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Author: Avneesh Chhabra, MD, Staff Radiologist, Department of Radiology, Drexel University College of Medicine

Avneesh Chhabra is a member of the following medical societies: American Medical Association, American Roentgen Ray Society, and Radiological Society of North America

Coauthor(s): Kiran Batra, MD, DNB, Fellow, Department of Neuroradiology, Hahnemann University Hospital, Drexel University College of Medicine; Robert A Koenigsberg, DO, MSc, FAOCR, Director of Neuroradiology, Professor, Department of Radiology, Drexel University College of Medicine

Editors: David S Levey, MD, PhD, Orthopedic/Spine MRI TeleRadiologist, Radsource, LLC; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; C Douglas Phillips, MD, Professor, Departments of Radiology, Neurosurgery, and Otolaryngology, University of Virginia Health Sciences Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; James G Smirniotopoulos, MD, Professor of Radiology, Neurology, and Biomedical Informatics, Chairman, Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences

Author and Editor Disclosure

Synonyms and related keywords: DTI, diffusion-tensor imaging, diffusion-weighted imaging, DWI, anisotropy, apparent diffusion coefficient, ADC, eigenvector, eigenvalue, brain MRI, brain imaging, neuroimaging

Diffusion-weighted imaging (DWI) has been a well-established magnetic resonance imaging (MRI) method to diagnose cerebral ischemia. DWI is a routine protocol in most institutions that perform neuroimaging, and normal versus abnormal is easily interpreted on DWI and apparent diffusion coefficient (ADC) images by finding hyperintensity on DWI images that is correspondingly hypointense on ADC images (see Images 1-2). DWI is also useful in the investigation of other brain disorders such as epilepsy, multiple sclerosis, brain abscesses (see Image 3), brain tumors (see Image 4), and hypertensive encephalopathy.

Diffusion describes the random motion of molecules, which is also known as brownian movement. All molecules exhibit this kind of motion at temperatures greater than absolute zero. Diffusion is called isotropic if the motion is equal in all directions. However, water diffuses asymmetrically in the white matterthat is, diffusion is restricted perpendicular to the long axis of the axons; by comparison, water diffuses faster along the Z axis (see Image 5). This property is known as anisotropy, which can be used to define the direction of the axons in a particular voxel.

Imaging and interpretation of water diffusion have been further improved with the development of diffusion tensor imaging (DTI), which allows for direct in vivo examination of aspects of the tissue microstructure. With DTI, the effects of diffusion anisotropy can be characterized to provide excellent details of the brain, including mapping the orientation of the white-matter tracts.



On DWIs commonly used to diagnose acute stroke (see Image 2), diffusion is described by using the ADC. This is sufficient for pathologies in areas such as gray matter, where diffusion is usually isotropic.

To measure the presence of anisotropy in the white matter requires a tensor D, which describes the mobility of molecules in a particular direction and correlation between these directions. The tensor is symmetric, and at least 6 elements are required to characterize it.

The diffusion ellipsoid defines the magnitude and direction of the diffusion of water molecules in each voxel in the brain. The tensor can be diagonalized such that 3 elements called eigenvalues remain along the diagonal. Three eigenvalues, lambda 1, lambda 2, and lambda 3, are derived.

DTI allows clinicians to look at anisotropic diffusion in white-matter tracts, but it is limited in demonstrating spatial and directional anisotropy. Advanced methods such as color coding and tractography (fiber tracking) have been used to investigate the directionality.

The eigenvector corresponding to the largest eigenvalue, termed the principal eigenvector, defines the main direction of diffusion of water molecules in that voxel (see Image 5). Mapping the directional principal eigenvectors in each of the voxels forms the basis for tractography (see Images 6-7), with the assumption that the principal eigenvector is aligned with the direction of the fiber bundle. On these images, the fibers are given different colors by their direction of diffusion: blue for superior and inferior, green for anterior and posterior, and red for left and right.



Brain MRI should be performed by using a 1.5- or 3-T MRI machine. High gradient strength in the range of 20-60 mT/m with a slew rate of 120 T/m/s is ideal. Typical parameters for a single-shot spin-echo echo-planar imaging (EPI) sequence are a repetition time (TR) of 6000 ms, an echo time (TE) of 100 ms, and a field of view of 24 cm to obtain 3- to 5-mm axial or coronal sections with a 5-mm intersection gap. The acquisition matrix is 96 X 96 with a reconstruction matrix of 128 X 128. The images are obtained by using 4 linearly increasing b values in 6-7 noncolinear directions (bmax = 703-1000 s/mm2). In addition, a T2-weighted (T2W) image is obtained without diffusion weighting (b = 0 s/mm2).



A prudent approach to image interpretation is to use an image workstation other than one used to acquire the images. Motion artifacts and image distortion may be corrected by using a coregistration program and filtration.

Diffusion tensor measurements result in a rich data set. Diffusion anisotropy can be measured by applying simple or complicated mathematical formulas. However, an easy and common way to summarize diffusion measurements on DTIs is to calculate parameters for overall diffusivity and for the degree of anisotropy.

Imaging findings include the ADC, which is a measure of the magnitude of molecular motion divided by overall diffusivity; fractional anisotropy (FA), which is the measure of the portion of the diffusion tensor that is due to anisotropy (ie, a measure of the directionality of the molecular motion of water); relative anisotropy (RA), or the ratio between anisotropic and isotropic portions of the diffusion tensor; and the volume ratio (VR), which expresses the relationship between the diffusion ellipsoid volume and that of a sphere, the radius of which is the averaged diffusivity.

Maps of both FA and RA can be presented as gray-scale images. Maps of mean diffusivity and FA can be generated by using Pierpaoli and Basser's method on a pixel-by-pixel basis. Regions of interest (ROI) are placed on both maps to calculate diffusivity and FA.

FA is sensitive to low values of diffusion anisotropy, VR is sensitive to high values of diffusion anisotropy, and RA is linearly scaled for different levels of anisotropy. Both FA and RA vary from 0 (isotropic) to 1 (anisotropic). Both measurements markedly differ between pediatric and adult brains, each varying with increasing age. Mean diffusivity is approximately 0.7 X 10-3 in adults and 2 X 10-3 in neonates. Because anisotropy is greater in ordered structures, such as myelinated axons, DTIs provide useful information regarding the myelination of white matter.

In many pathologic conditions, FA and ADC vary because of altered diffusivity and disorganization of the white-matter fibers leading to decreased anisotropy. These measurements may become abnormal even before the lesion is morphologically apparent on the conventional MRIs and may therefore help in the early detection and in defining the extent of these lesions.

FA and ADC can vary independently. This observation may be explained by the fact that damaged or malformed brain has glia and neurons, respectively. Therefore, they have enough cell density to prevent effects on ADC; however, because of the disorganization, FA is reduced.

Artifacts

The main artifacts in DTI data are associated with acquiring DWI data from which the diffusion tensor is estimated or measured. Artifacts include misregistration of data due to eddy currents, ghosting due to motion artifacts, and signal loss due to susceptibility variations. However, these artifacts can be minimized by using motion-corrected multishot EPI techniques such as periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) and sensitivity-encoding EPI (SENSE-EPI).



Normal brain development and maturation

Specific qualitative features established for conventional MRI can be used to distinguish normal from abnormal brain development. The changes in ADC occur predominantly in the first 6 months of life and are believed to be related to decreasing total water content, myelination, and organization of the white-matter tracts. All of these processes decrease diffusivity. Because DTI technique has the potential to improve objectivity and sensitivity in the detection of subtle developmental changes, it may prove to be more useful than relatively subjective evaluation based on conventional MRI sequences.

Stroke

DWI and DTI have been extensively used to detect acute ischemic brain injury (see Image 2). In the acute phase of ischemia, ADC is reduced and FA values are increased. In the chronic phase of ischemia, ADC is higher than normal. In contrast to the elevation of the ADC in chronic stroke, diffusion anisotropy remains significantly lower in the infarcted area than in the similar contralateral region of the brain, even 2-6 months after an ischemic stroke. By combining ADC and anisotropy data, the severity of strokes can be assessed and acute ischemic changes can be distinguished from chronic ischemic changes; that difference may affect treatment. Also, ADC values increase if purely vasogenic edema is presentfor example, in the reversible posterior leukoencephalopathy syndrome or in high-pressure hydrocephalus.

Epilepsy

A common cause of epilepsy is mesial temporal sclerosis or hippocampal sclerosis in patients with chronic epilepsy. Findings seen on DTIs include increased diffusivity and decreased anisotropy due to the loss of structural organization and expansion of the extracellular fluid space. Changes in DTI may also extend to involve areas of the brain that appear morphologically normal on conventional MRIs. In this way, the DTI may define the true extent of pathology and improve preoperative planning.

Refractory extratemporal neocortical epilepsy may be due to malformations in cortical development (MCD), which may not be apparent on conventional MRI. However, differences in ADC in the affected region, compared with the contralateral normal brain, may be seen and thus help in presurgical planning. However, DTI may erroneously depict regions of presumed seizure onset by showing subtle structural abnormalities caused by head injury or ischemia.

