Diffusion tensor imaging of the brain review of clinicalapplications
Background
Di?usion-weighted imaging(DWI)is a well-established method implemented as a part of a routine protocol at many institutions.It shows the di?usivity of water molecules[1]and the principles of measurement of di?usion with MRI are well described[2,3].DWI has shown to be very useful for early signs of ischemia[4,5], but is also increasingly used in the investigation of other brain diseases,e.g.,multiple sclerosis[6,7,8],trauma[9, 10],brain tumors[11,12],and hypertensive encepha-lopathy[13,14].
Improvements in the imaging of water di?usion have been made by the development of the more complex di?usion tensor imaging(DTI),which allows direct examination,in vivo,of some aspects of tissue micro-structure.DTI yields quantitative measures re?ecting the integrity of white-matter?ber tracts,by taking advantage of the intrinsic directionality of water di?usion in human brain.The di?usion of water molecules is characterized by Brownian motion.When water molecules are unconstrained,the direction of motion of a given molecule is random.The displace-ments of water molecules over time are described by a Gaussian distribution.Di?usion is called isotropic when motion is equal and unconstrained in all directions. However,the microstructure of brain tissue forms physical boundaries that limit the Brownian motion of water molecules,resulting in restriction of the total amount of di?usion.In structures such as the white-matter?bers,the di?usion of water molecules will be relatively more restricted perpendicular to than parallel to the microstructural boundaries and di?usion is then called anisotropic[15].
In DWI,di?usion is described using a scalar parameter,the di?usion coe?cient D.In tissues such as gray matter,where the measured apparent di?usivity is isotropic,it is su?cient to describe the di?usion char-acteristics with a single scalar apparent di?usion coe?-cient(ADC).In the presence of anisotropy,di?usion can no longer so be characterized,but requires a tensor D, which fully describes the mobility of the molecules each direction and the correlation between these directions.The mathematical construct used to characterize anisotropic Gaussian di?usion is a second-order di?usion tensor[16].Since the tensor is symmetric,
P.C.Sundgren Q.Dong
D.Go mez-Hassan S.K.Mukherji P.Maly
R.Welsh Diffusion tensor imaging of the brain: review of clinical applications
Received:15July2003 Accepted:2September2003 Published online:21April2004óSpringer-Verlag2004Abstract We review the theoretical
background to di?usion tensor
imaging(DTI)and some of its
commoner clinical applications,
such as cerebral ischemia,brain
maturation and traumatic brain
injury.We also review its potential
use in diseases such as epilepsy,
multiple sclerosis,and Alzheimer’s
disease.The value of DTI in the
investigation of brain tumors and
metabolic disorders is assessed.
Keywords Magnetic resonance
imaging?Di?usion tensor
imaging?Brain
Neuroradiology(2004)46:339–350
DOI10.1007/s00234-003-1114-x DIAGNOSTIC NEURORADIOLOGY P.C.Sundgren(&)?Q.Dong
D.Go mez-Hassan?S.K.Mukherji
P.Maly?R.Welsh
Department of Radiology,University of
Michigan Health System,1500E.Medical
Center Drive,Ann Arbor,MI48109-0030,
USA
E-mail:sundgren@https://www.wendangku.net/doc/b14211151.html,
Tel.:+1-734-7633253
Fax:+1-734-7642142
at least six unique elements are required to fully char-acterize it[3].The tensor can be diagonalized such that only three non-zero elements(k1,k2,and k3)remain along the diagonal.These are known as the eigenvalues. Each eigenvalue is associated with an eigenvector( 1, 2 and 3),where the largest of the three eigenvalues(k1) corresponds to the eigenvector 1and describes the principal direction of di?usion at that point.
The main artifacts in DTI data are the usual arti-facts and problems associated with acquiring DWI data from which the di?usion 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.Hardware issues such as background gradients,gradient non-linearity and miscalibration also have to be taken in consideration.However,improvements in image reso-lution and reduction of distortion have been made using motion-corrected multishot echoplanar imaging (EPI)PROPELLER and SENSE-EPI techniques[17, 18].
Di?usion tensor measurements result in a rich data set.Di?usion anisotropy can be measured in di?erent ways by applying simple or more complicated mathe-matical formulae and recalculations using the underly-ing eigenvectors[3,4,16,19].A common way to summarize di?usion measurements in DTI is calculation of a parameters for overall di?usivity and for anisot-ropy.The ADC serves for overall di?usivity and is derived from the trace of the di?usion tensor,while anisotropy is represented by fractional anisotropy(FA) or relative anisotropy(RA).FA is a measure of the portion of the di?usion tensor due to anisotropy.The RA is derived from a ratio between the anisotropic and isotropic portions of the di?usion tensor.Another commonly used value is the volume ratio(VR)which expresses the relationship between the di?usion ellipsoid volume and that of a sphere,radius{k}[20].Both water ADC and di?usion anisotropy di?er markedly between childhood and adult brains,each varies with increasing age[21,22,23].
The di?erences between these measurements lie in their sensitivity to anisotropy:FA is more sensitive to low and VR to high values of di?usion anisotropy,and RA scales linearly for di?erent levels of anisotropy[3]. Both FA and RA are0.0for a purely isotropic medium. For higher symmetric anisotropic media FA tends to-wards1,while RA tends towards?2.Both FA and RA maps can be presented as gray-scale images.VR ranges from1(isotropic di?usion)to0;some workers therefore prefer to use(1-VR).In contrast to the aforementioned measurements,which all represent intravoxel anisot-ropy,the lattice anisotropy index—another way of assessing di?usion—measures intervoxel anisotropy. The lattice measures of di?usion anisotropy allow neighboring voxels to be considered together in a region of interest,without losing anisotropy e?ects that result from di?erent?ber orientations across voxels[20].
