Clinical Assessment of Blood-Brain Barrier Permeability: Magnetic Resonance Imaging

  • D. Barnes
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 103)


Despite the sensitivity of magnetic resonance imaging (MRI) to abnormalities in the central nervous system (CNS), the image appearances lack specificity. Signal intensity in MR images depends predominantly upon the proton density and relaxation times, T1 and T2, of tissues. Most pathological processes result in increased tissue water content which increases all three of these parameters. Pathologically dissimilar lesions may, therefore, have similar MRI appearances; for example, it may be impossible to differentiate between tumour tissue and surrounding vasogenic oedema, or between an active and an inactive multiple sclerosis (MS) lesion. It became apparent that as an aid to more accurate diagnosis and for the assessment of treatment efficacy, a contrast agent was required as a marker of abnormal blood-brain barrier (BBB) permeability. Numerous substances act as contrast agents for MRI, but unlike computerised tomography (CT), they produce signal enhancement indirectly via their influence of the relaxation times of neighbouring protons.


Multiple Sclerosis Multiple Sclerosis Lesion Human Leucocyte Antigen Nuclear Magnetic Resonance Imaging Active Multiple Sclerosis 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.



Blood-brain barrier


Central nervous system


Chronic relapsing experimental allergic encephalomyelitis


Cerebrospinal fluid


Computerised tomography


10-(2-hydroxypropyl) 1,4,7, 10-tetraazacyclododecane-1,4,7-triacetic acid


10-(2-hydroxypropyl) 1,4,7, 10-tetraazacyclododecane- 1,4,7-triacetic acid




Human immuno-defieiency virus


Human leucocyte antigen


Magnetic resonance imaging


Multiple sclerosis


Positron emission tomography


Restriction fragment length polymorphism


Single photon emission computerised tomography


Longitudinal relaxation time


Transverse relaxation time


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  1. Adams CWM (1977) Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 33:15–20PubMedGoogle Scholar
  2. Adams CWM, Poston RN, Buk SJ, Sidhu YS, Vipond H (1985) Inflammatory vasculitis in multiple sclerosis. J Neurol Sci 69:269–283PubMedCrossRefGoogle Scholar
  3. Aita JF, Bennett DR, Anderson RE, Ziter F (1978) Cranial CT appearance of acute multiple sclerosis. Neurology (NY) 28:251–255Google Scholar
  4. Barnes D, McDonald WI (1988) A magnetic resonance imaging study of experimental cerebral edema and its response to dexamethasone. Magn Reson Med 7:125–131PubMedCrossRefGoogle Scholar
  5. Barnes D, McDonald WI, Johnson G, Tofts PS, Landon DN (1987) Quantitative nuclear magnetic resonance imaging: characterisation of experimental cerebral oedema. J Neurol Neurosurg Psychiatry 50:125–133PubMedCrossRefGoogle Scholar
  6. Barnes D, Munro PMG, Youl BD, Prineas JW, McDonald WI (1991) The longstanding MS lesion: a quantitative MRI and electron microscopic study. Brain 114:1271–1280PubMedCrossRefGoogle Scholar
  7. Bockhorst K, Höhn-Berlage M, Kocher M, Hossmann K-A (1990) Proton relaxation enhancement in experimental brain tumors - in vivo NMR study of manganese (III) TPPS in rat brain gliomas. Magn Reson Imaging 8:499–504PubMedCrossRefGoogle Scholar
  8. Broman T (1964) Blood-brain barrier damage in multiple sclerosis: supravital dye observations. Acta Neurol Scand [Suppl 10] 40:21–24CrossRefGoogle Scholar
