Skip to main content
SpringerLink
Log in

Molecular Imaging of Blood–Brain Barrier Permeability in Preclinical Models Using PET and SPECT

  • Protocol
  • First Online:
Blood-Brain Barrier

Part of the book series: Neuromethods ((NM,volume 142))

Abstract

The blood–brain barrier (BBB) with tightest junction separates the systemic circulation and brain micro-environment to protect the brain from insults, such as infections. The integrity of BBB is preserved by multi-structural and functional components. Increasing evidence indicates that BBB is used as an important marker measured in variety of pathological condition with large permeability leaks, such as brain tumors and multiple sclerosis, to more subtle disruption such as vascular diseases, cognitive decline, and dementia. Several imaging modalities are available to study disruption of the BBB. In this chapter, we described the protocols for nuclear imaging studies such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) investigating BBB permeability in preclinical models.

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

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover 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

References

  1. Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7(1):41–53. https://doi.org/10.1038/nrn1824

    Article  CAS  PubMed  Google Scholar 

  2. Jamieson JJ, Searson PC, Gerecht S (2017) Engineering the human blood-brain barrier in vitro. J Biol Eng 11:37. https://doi.org/10.1186/s13036-017-0076-1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cardoso FL, Brites D, Brito MA (2010) Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev 64(2):328–363. https://doi.org/10.1016/j.brainresrev.2010.05.003

    Article  CAS  PubMed  Google Scholar 

  4. Kuhnline Sloan CD, Nandi P, Linz TH, Aldrich JV, Audus KL, Lunte SM (2012) Analytical and biological methods for probing the blood-brain barrier. Annu Rev Anal Chem (Palo Alto Calif) 5:505–531. https://doi.org/10.1146/annurev-anchem-062011-143002

    Article  CAS  Google Scholar 

  5. Bentivoglio M, Mariotti R, Bertini G (2011) Neuroinflammation and brain infections: historical context and current perspectives. Brain Res Rev 66(1–2):152–173. https://doi.org/10.1016/j.brainresrev.2010.09.008

    Article  CAS  PubMed  Google Scholar 

  6. Skoog I, Wallin A, Fredman P, Hesse C, Aevarsson O, Karlsson I, Gottfries CG, Blennow K (1998) A population study on blood-brain barrier function in 85-year-olds: relation to Alzheimer’s disease and vascular dementia. Neurology 50(4):966–971

    Article  CAS  Google Scholar 

  7. Taheri S, Gasparovic C, Huisa BN, Adair JC, Edmonds E, Prestopnik J, Grossetete M, Shah NJ, Wills J, Qualls C, Rosenberg GA (2011) Blood-brain barrier permeability abnormalities in vascular cognitive impairment. Stroke 42(8):2158–2163. https://doi.org/10.1161/strokeaha.110.611731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wallin A, Blennow K, Fredman P, Gottfries CG, Karlsson I, Svennerholm L (1990) Blood brain barrier function in vascular dementia. Acta Neurol Scand 81(4):318–322

    Article  CAS  Google Scholar 

  9. Larobina MBA, Salvatore M (2006) Small animal PET: a review of commercially available imaging systems. Curr Med Imaging Rev 2(2):187–192

    Article  Google Scholar 

  10. Cuccurullo V, Di Stasio GD, Schillirò ML, Mansi L (2016) Small-animal molecular imaging for preclinical cancer research: .μPET and μ.SPECT. Curr Radiopharm 9(2):102–113

    Article  Google Scholar 

  11. Aid S, Silva AC, Candelario-Jalil E, Choi SH, Rosenberg GA, Bosetti F (2010) Cyclooxygenase-1 and -2 differentially modulate lipopolysaccharide-induced blood-brain barrier disruption through matrix metalloproteinase activity. J Cereb Blood Flow Metab 30(2):370–380. https://doi.org/10.1038/jcbfm.2009.223

