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Neuroimaging of White Matter Injury: A Multimodal Approach to Vascular Disease

  • Gary A. Rosenberg
  • Branko Huisa
  • Fakhreya Y. Jalal
  • Yi Yang
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR, volume 4)

Abstract

Neuroimaging has advanced greatly since the initial introduction of computed tomography (CT) and magnetic resonance imaging (MRI). These new modalities enabled clinicians and researchers to observe changes in normal and pathological white matter that could only be seen at autopsy. While greatly enhancing our understanding in multiple sclerosis and cerebrovascular diseases, these modalities have also raised important questions about the normal changes that occur in white matter with aging. CT has limited application in white matter because of the lack of resolution. On the contrary, MRI provides exquisite images of white matter pathology, including information on the state of the blood–brain barrier (BBB) with paramagnetic contrast agents. Many diseases produce similar changes on the MRI, and these pathological changes overlap with normal aging. More sophisticated methods are now available to distinguish underlying pathology, including nuclear magnetic resonance spectroscopy (NMRS) to show neurochemistry, diffusion tensor imaging (DTI) to define white matter fiber tract integrity, and dynamic contrast-enhanced MRI (DCEMRI) to study vascular permeability. While each of these novel methods taken alone provides limited information, the combination of multiple modalities gives a more complete picture of the state of the white matter. These new methods, which are still at an early research stage, should shortly enter into clinical diagnosis of white matter diseases. This review focuses on the impact of neuroimaging in acute and chronic cerebrovascular diseases, particularly on their role in acute stroke and chronic vascular disease associated with cognitive decline.

Keywords

White Matter Apparent Diffusion Coefficient Fractional Anisotropy Diffusion Tensor Imaging White Matter Lesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Auer DP, Putz B, Gossl C et al (2001) Differential lesion patterns in CADASIL and sporadic subcortical arteriosclerotic encephalopathy: MR imaging study with statistical parametric group comparison. Radiology 218:443–451PubMedCrossRefGoogle Scholar
  2. Awad IA, Johnson PC, Spetzler RF et al (1986) Incidental subcortical lesions identified on magnetic resonance imaging in the elderly. II. Postmortem pathological correlations. Stroke 17: 1090–1097PubMedCrossRefGoogle Scholar
  3. Bennett DA, Wilson RS, Gilley DW et al (1990) Clinical diagnosis of Binswanger’s disease. J Neurol Neurosurg Psychiatry 53:961–965, see commentsPubMedCrossRefGoogle Scholar
  4. Boone KB, Miller BL, Lesser IM et al (1992) Neuropsychological correlates of white-matter lesions in healthy elderly subjects. A threshold effect. Arch Neurol 49:549–554PubMedCrossRefGoogle Scholar
  5. Bousser MG, Tournier-Lasserve E (1994) Summary of the proceedings of the First International Workshop on CADASIL. Paris, May 19–21, 1993. Stroke 25:704–707PubMedCrossRefGoogle Scholar
  6. Bradbury MW (1993) The blood–brain barrier. Exp Physiol 78:453–472, ReviewPubMedGoogle Scholar
  7. Brooks WM, Wesley MH, Kodituwakku PW et al (1997) 1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly. Stroke 28:1940–1943PubMedCrossRefGoogle Scholar
  8. Candelario-Jalil E, Thompson J, Taheri S et al (2011) Matrix metalloproteinases are associated with increased blood–brain barrier opening in vascular cognitive impairment. Stroke 42: 1345–1350PubMedCrossRefGoogle Scholar
  9. Chalela JA, Kidwell CS, Nentwich LM et al (2007) Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison. Lancet 369:293–298PubMedCrossRefGoogle Scholar
  10. Cvoro V, Wardlaw JM, Marshall I et al (2009) Associations between diffusion and perfusion parameters, N-acetyl aspartate, and lactate in acute ischemic stroke. Stroke 40:767–772PubMedCrossRefGoogle Scholar
  11. De Reuck J, Crevits L, De Coster W et al (1980) Pathogenesis of Binswanger chronic progressive subcortical encephalopathy. Neurology 30:920–928PubMedCrossRefGoogle Scholar
