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However, lack of standardized terminology and diverse methodologies in PET connectivity studies has resulted in inconsistencies, complicating the interpretation and comparison of results across studies. A standardized nomenclature is thus needed to reduce ambiguity, enhance reproducibility, and facilitate interpretability across radiotracers, imaging modalities and studies. Here, we define and differentiate the terms \u201cmolecular connectivity\u201d and \u201cmolecular covariance\u201d. Drawing parallels from other imaging modalities, we propose \u201cmolecular connectivity\u201d as an umbrella term to characterize statistical dependencies between the measured PET signal across brain regions at a\n                    <jats:italic>within-subject<\/jats:italic>\n                    level. Like fMRI resting-state functional connectivity, \u201cmolecular connectivity\u201d leverages spatio-temporal associations in the PET signal to derive brain network associations. Conversely, \u201cmolecular covariance\u201d denotes group-level computations of covariance matrices\n                    <jats:italic>between-subjects<\/jats:italic>\n                    . Further specification of the terminology can be achieved by including the target of the employed radioligand, such as \u201cmetabolic connectivity\/covariance\u201d for [\n                    <jats:sup>18<\/jats:sup>\n                    F]FDG or \u201camyloid covariance\u201d for [\n                    <jats:sup>18<\/jats:sup>\n                    F]flutemetamol and \u201ctau covariance\u201d for [\n                    <jats:sup>18<\/jats:sup>\n                    F]flortaucipir. While this approach to standardization aims to clarify terminology, open questions remain about the neurobiological underpinnings of these connectivity metrics. Future research should focus on elucidating these mechanisms and developing advanced computational methodologies that evaluate diverse feature relationships and improve the robustness of PET-based connectivity metrics.\n                  <\/jats:p>","DOI":"10.1007\/s00259-025-07357-1","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T03:05:25Z","timestamp":1748833525000},"page":"48-58","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Connecting the dots: approaching a standardized nomenclature for molecular connectivity in positron emission tomography"],"prefix":"10.1007","volume":"53","author":[{"given":"Murray B.","family":"Reed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin Y.","family":"Sander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Granville J.","family":"Matheson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Volpi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikkita","family":"Khattar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"DeLorenzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Gryglewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo R.","family":"Silberbauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matej","family":"Murga\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Godber M.","family":"Godbersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Nics","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Walter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Hacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bertoldo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Lubberink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Silfstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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Lanzenberger received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET\/MR and travel grants and\/or conference speaker honoraria from Janssen-Cilag Pharma GmbH in 2023, and Bruker BioSpin, Shire, AstraZeneca, Lundbeck A\/S, Dr. Willmar Schwabe GmbH, Orphan Pharmaceuticals AG, Janssen-Cilag Pharma GmbH, Heel and Roche Austria GmbH., and Janssen-Cilag Pharma GmbH in the years before 2020. He is a shareholder of the start-up company BM Health GmbH, Austria since 2019. M. Hacker received consulting fees and\/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. L. Cocchi is involved in a not-for-profit clinic administering fMRI-guided brain stimulation therapy (Queensland Neurostimulation Centre). The author(s) declared no potential conflicts of interest with respect to the research, authorship, and\/or publication of this article.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Not applicable.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}}]}}