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NEURORADIOLOGY Table of Contents   
Year : 2008  |  Volume : 18  |  Issue : 1  |  Page : 45-52
Review: Clinical application of diffusion tensor imaging

1 Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
2 Department of Mathematics and Statistics, Indian Institute of Technology, Kanpur, India

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How to cite this article:
Trivedi R, Rathore RK, Gupta RK. Review: Clinical application of diffusion tensor imaging. Indian J Radiol Imaging 2008;18:45-52

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Trivedi R, Rathore RK, Gupta RK. Review: Clinical application of diffusion tensor imaging. Indian J Radiol Imaging [serial online] 2008 [cited 2020 May 26];18:45-52. Available from:
Diffusion tensor imaging (DTI), a relatively new MRI technique, has generated a tremendous amount of interest in the clinical and laboratory domains. This modality measures the  Brownian motion More Details of water molecules in tissue. [1] Two aspects of DTI, i.e., the microscopic length scale and orientation information render the modality very powerful. The microscopic length scale of water diffusion in tissue gives DTI microscopic spatial sensitivity, whereas the orientation information can be used to differentiate apparently homogenous white matter on conventional MRI into its constituent fiber tracts. Together, these two advantages have helped propagate the application of DTI in various pathologies.

To illustrate the ability of DTI to differentiate lesions from normal brain, this presentation reviews selected clinical applications of DTI.

   Physical Principles of DTI Top

Diffusion is a physical process that involves the translational movement of molecules via thermally driven random motion, the so-called Brownian motion. The underlying cellular microstructure of tissue complicates the situation and influences the overall mobility of the diffusing molecules by providing numerous barriers and by creating various individual compartments (e.g., intracellular, extracellular, neurons, glial cells, and axons) within tissue. In diffusion-weighted imaging (DWI), diffusion is described by using a scalar parameter, the diffusion coefficient D . However, in the presence of anisotropy, diffusion is characterized by a tensor, D, that describes local water diffusion. A tensor is a mathematical construct that describes the properties of an ellipsoid in 3-D space.

Quantities related to diffusion can be calculated from the tensor (matrix). Fractional anisotropy (FA) and mean diffusivity (MD) are the two most commonly used metrics for characterizing the tissue microstructural organization. FA (Equation 1) measures the degree of directionality of diffusion, while MD (Equation 2) describes the average diffusivity of water.

   Potential Applications of DTI in the Central Nervous System Top

Developmental disorders

DTI draws attention to developmental disorders, both congenital as well as natal, due to its potential for generating white matter tracts and aberrant connections in cases with disturbance of normal white matter development. In developmental central nervous system (CNS) disease, DTI demonstrates additional findings beyond those seen with conventional MRI and allows better understanding of a malformed brain.

Joubert syndrome: Joubert syndrome, a subtype of posterior fossa malformation, consists of vermian hypoplasia and derangement of the cerebellar-brainstem or cerebellar-cortical connections. The typical 'molar tooth appearance' of the superior cerebellar peduncle (SCP), with partial or complete absence of the vermis on MRI, is diagnostic of Joubert syndrome [Figure - 1]. [2]

Heterotopia: In heterotopic gray matter, the arrested neurons due to a faulty migrational process might have some degree of directionality like normal white matter tracts and show increased anisotropy. [3]

Callosal agenesis: Agenesis of the corpus callosum (ACC) [Figure - 2] is characterized by a 'cartwheel configuration' of the interhemispheric sulcal markings, absence of the cingulate gyrus, and colpocephalic features of the lateral ventricles. [4] DTI has shown a thick fiber bundle running anteroposteriorly (i.e., the Probst bundle) in these patients.

Cerebeller agenesis: [5] Complete cerebellar agenesis [Figure - 3] occurs during the early period of embryogenesis and is usually associated with severe motor dysfunction.

Polymicrogyria (PMG): PMG, a surface area derivative anomaly, commonly manifests as a seizure disorder. MRI is routinely used to study these patients in vivo . Though conventional MRI provides detailed anatomic demonstration of these lesions, it does not demonstrate the true extent of the lesion. DTI has shown significantly decreased FA values [Figure - 4] in the subcortical white matter subjacent to the polymicrogyric cortex, reflecting microstructural changes in the white matter, probably due to the presence of ectopic neurons. [6] An abnormality on DTI, seen beyond the margins of the obvious lesion on conventional MRI, may help in planning neurosurgical intervention.

