Blood-brain barrier permeability imaging using perfusion computed tomography

Open access


Background. The blood-brain barrier represents the selective diffusion barrier at the level of the cerebral microvascular endothelium. Other functions of blood-brain barrier include transport, signaling and osmoregulation. Endothelial cells interact with surrounding astrocytes, pericytes and neurons. These interactions are crucial to the development, structural integrity and function of the cerebral microvascular endothelium. Dysfunctional blood-brain barrier has been associated with pathologies such as acute stroke, tumors, inflammatory and neurodegenerative diseases.

Conclusions. Blood-brain barrier permeability can be evaluated in vivo by perfusion computed tomography - an efficient diagnostic method that involves the sequential acquisition of tomographic images during the intravenous administration of iodinated contrast material. The major clinical applications of perfusion computed tomography are in acute stroke and in brain tumor imaging.

1. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol 2006; 1: 223-36.

2. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 2005; 57: 173-85.

3. Kaur C, Ling EA. Blood brain barrier in hypoxic-ischemic conditions. Curr Neurovasc Res 2008; 5: 71-81.

4. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 2004; 16: 1-13.

5. Lin K, Kazmi KS, Law M, Babb J, Peccerelli N, Pramanik BK. Measuring elevated microvascular permeability and predicting hemorrhagic transformation in acute ischemic stroke using first-pass dynamic perfusion CT imaging. AJNR Am J Neuroradiol 2007; 28: 1292-8.

6. Zaharchuk G. Theoretical basis of hemodynamic MR imaging techniques to measure cerebral blood volume, cerebral blood flow, and permeability. AJNR Am J Neuroradiol 2007; 28: 1850-8.

7. Bisdas S, Hartel M, Cheong LH, Koh TS, Vogl TJ. Prediction of subsequent hemorrhage in acute ischemic stroke using permeability CT imaging and a distributed parameter tracer kinetic model. J Neuroradiol 2007; 34: 101-8.

8. Dankbaar JW, Hom J, Schneider T, Cheng SC, Lau BC, van der Schaaf I, et al. Accuracy and anatomical coverage of perfusion CT assessment of the bloodbrain barrier permeability: one bolus versus two boluses. Cerebrovasc Dis 2008; 26: 600-5.

9. Correale J, Villa A. Cellular elements of the blood-brain barrier. Neurochem Res 2009; 34: 2067-77.

10. Farrell CL, Pardridge WM. Blood-brain barrier glucose transporter is asymmetrically distributed on brain capillary endothelial lumenal and ablumenal membranes: an electron microscopic immunogold study. Proc Natl Acad Sci USA 1991; 88: 5779-83.

11. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 1993; 123: 1777-88.

12. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1998; 141: 1539-50.

13. Bazzoni G, Tonetti P, Manzi L, Cera MR, Balconi G, Dejana E. Expression of junctional adhesion molecule-A prevents spontaneous and random motility. J Cell Sci 2005; 118: 623-32.

14. Nasdala I, Wolburg-Buchholz K, Wolburg H, Kuhn A, Ebnet K, Brachtendorf G, et al. A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J Biol Chem 2002; 277: 16294-303.

15. Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM. The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 1998; 273: 29745-53.

16. Haskins J, Gu L, Wittchen ES, Hibbard J, Stevenson BR. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J Cell Biol 1998; 141: 199-208.

17. Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D. Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem 2000; 275: 27979-88.

18. Pardridge WM. Molecular biology of the blood-brain barrier. Mol Biotechnol 2005; 30: 57-70.

19. Hamm S, Dehouck B, Kraus J, Wolburg-Buchholz K, Wolburg H, Risau W, et al. Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts. Cell Tissue Res 2004; 315: 157-66.

20. Sa-Pereira I, Brites D, Brito MA. Neurovascular unit: a focus on pericytes. Mol Neurobiol 2012; 45: 327-47.

21. Tao-Cheng JH, Brightman MW. Development of membrane interactions between brain endothelial cells and astrocytes in vitro. Int J Dev Neurosci 1988; 6: 25-37.

22. Zloko vic BV. The blood-brain barrier in health and chronic eurodegenerative disorders. Neuron 2008; 57: 178-201.

23. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37: 13-25.

24. Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 2006; 7: 41-53.

25. Kellogg GE, Fornabaio M, Chen DL, Abraham DJ, Spyrakis F, Cozzini P, et al. Tools for building a comprehensive modeling system for virtual screening under real biological conditions: the computational titration algorithm. J Mol Graph Model 2006; 24: 434-9.

26. Bisdas S, Donnerstag F, Ahl B, Bohrer I, Weissenborn K, Becker H. Comparison of perfusion computed tomography with diffusion-weighted magnetic resonance imaging in hyperacute ischemic stroke. J Comput Assist Tomogr 2004; 28: 747-55.

