Review Article Applications of diffusion-weighted and diffusion tensor MRI to white matter diseases ± a review Mark A. Hors®eld 1 * and Derek K. Jones 2 1 Division of Medical Physics, University of Leicester, Leicester Royal In®rmary, Leicester LE1 5WW, UK 2 Section for Old Age Psychiatry, Institute of Psychiatry, Denmark Hill, London SE5 8AF, UK Received 5 June 2001; Revised 7 September 2001; Accepted 7 September 2001 ABSTRACT: This paper reviews the current applications of diffusion-weighted and diffusion tensor MRI in diseases of the brain white matter. The contribution that diffusion-weighted imaging has made to our understanding of white matter diseases is critically appraised. The quantitative nature of diffusion MRI is one of its major attractions; however, this is offset by the more advanced hardware required to collect diffusion-weighted images reliably, and the more complex processing to produce quantitative parametric diffusion images. With the now common availability of scanners equipped to perform echo-planar imaging, the acquisition of diffusion tensor images is sure to become more widespread and routine. Copyright  2002 John Wiley & Sons, Ltd. KEYWORDS: diffusion; tensor; MRI; DTI; white matter; disease INTRODUCTION The molecular translational motion of tissue water forms the basis of clinical diffusion-weighted (DW) magnetic resonance imaging (MRI). 1 In biological tissues, diffu- sion may be hindered by interactions with barriers such as cell membranes and organelles. 2 Instead of spreading out with a Gaussian distribution, diffusing molecules may be reflected by, or at least have their mobility interrupted by, interactions with the cell membranes and other intracel- lular and extracellular structures. Thus, the shape of the distribution of a parcel of diffusing molecules is influenced by these interactions, and in some sense will conform to the shape of the compartment that is accessible to the diffusing molecules. Of course, with MRI, we do not measure the signal from just a few of the spins, but the total signal from all spins within an image voxel. Thus we are measuring the volume-averaged propagation of the diffusing molecules as they interact with the cellular structures present with the voxel. Because the water molecules are no longer able to move freely, diffusion in biological systems is termed hindered diffusion. The diffusion coefficient that is measured in a large sample of fluid characterizes the rate at which a parcel of fluid at a given location subsequently spreads out. This is termed the ‘bulk’ diffusion coefficient, and depends on the chemical properties of the fluid and temperature of the sample. In biological tissues, the underlying physical properties of the tissue water are the same as in a bulk sample; however, the mean square displacement per unit time is lessened by the restricting barriers. Diffusion-weighted MRI provides a means of measuring these distances, and in biological systems it appears that the diffusion coefficient is lower than that of the bulk sample. Hence, the term apparent diffusion coefficient (ADC) was coined 3 in order to indicate that it is understood that the diffusion process is the same as in free water, but the mean square displacement per unit time is lessened by these interactions, not by a reduction in the diffusion coefficient. Thus, it would seem that diffusion-weighted imaging might provide some insight into the nature and degree of pathological damage that occurs in diseases of the central nervous system (CNS) when cellular structures are NMR IN BIOMEDICINE NMR Biomed. 2002;15:570–577 Published online in Wiley InterScience (www.interscience.wiley.com). DOI:10.1002/nbm.787 *Correspondence to: M. A. Horsfield, Division of Medical Physics, University of Leicester, Leicester Royal Infirmary, Leicester LE1 5WW, UK. Email: mah5@le.ac.uk Contract/grant sponsor: Wellcome Trust; contract grant number: 054030/Z/98. Abbreviations used: AD, Alzheimer’s disease; ADC, apparent diffusion coefficient; ALD, adrenoleukodystrophy; ALS, amyotrophic lateral sclerosis; CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CJD, Creutzfeldt– Jakob disease; CNS, central nervous system; CT, computerised tomography; DTI, diffusion tensor imaging; DW, diffusion-weighted; EPI, echo planar imaging; HIV, human immunodeficiency virus; MMSE, mini-mental state examination; MR, magnetic resonance; MRI, magnetic resonance imaging; MS, multiple sclerosis; MTR, magnetisation transfer ratio; NAWM, normal-appearing white matter; PP, primary progressive; RR, relapsing-remitting; SP, secondary progressive; WM, white matter. Copyright  2002 John Wiley & Sons, Ltd. NMR Biomed. 2002;15:570–577