    Article  CAS  PubMed  Google Scholar 

  12. Paxinos PWC (2004) The rat brain in stereotaxic coordinates, 5th edn. Elsevier Academic Press, San Diego

    Google Scholar 

  13. Yang FY, Lin GL, Horng SC, Chang TK, Wu SY, Wong TT, Wang HE (2011) Pulsed high-intensity focused ultrasound enhances the relative permeability of the blood-tumor barrier in a glioma-bearing rat model. IEEE Trans Ultrason Ferroelectr Freq Control 58(5):964–970. https://doi.org/10.1109/tuffc.2011.1897

    Article  PubMed  Google Scholar 

  14. Yang FY, Lin YS, Kang KH, Chao TK (2011) Reversible blood-brain barrier disruption by repeated transcranial focused ultrasound allows enhanced extravasation. J Control Release 150(1):111–116. https://doi.org/10.1016/j.jconrel.2010.10.038

    Article  CAS  PubMed  Google Scholar 

  15. Kornblum HI, Araujo DM, Annala AJ, Tatsukawa KJ, Phelps ME, Cherry SR (2000) In vivo imaging of neuronal activation and plasticity in the rat brain by high resolution positron emission tomography (microPET). Nat Biotechnol 18(6):655–660. https://doi.org/10.1038/76509

    Article  CAS  PubMed  Google Scholar 

  16. Lasbennes F, Lestage P, Bobillier P, Seylaz J (1986) Stress and local cerebral blood flow: studies on restrained and unrestrained rats. Exp Brain Res 63(1):163–168

    CAS  PubMed  Google Scholar 

  17. Zunkeler B, Carson RE, Olson J, Blasberg RG, Girton M, Bacher J, Herscovitch P, Oldfield EH (1996) Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82. J Neurosurg 84(3):494–502. https://doi.org/10.3171/jns.1996.84.3.0494

    Article  CAS  PubMed  Google Scholar 

  18. Velikyan I (2013) Prospective of (6)(8)Ga-radiopharmaceutical development. Theranostics 4(1):47–80. https://doi.org/10.7150/thno.7447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Doi H, Sato K, Shindou H, Sumi K, Koyama H, Hosoya T, Watanabe Y, Ishii S, Tsukada H, Nakanishi K, Suzuki M (2016) Blood-brain barrier permeability of ginkgolide: comparison of the behavior of PET probes 7alpha-[(18)F]fluoro- and 10-O-p-[(11)C]methylbenzyl ginkgolide B in monkey and rat brains. Bioorg Med Chem 24(21):5148–5157. https://doi.org/10.1016/j.bmc.2016.08.032

    Article  CAS  PubMed  Google Scholar 

  20. Lin KJ, Liu HL, Hsu PH, Chung YH, Huang WC, Chen JC, Wey SP, Yen TC, Hsiao IT (2009) Quantitative micro-SPECT/CT for detecting focused ultrasound-induced blood-brain barrier opening in the rat. Nucl Med Biol 36(7):853–861. https://doi.org/10.1016/j.nucmedbio.2009.04.011

    Article  CAS  PubMed  Google Scholar 

  21. Kessler RM, Goble JC, Bird JH, Girton ME, Doppman JL, Rapoport SI, Barranger JA (1984) Measurement of blood-brain barrier permeability with positron emission tomography and [68Ga]EDTA. J Cereb Blood Flow Metab 4(3):323–328. https://doi.org/10.1038/jcbfm.1984.48

    Article  CAS  PubMed  Google Scholar 

  22. Schlageter NL, Carson RE, Rapoport SI (1987) Examination of blood-brain barrier permeability in dementia of the Alzheimer type with [68Ga]EDTA and positron emission tomography. J Cereb Blood Flow Metab 7(1):1–8. https://doi.org/10.1038/jcbfm.1987.1

    Article  CAS  PubMed  Google Scholar 

  23. Washburn LC, Blair LD, Byrd BL, Sun TT (1985) Comparison of 68Ga-EDTA, [1-11 C]alpha-aminoisobutyric acid, and [99mTc]sodium pertechnetate in an experimental blood-brain barrier lesion. Int J Nucl Med Biol 12(4):267–269

    Article  CAS  Google Scholar 

  24. Knight RA, Nagaraja TN, Ewing JR, Nagesh V, Whitton PA, Bershad E, Fagan SC, Fenstermacher JD (2005) Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia. Magn Reson Med 54(4):813–821. https://doi.org/10.1002/mrm.20629