DTI allows us to look at anisotropic di?usion within white-matter tracts but is limited in demonstrating spa-tial,directional di?usion anisotropy.New and/or more sophisticated methods for demonstrating di?usion directions,such as color-coding and?ber tracking,have therefore been proposed[24,25,26,27].
By choosing the eigenvector associated with the largest eigenvalue,the principal di?usion direction of the brain structure to be examined can be color-coded, resulting in color-coded maps or directionally encoded (DEC)FA maps.In these the?bers have been given di?erent colors(blue for superior-inferior,green for anterior-posterior and red for left to right)depending on their direction of di?usion(Fig.1).The magnitude of anisotropy,such as FA,can be used as an illumination factor of the calculation of a directionally coded color image[24].
In?ber tractography,or?ber tracking,white-matter tract directions are mapped on the assumption that in each voxel a measure of the local?ber orientation is obtained through di?usion tensor imaging.The task of tractography is sensibly to assign mathematical associ-ations between adjacent voxels based on eigenvalue and eigenvector information.In DTI tractography it is as-sumed that the eigenvector associated with the largest eigenvalue is aligned with the direction of the?ber bundle[25,26,27,28].There are several problems associated with quantitative?ber tract tractography. First,all the usual artifacts and problems associated with DWI,as mentioned above,can adversely a?ect?-ber tracking[27].Interaction between vectors in the where?bers are crossing or‘‘kissing’’or where they branch or merge poses additional problems.A further problem is that there is no reference standard for in vivo tractography.
Since?ber tracking requires more extensive computer calculations and manpower than DWI or DTI it remains more of a research instrument and has,to date,little or no clinical application.However,it seems likely that tractography will improve our understanding of brain pathology,especially that of white-matter abnormalities. Possible applications include closed head injury and stroke,and even peripheral nerve injuries.Fiber tracking can be used in conjunction with functional MRI to analyze the anatomical connections and functional pathways for diagnostic purposes and presurgical planning[26].
Clinical applications
While DWI has several clinical applications and is rou-tinely used in investigation of stroke,DTI is not routine in most institutions.However,an increased interest in
340
possible clinical applications and for evaluation of the value of DTI for examination of the brain has lead to intensive research and resulted in several reports.We reviews some clinical areas in which DTI has been shown to be of interest.
Cerebral ischemia,leukoariaosis and wallerian degeneration
A decrease in cerebral blood ?ow below 10–15ml/100g/min leads to an increased volume of intracellular wa-ter.This in?ux of water from the extracellular com-partment causes the cells to swell producing cytotoxic edema.With conventional MRI,the acute stage of ischemia is poorly assessed and the extent of the ische-mic parenchyma can be demonstrated only at a later stage,when vasogenic edema is present.DWI and DTI have been extensively used to detect acute ischemic brain injury while conventional MRI is still normal [1,29,30,31].They also make it possible to distinguish acute from chronic ischemic changes,which may have impact on treatment.In the acute phase,ADC are initially reduced by 30–50%within 30min of the onset of focal ischemia [29,30,31,32],more severely in the white than in the gray matter in acute and early subacute infarcts [33,34].With ischemic brain trauma,DTI parameters such as the D av (equivalent to ADC),initially decrease but subse-quently increase and become higher than normal.They remain elevated in the chronic phase of injury [35].In the short interval between decreases and subsequent increases in ADC there is a time during which the values are normal,a process referred to as pseudonormaliza-tion.This occurs approximately 9days after a cerebral infarct in adults and after 7days in newborns [35].In addition to the changes in the ADC,an acute
elevation
Fig.1a–d A healthy 30-year-old man.a Normal T2-weighted image b apparent di?usion coe?cient (ADC)map c
fractional anisotropy (FA)map d color-coded FA map.Highly directional white-matter struc-tures are clearly seen on the FA maps.In d the ?bers have been given di?erent colors:blue for superior-inferior,green for anterior-posterior,and red for left to right,depending on their direction of di?usion
341
in FA has been observed in ischemic white but not grey matter.This acute elevation is followed by a marked reduction in FA during the chronic phase[36].These changes are believed to be due to loss of organization in normal structures when their cytoarchitecture is disrupted.
In contrast to the renormalization and subsequent elevation of the ADC in chronic stroke,di?usion anisotropy remains signi?cantly lower in the infarcted area than in the homologous contralateral region of the brain,even2–6months after an ischemic stroke[37]. ADC threshold values are useful in predicting tissue viability and stroke outcome[33,38]and,combining ADC and anisotropy data,it is possible to assess the severity of strokes and predict outcome[33].
There are conditions under which ADC increase rather than decrease after an injury.In general,it appears that ADC decrease immediately after cell injury in the presence of cytotoxic edema.However it they be increased early when there is vasogenic edema,for example,in the reversible posterior leukoencephalopathy syndrome[13, 14],or in high-pressure hydrocephalus[39].
Leukoaraiosis is a nonspeci?c term for the radiolog-ical appearance of di?use changes in the periventricular white matter seen on CT or MRI[40].It may be seen in various diseases,including chronic ischemia,Alzhei-mer’s disease,and CADASIL(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy):histologically,axonal loss and proliferation of glia has been reported[41,42].In ischemic leukoaraiosis,DTI shows elevated mean dif-fusivity and reduced FA in areas of increased signal on T2-weighted images[41].Mean di?usivity in leukoarai-osis is signi?cantly lower than that in a lacunar infarct, probably due to proliferation of glial tissue in the former,interfering with water di?usion[43].