  9. Carr DH, Brown J, Bydder GM, Weinmann H-J, Speck U, Thomas DJ, Young IR (1984) Intravenous chelated gadolinium as a contrast agent in NMR imaging of cerebral tumours. Lancet 1:484–486PubMedCrossRefGoogle Scholar
  10. Carvlin M, Rosa L, Schellinger D, Francisco J, DeSimone D (1990) Report on clinical trials of ProHance: efficacy and safety evaluation of a new low osmolar MR contrast agent. In: Book of Abstracts, Society of Magnetic Resonance in Medicine, New York, p 731Google Scholar
  11. Cerdan S, Lötscher HR, Künnecke B, Seelig J (1989) Monoclonal antibody-coated magnetite particles as contrast agents in magnetic resonance imaging of tumors. Magn Reson Med 12:151–163PubMedCrossRefGoogle Scholar
  12. Claussen C, Laniado M, Kazner E, Schörner W, Felix R (1985) Application of contrast agents in CT and MRI (NMR): their potential in imaging of brain tumors. Neuroradiology 27:164–171PubMedCrossRefGoogle Scholar
  13. Cordes M, Henkes H, Roll D, Eichstädt H, Christe W, Langer M, Felix R (1989) Subacute and chronic cerebral infarctions: SPECT and gadolinium-DTPA enhanced MR imaging. J Comput Assist Tomogr 13:567–571PubMedCrossRefGoogle Scholar
  14. Crain MR, Yuh WTC, Greene GM, Ryals TJ, Sato Y, Loes DJ (1990) Application of Gd-DTPA in acute ischaemic stroke. In: Book of Abstracts Society of Magnetic Resonance in Medicine, New York, p 6Google Scholar
  15. DeWitt LD, Buonanno S, Kistler JP, Brady TJ, Pykett IL, Goldman MR, Davis KR (1984) Nuclear magnetic resonance imaging in evaluation of clinical stroke syndromes. Ann Neurol 16:535–545PubMedCrossRefGoogle Scholar
  16. Doppman JL, Frank JA, Dwyer AJ, Oldfield EH, Miller DL, Nieman LK, Chrousos GP, Cutler GB, Loriaux DL (1988) Gadolinium DTPA enhanced MR imaging of ACTH-secreting microadenomas of the pituitary gland. J Comput Assist Tomogr 12:728–735PubMedCrossRefGoogle Scholar
  17. Doran M, Bydder GM (1990) Magnetic resonance: perfusion and diffusion imaging. Neuroradiology 32:392–398PubMedCrossRefGoogle Scholar
  18. Ernst RJ, Weingarten K, Frissora CL, Zimmerman RD, Deck MDF (1990) Postoperative meningiomas: assessment with gadolinium-enhanced MR imaging. In: Bood of Abstracts, Society of Magnetic Resonance in Medicine, New York, p 262Google Scholar
  19. Gadian DG, Payne JA, Bryant DJ, Young IR, Carr DH, Bydder GM (1985) Gadolinium-DTPA as a contrast agent in MR imaging - theoretical projections and practical observations. J Comput Assist Tomogr 9:242–251PubMedCrossRefGoogle Scholar
  20. Gonzalez-Scarano F, Grossman RI, Galetta S, Atlas SW, Silberberg DH (1987) Multiple sclerosis disease activity correlates with gadolinium-enhanced magnetic resonance imaging. Ann Neurol 21:300–306PubMedCrossRefGoogle Scholar
  21. Graif M, Steiner RE (1986) Contrast-enhanced magnetic resonance imaging of tumours of the central nervous system: a clinical review. Br J Radiol 59:865–873PubMedCrossRefGoogle Scholar
  22. Grossman RI, Gonzalez-Scarano F, Atlas SW, Galetta S, Silberberg DH (1986) Multiple sclerosis: gadolinium enhancement in MR imaging. Radiology 161:721–725PubMedGoogle Scholar
  23. Hawkins CP, Munro PMG, Mackenzie F, Kesselring J, Tofts PS, DuBoulay EPGH, Landon DN, McDonald WI (1990) Duration and selectivity of blood-brain barrier breakdown in chronic relapsing experimental allergic encephalomyelitis studied by gadolinium-DTPA and protein markers. Brain 113:365–378PubMedCrossRefGoogle Scholar
  24. Henkes H, Schörner W, Sander B, Felix R (1989) Gd-DTPA enhanced MRI in cerebral infections, inflammations and AIDS. In: Book of Abstracts, Society of Magnetic Resonance in Medicine, Amsterdam, p 7Google Scholar