  12. Dewar D, Underhill SM, Goldberg MP (2003) Oligodendrocytes and ischemic brain injury. J Cereb Blood Flow Metab 23:263–274PubMedCrossRefGoogle Scholar
  13. Duering M, Zieren N, Herve D et al (2011) Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL. Brain 134: 2366–2375PubMedCrossRefGoogle Scholar
  14. Duvernoy H, Delon S, Vannson JL (1983) The vascularization of the human cerebellar cortex. Brain Res Bull 11:419–480PubMedCrossRefGoogle Scholar
  15. Ewing JR, Knight RA, Nagaraja TN et al (2003) Patlak plots of Gd-DTPA MRI data yield blood–brain transfer constants concordant with those of 14C-sucrose in areas of blood–brain opening. Magn Reson Med 50:283–292PubMedCrossRefGoogle Scholar
  16. Filippi M, Rocca MA (2008) Multiple sclerosis and allied white matter diseases. Neurol Sci 29(Suppl 3):319–322PubMedCrossRefGoogle Scholar
  17. Filippi M, Rocca MA, Barkhof F et al (2012) Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol 11:349–360PubMedCrossRefGoogle Scholar
  18. Gasparovic C, Bedrick EJ, Mayer AR et al (2011) Test-retest reliability and reproducibility of short-echo-time spectroscopic imaging of human brain at 3T. Magn Reson Med 66:324–332PubMedCrossRefGoogle Scholar
  19. Gorelick PB, Scuteri A, Black SE et al (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:2672–2713PubMedCrossRefGoogle Scholar
  20. Hachinski V, Iadecola C, Petersen RC et al (2006) National Institute of Neurological Disorders and Stroke-Canadian Stroke Network vascular cognitive impairment harmonization standards. Stroke 37:2220–2241PubMedCrossRefGoogle Scholar
  21. Hachinski VC, Potter P, Merskey H (1987) Leuko-araiosis. Arch Neurol 44:21–23PubMedCrossRefGoogle Scholar
  22. Henderson AP, Barnett MH, Parratt JD et al (2009) Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol 66:739–753PubMedCrossRefGoogle Scholar
  23. Hom J, Dankbaar JW, Soares BP et al (2011) Blood–brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke. AJNR Am J Neuroradiol 32:41–48PubMedCrossRefGoogle Scholar
  24. Hounsfield GN (1980) Computed medical imaging. Science 210:22–28PubMedCrossRefGoogle Scholar
  25. Huisa BN, Gasparovic C, Taheri S et al (2013) Imaging of subacute blood–brain barrier disruption after methadone overdose. J Neuroimaging 23(3):441–444PubMedCrossRefGoogle Scholar
  26. Hunt AL, Orrison WW, Yeo RA et al (1989) Clinical significance of MRI white matter lesions in the elderly. Neurology 39:1470–1474PubMedCrossRefGoogle Scholar
  27. Ihara M, Tomimoto H, Kinoshita M et al (2001) Chronic cerebral hypoperfusion induces MMP-2 but not MMP-9 expression in the microglia and vascular endothelium of white matter. J Cereb Blood Flow Metab 21:828–834PubMedCrossRefGoogle Scholar
  28. Jalal FY, Yang Y, Thompson J et al (2012) Myelin loss associated with neuroinflammation in hypertensive rats. Stroke 43:1115–1122PubMedCrossRefGoogle Scholar
  29. Kinkel WR, Jacobs L, Polachini I et al (1985) Subcortical arteriosclerotic encephalopathy (Binswanger’s disease). Computed tomographic, nuclear magnetic resonance, and clinical correlations. Arch Neurol 42:951–959PubMedCrossRefGoogle Scholar
  30. Knudsen KA, Rosand J, Karluk D et al (2001) Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 56:537–539PubMedCrossRefGoogle Scholar
  31. Lauterbur PC (1982) NMR zeugmatographic imaging in medicine. J Med Syst 6:591–597PubMedCrossRefGoogle Scholar
  32. Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4:399–415PubMedCrossRefGoogle Scholar
  33. Lucchinetti CF, Gavrilova RH, Metz I et al (2008) Clinical and radiographic spectrum of pathologically confirmed tumefactive multiple sclerosis. Brain 131:1759–1775PubMedCrossRefGoogle Scholar
  34. Mansfield P, Maudsley AA (1976) Line scan proton spin imaging in biological structures by NMR. Phys Med Biol 21:847–852PubMedCrossRefGoogle Scholar
  35. Masdeu JC, Wolfson L, Lantos G et al (1989) Brain white-matter changes in the elderly prone to falling. Arch Neurol 46:1292–1296, see commentsPubMedCrossRefGoogle Scholar
  36. Masumura M, Hata R, Nagai Y et al (2001) Oligodendroglial cell death with DNA fragmentation in the white matter under chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats. Neurosci Res 39:401–412PubMedCrossRefGoogle Scholar