Wallerian degeneration(WD)is as antegrade degen-eration of axons and their myelin sheath secondary to proximal axonal injury or cell death,and most com-monly involves the corticospinal tracts secondary to an ipsilateral cerebral infarct.DTI was more sensitive than T2-weighted imaging to WD[44].Di?usion anisotropy was reduced both in the primary lesion and in the areas of WD,whereas the ADC are only slightly increased in WD markedly increased in primary ischemic stroke lesions.ADC may thus have the potential to distinguish primary lesions from areas of WD[44].
Developing brain,maturation and aging
Several challenges exist for the application of DTI to the developing human brain.As mentioned above,the val-ues of water ADC and di?usion anisotropy vary with age[21,22,23].However,similar pulse sequences and post processing methods are used for both childhood and adult DTI with the exception of the b value which is typically of the order of1000mm2/s for adults and 700–800mm2/s for infants.
Signi?cantly higher ADC and lower FA have been found in neonates than in adults[45].The ADC have also been shown to be higher in the white than in the gray matter in childhood[21,22].ADC for the white matter of the centrum semiovale in premature infants approach 2.0·10-3mm2/s.Thereafter,with increasing age,they decrease and the anisotropy values,especially the RA increase in a non-linear fashion during devel-opment until they reach the ADC of the adult brain, typically0.7·10-3mm2/s[21,22](Fig.2).The changes in ADC occur predominantly occur within the?rst 6months of life and are believed to be related to decreasing total water content,myelination,and the organization of the white-matter tracts,which all de-crease di?usivity[46,47,48].ADC change with increasing age and when measured in di?erent parts of the brain[45,49].
DTI has been used in the investigation of normal aging,to detect age-related degeneration[23,50].ADC are higher in the cerebral white matter of individuals older than40years of age than in younger individuals [51].In addition,a decrease in di?usion anisotropy has been shown to occur after20years of age.Signi?cant age-related declines in median FA have been demon-strated in densely packed white matter?ber areas, especially the genu of the corpus callosum and the centrum semiovale[23].These interesting?ndings must be taken into account when assessing the e?ects of disease,especially in the elderly.
Di?use axonal injury
Focal brain injuries other than stroke have not been widely studied with DTI,and it is not known whether mechanisms similar to those reported in ischemic stroke are involved in their recovery.Traumatic brain injuries can be classi?ed as focal and di?use.A focal head injury results from direct impact trauma,such as hematoma or cerebral contusion,whereas di?use injuries result from shearing injuries and tensile strain on the brain as a result of rotation or deceleration of adjacent tissues that di?er in density or rigidity.DWI can be used to show shearing injuries not visible on spin-echo or?uid attenuated inversion-recovery(FLAIR)T2-weighted images but is less sensitive than T2*imaging to hem-orrhagic lesions[52].In one study ADC maps were obtained in all patients and65%of the DWI-positive lesions showed decreased di?usion[52](Fig.3).Sur-rounding a focal brain lesion such as a contusion or a focal hematoma,there is zone of‘‘tissue at risk’’de?ned by reduced di?usivity.This zone might be of importance in the development of new rescue therapy for patients
342
with head trauma [53].Most of the histopathologic abnormalities seen in with altered di?usion anisotropy appear to be in the internal capsule and corpus callosum.The signi?cant reduction in di?usion anisotropy seen in
white matter appearing normal on conventional MRI in the ?rst 24h after di?use axonal injury will be less evident,although still abnormal weeks after the trauma [54].A decrease in di?usion coe?cient have been dem-onstrated in normal or almost normal appearing areas on T1-weighted and spin-echo or FLAIR T2-weighted images in the ?rst day of life in newborns with high risk of perinatal brain injury.However,this decrease became more obvious on the third day of life,with pseudonor-malization of the values within a week,by which time conventional MRI was abnormal.This suggests that DTI on the ?rst day after trauma might not show the full extent of the injury in a neonate and that images 3days after the injury might be better predictors of the ?nal extent of the damage [55].Further research in this area is needed to fully evaluate the use of DTI to esti-mate the full extent of a brain injury,optimal timing for MRI and prediction of
outcome.
Fig.2a–e A 45-year-old woman with a partly resected intraven-tricular ependymoma and a postoperative course complicated by left,dominant hemisphere ischemia,leading to aphasia.a A T2-weighted ?uid-attenuated inversion recovery (FLAIR)image demonstrates a slightly high-signal area medially in the left frontal lobe (arrow )and a large area of more increased signal in the deep subcortical and cortical regions of the left frontal lobe (arrow-heads ),which,on a contrast-enhanced T1-weighted image b gives low signal without obvious contrast enhancement.c Di?usion-weighted imaging (DWI)shows an area of restricted di?usion consistent with acute ischemia.The ADC were decreased (0.50±06·10-9±mm 2/s)in this area (arrow )and d increased (1.5±0.05·10-9mm 2/s)in an area of chronic ischemia (arrowhead ).FA was decreased (0.22±0.05)in the area of acute ischemia (arrow )and even more so (0.07±0.02)in the area of chronic ischemia (arrowhead )
343
Multiple sclerosis
Numerous studies on multiple sclerosis (MS)have shown that mean di?usivity is elevated in the lesions seen on T2-weighted images.The degree of elevation seems to be related to the clinical course of the disease.The lesions with more ‘‘destructive’’pathology are generally shown to have the highest di?usivity [7,50,56,57,58].Increased di?usivity (4–13%)has also been found in normal-appearing white matter of patients with MS,which may suggest that it is a di?use white matter disease as well as multifocal.On the other hand,this may also suggest that the white matter is subject to wallerian degeneration proximal and distal to the visible lesions [7,8,57,58,59].A recent study has demon-strated increased water di?usivity in the cerebral gray matter of patients with MS,suggesting that the gray matter may not be spared by the pathological process [60].
