Diffusion imaging

is introduced The development of diffusion tensor imaging (DTI) has made it possible to investigate white matter in the brain, in vivo, in a manner not possible with conventional MRI. The work that led to the first imaging of white matter in humans began with the work of Steiskal and Tanner18 in 1965, followed by the work of Le Bihan et al19 in 1986 who introduced diffusion MR, and Basser et al20 in 1994, who developed DTI. The first DTI of the human brain was conducted by Pierpaoli et al21 in 1996, and the first DTI study in patients with schizophrenia was conducted by Buchsbaum et al22 in 1998. Inhibitors,research,lifescience,medical These time periods are highlighted to emphasize just how recently this technology has been developed. The basic principle underlying diffusion imaging is that the diffusion of water molecules is restricted equally in all directions in CSF (learn more isotropic diffusion), and not restricted equally in white matter, where it exhibits strong anisotropic diffusion, or in gray matter, where it exhibits weak anisotropic diffusion. By calculating the

distance that water diffuses Inhibitors,research,lifescience,medical from a given point in a given time period, in a number of directions, it is possible to construct a three-dimensional shape that describes the diffusion, ie, an ellipsoid, with the shape and size of the ellipsoid providing information about the underlying tissue. The two most common diffusion measures Inhibitors,research,lifescience,medical used are fractional anisotropy (FA, shape of ellipsoid) and mean diffusivity (MD, size of ellipsoid).

FA is a measure of the anisotropy or nonsphericity of the shape of the diffusion ellipsoid. FA varies between 0 and 1, with the most isotropic diffusion having a value of 0 and the Inhibitors,research,lifescience,medical most anisotropic diffusion having a value of 1. FA decrease is generally thought to reflect damage to myelin or axons, reduced axonal density, and/or reduced axonal coherence (see review in Kubicki et al23). In contrast, MD provides quantitative information about the Inhibitors,research,lifescience,medical size of the diffusion ellipsoid, or the average displacement of water molecules resulting from diffusion at a given point in time. MD is highest in tissues where there are fewer restrictions to diffusion Ketanserin (eg, CSF), and lowest in tissues where diffusion is restricted by densely packed tissue elements (ie, cells). In schizophrenia studies, reviewed later in this chapter, FA and MD are the most common measures used, with decreased FA and increased MD consistently evinced by patients with schizophrenia. As mentioned above, these diffusion abnormalities likely reflect subnormal levels of fiber coherence, demyelination/dysmyelination, and/or subnormal levels of axon packing density. Figure 4 provides a graph depicting the number of diffusion imaging studies that have investigated white matter pathology in schizophrenia, each year, starting with Buchsbaum et al’s22 first diffusion tensor imaging study in 1998 (Total =178 compared with 6305 MRI studies).