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Quantitative PET imaging and modeling of molecular blood-brain barrier permeability

Author

Listed:
  • Kevin J. Chung

    (University of California Davis Health)

  • Yasser G. Abdelhafez

    (University of California Davis Health)

  • Benjamin A. Spencer

    (University of California Davis Health)

  • Terry Jones

    (University of California Davis Health)

  • Quyen Tran

    (University of California Davis Health)

  • Lorenzo Nardo

    (University of California Davis Health)

  • Moon S. Chen

    (University of California Davis Health)

  • Souvik Sarkar

    (University of California Davis Health
    University of California Davis Health)

  • Valentina Medici

    (University of California Davis Health
    University of California Davis Health)

  • Victoria Lyo

    (University of California Davis Health
    University of California Davis Health)

  • Ramsey D. Badawi

    (University of California Davis Health
    University of California at Davis)

  • Simon R. Cherry

    (University of California Davis Health
    University of California at Davis)

  • Guobao Wang

    (University of California Davis Health)

Abstract

Neuroimaging of blood-brain barrier permeability has been instrumental in identifying its broad involvement in neurological and systemic diseases. However, current methods evaluate the blood-brain barrier mainly as a structural barrier. Here we developed a non-invasive positron emission tomography method in humans to measure the blood-brain barrier permeability of molecular radiotracers that cross the blood-brain barrier through its molecule-specific transport mechanism. Our method uses high-temporal resolution dynamic imaging and kinetic modeling for multiparametric imaging and quantification of the blood-brain barrier permeability-surface area product of molecular radiotracers. We show, in humans, our method can resolve blood-brain barrier permeability across three radiotracers and demonstrate its utility in studying brain aging and brain-body interactions in metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to effectively study the molecular permeability of the human blood-brain barrier in vivo using the large catalogue of available molecular positron emission tomography tracers.

Suggested Citation

  • Kevin J. Chung & Yasser G. Abdelhafez & Benjamin A. Spencer & Terry Jones & Quyen Tran & Lorenzo Nardo & Moon S. Chen & Souvik Sarkar & Valentina Medici & Victoria Lyo & Ramsey D. Badawi & Simon R. Ch, 2025. "Quantitative PET imaging and modeling of molecular blood-brain barrier permeability," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58356-7
    DOI: 10.1038/s41467-025-58356-7
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    References listed on IDEAS

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    1. Sophie E. Holmes & Dustin Scheinost & Sjoerd J. Finnema & Mika Naganawa & Margaret T. Davis & Nicole DellaGioia & Nabeel Nabulsi & David Matuskey & Gustavo A. Angarita & Robert H. Pietrzak & Ronald S., 2019. "Lower synaptic density is associated with depression severity and network alterations," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Michael J. Hawrylycz & Ed S. Lein & Angela L. Guillozet-Bongaarts & Elaine H. Shen & Lydia Ng & Jeremy A. Miller & Louie N. van de Lagemaat & Kimberly A. Smith & Amanda Ebbert & Zackery L. Riley & Chr, 2012. "An anatomically comprehensive atlas of the adult human brain transcriptome," Nature, Nature, vol. 489(7416), pages 391-399, September.
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