It would appear that the FA is more sensitive than ADC values to white-matter abnormalities in MS [57,61,62].Some studies have demonstrated generally reduced di?usion anisotropy in MS plaques (Fig.4);in one,the lowest anisotropy was seen in acute lesions [57]while in another,the lowest anisotropy was found in ‘‘black holes’’,the lesions giving low signal on T1-weighted images [58].Epilepsy
A common cause of refractory complex partial seizures arising in the temporal lobes is hippocampal sclerosis [63].High-resolution MRI has been used to identify speci?c features such as hippocampal volume loss and high signal on spin-echo or FLAIR T2-weighted images [64,65].Recent studies applying DTI to patients with chronic epilepsy and hippocampal sclerosis
have
Fig.3a–d A 23-year-old man with a severe brain injury,unresponsive after a motor vehicle accident.a T2-weighted FLAIR and b T2-weighted images 30h after the accident demonstrate high signal in the body and splenium of the cor-pus callosum,without hemor-rhage,consistent with axonal shearing.c,d ADC were in-creased (1.1±0.06·10)9mm 2/s)(arrow )and FA was decreased (0.38±0.05)(arrow )
344
demonstrated increased di?usivity and reduced anisot-ropy in sclerotic hippocampi,suggesting loss of struc-tural organization and expansion of the extracellular space [66,67].The changes in di?usion extend to involve normal-appearing brain [67].In contrast to these patients,high-resolution techniques have been used to identify malformations of cortical development (MCD)as potential epileptogenic foci in patients with refractory extratemporal,neocortical epilepsy.Preliminary studies of in 12patients with refractory epilepsy and cortical signal abnormalities showed di?erences in ADC within the lesion and contralateral normal brain in the same location;there was a signi?cant overlap between the FA [68].Several investigations using DTI revealed higher di?usivity and lower anisotropy in the zones of MCD [69],and in surrounding brain that appeared normal on conventional MRI [69,70].DTI may prove valuable for identifying epileptogenic foci as well as more optimally de?ning the extent of the lesion for surgical resection.Alzheimer’s disease (AD)
Studies of patients with a clinical diagnosis of AD have concentrated on changes in anisotropy associated with progression of the disease.Changes in di?usion anisot-ropy have been demonstrated by measuring di?usivity in the corpus callosum in the midline,where axons are predominantly oriented transversely.One study showed that anisotropy was lower in the genu and splenium in patients with presumed AD than in sex-and age-mat-ched controls,probably due to axonal loss or demye-lination in these areas [71].In another study the integrity
of axonal tracts in areas associated with cognitive function was compared with that of tracts associated with motor function [72].Using the lattice index [20]as a measure of white-matter tract integrity,the motor tracts appeared preserved,but there was presumed axonal degeneration in the cognitive tracts [72].
DTI has also been used in the investigation of other forms of cognitive impairment,such as in adults with reading di?culties [73],and for detecting degenerate ?ber tracts in the disconnection syndrome [74].A recent investigation showed decreased di?usion anisotropy bilaterally in the temporoparietal white matter in pa-tients with reading di?culty.White-matter di?usion anisotropy in the left temporoparietal region correlated signi?cantly with the reading scores of the reading-im-paired adults and a control group [73],presumably re?ecting the microstructure of white-matter tracts,which may contribute to reading ability.Brain tumors
Radiological speci?cation and grading of a brain tumor is limited,although conventional MRI can be used to demonstrate the site and extent of the tumor.There has been an increasing interest in the use of DWI and DTI to identify di?erent tumor components,and to di?erentiate tumor invasion from normal brain tissue or edema.ADC maps have proved helpful in de?ning solid,enhancing tumor,nonenhancing lesion,peritumoral edema,and necrotic and/or cystic regions from normal surrounding brain.
Cystic or necrotic regions have the highest ADC [75]while the contrast-enhancing part of a tumor has lower ADC than the cystic or necrotic areas and the edema [11,12,75,76,77,78,79,80].Signi?cantly higher mean di?usivity and lower FA than in normal-appearing
white
Fig.4a–c A 45-year-old woman with multiple sclerosis.a A T2-weighted image demonstrates areas of increased signal repre-senting plaques (arrows ).These show b increased ADC (arrows)and c decreased FA (arrows )
345
matter have been demonstrated in the peritumoral region of both gliomas and metastases.Peritumoral mean di?usivity of metastases was signi?cantly higher than that of gliomas whereas the FA was similar,sug-gesting that the FA changes surrounding gliomas can be attributed to both increased water content and tumor in?ltration [81].
The possibility of determining the type and grade of a tumor using DWI and DTI has been explored in both adults and children.Low-grade astrocytomas have higher and high-grade malignant gliomas lower ADC values,re?ecting more restricted di?usion with increas-ing tumor cellularity [12,77,78,82].However a recent study showed that FA values,which are generally re-duced in tumors,suggesting structural disorder,do not add additional information for tissue di?erentiation [79],but may help in the understanding of the e?ect of brain tumors on white-matter ?bers,which might be impor-tant in surgical planning [83,84](Fig.5).
Obtaining reliable information about tumor response to therapy is crucial to treatment.New data from both
animal models and human studies suggest that di?usion imaging may be sensitive to tumor response to therapy [85,86,87].An early increase in ADC during therapy may relate to therapy-induced cell necrosis.A sub-sequent fall in ADC to pretreatment levels within the tumor is thought to indicate tumor regrowth.Metabolic disorders
Reports on DTI in metabolic disorders,such as adre-noleukodystrophy (ALD)[88,89,90],and Krabbe’s disease [91],and in the di?erentiation of dysmyelinating from the demyelinating disorders [92,93]have been published.In X-linked ALD a decrease in FA and an increase in ADC have been demonstrated [89,90],correlating with the well-recognised histopathological zones described in this disease [94](Fig.6).These ?nd-ings suggest increased di?usivity due to an increase in free water and loss of the integrity of the myelin sheaths and axons in the white
matter.
