Skip to main content
SpringerLink
Log in

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

  • Chapter
Physiology and Pharmacology of the Blood-Brain Barrier

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 103))

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

BBB:

Blood-brain barrier

CNS:

Central nervous system

CREAE:

Chronic relapsing experimental allergic encephalomyelitis

CSF:

Cerebrospinal fluid

CT:

Computerised tomography

DOTA:

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

DTPA:

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

Gd:

Gadolinium

HIV:

Human immuno-defieiency virus

HLA:

Human leucocyte antigen

MRI:

Magnetic resonance imaging

MS:

Multiple sclerosis

PET:

Positron emission tomography

RFLP:

Restriction fragment length polymorphism

SPECT:

Single photon emission computerised tomography

T1 :

Longitudinal relaxation time

T2 :

Transverse relaxation time

References

  • Adams CWM (1977) Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 33:15–20

    PubMed  CAS  Google Scholar 

  • Adams CWM, Poston RN, Buk SJ, Sidhu YS, Vipond H (1985) Inflammatory vasculitis in multiple sclerosis. J Neurol Sci 69:269–283

    Article  PubMed  CAS  Google Scholar 

  • Aita JF, Bennett DR, Anderson RE, Ziter F (1978) Cranial CT appearance of acute multiple sclerosis. Neurology (NY) 28:251–255

    CAS  Google Scholar 

  • Barnes D, McDonald WI (1988) A magnetic resonance imaging study of experimental cerebral edema and its response to dexamethasone. Magn Reson Med 7:125–131

    Article  PubMed  CAS  Google Scholar 

  • 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 50:125–133

    Article  PubMed  CAS  Google Scholar 

  • Barnes D, Munro PMG, Youl BD, Prineas JW, McDonald WI (1991) The longstanding MS lesion: a quantitative MRI and electron microscopic study. Brain 114:1271–1280

    Article  PubMed  Google Scholar 

  • 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 8:499–504

    Article  PubMed  CAS  Google Scholar 

  • Broman T (1964) Blood-brain barrier damage in multiple sclerosis: supravital dye observations. Acta Neurol Scand [Suppl 10] 40:21–24

    Article  Google Scholar 

  • 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 1:484–486

    Article  PubMed  CAS  Google Scholar 

  • 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 731

    Google Scholar 

  • 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 12:151–163

    Article  PubMed  CAS  Google Scholar 

  • 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 27:164–171

    Article  PubMed  CAS  Google Scholar 

  • 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 13:567–571

    Article  PubMed  CAS  Google Scholar 

  • 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 6

    Google Scholar 

  • 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 16:535–545

    Article  PubMed  CAS  Google Scholar 

  • 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 12:728–735

    Article  PubMed  CAS  Google Scholar 

  • Doran M, Bydder GM (1990) Magnetic resonance: perfusion and diffusion imaging. Neuroradiology 32:392–398

    Article  PubMed  CAS  Google Scholar 

  • 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 262

    Google Scholar 

  • 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 9:242–251

    Article  PubMed  CAS  Google Scholar 

  • 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 21:300–306

    Article  PubMed  CAS  Google Scholar 

  • Graif M, Steiner RE (1986) Contrast-enhanced magnetic resonance imaging of tumours of the central nervous system: a clinical review. Br J Radiol 59:865–873

    Article  PubMed  CAS  Google Scholar 

  • Grossman RI, Gonzalez-Scarano F, Atlas SW, Galetta S, Silberberg DH (1986) Multiple sclerosis: gadolinium enhancement in MR imaging. Radiology 161:721–725

    PubMed  CAS  Google Scholar 

  • 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 113:365–378

    Article  PubMed  Google Scholar 

  • 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 7

    Google Scholar 

  • Henkes H, Sperner J, Sander B (1990) Magnetic resonance tomography of adrenoleukodystrophy. Rontgenblatter 43:7–10

    PubMed  CAS  Google Scholar 

  • Hesselink JR, Healy ME, Press GA, Brahme FJ (1988) Benefite of Gd-DTPA for MR imaging of intracranial abnormalities. J Comput Assist Tomogr 12:266–274

    Article  PubMed  CAS  Google Scholar 

  • 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 40:229–235

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 16:117–131

    Article  PubMed  CAS  Google Scholar 

  • 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 161:401–407

    CAS  Google Scholar 

  • 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 168:497–505

    CAS  Google Scholar 

  • 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 523

    Google Scholar 

  • 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 148

    Google Scholar 

  • 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 111:927–939

    Article  PubMed  Google Scholar 

  • Niendorf HP, Laniado M, Semmler W, Schörner W, Felix R (1987) Dose administration of Gd-DTPA in MR imaging of intracranial tumors. AJNR 8:803–815

    PubMed  CAS  Google Scholar 

  • 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 86:7113–7117

    Article  PubMed  CAS  Google Scholar 

  • 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 110:1579–1616

    Article  PubMed  Google Scholar 

  • 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: 378–385

    Article  PubMed  CAS  Google Scholar 

  • Peterman SB, Steiner RE, Bydder GM, Thomas DJ, Tobias JS, Young IR (1985) Nuclear magnetic resonance imaging (NMR), (MRI), of brain stem tumours. Neuroradiology 27:202–207

    Article  PubMed  CAS  Google Scholar 

  • Prineas JW, Connell F (1978) The fine structure of chronically active multiple sclerosis plaques. Neurology (Minneap) 28:68–75

    CAS  Google Scholar 

  • 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 260

    Google Scholar 

  • 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 14:11–17

    Article  PubMed  CAS  Google Scholar 

  • Scolding NJ, Morgan BP, Houston A, Campbell AK, Linington C, Compston DAS (1989) Normal rat serum cytotoxicity against syngeneic oligodendrocytes. J Neurol Sci 89:289–300

    Article  PubMed  CAS  Google Scholar 

  • Sears ES, Hayman LA, Bigelow R (1981) Emerging patterns of lesion activity during multiple sclerosis exacerbations. Trans Am Neurol Soc 106:259–261

    Google Scholar 

  • Sipponen JT (1984) Visualization of brain infarction with nuclear magnetic resonance imaging. Neuroradiology 26:387–391

    Article  PubMed  CAS  Google Scholar 

  • Sze G (1990) New applications of MR contrast agents in neuroradiology. Neuroradiology 32:421–438

    Article  PubMed  CAS  Google Scholar 

  • Sze G, Milano E, Johnson C, Heier L (1990) Intraparenchymal metastases: contrast MR versus non-contrast MR versus contrast CT. Am J Neuroradiol 11:785–791

    PubMed  CAS  Google Scholar 

  • Thompson AJ, Kermode AG, MacManus DG, Kingsley DPE, Kendall BE, Moseley IF, McDonald WI (1989) Pathogenesis of progressive multiple sclerosis. Lancet 1:1322–1323

    Article  PubMed  CAS  Google Scholar 

  • 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 300:631–634

    Article  CAS  Google Scholar 

  • 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 29:53–62

    Article  PubMed  CAS  Google Scholar 

  • Tofts PS, Kermode AG (1989) Measurement of blood brain barrier permeability using Gd-DTPA scanning. Magn Reson Imaging 7 (Suppl 1):150

    Google Scholar 

  • 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 17:357–367

    Article  PubMed  CAS  Google Scholar 

  • Walker RHW, Thompson EJ, McDonald WI (1985) CSF in multiple sclerosis: relationships between immunoglobulins, leucocytes and clinical features. J Neurol 232:250–259

    Article  PubMed  CAS  Google Scholar 

  • Weinmann HJ, Brasch RC, Press WR, Wesbey GE (1984) Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent. AJR 142:619–624

    PubMed  CAS  Google Scholar 

  • Whelan HT, Clanton JA, Moore PM, Tolner DJ, Kessler RM, Whetsell WO Jr (1987) Magnetic resonance brain tumor imaging in canine glioma. Neurology 37:1235–1239

    PubMed  CAS  Google Scholar 

  • Yeager AM, Brennan S, Tiffany C, Moser HW, Santos GW (1984) Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse. Science 225:1052–1054

    Article  PubMed  CAS  Google Scholar 

  • 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 7:9–15

    Article  PubMed  CAS  Google Scholar 

  • 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: 1063–1066

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. D. Barnes
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Physiology Group Biomedical Sciences Division King’s College London, University of London, Strand, WC2R 2LS, London, Great Britain

    Michael W. B. Bradbury M.A., D.M. (Oxon)

Rights and permissions

Reprints and permissions

Copyright information

© 1992 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Barnes, D. (1992). Clinical Assessment of Blood-Brain Barrier Permeability: Magnetic Resonance Imaging. In: Bradbury, M.W.B. (eds) Physiology and Pharmacology of the Blood-Brain Barrier. Handbook of Experimental Pharmacology, vol 103. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76894-1_12

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-76894-1_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-76896-5

  • Online ISBN: 978-3-642-76894-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation