Quantifying Infarct Growth and Secondary Injury Volumes

Harston, George; Carone, Davide; Sheerin, Fintan; Jenkinson, Mark; Kennedy, James S.

doi:10.1161/strokeaha.118.020788

Cited by 17 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As previously observed, in our model ( Debatisse et al , 2020 ), acute infarcts were generally not as massive as in human ischaemic stroke limiting the occurrence of malignant oedema, and the few cases with very large lesion died prematurely. With no massive oedema at Day 7, the non-linear registration performed well to correct for minor oedema as observed in our previous study ( Debatisse et al , 2020 ) and as also demonstrated in clinical data ( Harston et al , 2018 ). Between Day 7 and Day 30, there is substantial infarct size reduction but the tissue loss in the ipsilateral hemisphere was not large enough to disturb the non-linear registration to the template space.…”

Section: Discussionsupporting

confidence: 83%

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

Debatisse

Wateau²,

Cho

et al. 2020

Brain Communications

View full text Add to dashboard Cite

In acute ischemic stroke, understanding the dynamics of blood–brain barrier injury is of particular importance for the prevention of symptomatic hemorrhagic 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 ischemic 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 MRI, the baseline transfer constant Ktrans was 0.94 [0.48, 1.72] and 0.16 [0.08, 0.33] x10−3 min−1, respectively, in normal brain parenchyma, consistent with their respective sizes, and 1.90 [1.23, 3.95] and 2.86 [1.39, 4.52] x10−3 min−1 in choroid plexus, confirming higher permeability than brain parenchyma. At early reperfusion, Ktrans for both Gd-DOTA and AGuIX® nanoparticles was significantly higher within the ischemic area compared to the contralateral hemisphere; 2.23 [1.17, 4.13] and 0.82 [0.46, 1.87] x10−3 min−1 for Gd-DOTA and AGuIX® nanoparticles, respectively. With AGuIX® nanoparticles, Ktrans also increased within the ischemic growth areas, suggesting added value for AGuIX®. Finally, Ktrans 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). Ktrans quantification with AGuIX® nanoparticles can monitor early blood–brain barrier damage and treatment effect in ischemic stroke after reperfusion.

show abstract

Section: Discussionsupporting

confidence: 83%

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

Debatisse

Wateau²,

Cho

et al. 2020

Brain Communications

View full text Add to dashboard Cite

show abstract

“…However, vasogenic edema usually occurs in the first week and can artificially inflate lesion volume. Previous studies demonstrated that 24 h evaluation of infarct volume by non-contrast computed tomodensitometry is as well correlated to 3 month-mRS than is 1 week evaluation ( 59 , 60 ). There is currently no consensus about the best time-point to evaluate infarct growth, and future stroke studies are needed to address this issue.…”

Section: Discussionmentioning

confidence: 98%

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA)

et al. 2018

View full text Add to dashboard Cite

Background: Stroke is a major cause of death and disability worldwide. The related burden is expected to further increase due to aging populations, calling for more efficient treatment. Ischemic stroke results from a focal reduction in cerebral blood flow due to the sudden occlusion of a brain artery. Ischemic brain injury results from a sequence of pathophysiological events that evolve over time and space. This cascade includes excitotoxicity and peri-infarct depolarizations (PIDs). Focal impairment of cerebral blood flow restricts the delivery of energetics substrates and impairs ionic gradients. Membrane potential is eventually lost, and neurons depolarize. Although recanalization therapies target the ischemic penumbra, they can only rescue the penumbra still present at the time of reperfusion. A promising novel approach is to “freeze” the penumbra until reperfusion occurs. Transcranial direct current stimulation (tDCS) is a non-invasive method of neuromodulation. Based on preclinical evidence, we propose to test the penumbra freezing concept in a clinical phase IIa trial assessing whether cathodal tDCS—shown in rodents to reduce infarction volume—prevents early infarct growth in human acute Middle Cerebral Artery (MCA) stroke, in adjunction to conventional revascularization methods.Methods: This is a monocentric randomized, double-blind, and placebo-controlled trial performed in patients with acute MCA stroke eligible to revascularization procedures. Primary outcome is infarct volume growth on diffusion weighted imaging (DWI) at day 1 relative to baseline. Secondary outcomes include safety and clinical efficacy.Significance: Results from this clinical trial are expected to provide rationale for a phase III study.Clinical trial registration—EUDRACT: 2016-A00160-51

show abstract

“…13 In addition, in these studies, true lesion growth was not distinguished from edema, although the latter may account for up to one-third of the lesion volume. 3,4,23 The use of a nonlinear coregistered MRI approach may limit this bias.…”

Section: Discussionmentioning

confidence: 99%

Association of Blood Biomarkers of Inflammation With Penumbra Consumption After Mechanical Thrombectomy in Patients With Acute Ischemic Stroke

et al. 2022

View full text Add to dashboard Cite

Objectives:To assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT).Methods:HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT following MRI. Lesion growth within the penumbra was assessed on day-6 MRI using a voxel-based nonlinear coregistration method and dichotomized into low and high according to the median. C-reactive protein (CRP), interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), soluble tumor necrosis factor receptor I (sTNF-RI), soluble form suppression of tumorigenicity 2 (sST2), soluble P-selectin (sP-selectin), vascular cellular adhesion molecule-1 (VCAM-1) and matrix metalloproteinase-9 (MMP-9) were measured in sera at 4 timepoints within the first 48 hours. Reperfusion was considered as successful if Thrombolysis in Cerebral Infarction (TICI) score was 2b/2c/3. A multiple logistic regression model was performed to detect any association between area under the curve (AUC) of these biomarkers within the first 48 hours and a high lesion growth within the penumbra.Results:90 patients were included. Median lesion growth within the penumbra was 2.3 [0.7-6.2] mL. On multivariable analysis, a high sST2 AUC (odds ratio (OR) 3.77, 95% confidence interval (CI) 1.36-10.46) as well as a high baseline DWI volume (OR 3.65, 95% CI 1.32-10.12) and lack of successful reperfusion (OR 0.19, 95% CI 0.04-0.92) were associated with a high lesion growth within the penumbra. When restricting analyses to patients with successful reperfusion (n=76), a high sST2 AUC (OR 5.03, 95% CI 1.64-15.40), a high baseline DWI volume (OR 3.74, 95% CI 1.22-11.53) and a high penumbra volume (OR 3.25, 95% CI 1.10-9.57) remained associated with a high lesion growth within the penumbra.Conclusions: sST2 levels within the first 48 hours are associated with a high lesion growth within the penumbra.

show abstract

Quantifying Infarct Growth and Secondary Injury Volumes

Abstract: Supplemental Digital Content is available in the text.

Cited by 17 publications

References 35 publications

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

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

Design and Methodology of a Pilot Randomized Controlled Trial of Transcranial Direct Current Stimulation in Acute Middle Cerebral Artery Stroke (STICA)

Association of Blood Biomarkers of Inflammation With Penumbra Consumption After Mechanical Thrombectomy in Patients With Acute Ischemic Stroke

Contact Info

Product

Resources

About