Magnetic resonance microscopy.

MRI, one of the major clinical imaging modalities, has gained an important role in studying small animal models, e.g., rats and mice. But imaging rodents comes with challenges, since the image resolution needs to be ~ 3000-times higher to resolve anatomical details at a level comparable to clinical imaging. A resolution on the order of 100 microns or less redefines MR imaging as MR microscopy. We discuss in this chapter the basic components of the MR imaging chain, with a particular emphasis on small animal imaging demands: from hardware design to basic physical principles of MR image formation, and contrast mechanisms. We discuss special considerations of animal preparation for imaging, and staining methods to enhance contrast. Attention is given to factors that increase sensitivity, including exogenous contrast agents, high performance radiofrequency detectors, and advanced MR encoding sequences. Among these, diffusion tensor imaging and tractography add novel information on white matter tracts, helping to better understand important aspects of development and neurodegeneration. These developments open avenues for efficient phenotyping of small animal models, in vivo - to include anatomical as well as functional estimates, or ex-vivo - with exquisite anatomical detail. The need for higher resolution results in larger image arrays that need to be processed efficiently. We discuss image-processing approaches for quantitative characterization of animal cohorts, and building population atlases. High throughput is essential for these methods to become practical. We discuss current trends for increasing detector performance, the use of cryoprobes, as well as strategies for imaging multiple animals at the same time. Ultimately, the development of highly specific probes, with the possibility to be used in multimodal imaging, will offer new insights into histology. MRM, alone or in combination with other imaging modalities, will increase the knowledge of fundamental biological processes, help understanding the genetic basis of human diseases, and test pharmacological interventions.