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

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-03-30 DOI:10.1038/s41467-025-58356-7

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. Cherry, Guobao Wang

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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.

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血脑屏障通透性的神经成像技术在确定血脑屏障广泛参与神经和全身疾病方面发挥了重要作用。然而，目前的方法主要将血脑屏障作为结构屏障进行评估。在此，我们开发了一种非侵入性正电子发射断层扫描方法，用于测量分子放射性核素的血脑屏障通透性，这种分子放射性核素可通过其分子特异性转运机制穿过血脑屏障。我们的方法利用高时间分辨率动态成像和动力学模型对分子放射性核素的血脑屏障通透性-表面积乘积进行多参数成像和量化。我们显示，在人体中，我们的方法可以解析三种放射性核素的血脑屏障通透性，并证明了它在研究代谢功能障碍相关脂肪肝炎症的脑衰老和脑体相互作用方面的实用性。我们的方法为利用现有的大量分子正电子发射断层扫描示踪剂有效研究体内人体血脑屏障的分子通透性开辟了新的方向。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.