Cerebral palsy (CP): CP is a nonprogressive disorder of diverse etiology, characterized by varying motor dysfunction. The most common cause of childhood CP is hypoxic brain injury and periventricular leukomalacia (PVL) in premature neonates. An impairment of the corticospinal tracts (CST) is believed to be responsible for the motor dysfunction. MRI is useful for investigating the cause and timing of injury in children with CP [7] and has shown pathology in almost 70-90% of CP patients. A few recent DTI studies [8],[9] have demonstrated decreased FA values in the posterior limb of the internal capsule and CST [Figure - 5], even in patients with near-normal conventional imaging. Decreased CST FA values in CP patients may help in better defining the clinical outcome in these patients.

Ischemic brain injury

A reduction in the delivery of oxygen and nutrients to the brain parenchyma secondary to obstructed blood flow results in cerebral ischemia. The rapid failure of high-energy metabolism and associated ionic pumps during acute cerebral ischemia leads to intracellular migration of sodium and calcium. The subsequent influx of osmotically obligated water results in cytotoxic edema.

Hypoxic-ischemic encephalopathy (HIE): Permanent damage to neuronal cells caused by hypoxic-ischemic injury may result in neonatal death or be manifested later as CP or impaired cognition. [10] Due to incomplete myelination and the higher brain water content [11] in term neonates, conventional MRI is limited in its ability to detect the presence and extent of hypoxic-ischemic injury in stage I HIE; structural changes usually manifest after 4-8 months in infants with stage I and II HIE. [12] In term neonates with HIE, the detection of injury on DWI is dependent on the timing of imaging after injury. DTI imaging shows abnormal FA and mean diffusivity (MD) values in HIE patients even when they have near-normal conventional imaging [Figure - 6]. [13] An altered pattern of age-related changes in FA and MD values, which may help in earlier and more accurate assessment of microstructural damage in this setting, [13] has also been demonstrated using serial DTI scans.

Adult stroke: Diffusion imaging is a valuable clinical tool in the assessment of stroke because of its high sensitivity during the hyperacute period [14] and its ability to distinguish acute infarcts from chronic infarcts. In the transition from acute to subacute to chronic stroke, the MD first decreases in the acute phase and then renormalizes and subsequently increases. On the other hand, diffusion anisotropy measures (e.g., FA) decline and remain low in chronic infarcts. Several experimental and human stroke DTI studies [15],[16] in acute as well as chronic stroke settings have shown decreased FA values in infarcted areas as well as in the adjacent regions [Figure - 7].


Though the major application of DTI is to investigate white matter abnormalities in various neuropathologies, Gupta and his coworkers have demonstrated its use in many different infections. [17],[18],[19],[20],[21]

Brain abscess: Increased FA values, comparable to those seen in white matter, are seen in abscess cavities [Figure - 8],[Figure - 9]. [18] These are due to the presence of oriented neuroinflammatory molecules, as shown by experimental ex vivo imaging of cell lines treated with heat-killed Staphylococcus aureus . [21] FA may be used as a noninvasive surrogate marker for disease activity at the site of the local infective process.

Meningitis: Gadolinium (Gd)-DTPA MRI can detect abnormal meningeal enhancement. [22] High FA values in enhancing and nonenhancing cortical ribbons in adults [Figure - 10] as well as in neonates with bacterial meningitis have been shown [19],[20] as compared to age-matched controls. This may be due to oriented inflammatory cells in the subarachnoid space as a result of an up-regulated immune response in meningitis. Increased FA values in the enhancing as well as nonenhancing cortical regions suggest diffuse inflammatory activity in the pia-arachnoid in these patients. FA may be a better indicator of active and diffuse meningeal inflammation than post-contrast T1W imaging.

The periventricular white matter of the neonatal brain is known to be vulnerable to oxidative and hypoxic-ischemic injury secondary to neuroinfections. A recent DTI study has shown decreased FA values in the normal appearing periventricular white matter of neonates with bacterial meningitis compared to age/sex-matched healthy controls. [20]

Subacute sclerosing panencephalitis (SSPE): SSPE is a rare progressive degenerative disease. It is caused by persistent infection by a defective measles virus. Imaging in these patients is not used for diagnosis but for following the course of disease. To date, no significant correlation between conventional MRI and clinical staging has been demonstrated; even severely affected patients may show a normal MRI study. [23] DTI has shown decreased FA and increased MD values in the parietooccipital white matter [Figure - 11] even in those with near-normal conventional imaging. [17]

HIV infection: During the early stages of infection, HIV-1 enters the central nervous system and preferentially affects the subcortical white matter. Immunohistochemical and in situ hybridization studies in patients with HIV encephalitis have shown HIV-1 infected macrophages and multinucleated giant cells preferentially invading the cerebral white matter, the corpus callosum, and the internal capsule. [24] White matter involvement is detectable in the form of vasculitis and gliosis even in asymptomatic HIV-1 positive patients. [25] DTI studies in HIV patients with near-normal conventional imaging have demonstrated reduced FA values in white matter tracts. Fillipi et al . have demonstrated a linear relation between the viral load and DTI measures in white matter. [26]