  37. Moffett JR, Ross B, Arun P et al (2007) N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Prog Neurobiol 81:89–131PubMedCrossRefGoogle Scholar
  38. Moody DM, Thore CR, Anstrom JA et al (2004) Quantification of afferent vessels shows reduced brain vascular density in subjects with leukoaraiosis. Radiology 233:883–890PubMedCrossRefGoogle Scholar
  39. Moorhouse P, Rockwood K (2008) Vascular cognitive impairment: current concepts and clinical developments. Lancet Neurol 7:246–255PubMedCrossRefGoogle Scholar
  40. Moseley ME, Cohen Y, Kucharczyk J et al (1990) Diffusion-weighted MR imaging of anisotropic water diffusion in cat central nervous system. Radiology 176:439–445PubMedGoogle Scholar
  41. Nakaji K, Ihara M, Takahashi C et al (2006) Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke 37:2816–2823PubMedCrossRefGoogle Scholar
  42. Narayan SK, Gorman G, Kalaria RN et al (2012) The minimum prevalence of CADASIL in northeast England. Neurology 78:1025–1027PubMedCrossRefGoogle Scholar
  43. Noseworthy JH, Lucchinetti C, Rodriguez M et al (2000) Multiple sclerosis. N Engl J Med 343:938–952PubMedCrossRefGoogle Scholar
  44. Olszewski J (1962) Subcortical arteriosclerotic encephalopathy: review of the literature on the so-called Binswanger’s disease and presentation of 2 cases. World Neurol 3:359–375PubMedGoogle Scholar
  45. Ordidge RJ, Mansfield P, Coupland RE (1981) Rapid biomedical imaging by NMR. Br J Radiol 54:850–855PubMedCrossRefGoogle Scholar
  46. Pantoni L (2010) Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol 9:689–701PubMedCrossRefGoogle Scholar
  47. Pantoni L, Garcia JH, Gutierrez JA (1996) Cerebral white matter is highly vulnerable to ischemia. Stroke 27:1641–1646PubMedCrossRefGoogle Scholar
  48. Patlak CS, Blasberg RG, Fenstermacher JD (1983) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 3:1–7PubMedCrossRefGoogle Scholar
  49. Peters N, Holtmannspotter M, Opherk C et al (2006) Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease. Neurology 66:1517–1522PubMedCrossRefGoogle Scholar
  50. Protass LM (1971) Delayed postanoxic encephalopathy after heroin use. Ann Intern Med 74:738–739PubMedCrossRefGoogle Scholar
  51. Rosenberg GA (2009) Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 8:205–216PubMedCrossRefGoogle Scholar
  52. Rosenberg GA (2012) Neurological diseases in relation to the blood–brain barrier. J Cereb Blood Flow Metab 32:1139–1151PubMedCrossRefGoogle Scholar
  53. Rosenberg GA, Sullivan N, Esiri MM (2001) White matter damage is associated with matrix metalloproteinases in vascular dementia. Stroke 32:1162–1168PubMedCrossRefGoogle Scholar
  54. Sappey Marinier D, Calabrese G, Hetherington HP et al (1992) Proton magnetic resonance spectroscopy of human brain: applications to normal white matter, chronic infarction, and MRI white matter signal hyperintensities. Magn Reson Med 26:313–327PubMedCrossRefGoogle Scholar
  55. Schmidt R, Scheltens P, Erkinjuntti T et al (2004) White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease. Neurology 63:139–144PubMedCrossRefGoogle Scholar
  56. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–346PubMedCrossRefGoogle Scholar
  57. Sironi L, Gelosa P, Guerrini U et al (2004a) Anti-inflammatory effects of AT1 receptor blockade provide end-organ protection in stroke-prone rats independently from blood pressure fall. J Pharmacol Exp Ther 311:989–995PubMedCrossRefGoogle Scholar
  58. Sironi L, Gianazza E, Gelosa P et al (2005) Rosuvastatin, but not simvastatin, provides end-organ protection in stroke-prone rats by antiinflammatory effects. Arterioscler Thromb Vasc Biol 25:598–603PubMedCrossRefGoogle Scholar
  59. Sironi L, Guerrini U, Tremoli E et al (2004b) Analysis of pathological events at the onset of brain damage in stroke-prone rats: a proteomics and magnetic resonance imaging approach. J Neurosci Res 78:115–122PubMedCrossRefGoogle Scholar
  60. Smith EE, Gurol ME, Eng JA et al (2004) White matter lesions, cognition, and recurrent hemorrhage in lobar intracerebral hemorrhage. Neurology 63:1606–1612PubMedCrossRefGoogle Scholar
  61. Sood R, Yang Y, Taheri S et al (2009) Increased apparent diffusion coefficients on MRI linked with matrix metalloproteinases and edema in white matter after bilateral carotid artery occlusion in rats. J Cereb Blood Flow Metab 29(2):308–316PubMedCrossRefGoogle Scholar
