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


ABSTRACT: Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different transport mechanisms. Our method uses high-temporal resolution dynamic imaging and kinetic modeling to jointly estimate cerebral blood flow and tracer-specific BBB transport rate from a single dynamic PET scan and measure the molecular permeability-surface area (PS) product of the radiotracer. We show our method can resolve BBB PS across three PET radiotracers with greatly differing permeabilities, measure reductions in BBB PS of 18F-fluorodeoxyglucose (FDG) in healthy aging, and demonstrate a possible brain-body association between decreased FDG BBB PS in patients with metabolic dysfunction-associated steatotic liver inflammation. Our method opens new directions to efficiently study the molecular permeability of the human BBB in vivo using the large catalogue of available molecular PET tracers.

SUBMITTER: Chung KJ 

PROVIDER: S-EPMC11302722 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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

Chung Kevin J KJ   Abdelhafez Yasser G YG   Spencer Benjamin A BA   Jones Terry T   Tran Quyen Q   Nardo Lorenzo L   Chen Moon S MS   Sarkar Souvik S   Medici Valentina V   Lyo Victoria V   Badawi Ramsey D RD   Cherry Simon R SR   Wang Guobao G  

medRxiv : the preprint server for health sciences 20240727


Blood-brain barrier (BBB) disruption is involved in the pathogenesis and progression of many neurological and systemic diseases. Non-invasive assessment of BBB permeability in humans has mainly been performed with dynamic contrast-enhanced magnetic resonance imaging, evaluating the BBB as a structural barrier. Here, we developed a novel non-invasive positron emission tomography (PET) method in humans to measure the BBB permeability of molecular radiotracers that cross the BBB through different t  ...[more]

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