Radiation oncology

Radiotherapy causes injury to normal brain that may not be detected on conventional imaging. [27] Quantitative evaluation of changes in normal-appearing white matter (NAWM) of brain tumor patients receiving radiotherapy has been described using DTI metrics. Also reported are a significant reduction in FA and increase in MD in the brains of children (aged between 3-14 years and treated for medulloblastoma) and adults (with diverse brain tumors) who received various combinations of chemotherapy and radiotherapy. [28],[29] In a recent study, FA values also demonstrated a differential effect in the frontal lobe, as compared to the parietal lobe, in medulloblastoma survivors. [30] Decreased FA values have been demonstrated in the NAWM of adult patients with low-grade gliomas, for dose bins of >55 Gy, 50-55 Gy, and 45-50 Gy, 3 months post-radiotherapy, suggesting that the threshold dose limit for changes in NAWM using DTI is 55-50 Gy. [31]

   References Top

1.Le Bihan D, Mangin JF, Poupon C, Clark CA, Pappata S, Molko N, et al . Diffusion tensor imaging: Concepts and applications. J Magn Reson Imaging 2001;13:534-46.  Back to cited text no. 1    
2.Romano S, Boddaert N, Desguerre I, Hubert L, Salomon R, Seidenwurm D, et al . Molar tooth sign and superior vermian dysplasia: A radiological, clinical and genetic study. Neuropediatrics 2006;37:42-5.  Back to cited text no. 2    
3.Lee SK, Kim DI, Kim J, Kim DJ, Kim HD, Kim DS, et al . Diffusion-tensor MR imaging and fiber tractography: A new method of describing aberrant fiber connections in developmental CNS anomalies. Radiographics 2005;25:53-65.  Back to cited text no. 3    
4.Utsunomiya H, Yamashita S, Takano K, Okazaki M. Arrangement of fiber tracts forming Probst bundle in complete callosal agenesis: Report of two cases with an evaluation by diffusion tensor tractography. Acta Radiol 2006;47:1063-6.  Back to cited text no. 4    
5.Gupta A, Malik GK, Gupta A, Saksena S, Gupta RK. MR demonstration of complete cerebellar and corpus callosum agenesis. Pediatr Neurosurg 2007;43:29-31.  Back to cited text no. 5    
6.Trivedi R, Gupta RK, Hasan KM, Hou P, Prasad KN, Narayana PA. Diffusion tensor imaging in polymicrogyria: A report of three cases. Neuroradiology 2006;48:422-7.  Back to cited text no. 6    
7.Krδgeloh-Mann I, Horber V. The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: A systematic review. Dev Med Child Neurol 2007;49:144-51.  Back to cited text no. 7    
8.Thomas B, Eyssen M, Peeters R, Molenaers G, Van Hecke P, De Cock P, et al . Quantitative diffusion tensor imaging in cerebral palsy due to periventricular white matter injury. Brain 2005;128:2562-77.  Back to cited text no. 8    
9.Trivedi R, Gupta RK, Shah V, Hasan KM, Tripathi M, Narayana PA. Assessment of white matter damage in cerebral palsy using quantitative diffusion tensor imaging. Proc Intl Soc Mag Reson Med 2007 - conference abstract 718.  Back to cited text no. 9    
10.Stoll BJ, Kliegman RM. Hypoxia-ischemia. In : Behrman RE, Kliegman RM, Jenson HB, editors. Nelson Textbook of Pediatrics. Saunders: Philadelphia; 2004. p. 566-8.  Back to cited text no. 10    
11.Huppi PS, Barnes PD. Magnetic resonance techniques in the evaluation of the newborn brain. Clin Perinatol 1997;24:693-723.  Back to cited text no. 11    
12.Byrne P, Welch R, Johnson MA, Darrah J, Piper M. Serial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy. J Pediatr 1990;117:694-700.  Back to cited text no. 12    
13.Malik GK, Trivedi R, Gupta RK, Hasan KM, Hasan M, Gupta A, et al . Serial quantitative diffusion tensor MRI of the term neonates with hypoxic-ischemic encephalopathy (HIE). Neuropediatrics 2006;37:337-43.  Back to cited text no. 13    
14.Hacke W, Kaste M, Fieschi C, von Kummer R, Davalos A, Meier D, et al . Random double-blind placebo-controlled trial of thrombolytic treatment with intravenous Alteplase in acute ischemic stroke (ECASS II). Lancet 1998;352:1245-51.  Back to cited text no. 14    
15.Sorensen AG, Wu O, Copen WA, Davis TL, Gonzalez RG, Koroshetz WJ, et al . Human acute cerebral ischemia: Detection of changes in water diffusion anisotropy by using MR imaging. Radiology 1999;212:785-92.  Back to cited text no. 15    
