A blood-free modeling approach for the quantification of the blood-to-brain tracer exchange in TSPO PET imaging

Journal article

Maccioni, L., Michelle, C.M., Brusaferri, L., Silvestri, E., Bertoldo, A., Schubert, J.J., Nettis, M.A., Mondelli, V., Howes, O., Turkheimer, F.E., Bottlaender, M., Bodini, B., Stankoff, B., Loggia, M.L. and Veronese, M. (2024). A blood-free modeling approach for the quantification of the blood-to-brain tracer exchange in TSPO PET imaging. Frontiers in Neuroscience. 18, p. 1395769. https://doi.org/10.3389/fnins.2024.1395769
AuthorsMaccioni, L., Michelle, C.M., Brusaferri, L., Silvestri, E., Bertoldo, A., Schubert, J.J., Nettis, M.A., Mondelli, V., Howes, O., Turkheimer, F.E., Bottlaender, M., Bodini, B., Stankoff, B., Loggia, M.L. and Veronese, M.
AbstractIntroduction: Recent evidence suggests the blood-to-brain influx rate (K1) in TSPO PET imaging as a promising biomarker of blood–brain barrier (BBB) permeability alterations commonly associated with peripheral inflammation and heightened immune activity in the brain. However, standard compartmental modeling quantification is limited by the requirement of invasive and laborious procedures for extracting an arterial blood input function. In this study, we validate a simplified blood-free methodologic framework for K1 estimation by fitting the early phase tracer dynamics using a single irreversible compartment model and an image-derived input function (1T1K-IDIF). Methods: The method is tested on a multi-site dataset containing 177 PET studies from two TSPO tracers ([11C]PBR28 and [18F]DPA714). Firstly, 1T1K-IDIF K1 estimates were compared in terms of both bias and correlation with standard kinetic methodology. Then, the method was tested on an independent sample of [11C]PBR28 scans before and after inflammatory interferon-α challenge, and on test–retest dataset of [18F]DPA714 scans. Results: Comparison with standard kinetic methodology showed good-to-excellent intra-subject correlation for regional 1T1K-IDIF-K1 (ρintra = 0.93 ± 0.08), although the bias was variable depending on IDIF ability to approximate blood input functions (0.03–0.39 mL/cm3/min). 1T1K-IDIF-K1 unveiled a significant reduction of BBB permeability after inflammatory interferon-α challenge, replicating results from standard quantification. High intra-subject correlation (ρ = 0.97 ± 0.01) was reported between K1 estimates of test and retest scans. Discussion: This evidence supports 1T1K-IDIF as blood-free alternative to assess TSPO tracers’ unidirectional blood brain clearance. K1 investigation could complement more traditional measures in TSPO studies, and even allow further mechanistic insight in the interpretation of TSPO signal.
KeywordsTSPO; BBB; kinetic modeling; PET; IDIF; neuroinflammation
Year2024
JournalFrontiers in Neuroscience
Journal citation18, p. 1395769
PublisherFrontiers Media S.A.
ISSN1662-453X
Digital Object Identifier (DOI)https://doi.org/10.3389/fnins.2024.1395769
Web address (URL)https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1395769/full
Publication dates
Online22 Jul 2024
Publication process dates
Accepted02 Jul 2024
Deposited06 Aug 2024
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