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. 2025 Feb;52(3):836-850.
doi: 10.1007/s00259-024-06956-8. Epub 2024 Oct 30.

Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard

Giulia Vallini  1 , Erica Silvestri #  1 , Tommaso Volpi #  2   3 , John J Lee  4 , Andrei G Vlassenko  4 , Manu S Goyal  4 , Diego Cecchin  2   5 , Maurizio Corbetta  2   6 , Alessandra Bertoldo  7   8
Affiliations

Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard

Giulia Vallini et al. Eur J Nucl Med Mol Imaging. 2025 Feb.

Abstract

Purpose: This study evaluates the potential of within-individual Metabolic Connectivity (wi-MC), from dynamic [18F]FDG PET data, based on the Euclidean Similarity method. This approach leverages the biological information of the tracer's full temporal dynamics, enabling the direct extraction of individual metabolic connectomes. Specifically, the proposed framework, applied to glioma pathology, seeks to assess sensitivity to metabolic dysfunctions in the whole brain, while simultaneously providing further insights into the pathophysiological mechanisms regulating glioma progression.

Methods: We designed an index (Distance from Healthy Group, DfHG) based on the alteration of wi-MC in each patient (n = 44) compared to a healthy reference (from 57 healthy controls), to individually quantify metabolic connectivity abnormalities, resulting in an Impairment Map highlighting significantly compromised areas. We then assessed whether our measure of metabolic network alteration is associated with well-established markers of disease severity (tumor grade and volume, with and without edema). Subsequently, we investigated disruptions in wi-MC homotopic connectivity, assessing both affected and seemingly healthy tissue to deepen the pathology's impact on neural communication. Finally, we compared network impairments with local metabolic alterations determined from SUVR, a validated diagnostic tool in clinical practice.

Results: Our framework revealed how gliomas cause extensive alterations in the topography of brain networks, even in structurally unaffected regions outside the lesion area, with a significant reduction in connectivity between contralateral homologous regions. High-grade gliomas have a stronger impact on brain networks, and edema plays a mediating role in global metabolic alterations. As compared to the conventional SUVR-based analysis, our approach offers a more holistic view of the disease burden in individual patients, providing interesting additional insights into glioma-related alterations.

Conclusion: Considering our results, individual PET connectivity estimates could hold significant clinical value, potentially allowing the identification of new prognostic factors and personalized treatment in gliomas or other focal pathologies.

Keywords: Brain network alterations; Cancer neuroscience; Glioma; Individual-level metabolic connectivity; SUVR; [18F]FDG dynamic PET.

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Conflict of interest statement

Declarations. Ethical approval: All assessments and imaging procedures were approved by Human Research Protection Office and Radioactive Drug Research Committee at Washington University in St. Louis (healthy controls). Concerning glioma patients, the protocol has been approved by the local Ethics Committee of the University Hospital of Padova. All procedures performed in studies were conducted in accordance with the 1964 Declaration of Helsinki and its subsequent amendments. Consent to participate: Informed written consent was obtained from all individual participants included in the study. Consent to publish: Participants signed informed consent regarding publishing their data. Competing interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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