Fig.5a–d A 53-year old man who had received radiation therapy for a left posterior frontal glioblastoma multi-forme.a T2-weighted (arrows )and b contrast-enhanced T1-weighted images show an enhancing lesion adjacent to the left lateral ventricle.In region of interest 2ADC are slightly increased (0.87±0.08·10-9
mm 2/s),compared to the normal region of interest 3(0.76±0.03·10-9mm 2/s
(arrows ).d FA are decreased (0.09±0.02)compared to (0.5±0.04)(arrows )
346
DTI has been found to be superior to conventional MRI in di?erentiating dysmyelinating disorders,such as Pelizaeus-Merzbacher disease from demyelinating dis-orders,such as Krabbe’s disease and Alexander’s dis-ease.Di?usional anisotropy is present in dysmyelinated lesions but is lost in demyelinated lesions;these ?ndings have been veri?ed in both humans and in mice with conditions thought to parallel the human diseases [92,93].
Recent reports describe the use of DTI to character-ize and diagnose other diseases such as amyotrophic lateral sclerosis [95],hereditary disorders such as CA-DASIL [96,97],and infectious diseases including HIV [98].
Conclusions
The recent development of DTI allows direct examina-tion,in vivo,of some aspects of brain microstructure.DTI has already shown to be of value in studies of neuroanatomy,?ber connectivity,and brain develop-ment.It has become interesting for investigation of di?erent brain pathology,such as cerebral ischemia,trauma,MS,presumed AD and cognitive impairment,epilepsy,brain tumors and metabolic disorders.How-ever,further improvement in technique and stable post-processing analyses is needed to increase the utility of DTI in both research and clinical applications.
Acknowledgements We wish to say a special thank you to Pro-fessor Thomas Chenevert,Department of Radiology,University of Michigan Hospitals,for valuable comments and support in the preparation of this
manuscript.
Fig.6a–c A 6-year-old boy with x-linked adrenoleukodystrophy.a High signal on a T2-weighted image extends along the splenium the of corpus callosum bilaterally,with minimal extension into the peritrigonal white matter of both occipital lobes.b ADC are markedly increased ADC,while c FA is decreased.On the FA map the splenium of the corpus callosum appears darker (arrows )than the genu of the corpus callosum
References
1.Moseley M,Cohen Y,Kucharczyk J,et al (1990)Di?usion-weighted MR-imaging of anisotropic water
di?usion in cat central nervous system.Radiology 176:439–445
2.Le Bihan D (1991)Molecular di?usion nuclear magnetic resonance imaging.Magn Reson Q 7:1–30
3.Bammer R (2003)Basic principles of di?usion-weighted imaging.Eur J Radiol 45:169–184
4.Moseley ME,Kucharczyk J,
Mintorovitch J,et al (1990)Di?usion-weighted MR imaging of acute stroke:correlation with T2-weighted and magnetic susceptibility-enhanced MR imaging in cats.AJNR 11:423–https://www.wendangku.net/doc/b14211151.html,nsberg MG,Norbash AM,Marks MP,Tong DC,Moseley ME,Albers GW (2000)Advantages of adding dif-fusion-weighted magnetic resonance imaging to conventional magnetic res-onance imaging for evaluating acute stroke.Arch Neurol 57:1311–1316
https://www.wendangku.net/doc/b14211151.html,rsson HBW,Thomsen C,Fredriksen J,Stubgaard M,Henriksen O (1992)In vivo magnetic resonance di?usion measurements in the brain of patients with multiple sclerosis.Magn Reson Imaging 10:7–12
7.Hors?eld MA,Lai M,Webb S,et al (1996)Apparent di?usion coe?cients in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance.Magn Reson Med 36:393–400
347
8.Christensen P,Gideon P,Thomsen C,
Stubgaard M,Henriksen O,Larsson
HBW(1993)Increased water
self-di?usion in chronic plaques and
in apparently normal white matter in
patients with multiple sclerosis.Acta
Neurol Scand87:195–197
9.Nakahara M,Ericsson K,Bellander
BM(2001)Di?usion-weighted MR and apparent di?usion coe?cient in the
evaluation of severe brain injury.Acta
Radiol42:365–369
10.Sundgren PC,Reinstrup P,Romner B,
Holta s S,Maly P(2002)Value of
conventional,and di?usion-and
perfusion weighted MRI in the
management of patients with unclear
cerebral pathology,admitted to the
intensive care unit.Neuroradiology44: 674–680
11.Stadnik T,Chaskis C,Michotte A,et al
(2001)Di?usion-weighted MR
imaging of intracerebral masses:
comparison with conventional MR
imaging and histologic?ndings.ANJR 22:969–976
12.Kono K,Inoue Y,Nakayama K,et al
(2001)The role of di?usion-weighted
imaging in patients with brain tumors.
AJNR22:1081–1088
13.Sundgren PC,Edvardssson B,Holta s S
(2002)Serial investigation of
perfusion disturbances and vasogenic
oedema in hypertensive encephalopathy by di?usion and perfusion weighted
imaging.Neuroradiology44:
299–304
14.Hinchey J,Chaves C,Applgnani B,
(1996)A reversible posterior leukoen-
cephalopathy syndrome.N Engl J Med 334:494–500
15.Le Bihan D(ed.)(1995)Di?usion and
perfusion magnetic resonance imaging.