  25. Henkes H, Sperner J, Sander B (1990) Magnetic resonance tomography of adrenoleukodystrophy. Rontgenblatter 43:7–10PubMedGoogle Scholar
  26. Hesselink JR, Healy ME, Press GA, Brahme FJ (1988) Benefite of Gd-DTPA for MR imaging of intracranial abnormalities. J Comput Assist Tomogr 12:266–274PubMedCrossRefGoogle Scholar
  27. Kermode AG, Tofts PS, Thompson AJ, MacManus DG, Rudge P, Kendall BE, Kingsley DPE, Moseley IF, DuBoulay EPGH, McDonald WI (1990) Heterogeneity of blood-brain barrier changes in multiple sclerosis: an MRI study. Neurology 40:229–235PubMedGoogle Scholar
  28. Lang DA, Hadley DM, Teasdale GM, Macpherson P, Teasdale E (1991) Gadolinium enhanced MRI following acute head injury. Acta Neurochir (Wien) (in press)Google Scholar
  29. Larsson HBW, Stubgaard M, Frederiksen JL, Jensen M, Henriksen O, Paulson OB (1990) Quantitation of blood-brain barrier defect by magnetic resonance imaging and gadolinium-DTPA in patients with multiple sclerosis and brain tumors. Magn Reson Med 16:117–131PubMedCrossRefGoogle Scholar
  30. LeBihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M (1986) MR imaging of intra voxel incoherent motions: application of diffusion and perfusion in neurological disorders. Radiology 161:401–407Google Scholar
  31. LeBihan D, Breton E, Lallemand D, Ubin ML, Vignaud J, Laval-Jeantet M (1988) Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. Radiology 168:497–505Google Scholar
  32. Macri MA, de Luca F, Maraviglia B, Polizio F, Stella A, Cavallo S, Natali PJ (1988) Relaxation study of Gadolinium labelled monoclonal antibody. In: Book of Abstracts, Society of Magnetic Resonance in Medicine, San Fransisco, p 523Google Scholar
  33. Mikhael MA (1990) Serial enhanced MR of the spinal cord and the evolution of multiple sclerosis plaques. In: Book of Abstracts, Society of Magnetic Resonance in Medicine, New York, p 148Google Scholar
  34. Miller DH, Rudge P, Johnson G, Kendall BE, MacManus DG, Moseley IF, Barnes D, McDonald WI (1988) Serial gadolinium enhanced magnetic resonance imaging in multiple sclerosis. Brain 111:927–939PubMedCrossRefGoogle Scholar
  35. Niendorf HP, Laniado M, Semmler W, Schörner W, Felix R (1987) Dose administration of Gd-DTPA in MR imaging of intracranial tumors. AJNR 8:803–815PubMedGoogle Scholar
  36. Olerup O, Hillert J, Fredrikson S, Olsson T, Kam-Hansen S, Möller E, Carlson B, Wallin J (1989) Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities. Proc Natl Acad Sci USA 86:7113–7117PubMedCrossRefGoogle Scholar
  37. Ormerod IEC, Miller DH, McDonald WI, DuBoulay EPGH, Rudge P, Kendall BE, Moseley IF, Johnson G, Tofts PS, Halliday AM, Bronstein AM, Scaravilli F, Harding AE, Barnes D, Zilkha KJ (1987) The role of NMR imaging in the assessment of multiple sclerosis and isolated lesions: a quantitative study. Brain 110:1579–1616PubMedCrossRefGoogle Scholar
  38. Parizel PM, Degryse HR, Gheuens J, Martin J-J, van Vyve M, de La Porte C, Selosse P, van de Heyning P, de Schepper AM (1989) Gadolinium-DOTA enhanced MR imaging of intracranial lesions. J Comput Assist Tomogr 13: 378–385PubMedCrossRefGoogle Scholar
  39. Peterman SB, Steiner RE, Bydder GM, Thomas DJ, Tobias JS, Young IR (1985) Nuclear magnetic resonance imaging (NMR), (MRI), of brain stem tumours. Neuroradiology 27:202–207PubMedCrossRefGoogle Scholar
  40. Prineas JW, Connell F (1978) The fine structure of chronically active multiple sclerosis plaques. Neurology (Minneap) 28:68–75Google Scholar
