Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging

Cheung, Jesse; Doerr, Madeline; Hu, Ranliang; Sun, Phillip Zhe

doi:10.1007/s12975-020-00868-z

Cited by 25 publications

(19 citation statements)

References 148 publications

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“…Besides the penumbra, researchers also realized that the acute restricted diffusion lesions comprise benign oligemia, which is likely to reverse (Olivot et al, 2009b;Cheung et al, 2020). The reversibility of diffusion lesions is associated with early reperfusion or recanalization of the ischemic tissue with or without endovascular therapies (Albach et al, 2013;Asdaghi et al, 2014) and absent or less severe perfusion deficit within diffusion lesions (Olivot et al, 2009a).…”

Section: Discussionmentioning

confidence: 99%

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke

Zhou

Cho

et al. 2021

Front. Neurosci.

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PurposeThis study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ).MethodOne hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed.ResultsCompared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (p < 0.05) and showed a declining tendency from the acute to the chronic phase (p = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI (p = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously.ConclusionThe spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.

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Section: Discussionmentioning

confidence: 99%

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke

Zhou

Cho

et al. 2021

Front. Neurosci.

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“…In addition, preclinical studies are needed to screen the pharmacological candidate molecules able to rescue the penumbra. Then, future trials including fast physiologic imaging examinations must be initiated to assess the effects of new treatments acting on the cortical collateral circulation or on brain neuroprotection that can rescue the penumbra in humans (see reviews of Leigh et al 2018 [ 66 ], of Catanese et al 2017 [ 68 ], and of Cheung et al 2021 [ 69 ]).…”

Section: Discussionmentioning

confidence: 99%

Collateral Supply in Preclinical Cerebral Stroke Models

Bonnin

Kubis

Charriaut‐Marlangue

2021

Transl. Stroke Res.

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Enhancing the collateral blood supply during the acute phase of cerebral ischemia may limit both the extension of the core infarct, by rescuing the penumbra area, and the degree of disability. Many imaging techniques have been applied to rodents in preclinical studies, to evaluate the magnitude of collateral blood flow and the time course of responses during the early phase of ischemic stroke. The collateral supply follows several different routes at the base of the brain (the circle of Willis) and its surface (leptomeningeal or pial arteries), corresponding to the proximal and distal collateral pathways, respectively. In this review, we describe and illustrate the cerebral collateral systems and their modifications following pre-Willis or post-Willis occlusion in rodents. We also review the potential pharmaceutical agents for stimulating the collateral blood supply tested to date. The time taken to establish a collateral blood flow supply through the leptomeningeal anastomoses differs between young and adult animals and between different species and genetic backgrounds. Caution is required when transposing preclinical findings to humans, and clinical trials must be performed to check the added value of pharmacological agents for stimulating the collateral blood supply at appropriate time points. However, collateral recruitment appears to be a rapid, beneficial, endogenous mechanism that can be stimulated shortly after artery occlusion. It should be considered a treatment target for use in addition to recanalization strategies.

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“…In an attempt to summarize the above-mentioned data, we can conclude that A 3 R stimulation during prolonged OGD is protective in the first phases of the insult by participating, together with A 1 Rs, in the (Gi-mediated) inhibition of excitatory neurotransmission [ 68 ], whereas, at later times, prolonged receptor activation might lead to (Gq-mediated) intracellular calcium accumulation, contributing to cell damage (for a review, see: [ 16 ]). In this view, even if agonists of A 3 Rs are neuroprotective in the acute phases of stroke, at later times, corresponding to when most ischemic patients approach clinics, antagonists are the most advantageous strategy for an eventual post-ischemic A 3 R-based therapy because they might protect neurons, especially those “salvageable” in the penumbral area, from neurodegeneration and death [ 75 , 76 , 77 ].…”

Section: Therapeutic Potential Of a 3 R Ligandsmentioning

confidence: 99%

Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System

et al. 2022

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Ligands of the Gi protein-coupled adenosine A3 receptor (A3R) are receiving increasing interest as attractive therapeutic tools for the treatment of a number of pathological conditions of the central and peripheral nervous systems (CNS and PNS, respectively). Their safe pharmacological profiles emerging from clinical trials on different pathologies (e.g., rheumatoid arthritis, psoriasis and fatty liver diseases) confer a realistic translational potential to these compounds, thus encouraging the investigation of highly selective agonists and antagonists of A3R. The present review summarizes information on the effect of latest-generation A3R ligands, not yet available in commerce, obtained by using different in vitro and in vivo models of various PNS- or CNS-related disorders. This review places particular focus on brain ischemia insults and colitis, where the prototypical A3R agonist, Cl-IB-MECA, and antagonist, MRS1523, have been used in research studies as reference compounds to explore the effects of latest-generation ligands on this receptor. The advantages and weaknesses of these compounds in terms of therapeutic potential are discussed.

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Refined Ischemic Penumbra Imaging with Tissue pH and Diffusion Kurtosis Magnetic Resonance Imaging

Cited by 25 publications

References 148 publications

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke

The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke

Collateral Supply in Preclinical Cerebral Stroke Models

Therapeutic Potential of Highly Selective A3 Adenosine Receptor Ligands in the Central and Peripheral Nervous System

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