Raven Press,New York
16.Le Bihan,D,Mangin JF,Poupon C,
Clark CA,Pappata S,Molko N(2001) Di?usion tensor imaging:concepts and applications.Magn Reson Imaging13: 534–546
17.Pipe JG,Farthing VG,Forbes KP
(2002)Multishot di?usion FSE using
PROPELLER MRI.Magn Reson Med 47:42–52
18.Bammer R,Auer M,Keeling SL,et al
(2002)Di?usion tensor imaging using
single shot SENSE-EPI.Magn Reson
Med48:123–136
19.Basser PJ,Jones DK(2002)Di?usion
tensor MRI:theory,experimental
design and data analysis—a technical
review.NMR Biomed14:456–467 20.Pierpaoli C,Basser PJ(1996)Toward a
quantitative measurement of di?usion
anisotropy.Magn Reson Med36:
893–90621.Mukherjee P,Miller JH,Shimony JS,
et al(2001)Normal brain maturation
during childhood:developmental trends
characterized with di?usion-tensor MR
imaging.Radiology221:349–358
22.Morris MC,Zimmerman RA,Bilaniuk
LT,Hunter JV,Hasselgrove JC(1999)
Changes in brain water di?usion during
childhood.Neuroradiology41:929–934
23.Pfe?erbaum,A,Sullivan EV,Hedehus
M,Lim KO,Adalsteinsson E,Moseley
M(2000)Age-related decline in brain
white matter anisotropy measured with
spatially corrected echo-planar di?usion
tensor imaging.Magn Reson Med44:
259–268
24.Pajevic S,Pierpaoli C(1999)Color
schemes to represent the orientation of
anisotropic tissues from di?usion tensor
data;application to white matter?ber
tract mapping in the human brain.
Magn Reson Med42:526–540
25.Mori S,Van Zijl PC(2002)Fiber
tracking:principles and strategies—a
technical review.NMR Biomed15:
468–480
26.Lori NF,Akbudak E,Shimony JS,et al
(2002)Di?usion tensor?ber tracking of
human brain connectivity:acquisition
methods,reliability analysis and bio-
logical results.NMR Biomed15:493–
515
27.Basser PJ,Pajevic S,Pierpaoli C,Duda
J,Aldroubi A(2000)In vivo?ber trac-
tography using DT-MRI data.Magn
Reson Med44:625–632
28.Bammer R,Acar,B,Moseley M(2002)
In vivo MR tractography using di?u-
sion imaging.Eur J Radiol45:223–234
29.Sorensen AG,Buonanno FS,Gonzalez
RG,(1996)Hyperacute stroke:evalua-
tion with combined multisection di?u-
sion-weighted and hemodynamically
weighted echo-planar MR imaging.
Radiology199:391–401
30.Lutsep HL,Albers GW,DeCrespigny
A,Kamat GN,Marks MP,Moseley
ME(1997)Clinical utility of di?usion-
weighted magnetic resonance imaging in
the assessment of ischemic stroke.Ann
Neurol41:574–580
31.Zelaya F,Flood N,Chalk JB,et al
(1999)An evaluation of the time
dependence of the anisotropy of the
water di?usion tensor in acute human
ischemia.Magn Reson Imaging17:
331–348
32.Weber J,Mattle HP,Heid O,Remonda
L,Schroth G(2000)Di?usion-weighted
imaging in ischaemic stroke:a follow-up
study.Neuroradiology42:184–191
33.Yang Q,Tress BM,Barber PA,et al
(1999)Serial study of apparent di?usion
coe?cient and anisotropy in patients
with acute stroke.Stroke30:2382–2390
34.Mukherjee P,Bahn MM,McKinstry
RC,et al(2000)Di?erences between
gray matter and white matter di?usion
in stroke:di?usion-tensor MR imaging
in12patients.Radiology215:211–220
35.Copen WA,Schwamm LH,Gonzalez
RG,et al(2001)Ischemic stroke:e?ects
of etiology and patient age in the time
course of the core apparent di?usion
coe?cient.Radiology221:27–34
36.Sorensen AG,Wu O,Copen WA,et al
(1999)Human acute cerebral ischemia:
detection of changes in water di?usion
anisotropy by using MR imaging.
Radiology212:785–792
37.Werring DJ,Toosy AT,Clark CA,et al
(2000)Di?usion tensor imaging can
detect and quantify corticospinal tract
degeneration after stroke.J.Neurol
Neurosurg Psychiatry69:269–272
38.Schlaug G,Siewert B,Ben?eld A,
Edelman RR,Warach S(1997)Time
course of the apparent di?usion
coe?cient(ADC)abnormality in
human stroke.Neurology49:113–119
39.Gideon P,Stahlberg F,Thomsen C,
Gjerris F,Sorensen PS,Henriksen O
(1994)Cerebrospinal?uid?ow and
production in patients with normal
pressure hydrocephalus studied by
MRI.Neuroradiology36:210–215
40.Hachinski VC,Potter P,Merskey H
(1987)Leuko-araiosis.Arch Neurol44:
21–33
41.Brown MM(1995)Leukoaraiosis.In:
Dooan GA,Norrving B,Bamford JM,
Bogousslavsky J(eds)Lacunar and
other subcortical infarctions Oxford
University Press,Oxford,pp47–66
42.Pantoni L,Garcia JH(1997)Patho-
genesis of leukoaraiosis:a review.
Stroke28:652–659
43.Jones DK,Lythgoe D,Hors?eld MA,
Simmons A,Williams SCR,Markus HS
(1999)Characterization of white matter
damage in ischemic leukoaraiosis with
di?usion tensor MRI.Stroke30:
393–397
44.Pierpaoli C,Barnett A,Pajevic S,et al
(2001)Water di?usion changes in
Wallerian degeneration and their
dependence on white matter architec-
ture.NeuroImage13:1174–1185
45.Nell J,Shiran S,McKinstry R,et al
(1998)Normal brain in human new-
borns:Apparent di?usion coe?cient
and di?usion anisotropy measured by
using di?usion tensor MR imaging.
