MR techniques for in vivo molecular and cellular imaging.

MR-based molecular imaging is a science in infancy. Current clinical contrast agents are often geared toward the assessment of gross physiologic function, rather than targeting specific biochemical pathways. The development of specific targeted smart contrast agents for Food and Drug Administration approval or clinical trials has only begun. The fact that MR imaging can obtain images of extremely high resolution, coupled with its ability to simultaneously assess structure and function through the use of targeted contrast agents indicates that MR will play a pivotal role in clinical molecular imaging of the future. Many of the challenges that face MR imaging and spectroscopy are inherent to all modalities in the rapidly growing field of molecular imaging. The development of smart contrast agents to report on receptor function, and to monitor gene expression or the results of gene therapy in humans is paramount. These compounds need to undergo rigorous testing to be approved for clinical use: the assessment of acute toxicity, pharmacokinetics, long-term accumulation, and subsequent chronic effects. For receptor-targeted contrast agents, the degree of receptor occupancy and the intrinsic agonist or antagonist properties of the probe that may affect normal cellular function need to be determined to avoid undesired side effects. The particular problems that face MR imaging, those of sensitivity and target specificity, need to be overcome. Signal amplification achieved through high relaxivity contrast agents containing multiple paramagnetic centers, or of larger superparamagnetic particles, is the first step in this direction. The modulation of relaxivity through oligomerization, or other modifications that cause restriction of rotational motions, shows great promise for improving the discriminative powers of MR imaging, and may permit multiple targets to be assessed simultaneously. Moreover, the introduction of smart indicators that lead to changes in spectroscopic properties will allow further discrimination to be achieved through the implementation of chemical shift or spectroscopic imaging. The growing number of MR imaging applications in this rapidly expanding field point to a bright future for MR imaging in molecular imaging.