins (700 nm-800 nm) are used due to low autofluorescence and deeper tissue penetration at these wavelengths. Bioluminescence imaging, on the other hand, is based on light generated by chemiluminescent enzymatic reactions such as luciferase. In both fluorescence and bioluminescence, the light signals are captured by Charged Coupled Device (CCD) cameras cooled up to -95 °F to be extremely light sensitive.