  62. Sood RR, Taheri S, Candelario-Jalil E et al (2008) Early beneficial effect of matrix metalloproteinase inhibition on blood–brain barrier permeability as measured by magnetic resonance imaging countered by impaired long-term recovery after stroke in rat brain. J Cereb Blood Flow Metab 28:431–438PubMedCrossRefGoogle Scholar
  63. Srikanth V, Phan TG, Chen J et al (2010) The location of white matter lesions and gait–a voxel-based study. Ann Neurol 67:265–269PubMedCrossRefGoogle Scholar
  64. Starr JM, Wardlaw J, Ferguson K et al (2003) Increased blood–brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry 74:70–76PubMedCrossRefGoogle Scholar
  65. Taheri S, Gasparovic C, Huisa BN et al (2011a) Blood-brain barrier permeability abnormalities in vascular cognitive impairment. Stroke 42:2158–2163PubMedCrossRefGoogle Scholar
  66. Taheri S, Gasparovic C, Shah NJ et al (2011b) Quantitative measurement of blood–brain barrier permeability in human using dynamic contrast-enhanced MRI with fast T(1) mapping. Magn Reson Med 65(4):1036–1042PubMedCrossRefGoogle Scholar
  67. Tekkok SB, Goldberg MP (2001) Ampa/kainate receptor activation mediates hypoxic oligodendrocyte death and axonal injury in cerebral white matter. J Neurosci 21:4237–4248PubMedGoogle Scholar
  68. Thal DR, Capetillo-Zarate E, Larionov S et al (2009) Capillary cerebral amyloid angiopathy is associated with vessel occlusion and cerebral blood flow disturbances. Neurobiol Aging 30:1936–1948PubMedCrossRefGoogle Scholar
  69. Tomimoto H, Akiguchi I, Akiyama H et al (1999) Vascular changes in white matter lesions of Alzheimer’s disease. Acta Neuropathol 97:629–634PubMedCrossRefGoogle Scholar
  70. Ueno M, Tomimoto H, Akiguchi I et al (2002) Blood–brain barrier disruption in white matter lesions in a rat model of chronic cerebral hypoperfusion. J Cereb Blood Flow Metab 22:97–104PubMedCrossRefGoogle Scholar
  71. Vermeer SE, Prins ND, Den Heijer T et al (2003) Silent brain infarcts and the risk of dementia and cognitive decline. N Engl J Med 348:1215–1222PubMedCrossRefGoogle Scholar
  72. Vinters HV, Gilbert JJ (1983) Cerebral amyloid angiopathy: incidence and complications in the aging brain. II. The distribution of amyloid vascular changes. Stroke 14:924–928PubMedCrossRefGoogle Scholar
  73. Wahlund LO, Barkhof F, Fazekas F et al (2001) A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 32:1318–1322PubMedCrossRefGoogle Scholar
  74. Wakefield DB, Moscufo N, Guttmann CR et al (2010) White matter hyperintensities predict functional decline in voiding, mobility, and cognition in older adults. J Am Geriatr Soc 58:275–281PubMedCrossRefGoogle Scholar
  75. Wakita H, Tomimoto H, Akiguchi I et al (2002) Axonal damage and demyelination in the white matter after chronic cerebral hypoperfusion in the rat. Brain Res 924:63–70PubMedCrossRefGoogle Scholar
  76. Wallin A, Blennow K, Fredman P et al (1990) Blood brain barrier function in vascular dementia. Acta Neurol Scand 81:318–322PubMedCrossRefGoogle Scholar
  77. Wardlaw JM, Doubal F, Armitage P et al (2009) Lacunar stroke is associated with diffuse blood–brain barrier dysfunction. Ann Neurol 65:194–202PubMedCrossRefGoogle Scholar
  78. White WB, Wolfson L, Wakefield DB et al (2011) Average daily blood pressure, not office blood pressure, is associated with progression of cerebrovascular disease and cognitive decline in older people. Circulation 124:2312–2319PubMedCrossRefGoogle Scholar
  79. Wintermark M, Albers GW, Alexandrov AV et al (2008) Acute stroke imaging research roadmap. AJNR Am J Neuroradiol 29:e23–e30PubMedCrossRefGoogle Scholar
  80. Yang Y, Jalal FY, Thompson JF et al (2011) Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-alpha/TACE in focal cerebral ischemia in mice. J Neuroinflammation 8:108PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Gary A. Rosenberg
    • 1
  • Branko Huisa
    • 1
  • Fakhreya Y. Jalal
    • 1
  • Yi Yang
    • 1
  1. 1.Department of Neurology, HSC Neurology, MSC 10 5620University of New Mexico Health Sciences CenterAlbuquerqueUSA

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