Optical molecular imaging

Molecular imaging is a rapidly growing research field in which contrast agents are bound to specific proteins or genes and used to image the distribution of targeted molecules in small animal models (Weisslader and Ntziachristos 2003, Cherry 2004). The recent growth in molecular imaging has largely been triggered by the success of the Human Genome Project and improvements in biochemical techniques. Molecular imaging has traditionally involved tracking radioactive tracers (Goertzen et al. 2002, Comtat et al. 2002) but optical techniques, particularly fluorescence imaging, are increasingly finding a role (Cubeddu et al. 2002, Ntziachristos et al. 2002b). Combining the new contrast agents with diffuse optical imaging in animal models is likely to become a very powerful tool in the development of new drugs and the study of haemodynamics in animal models (Culver et al. 2003).

Several interesting theoretical issues must be addressed in molecular imaging. The animal typically used in drug development is small compared to human organs and photons may travel only a few transport scattering lengths before detection. This means that the diffusion approximation may not be valid, and therefore higher order approximations are required (Klose and Hielscher 2003). Because of the difficulty of attaching optical fibres to such a small experimental model, (Schulz et al. 2003, 2004) have developed non-contact imaging techniques, based on first determining the surface of the animal and then solving a forward model where a free-space region is coupled to a diffusive region. Hillman et al. (2004) have developed an approach, designed for imaging the rat cortex, in which a microscope acts as a non-contact source and detector, providing data which is modelled using a Monte Carlo simulation and reconstructed using diffuse optical tomography techniques. The use of prior information in optical molecular imaging is also valuable, both to assist the optical image reconstruction (Xu et al. 2003) and to independently validate the optical results (Siegel et al. 2003).

Fluorescence imaging is ideally suited to molecular imaging as the small penetration depths in small animals ensures that a strong signal is obtained. However, Ntziachristos et al. (2002a) are optimistic that, given improvements in detector technology, it will be possible to measure a fluorescence signal across the breast, and Godovarty et al. (2004) have already measured fluorescence signals across a breast-like phantom. Progress in this area could lead to development of a range of valuable clinical techniques (Ntziachristos and Chance 2001). Fluorescence imaging of the breast has been reviewed in detail by Hawrysz and Sevick-Muraca (2000).