Quantitative PET imaging and modeling of molecular blood-brain barrier permeability
Kevin J. Chung, Yasser G. Abdelhafez, Benjamin A. Spencer, Terry Jones, Tran Nhan Tam Quyen, Lorenzo Nardo, Moon S. Chen, Souvik Sarkar, Valentina Medici, Victoria Lyo, Ramsey D. Badawi, Simon R. Cherry, Guobao Wang
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.