  41. Schoerner W, Henkes H, Mitrovics T, Heim T, Iglesias J, Lanksch W, Felix R (1990) Gd-DTPA enhanced MR imaging in the postoperative follow-up of recurrenet brain tumor. In: Book of Abstracts, Society of Magnetic Resonance in Medicine, New York, p 260Google Scholar
  42. Schwaighofer BW, Klein MV, Wesbey G, Hesselink JR (1990) Clinical experience with routine Gd-DTPA administration for MR imaging of the brain. J Comput Assist Tomogr 14:11–17PubMedCrossRefGoogle Scholar
  43. Scolding NJ, Morgan BP, Houston A, Campbell AK, Linington C, Compston DAS (1989) Normal rat serum cytotoxicity against syngeneic oligodendrocytes. J Neurol Sci 89:289–300PubMedCrossRefGoogle Scholar
  44. Sears ES, Hayman LA, Bigelow R (1981) Emerging patterns of lesion activity during multiple sclerosis exacerbations. Trans Am Neurol Soc 106:259–261Google Scholar
  45. Sipponen JT (1984) Visualization of brain infarction with nuclear magnetic resonance imaging. Neuroradiology 26:387–391PubMedCrossRefGoogle Scholar
  46. Sze G (1990) New applications of MR contrast agents in neuroradiology. Neuroradiology 32:421–438PubMedCrossRefGoogle Scholar
  47. Sze G, Milano E, Johnson C, Heier L (1990) Intraparenchymal metastases: contrast MR versus non-contrast MR versus contrast CT. Am J Neuroradiol 11:785–791PubMedGoogle Scholar
  48. Thompson AJ, Kermode AG, MacManus DG, Kingsley DPE, Kendall BE, Moseley IF, McDonald WI (1989) Pathogenesis of progressive multiple sclerosis. Lancet 1:1322–1323PubMedCrossRefGoogle Scholar
  49. Thompson AJ, Kermode AG, MacManus DG, Kendall BE, Kingsley DPE, Moseley IF, McDonald WI (1990) Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study. Br Med J 300:631–634CrossRefGoogle Scholar
  50. Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DPE, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62PubMedCrossRefGoogle Scholar
  51. Tofts PS, Kermode AG (1989) Measurement of blood brain barrier permeability using Gd-DTPA scanning. Magn Reson Imaging 7 (Suppl 1):150Google Scholar
  52. Tofts PS, Kermode AG (1991) Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging - 1 fundamental concepts. Magn Reson Med 17:357–367PubMedCrossRefGoogle Scholar
  53. Walker RHW, Thompson EJ, McDonald WI (1985) CSF in multiple sclerosis: relationships between immunoglobulins, leucocytes and clinical features. J Neurol 232:250–259PubMedCrossRefGoogle Scholar
  54. Weinmann HJ, Brasch RC, Press WR, Wesbey GE (1984) Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR 142:619–624PubMedGoogle Scholar
  55. Whelan HT, Clanton JA, Moore PM, Tolner DJ, Kessler RM, Whetsell WO Jr (1987) Magnetic resonance brain tumor imaging in canine glioma. Neurology 37:1235–1239PubMedGoogle Scholar
  56. Yeager AM, Brennan S, Tiffany C, Moser HW, Santos GW (1984) Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse. Science 225:1052–1054PubMedCrossRefGoogle Scholar
  57. Yoshida K, Furuse M, Kaneoke Y, Saso Y, Inao S, Motegi Y, Ichihara K, Izawa A (1989) Assessment of T1 time course changes and tissue-blood ratios after Gd-DTPA administration in brain tumors. Magn Reson Imaging 7:9–15PubMedCrossRefGoogle Scholar
  58. Young IR, Hall AS, Pallis CA, Legg NJ, Bydder GM, Steiner RE (1981) Nuclear magnetic resonance imaging of the brain in multiple sclerosis. Lancet 2: 1063–1066PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1992

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  • D. Barnes

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