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PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

ABSTRACT: In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate could better characterize blood-brain barrier damage and refine the delivery of neuroprotective agents. We previously developed an original endovascular stroke model of acute ischaemic stroke treated by mechanical thrombectomy followed by positron emission tomography-magnetic resonance imaging. Cerebral capillary permeability was quantified for two molecule sizes: small clinical gadolinium Gd-DOTA (<1?nm) and AGuIX^® nanoparticles (?5?nm) used for brain theranostics. On dynamic contrast-enhanced magnetic resonance imaging, the baseline transfer constant K _trans was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] ×10^-3?min^-1, respectively, in the normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] ×10^-3?min^-1 in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, K _trans for both Gd-DOTA and AGuIX^® nanoparticles was significantly higher within the ischaemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] ×10^-3?min^-1 for Gd-DOTA and AGuIX^® nanoparticles, respectively. With AGuIX^® nanoparticles, K _trans also increased within the ischaemic growth areas, suggesting added value for AGuIX^®. Finally, K _trans was significantly lower in both the lesion and the choroid plexus in a drug-treated group (ciclosporin A, n?=?7) compared to placebo (n?=?5). K _trans quantification with AGuIX^® nanoparticles can monitor early blood-brain barrier damage and treatment effect in ischaemic stroke after reperfusion.

SUBMITTER: Debatisse J

PROVIDER: S-EPMC7716090 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

Debatisse Justine J Eker Omer Faruk OF Wateau Océane O Cho Tae-Hee TH Wiart Marlène M Ramonet David D Costes Nicolas N Mérida Inés I Léon Christelle C Dia Maya M Paillard Mélanie M Confais Joachim J Rossetti Fabien F Langlois Jean-Baptiste JB Troalen Thomas T Iecker Thibaut T Le Bars Didier D Lancelot Sophie S Bouchier Baptiste B Lukasziewicz Anne-Claire AC Oudotte Adrien A Nighoghossian Norbert N Ovize Michel M Contamin Hugues H Lux François F Tillement Olivier O Canet-Soulas Emmanuelle E

Brain communications 20201111 2

In an acute ischaemic stroke, understanding the dynamics of blood-brain barrier injury is of particular importance for the prevention of symptomatic haemorrhagic transformation. However, the available techniques assessing blood-brain barrier permeability are not quantitative and are little used in the context of acute reperfusion therapy. Nanoparticles cross the healthy or impaired blood-brain barrier through combined passive and active processes. Imaging and quantifying their transfer rate coul ...[more]

PMID: 33305265

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Project description:Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors.Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following (64)Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis.The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both (18)F-FDG and a (64)Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass.The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.

Dataset Information

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

Publications

PET-MRI nanoparticles imaging of blood-brain barrier damage and modulation after stroke reperfusion.

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