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Multiple sclerosis (MS), a demyelinating disease, occurs principally in the white matter (WM) of the central nervous system. Conventional magnetic resonance imaging (MRI) is sensitive to some, but not all, brain changes associated with MS. Diffusionweighted imaging (DWI) provides information about water diffusion in tissue and diffusion tensor MRI (DT-MRI) about fiber direction, allowing for the identification of WMabnormalities that are not apparent on conventional MRI images. These techniques can quantitatively characterize the local microstructure of tissues. MS-associated disease processes lead to regions characterized by an increased amount of water diffusion and a decrease in the anisotropy of diffusion direction. These changes have been found to produce different patterns in MS patients presenting different courses of the disease. Changes in water diffusion may allow examination of the type, appearance, enhancement, and location of lesions not readily visible by other means. Ongoing studies of MSare integrating conventional MRI and DT-MRI measures with connectivity-based regional assessment, aiming to provide a better understanding of the nature and the location of WM lesions. This integration and the development of novel image-processing and visualization techniques may improve the understanding of WM architecture and its disruption in MS. This article presents a brief history of DWI, its basic principles and applications in the study of MS, a review of the properties and applications of DT-MRI, and their use in the study of MS. In addition, this article illustrates the methodology for the analysis of DT-MRI in ongoing studies of MS. [ABSTRACT FROM AUTHOR]

Matrix metalloproteases (MMPs) play an important rolein cartilagehomeostasis under both normal and inflamed disease states and, thus,have become attractive targets for the treatment of arthritic diseases.Herein, we describe the identification of a potent, selective MMP-13inhibitor, developed using fragment-based structure-guided lead identificationand optimization techniques. Virtual screening methods identifieda novel, indole-based MMP-13 inhibitor that bound into the S1′pocket of the protein exhibiting a novel interaction pattern hithertonot observed in MMP-13 inhibitors. X-ray crystallographic structureswere used to guide the elaboration of the fragment, ultimately leadingto a potent inhibitor that was >100-fold selective over nine otherMMP isoforms tested. [ABSTRACT FROM AUTHOR]