Molecular connectivity studies of cerebral glucose metabolism and blood flow: A scoping review

The brain's functional organization relies on neural, metabolic, and vascular interactions. Molecular neuroimaging offers powerful tools for assessing macroscale brain connectivity by capturing relationships between regional perfusion and glucose metabolism. This review summarizes molecular connectivity studies of cerebral blood flow (CBF) and metabolism, focusing on methodological approaches and key findings. A systematic search across MEDLINE, EMBASE, and Scopus identified studies employing radiotracers to examine brain perfusion or glucose metabolic connectivity. Data extraction focused on tracer type, connectivity methodology, population, and clinical relevance. Overall, 384 studies were included, covering healthy condition, dementia, movement disorders, psychiatric diseases, epilepsy, and disorders of consciousness. Both resting-state and task-based paradigms were identified, with perfusion studies being popular for detecting fast task-induced molecular connectivity changes. Metabolic connectivity, assessed via [<sup>18</sup>F]FDG-PET at rest, emerged as robust marker of functional integrity and disease progression, especially in neurodegenerative conditions. Multimodal PET/MRI studies revealed partial overlap between metabolic and hemodynamic connectivity. Noteworthy findings include the identification of default mode network through the study of CBF and disease-related covariance patterns in neurodegenerative disorders through the study of glucose metabolism. Integrating macroscale molecular brain organization studies with neurophysiological techniques will deepen the understanding of brain connectivity in health and disease. Additionally, total-body PET/MRI data may in the future elucidate brain-body interactions fostering a more comprehensive connectome framework.

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Publication Details

Journal
Neuroscience & Biobehavioral Reviews
Published
2026-03-05
DOI
https://doi.org/10.1016/j.neubiorev.2026.106623
Primary Topic
Bioinformatics and Genomic Networks
Type
article
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article

Molecular connectivity studies of cerebral glucose metabolism and blood flow: A scoping review

Mario Severino, Marjorie Bardiau, Christian Habeck, Chunmeng Tang et al.
Neuroscience & Biobehavioral Reviews
Bioinformatics and Genomic Networks
article

Molecular connectivity studies of cerebral glucose metabolism and blood flow: A scoping review

Mario Severino, Marjorie Bardiau, Christian Habeck, Chunmeng Tang, Tommaso Volpi, Daniel Talmasov, Débora Elisa Peretti, Xin Di, Matej Perovnik, Igor Yu. Yakushev, Daniela Perani, Vesna Sossi, Tatiana Horwitz, Zhilei Xu, Simon B. Eickhoff, Gabriel Gonzalez-Escamilla, Joana B. Pereira, Alice Galli, Sharna Jamadar, Chiara Meneghini, Anna Lisa Martini, Vince Calhoun, Arianna Sala, Michael Rullmann, Silvia Paola Caminiti, Carlo Cavaliere, Martin Nørgaard, Matthieu Doyen
article en

Abstract

The brain's functional organization relies on neural, metabolic, and vascular interactions. Molecular neuroimaging offers powerful tools for assessing macroscale brain connectivity by capturing relationships between regional perfusion and glucose metabolism. This review summarizes molecular connectivity studies of cerebral blood flow (CBF) and metabolism, focusing on methodological approaches and key findings. A systematic search across MEDLINE, EMBASE, and Scopus identified studies employing radiotracers to examine brain perfusion or glucose metabolic connectivity. Data extraction focused on tracer type, connectivity methodology, population, and clinical relevance. Overall, 384 studies were included, covering healthy condition, dementia, movement disorders, psychiatric diseases, epilepsy, and disorders of consciousness. Both resting-state and task-based paradigms were identified, with perfusion studies being popular for detecting fast task-induced molecular connectivity changes. Metabolic connectivity, assessed via [<sup>18</sup>F]FDG-PET at rest, emerged as robust marker of functional integrity and disease progression, especially in neurodegenerative conditions. Multimodal PET/MRI studies revealed partial overlap between metabolic and hemodynamic connectivity. Noteworthy findings include the identification of default mode network through the study of CBF and disease-related covariance patterns in neurodegenerative disorders through the study of glucose metabolism. Integrating macroscale molecular brain organization studies with neurophysiological techniques will deepen the understanding of brain connectivity in health and disease. Additionally, total-body PET/MRI data may in the future elucidate brain-body interactions fostering a more comprehensive connectome framework.

Neuroscience & Biobehavioral ReviewsVol. 185
New Jersey Institute of Technology (US), Centre National de la Recherche Scientifique (FR), University of Padua (IT), University of British Columbia (CA), Vita-Salute San Raffaele University (IT), Inserm (FR), University of Liège (BE), King's College London (GB), University of Pavia (IT), Columbia University Irving Medical Center (US), Ljubljana University Medical Centre (SI), Karolinska Institutet (SE), Yale University (US), Assistance Publique Hôpitaux de Marseille (FR), Düsseldorf University Hospital (DE), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), University Hospital of Geneva (CH), Imagerie Adaptative Diagnostique et Interventionnelle (FR), Max Planck Institute for Human Cognitive and Brain Sciences (DE), Center for Translational Research in Neuroimaging and Data Science (US), Ospedale di Prato Santo Stefano (IT), National Institute of Mental Health (US), Hôpital de la Timone (FR), Heinrich Heine University Düsseldorf (DE), Monash University (AU), Technical University of Munich (DE), University of Brescia (IT), Université de Lorraine (FR), Saarland University (DE), KU Leuven (BE)
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