16.Thomalla G, Glauche V, Weiller C, R φther J. Time course of wallerian degeneration after ischaemic stroke revealed by diffusion tensor imaging. J Neurol Neurosurg Psychiatry 2005;76:266-8.  Back to cited text no. 16    
17.Trivedi R, Gupta RK, Agarawal A, Hasan KM, Gupta A, Prasad KN, et al . Assessment of white matter damage in subacute sclerosing panencephalitis using quantitative diffusion tensor MR imaging. AJNR Am J Neuroradiol 2006;27:1712-6.  Back to cited text no. 17    
18.Gupta RK, Hasan KM, Mishra AM, Jha D, Husain M, Prasad KN, et al . High fractional anisotropy in brain abscesses versus other cystic intracranial lesions. AJNR Am J Neuroradiol 2005;26:1107-14.  Back to cited text no. 18    
19.Nath K, Trivedi R, Gupta RK, Prasad KN, Husain M, Narayana PA. Increased cortical fractional anisotropy is a marker of infection in meningitis patients associated with brain abscess. Proc Intl Soc Mag Reson Med 2007 - conference abstract. 673.  Back to cited text no. 19    
20.Trivedi R, Malik GK, Gupta RK, Gupta A, Nath K, Prasad KN, et al . Increased anisotropy in neonatal meningitis: An indicator of meningeal inflammation. Neuroradiology 2007;49:767-75.  Back to cited text no. 20    
21.Gupta RK, Nath K, Prasad A, Prasad KN, Husain M, Rathore RK, et al . In vivo Demonstration of neuroinflammatory molecules expression in brain abscess with diffusion tensor imaging. AJNR Am J Neuroradiol 2007; [Epub ahead of print].  Back to cited text no. 21    
22.Kastrup O, Wanke I, Maschke M. Neuroimaging of infections. NeuroRx 2005;2:324-32.  Back to cited text no. 22    
23.Brismar J, Gascon GG, Steyern KV, Bohlega S. Subacute sclerosing panencephalitis: Evaluation with CT and MR. AJNR Am J Neuroradiol 1996;17:761-72.  Back to cited text no. 23    
24.Gosztonyi G, Artigas J, Lamperth L, Webster HD. Human immunodeficiency virus (HIV) distribution in HIV encephalitis: Study of 19 cases with combined use of in situ hybridization and immunocytochemistry. J Neuropathol Exp Neurol 1994;53:521-34.  Back to cited text no. 24    
25.Gray F, Scaravilli F, Everall I, Chretien F, An S, Boche D, et al . Neuropathology of early HIV-1 infection. Brain Pathol 1996;6:1-15.  Back to cited text no. 25    
26.Filippi CG, Ulug AM, Ryan E, Ferrando SJ, van Gorp W. Diffusion tensor imaging of patients with HIV and normalappearing white matter on MR images of the brain. AJNR Am J Neuroradiol 2001;22:277-83.  Back to cited text no. 26    
27.Schultheiss TE, Kun LE, Ang KK, Stephens LC. Radiation response of the central nervous system. Int J Radiat Oncol Biol Phys 1995;31:1093-12.  Back to cited text no. 27    
28.Khong PL, Kwong DL, Chan GC, Sham JS, Chan FL, Ooi GC. Diffusion-tensor imaging for the detection and quantification of treatment-induced white matter injury in children with medulloblastoma: A pilot study. AJNR Am J Neuroradiol 2003;24:734-40.  Back to cited text no. 28    
29.Kitahara S, Nakasu S, Murata K, Sho K, Ito R. Evaluation of ­treatment-induced cerebral white matter injury by using diffusion-tensor MR imaging: Initial experience. AJNR Am J Neuroradiol 2005;26:2200-6.  Back to cited text no. 29    
30.Qui D, Kwong DL, Chan GC, Leung LH, Khong PL. Diffusion tensor magnetic resonance imaging finding of discrepant fractional anisotropy between the frontal and parietal lobes after whole-brain irradiation in childhood medulloblastoma survivors: Reflection of regional white matter radiosensitivity? Int J Radiation Oncology Biol Phys 2007;69:846-51.  Back to cited text no. 30    
31.Haris MD, Sapru S, Das KJ, Raj MK, Purwar A, Rathore DK, et al . Changes in DTI metrics in normal appearing white matter after radiotherapy in patients with low grade glioma. Proc Intl Soc Mag Reson Med 2007 - conference abstract. 672.  Back to cited text no. 31    

Correspondence Address:
Rakesh K Gupta
Department of Radiodiagnosis, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, UP
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-3026.38505

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  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7], [Figure - 8], [Figure - 9], [Figure - 10], [Figure - 11]

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