Radiology209:57–66
46.Wimberger D.M,Roberts T.R,Bar-
kovitch A.J,Prayer LM,Moseley ME,
Kucharczyk J(1995)Identi?cation of
‘‘premyelination’’by di?usion-weighted
MRI.J Comput Assist Tompogr19:
28–33
348
47.Sakuma H,Nomura Y,Takeda K,et al
(1991)Adult and neonatal human
brain:di?usional anisotropy and mye-
lination with di?usion-weighted MR
imaging.Radiology180:229–233
48.Nomura Y,Sakuma H,Takeda K,Ta-
gami T,Okuda Y,Nakagawa T(1994) Di?usion anisotropy of the human
brain assessed with di?usion-weighted
MR:relation with normal brain devel-
opment and aging.AJNR15:231–238 49.Huppi P,Maier S,Peled S,et al(1998)
Microstructural development of human newborn cerebral white matter assessed in vivo by di?usion tensor MRI.Pediatr Res44:584–590l
50.Nusbaum AO,Lu D,Tang CY,Altas
SW(2000)Quantitative di?usion
measurements in focal multiple sclerosis lesions:correlations with appearance on T1-weighted images.Am J Roentgenol 175:821–825
51.Gideon P,Thomsen C,Henriksen O
(1994)Increased self-di?usion of brain
water in normal aging.Magn Reson
Imaging4:185–188
52.Huisman AGM,Sorensen AG,Hergan
K,Gonzalez RG,Schaefer PW(2003)
Di?usion-weighted imaging for the
evaluation of di?use axonal injury in
closed head injury.J Comput Assist
Tomogr27:5–11
53.Jones DK,Dardis R,Ervine M,et al
(2000)Cluster analysis of di?usion ten-sor magnetic resonance images in hu-
man head injury.Neurosurgery47:306–317
54.Arfanakis K,Haughton VM,Carew
JD,Rogers BP,Dempsey RJ,Meyerand ME(2002)Di?usion tensor MR imag-ing in di?use axonal injury.AJNR23:
794–802
55.Mckinstry RC,Miller JH,Snyder AZ,
et al(2003)A prospective,longitudinal di?usion tensor imaging study of brain injury in newborns.Neurology59:
824–833
56.Droogan AG,Clark CA,Werring DJ,
Barker GJ,McDonald WI,Miller DH
(1999)Comparison of MS clinical
subgroups using navigated di?usion-
weighted imaging.Magn Reson
Imaging17:653–661
57.Werring DJ,Clark CA,Barker GJ,
Thompson AJ,Miller DH(1999)
Di?usion tensor imaging of lesions and normal-appearing white matter in mul-tiple sclerosis.Neurology52:1626–1632 58.Bammer R,Augustin M,Strasser-Fuchs
S,et al(2000)Magnetic resonance
di?usion tensor imaging for
characterizing di?use and focal white
matter abnormalities in multiple
sclerosis.Magn Reson Med44:583–59159.Filippi M,Ianucci G,Cercignani M,
Rocca MA,Praseti A,Comi G(2000)A
quantitative study of water di?usion in
multiple sclerosis lesions and normal-
appearing white matter using echo-pla-
nar imaging.Arch Neurol57:1017–
1021
60.Bozzali M,Cercignani M,Sormani M,
Comi G,Filippi M(2002)Quanti?ca-
tion of brain gray matter damage in
di?erent MS phenotypes by use of dif-
fusion tensor MR imaging.AJNR23:
985–988
61.Guo A,MacFall J,Provenzale J(2002)
Multiple sclerosis;di?usion tensor MR
imaging for evaluation of normal-
appearing white matter.Radiology222:
729–736
62.Filippi M,Cercignani M,Inglese M,
Hors?eld M,Comi G(2001)Di?usion
tensor magnetic resonance imaging in
multiple sclerosis.Neurology56:304–
311
63.Brown WJ,Babb TL(1987)Neuro-
pathological changes in the temporal
lobe associated with complex partial
seizures.In Hopkins A(ed)Epilepsy.
Demos,New York,pp300–323
64.Brooks BS,King DW,el Gammal T,
et al(1990)MR imaging in patients with
intractable complex partial epileptic
seizures.ANJR11:93–99
65.Tien R,Felsberg G,Castro C,et al
(1993)Complex partial seizure and
mesial temporal sclerosis:evaluation
with fast spin-echo MR imaging.
Radiology189:835–842
66.Wieshman UC,Clark CA,Symms MR,
Franconi F,Barker GJ,Shorvon SD
(1999)Reduced anisotropy of water
di?usion in human hippocampus in
epilepsy.Magn Reson Imaging17:
29–36
67.Yoo SY,Chang KH,Song IC,et al
(2002)Apparent di?usion coe?cient
value of the hippocampus in patients
with hippocampal sclerosis and in
healthy volunteers.ANJR23:809-812
68.Eriksson SH,Rugg-Gunn FJ,Symms
MR,Barker GJ,Duncan JS(2001)
Di?usion tensor imaging in patients
with epilepsy and malformations of
cortical development.Brain124:617–
626
69.Arfanakis K,Hermann BP,Rogers BP,
Carew JD,Seidenberg M,Meyerand
ME(2002)Di?usion tensor MRI in
temporal lobe epilepsy.Magn Reson
Imaging20:511–519
70.Rugg-Gunn FJ,Eriksson SH,Symms
MR,Barker GJ,Duncan JS(2001)
Di?usion tensor imaging of cryptogenic
and acquired partial epilepsies.Brain
124:627–636
71.Hanyu H,Sakurai H,Iwamoto T,
Takasaki M,Shindo H,Abe K(1998)
Di?usion-weighted MR imaging of the
hippocampus and temporal white
matter in Alzheimer’s disease.J Neurol
Sci156:195–200
72.Rose SE,Chen F,Chalk JB,et al(2000)
Loss of connectivity in Alzheimer’s
disease:an evaluation of the white
matter tract integrity with color coded
MR di?usion tensor imaging.
