DTI fiber tractography DTI has enabled quantitative fiber tracking for in vivo noninvasive mapping of inter-regional white matter fiber connections and the segmentation of axonal tracts in normal54-56 and degraded brain systems57,58 (for a review see ref 59). DTI permits examination of the integrity of the microstructure of cerebral white matter by measuring the

orientational displacement and distribution of water molecules in vivo across tissue components.60 Water diffusion modeled with DTI is represented mathematically by an ellipsoid on a voxel-by-voxel basis. In fibers with a homogeneous or linear structure such as healthy white matter, Inhibitors,research,lifescience,medical the ellipsoid is long and narrow and has a preferential orientation, presumed to indicate the course of white matter fiber tracts. As such, DTIbased fiber tracking represents an indirect in vivo measure of neuronal pathways in the brain. DTI metrics include fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) or mean diffusivity (MD), which can be decomposed into two components, Inhibitors,research,lifescience,medical the longitudinal or axial diffusivity (Xl) and transverse or radial diffusivity (lt). High axial diffusivity is taken as an index of degradation of axonal health or integrity and radial diffusivity Inhibitors,research,lifescience,medical indexes the fibers’ myelin sheath integrity.61-63 This information can be used

to determine which fiber tracts are and are not affected by chronic alcohol consumption;

whether fiber compromise is due to axonal damage, a breakdown Inhibitors,research,lifescience,medical of the myelin sheath, or both; and how fiber microstructural integrity may relate to brain functional compromise.64-66 DTI-based quantitative fiber tracking in alcoholism Until recently, few studies had investigated alcohol effects Inhibitors,research,lifescience,medical on microstructural integrity of fiber tracts by using DTI-based quantitative fiber tractography (chronic alcoholism27,67-69; fetal alcohol spectrum disorder7071; for review see ref 72). In our laboratory, we tracked 11 major white matter fiber bundles in 87 alcoholic and 88 control men and women.27 Alcoholics demonstrated the greatest abnormalities in frontal, ie, frontal forceps, internal and external capsules, and more superior bundles, ie, fornix, superior cingulum, and superior longitudinal fasciculus, whereas posterior and inferior fibers were relatively spared. isothipendyl Tracking corpus callosum fibers, we found stronger alcohol effects for FA and radial than axial diffusivity, suggesting alcohol-related myelin degradation consistent with previously reported alcoholism-related neuropathology that included demyelination and loss of Apoptosis Compound Library myelinated fibers.28 Structure-function relationships between poorer performances on cognitive tests and DTI signs of regional white matter compromise in several fibers indicated that fiber degradation in alcoholism affects cognitive functions, and specifically cognitive processing speed.