Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience Research

Abstract

The brain contains more than 100 billion neurons that communicate with each other via axons for the formation of complex neural networks. The structural mapping of such networks during health and disease states is essential for understanding brain function. However, our understanding of brain structural connectivity is surprisingly limited, due in part to the lack of noninva-sive methodologies to study axonal anatomy. Diffusion tensor imaging (DTI) is a recently developed MRI technique that can measure macroscopic axonal organization in nervous system tissues. In this article, the principles of DTI methodologies are explained, and several applications introduced, including visualization of axonal tracts in myelin and axonal injuries as well as human brain and mouse embryonic development. The strengths and limitations of DTI and key areas for future research and development are also discussed. Introduction The human brain consists of more than 100 billion neu-rons, and it is arguably the most complex structure in our body. Imaging has been a powerful technique to navigate us through this vast entity and identify the places where biological events of interest occur. In animal studies, histology followed by examination with light or electron microscopy has been one of the most widely used imaging methods. Various staining techniques can highlight the locations of proteins and genes of interests, and electron microscopy can extend our observation to objects at the molecular level. However, histology-based imaging has several serious drawbacks. First, it is invasive. Second, its labor-intensive and destructive nature makes it a nonideal choice for examining the entire brain or for performing quantitative three-dimensional analyses. MRI is probably at the other end of the spectrum of imaging modalities. It is noninva-sive, three-dimensional, and requires as little as a few minutes to characterize the entire brain anatomy. The end results are often merely a few megabytes (MBs) of data, in which all the relevant brain information is condensed by a consistent sampling scheme. Its strength is, however, also its weakness. While the brain anatomical information is condensed, much biological information is degenerated, which causes a loss of specificity and sensitivity to certain biological processes. It is a never-ending quest for the MRI research community to attempt to recover more types of biological information that would otherwise be lost with conventional MRI techniques. In this review, we would like to introduce a new MRI technique called diffusion tensor imaging (DTI). This imaging technique can delineate the axonal organization of the brain, which we could not appreciate with conventional MRI. DTI was introduced in the mid 1990s (Basser et al., 1994), and its applications to small animal studies have only recently been initiated (Ahrens et al., 1998; Harsan et al., 2006; Kroenke et al., 2006; Mori et al., 2001; Nair et al., 2005). The purpose of this review is to explain how DTI works and to introduce state-of-the-...

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