    Article  CAS  PubMed  Google Scholar 

  25. Blasberg RG, Fenstermacher JD, Patlak CS (1983) Transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes. J Cereb Blood Flow Metab 3(1):8–32. https://doi.org/10.1038/jcbfm.1983.2

    Article  CAS  PubMed  Google Scholar 

  26. Weyerbrock A, Walbridge S, Saavedra JE, Keefer LK, Oldfield EH (2011) Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas. Neuro-Oncology 13(2):203–211. https://doi.org/10.1093/neuonc/noq161

    Article  CAS  PubMed  Google Scholar 

  27. Leroy C, Roch C, Koning E, Namer IJ, Nehlig A (2003) In the lithium-pilocarpine model of epilepsy, brain lesions are not linked to changes in blood-brain barrier permeability: an autoradiographic study in adult and developing rats. Exp Neurol 182(2):361–372

    Article  Google Scholar 

  28. Okada M, Kikuchi T, Okamura T, Ikoma Y, Tsuji AB, Wakizaka H, Kamakura T, Aoki I, Zhang MR, Kato K (2015) In-vivo imaging of blood-brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid. Nucl Med Commun 36(12):1239–1248. https://doi.org/10.1097/mnm.0000000000000385

    Article  CAS  PubMed  Google Scholar 

  29. Liu HL, Wai YY, Chen WS, Chen JC, Hsu PH, Wu XY, Huang WC, Yen TC, Wang JJ (2008) Hemorrhage detection during focused-ultrasound induced blood-brain-barrier opening by using susceptibility-weighted magnetic resonance imaging. Ultrasound Med Biol 34(4):598–606. https://doi.org/10.1016/j.ultrasmedbio.2008.01.011

    Article  PubMed  Google Scholar 

  30. Hynynen K (1991) The threshold for thermally significant cavitation in dog’s thigh muscle in vivo. Ultrasound Med Biol 17(2):157–169

    Article  CAS  Google Scholar 

  31. Udaka K, Takeuchi Y, Movat HZ (1970) Simple method for quantitation of enhanced vascular permeability. Proc Soc Exp Biol Med 133(4):1384–1387

    Article  CAS  Google Scholar 

  32. Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA (2001) Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology 220(3):640–646. https://doi.org/10.1148/radiol.2202001804

    Article  CAS  PubMed  Google Scholar 

  33. Laruelle M, Slifstein M, Huang Y (2002) Positron emission tomography: imaging and quantification of neurotransporter availability. Methods 27(3):287–299

    Article  CAS  Google Scholar 

  34. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27(9):1533–1539. https://doi.org/10.1038/sj.jcbfm.9600493

    Article  CAS  PubMed  Google Scholar 

  35. Ogasawara K, Ito H, Sasoh M, Okuguchi T, Kobayashi M, Yukawa H, Terasaki K, Ogawa A (2003) Quantitative measurement of regional cerebrovascular reactivity to acetazolamide using 123I-N-isopropyl-p-iodoamphetamine autoradiography with SPECT: validation study using H2 15O with PET. J Nucl Med 44(4):520–525

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The Translational Psychiatry Program is funded by the Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth). National Institute for Molecular Medicine (INCT-MM) and Center of Excellence in Applied Neurosciences of Santa Catarina (NENASC).

Author information

Authors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Tatiana Barichello

  2. Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil

    Tatiana Barichello

  3. Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Sudhakar Selvaraj

  4. Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Vijayasree V. Giridharan

Authors
  1. Vijayasree V. Giridharan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatiana Barichello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sudhakar Selvaraj
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vijayasree V. Giridharan .

Editor information

Editors and Affiliations

  1. Department of Psychiatry & Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA

    Tatiana Barichello

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Giridharan, V.V., Barichello, T., Selvaraj, S. (2019). Molecular Imaging of Blood–Brain Barrier Permeability in Preclinical Models Using PET and SPECT. In: Barichello, T. (eds) Blood-Brain Barrier. Neuromethods, vol 142. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8946-1_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8946-1_19

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8945-4

  • Online ISBN: 978-1-4939-8946-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation