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Quantitative PET imaging and modeling of molecular blood-brain barrier permeability
- Chung, Kevin J;
- Abdelhafez, Yasser G;
- Spencer, Benjamin A;
- Jones, Terry;
- Tran, Quyen;
- Nardo, Lorenzo;
- Chen, Moon S;
- Sarkar, Souvik;
- Medici, Valentina;
- Lyo, Victoria;
- Badawi, Ramsey D;
- Cherry, Simon R;
- Wang, Guobao
Published Web Location
https://doi.org/10.1038/s41467-025-58356-7Abstract
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.
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