27. Bisdas S, Donnerstag F, Berding G, Vogl TJ, Thng CH, Koh TS. Computed tomography assessment of cerebral perfusion using a distributed parameter tracer kinetics model: validation with H(2)((15))O positron emission tomography measurements and initial clinical experience in patients with acute stroke. J Cereb Blood Flow Metab 2008; 28: 402-11.

28. Cenic A, Nabavi DG, Craen RA, Gelb AW, Lee TY. A CT method to measure hemodynamics in brain tumors: validation and application of cerebral blood flow maps. Am J Neuroradiol 2000; 21: 462-70.

29. Hoeffner EG, Case I, Jain R, Gujar SK, Shah GV, Deveikis JP, et al. Cerebral perfusion CT: technique and clinical applications. Radiology 2004; 231: 632-44.

30. Wintermark M. Brain perfusion-CT in acute stroke patients. Eur Radiol 2005; 15(Suppl 4): D28-31.

31. Miles KA, Griffiths MR. Perfusion CT: a worthwhile enhancement? Br J Radiol 2003; 76: 220-31.

32. Lee TY, Purdie TG, Stewart E. CT imaging of angiogenesis. Q J Nucl Med 2003; 47: 171-87.

33. Patlak CS, Blasberg RG, Fenstermacher JD. Graphical evaluation of bloodto- brain transfer constants from multiple-time uptake data. J Cereb Blood Flow Metab 1983; 3: 1-7.

34. Dankbaar JW, Hom J, Schneider T, Cheng SC, Lau BC, van der Schaaf I, et al. Dynamic perfusion CT assessment of the blood-brain barrier permeability: first pass versus delayed acquisition. Am J Neuroradiol 2008; 29: 1671-6.

35. Hom J, Dankbaar JW, Schneider T, Cheng SC, Bredno J, Wintermark M. Optimal duration of acquisition for dynamic perfusion CT assessment of blood-brain barrier permeability using the Patlak model. Am J Neuroradiol 2009; 30: 1366-70.

36. Jain R, Ellika SK, Scarpace L, Schultz LR, Rock JP, Gutierrez J, et al.Quantitative estimation of permeability surface-area product in astroglial brain tumors using perfusion CT and correlation with histopathologic grade. Am J Neuroradiol 2008; 29: 694-700.

37. Johnson JA, Wilson TA. A model for capillary exchange. Am J Physiol 1966; 210: 1299-303.

38. Koh TS, Cheong LH, Tan CK, Lim CC. A distributed parameter model of cerebral blood-tissue exchange with account of capillary transit time distribution. Neuroimage 2006; 30: 426-35.

39. Sourbron SP, Buckley DL. Tracer kinetic modelling in MRI: estimating perfusion and capillary permeability. Phys Med Biol 2012; 57: R1-33.

40. Schneider T, Hom J, Bredno J, Dankbaar JW, Cheng SC, Wintermark M. Delay correction for the assessment of blood-brain barrier permeability using firstpass dynamic perfusion CT. Am J Neuroradiol 2011; 32: E134-8.

41. Crone C. The Permeability of Capillaries in Various Organs as Determined by Use of the ‘Indicator Diffusion’ Method. Acta Physiol Scand 1963; 58: 292-305.

42. Miles KA. Perfusion CT for the assessment of tumour vascularity: which protocol? Br J Radiol 2003; 76 (Spec No 1): S36-42.

43. Lee TY. Functional CT: physiological models. Trends Biotechnol 2002; 20 (Suppl 8): S3-S10.

44. Larson KB, Markham J, Raichle ME. Tracer-kinetic models for measuring cerebral blood flow using externally detected radiotracers. J Cereb Blood Flow Metab 1987; 7: 443-63.

45. St Lawrence KS, Lee TY. An adiabatic approximation to the tissue homogeneity model for water exchange in the brain: I. Theoretical derivation. J Cereb Blood Flow Metab 1998; 18: 1365-77.

46. Hashizume H, Baluk P, Morikawa S, McLean JW, Thurston G, Roberge S, et al. Openings between defective endothelial cells explain tumor vessel leakiness. Am J Pathol 2000; 156: 1363-80.

47. Bisdas S, Yang X, Lim CC, Vogl TJ, Koh TS. Delineation and segmentation of cerebral tumors by mapping blood-brain barrier disruption with dynamic contrast-enhanced CT and tracer kinetics modeling-a feasibility study. Eur Radiol 2008; 18: 143-51.

48. Ding B, Ling HW, Chen KM, Jiang H, Zhu YB. Comparison of cerebral blood volume and permeability in preoperative grading of intracranial glioma using CT perfusion imaging. Neuroradiol 2006; 48: 773-81.

Radiology and Oncology

The Journal of Association of Radiology and Oncology

Journal Information

IMPACT FACTOR 2017: 1.722
5-year IMPACT FACTOR: 1.729

CiteScore 2017: 1.84

SCImago Journal Rank (SJR) 2017: 0.574
Source Normalized Impact per Paper (SNIP) 2017: 0.814

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 110 110 11
PDF Downloads 46 46 9