Brain tumors

DTI has demonstrated a potential in distinguishing gliomas and solitary metastasis in the brain parenchyma. Significantly higher mean diffusivity and lower FA, compared with levels  in normal-appearing white matter, have been demonstrated in the peritumoral regions of both gliomas and metastases. Peritumoral mean diffusivity of metastases and meningioma (see Image 4) is significantly higher than that of gliomas, whereas the FA values are similar, confirming the infiltrating nature of gliomas. Tractography combined with functional MRI may potentially help in preoperative planning of brain tumors by mapping areas of active infiltration.

Multiple sclerosis

Various studies have demonstrated potential advantages of DTI in the diagnosis and follow-up of MS lesions. In MS, FA is more sensitive than ADC values to white-matter abnormalities. The lesions with destructive pathology or acuity generally have increased diffusivity and decreased FA values. On conventional T2-weighted and fluid-attenuated inversion recovery (FLAIR) images, normal-appearing white matter adjacent to the MS lesions may also demonstrate abnormality, displaying the actual extent of the lesions. The gray matter around the white-matter lesions is abnormal in some cases, indicating that disease may not be an isolated white-matter pathology.

Demyelinating versus dysmyelinating disorders

Diffusional anisotropy is present in a dysmyelinating disorder such as Pelizaeus-Merzbacher disease, and it may be lost in a demyelinating disease such as Krabbe disease or Alexander disease. Also, in contrast to relatively high signal intensity of the lesions of Krabbe disease on DWI, the lesions in Alexander disease have signal intensity. Therefore, DWI is clinically useful in differentiating dysmyelination from demyelination, as both have lesions of high intensity in the white matter, as shown on T2-weighted images.



Tractography potentially solves a problem for a neurosurgeon in terms of minimizing functional damage and determining the extent of diffuse infiltration of pathologic tissue to minimize residual tumor volume. In this way, tractography facilitates preoperative planning. Tractographic images (see Images 6-7) may help to clarify whether a tumor is compressing, abutting, or infiltrating the contiguous white-matter tracts. However, no consensus has been reached about an appropriate criterion standard for assessing the accuracy of DTI, and this technique is primarily investigational at present.



Diffusion in structured tissue, such as white matter, is anisotropic. DTI can be used to measure anisotropy per voxel and provides the directional information relevant for magnetic resonance tractography or fiber tracking in vivo. The recent development of DTI allows for direct examination of the brain microstructure, and DTI has become a useful tool for investigation of brain disorders such as stroke, epilepsy, MS, brain tumors, and demyelinating and dysmyelinating disorders. However, further improvements in the technique and in postprocessing analysis are needed to increase the widespread utility of DTI in both research and clinical applications.



Media file 1:  Normal brain appearance in axial DWI (left) and ADC (right) images in a 35-year-old man.
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Media type:  MRI

Media file 2:  Axial DWI image demonstrates a typical wedge-shaped, cortical-based, hyperintense lesion in the left temporoparietal lobes consistent with acute infarct.
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Media type:  MRI

Media file 3:  Axial fluid-attenuated inversion recovery (FLAIR) image (top left), diffusion-weighted image (DWI) (top right), and axial and sagittal T1-weighted (T1W) images (bottom) in a 40-year-old man with history of intravenous drug abuse and fever demonstrate multiple enhancing focal brain lesions in the gray-white matter junction (arrow) compatible with septic emboli. The lesions are hyperintense on both FLAIR and DWI images.
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Media type:  MRI

Media file 4:  Axial diffusion-weighted image (DWI) (top left), T2-weighted (T2W) image (top right), fluid-attenuated inversion recovery (FLAIR) image (bottom left), and contrast-enhanced T1W (bottom right) image demonstrate a right convexity meningioma appearing hypointense on DWI image. The perilesional brain edema (arrow) is hyperintense on T2W and DWI sequences.
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Media type:  MRI

Media file 5:  Diffusion ellipsoid. Three eigenvectors are demonstrated, with the principal eigenvector along the Z direction. Courtesy of Dr Andrei I. Holodny, MD.
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Media type:  Image

Media file 6:  Axial tractographic image demonstrates white-matter tracts in the brain in the left-right (red), anterior-posterior (green), and superior-inferior (blue) directions. Courtesy of Dr Andrei I. Holodny, MD.
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Media type:  Image

Media file 7:  Coronal tractographic image demonstrates various nerve-fiber tracts. Courtesy of Dr Andrei I. Holodny, MD.
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Media type:  Image



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Diffusion Tensor Imaging excerpt

Article Last Updated: Jul 31, 2007