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Diffusion Tensor Magnetic Resonance Imaging in Multiple Sclerosis

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10.1177/1051228405283363Journal of Neuroimaging Supplement to Vol 15 No 4Goldberg-Zimring et al:Diffusion Tensor MRI in MSDiffusion Tensor MagneticResonance Imaging inMultiple SclerosisDaniel Goldberg-Zimring, PhDAndrea U. J. Mewes, MDMahnaz Maddah, MScSimon K. Warfield, PhDABSTRACTMultiple sclerosis (MS), a demyelinating disease, occurs princi-pally in the white matter (WM) of the central nervous system.Conventional magnetic resonance imaging (MRI) is sensitive tosome, but not all, brain changes associated with MS. Diffusion-weighted imaging (DWI) provides information about water diffu-sion in tissue and diffusion tensor MRI (DT-MRI) about fiberdirection, allowing for the identification of WM abnormalities thatare not apparent on conventional MRI images. These tech-niques can quantitatively characterize the local microstructureof tissues. MS-associated disease processes lead to regionscharacterized by an increased amount of water diffusion and adecrease in the anisotropy of diffusion direction. These changeshave been found to produce different patterns in MS patientspresenting different courses of the disease. Changes in waterdiffusion may allow examination of the type, appearance,enhancement, and location of lesions not readily visible by othermeans. Ongoing studies of MS are integrating conventional MRIand DT-MRI measures with connectivity-based regionalassessment, aiming to provide a better understanding of thenature and the location of WM lesions. This integration and thedevelopment of novel image-processing and visualization tech-niques may improve the understanding of WM architecture andits disruption in MS. This article presents a brief history of DWI,its basic principles and applications in the study of MS, a reviewof the properties and applications of DT-MRI, and their use in thestudy of MS. In addition, this article illustrates the methodologyfor the analysis of DT-MRI in ongoing studies of MS.Key words: Diffusion-weighted imaging, diffusion tensor, DT-MRI, multiple sclerosis, magnetic resonance imaging,diffusivity, lesion, tractography.Goldberg-Zimring D, Mewes AUJ,Maddah M, Warfield SK.Diffusion tensor magnetic resonanceimaging in multiple sclerosis.J Neuroimaging 2005;15:68S-81S.DOI: 10.1177/1051228405283363.Multiple sclerosis (MS) is a demyelinating disease occur-ring in the white matter (WM) and gray matter (GM) ofthe central nervous system. In conventional magnetic res-onance imaging (MRI), MS lesions located in the WMproduce a hyperintense signal in both proton density andT2-weighted images, while the hypointense T1-weightedlesions are considered to be chronic.1In MS patients, WM may be disrupted in areas notapparent on conventional T2-weighted MRI. Abnormali-ties of normal-appearing WM (NAWM) on T2-weightedMRI have been detected using magnetization transferimaging (MTI),2-4diffusion-weighted imaging (DWI),5-9diffusion tensor MRI (DT-MRI),6,10-13and magnetic reso-nance spectroscopy (MRS).14-16(For separate, detailed dis-cussions of MTI and MRS, please see the accompanyingarticles in this supplement.4,16)In general, MS patients present an increased amountof water diffusion and a decreased anisotropy of diffusiondirection in the region of the lesions, in the surroundinglesion tissue, and in the remote NAWM. These changesare believed to be the result of either damage and removalof highly aligned cellular structures or replacement ofaxonal fibers with amorphous cells7-9,17,18and are appar-ently dependent on the clinical course of the patient.The correlation between WM lesion burden in MRIand clinical outcome measures is significant but notstrong.19WM lesion burden is typically measured overthe entire brain, which may underestimate the signifi-cance of the underlying connectivity of WM and the68S Copyright © 2005 by the American Society of NeuroimagingReceived August 18, 2005, and in revised form Septem-ber 27, 2005. Accepted for publication October 6, 2005.From the Computational Radiology Laboratory, Depart-ment of Radiology, Brigham and Women’s Hospital, Har-vard Medical School, Boston, Massachusetts (DG-Z,AUJM, SKW); the Computer Science and Artificial Intel-ligence Laboratory, Massachusetts Institute of Technol-ogy, Cambridge (MM); and the ComputationalRadiology Laboratory, Department of Radiology, Chil-dren’s Hospital, Harvard Medical School, Boston, Massa-chusetts (SKW).Address correspondence to Daniel Goldberg-Zimring,PhD, Department of Radiology, Brigham and Women’sHospital, Harvard Medical School, 75 Francis Street,Boston, MA 02115. E-mail: [email protected] effects on WM damage in functionally elo-quent WM tracts.18,20Recent advances in DT-MRI and image-processingtechniques are providing the image acquisition and visu-alization technology to enable in vivo assessment of theWM architecture of the human brain. These technologieswill enable future studies of the relationship between WMdisruption, WM connectivity, and clinical measures andwill ultimately lead to improved monitoring of patients,better prediction of the course of the disease, and morerapid assessment of new treatments or therapies. (For sep-arate, detailed discussions of image-processing tech-niques, please see the accompanying article in this supple-ment.21)This article presents a brief history of DWI and its basicprinciples and applications in the study of MS, followedby a review of the properties and applications of DT-MRIand its use in the study of MS. In addition, it presents aproposed methodology for the analysis of DT-MRI inongoing studies of MS.Diffusion-Weighted ImagingBrief HistoryDWI allows quantitative measurement of the molecularmotion of water. DWI is based on the continuous agita-tion of minute suspended particles, which is a phenome-non known as Brownian movement, named after RobertBrown, who observed the constant movement of pollengrains in 1827.22Brown suspended some of the pollengrains in water and examined them closely, only to seethem “filled with particles” that were “very evidently inmotion.” He was soon satisfied that the movement “aroseneither from currents in the fluid, nor from its gradualevaporation, but belonged to the particle itself.”22The ki-netic force in Brownian movement is directly related toparticle size, and the vector of the force that gives rise tothe movement is not consistent, nor does it result in mo-tion in a specific direction. Through his investigation ofBrownian movement (frequently referred to as Brownianmotion),


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