J Neurol Neurosurg Psychiatry69:
530
73.Klingberg T,Hedehus M,Temple E,
et al(2000)Microstructure of
temporo-parietal white matter as a basis
for reading ability:evidence from
di?usion tensor magnetic resonance
imaging.Neuron25:493–500
74.Molko N,Cohen L,Mangin JF,et al
(2002)Visualizing the neural bases of a
disconnection syndrome with di?usion
tensor imaging.J Cogn Neurosci14:
629–636
75.Brunberg J,Chenevert T,McKeever
PE,et al(1995)In vivo MR determi-
nation of water di?usion coe?cients
and di?usion anisotropy:correlation
with structural alteration in gliomas of
the cerebral hemispheres.ANJR16:
361–371
76.76Krabbe K,Gideon P,Wagn P,
Hansen U,Thomsen C,Madsen F
(1997)MR di?usion imaging of human
intracranial tumours.Neuroradiology
1997;39:483–489
77.Castillo M,Smith J,Kwock L,Wilbert
K(2001)Apparent di?usion coe?cients
in the evaluation of high-grade cerebral
gliomas.ANJR22:60–64
78.Guo A,Cummings T,Dash R,
Provenzale J(2002)Lymphomas and
high-grade astrocytomas:comparison
of water di?usibility and histologic
characteristics.Radiology224:
177–183
79.Sinha S,Bastin ME,Whittle IR,
Wardlaw JM(2002)Di?usion tensor
imaging of high-grade cerebral gliomas.
AJNR23:520–527
80.Bastin M,Sinha S,Whittle I,Wardlaw J
(2002)Measurements of water di?usion
and T1values in peritumoural oede-
matous brain.Neuroreport13:1335–
1340
81.Lu S,Ahn D,Johnson G,Cha S(2003)
Peritumoral di?usion tensor imaging of
high-grade gliomas and metastatic brain
tumors.AJNR24:937–941
82.Gauvain K,McKinstry R,Mukherjee
P,et al(2001)Evaluating pediatric
brain tumor cellularity with di?usion
tensor imaging.Am J Roentgenol177:
449–454
349
83.Wieshmann UC,Symms MR,Parker
GJ,et al(2000)Di?usion tensor imag-ing demonstrates deviation of?bres in
normal appearing white matter adjacent to a brain tumour.J Neurol Neurosurg Psychiatry68:501–503
84.Mori S,Fredriksen K,van Zijl PC,et al
(2002)Brain white matter anatomy of
tumor patients evaluated with di?usion tensor imaging.Ann Neurol51:
377–380
85.Chenevert TL,McKeever PE,Ross BD
(1997)Monitoring early response of
experimental brain tumors to therapy
using di?usion magnetic resonance
imaging.Clin Cancer Res3:
1457–1466
86.Chenevert TL,Stegman LD,Taylor JM
(2000)Di?usion magnetic resonance
imaging;an early surrogate marker of
therapeutic e?cacy in brain tumors.
J Natl Cancer Inst92:2029–2036
87.Mardor Y,Pfe?er R,Spiegelmann R,
et al(2003)Early detection of response to radiation therapy in patients with
brain malignancies using conventional
and high b-value di?usion weighted
magnetic resonance imaging.J Clin
Oncol21:1094–110088.Itoh R,Melhem ER,Mori S,Eichler
FS,Raymond GV,Moser HW(2001)
Di?usion tensor brain MR imaging in
X-linked cerebral adrenoleukodystro-
phy.Neurology56:544–547
89.Eichler F,Itoh R,Barker PB,(2003)
Proton MR spectroscopic and di?usion
tensor brain MR imaging in X-linked
adrenoleukodystrophy:initial
experience.Radiology225:245–252
90.Schneider JFL,Il’yasov KA,
Boltshauser E,Hennig J,Martin E
(2003)Di?usion tensor imaging in
cases of adrenoleukodystrophy:
preliminary experience as a marker
for early demyelination?ANJR24:
819–824
91.Guo AC,Petrella JR,Kurtzberg J,
Provenzale JM(2001)Evaluation of
white matter anisotropy in Krabbe
disease with di?usion tensor imaging:
initial experience.Radiology218:
245–252
92.Ono J,Harada K,Takahashi M,
et al(1995)Di?erentiation between
dysmyelination and demyelination
using magnetic resonance
di?usional anisotropy.Brain Res671:
141–148
93.Ono J,Harada K,Mano T,Sakurai K,
Okada S(1997)Di?erentiation of dys-
and demyelination using di?usional
anisotropy.Pediatr Neurol16:63–66
94.Schaumburg H,Powers J,Raine C,
Suzuki K,Richardson E(1975)
Adrenoleukodystrophy:a clinical and
pathological study of17cases.Arch
Neurol32:577–591
95.Ellis CM,Simmons A,Jones DK,
(1999)Di?usion tensor MRI assesses
corticospinal tract damage in ALS.
Neurology53:1051–1058
96.Chabriat H,Pappata S,Poupon C,et al
(1999)Di?usion tensor imaging in cere-
bral autosomal dominant arteriopathy
with subcortical infarcts and leukoence-
phalopathy(CADASIL):preliminary
results[abstract]Stroke30:P62
97.Chabriat H,Pappata S,Poupon C,et al
(1999)Clinical severity in CADASIL
related to ultrastructural damage to
white matter—in vivo study with di?u-
sion tensor MRI.Stroke30:2637–2643
98.Filippi CG,Ulug AM,Ryan E,Ferr-
ando SI,van Gorp W(2001)Di?usion
tensor imaging in patients with HIV and
normal-appearing white matter on MR
images of the brain.AJNR22:277–283
350