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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).

ReferencesEdit

  • Cherry S R (2004), "In vivo molecular and genomic imaging: new challenges for imaging physics" Phys. Med. Biol. 49 R13-48.
  • Comtat C, P E Hinahan, J A Fessler, T Beyer, D W Townsens, M Defrise, and C Michel (2002), "Clinically feasible reconstruction of 3D whole-body PET/CT data using blurred anatomical labels" Phys. Med. Biol. 47 1-20.
  • Cubeddu R, D Comelli, C D'Andrea, P Taroni, and G Valentini (2002), "Time-resolved fluorescence imaging in biology and medicine" J. Phys. D: Appl. Phys. 35 R61-76.
  • Culver J P, T Durduran, D Furuya, C Cheung, J H Greenberg, and A G Yodh (2003), "Diffuse optical tomography of cerebral blood flow, oxygenation and metabolism in rat during focal ischaemia" J. Cereb. Blood Flow & Metab. 23 911-924.
  • Godovarty A, A B Thompson, R Roy, M Gurfinkel, M Eppstein, C Zhang, and E M Sevick-Muraca (2004), "Diagnostic imaging of breast cancer using fluorescence-enhanced optical tomography: phantom studies" J. Biomed. Opt. 9(3) 488-496.
  • Goertzen A L, A K Meadors, R W Silverman, and S R Cherry (2002), "Simultaneous molecular and anatomical imaging of the mouse in vivo" Phys. Med. Biol. 47 4315-4328.
  • Hawrysz D J and E M Sevick-Muraca (2000), "Developments towards diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents" Neoplasia 2(5) 388-417.
  • Hillman E M C, D A Boas, A M Dale, and A K Dunn (2004), "Laminar optical tomography: demonstration of millimetre-scale depth-resolved imaging in turbid media" Opt. Lett. 29(14) 1650-1652.
  • Klose A D and A H Hielscher (2003), "Fluorescence tomography with simulated data based on the equation of radiative transfer" Opt. Lett. 28(12) 1019-1021.
  • Ntziachristos V and B Chance (2001), "Probing physiology and molecular function using optical imaging: applications to breast cancer" Breast Cancer Res. 3 41-46.
  • Ntziachristos V, J Ripoll, and R Weisslader (2002a), "Would near infra-red fluorescence signals propagate through large human organs for clinical studies? (with errata 27(18) p1652)" Optics Letters 27(5) 333-335.
  • Ntziachristos V, C-H Tung, C Bremer, and R Weisslader (2002b), "Fluorescence molecular tomography resolves protease activity in vivo" Nature Medicine 8(7) 757-760.
  • Schulz R B, J Ripoll, and V Ntziachristos (2003), "Noncontact optical tomography of turbid media" Optics Letters 28(18) 1701-1703.
  • Schulz R B, J Ripoll, and V Ntziachristos (2004), "Experimental fluorescence tomography of tissues with noncontact measurements" IEEE Trans. Med. Imag. 23(4) 492-500.
  • Siegel A M, J P Culver, J B Mandeville, and D A Boas (2003), "Temporal comparison of functional brain imaging with diffuse optical tomography and fMRI during rat forepaw stimulation" Phys. Med. Biol. 48 1391-1403.
  • Weisslader R and V Ntziachristos (2003), "Shedding light onto live molecular targets" Nature Medicine 9(1) 123-128.
  • Xu H, H Dehghani, B W Pogue, R Springett, K D Paulsen, and J F Dunn (2003), "Near-infrared imaging in the small animal brain: optimization of fiber positions" J. Biomed. Opt. 8(1) 102-110.

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