Efficacy Assessment of Cerebral Perfusion Augmentation Through Functional Connectivity in an Acute Canine Stroke Model.


Journal

AJNR. American journal of neuroradiology
ISSN: 1936-959X
Titre abrégé: AJNR Am J Neuroradiol
Pays: United States
ID NLM: 8003708

Informations de publication

Date de publication:
29 Apr 2024
Historique:
received: 07 02 2024
accepted: 16 04 2024
medline: 30 4 2024
pubmed: 30 4 2024
entrez: 29 4 2024
Statut: aheadofprint

Résumé

Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model. Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 μg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO. NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks. NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation. NEH= Norepinephrine and Hydralazine; RSN= Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

Sections du résumé

BACKGROUND AND PURPOSE OBJECTIVE
Ischemic stroke disrupts functional connectivity within the brain's resting-state networks (RSNs), impacting recovery. This study evaluates the effects of NEH (Norepinephrine and Hydralazine), a cerebral perfusion augmentation therapy, on RSN integrity in a hyper-acute canine stroke model.
MATERIALS AND METHODS METHODS
Fifteen adult purpose-bred mongrel canines, divided into treatment and control (natural history) groups, underwent endovascular induction of acute middle cerebral artery occlusion (MCAO). Post-occlusion, the treatment group received intra-arterial Norepinephrine (0.1-1.52 μg/kg/min, adjusted for 25-45 mmHg above baseline mean arterial pressure) and Hydralazine (20mg). Resting-state fMRI data were acquired with a 3.0 T scanner using a BOLD-sensitive EPI sequence (TR/TE=1400 ms/20ms, 2.5 mm slices, 300 temporal positions). Preprocessing included motion correction, spatial smoothing (2.5 mm FWHM), and high-pass filtering (0.01 Hz cutoff). Functional connectivity within RSNs were analyzed through group-level independent component analysis (ICA) and weighted whole-brain ROI-to-ROI connectome, pre-and post-MCAO.
RESULTS RESULTS
NEH therapy significantly maintained connectivity post-MCAO in the Higher-order Visual and Parietal RSNs, as evidenced by thresholded statistical mapping (TFCE p-corr > 0.95). However, this preservation was network-dependent, with no significant changes in the Primary Visual and Sensorimotor networks.
CONCLUSIONS CONCLUSIONS
NEH demonstrates potential as a proof-of-concept therapy for maintaining RSN functional connectivity following ischemic stroke, emphasizing the therapeutic promise of perfusion augmentation. These insights reinforce the role of functional connectivity as a measurable endpoint for stroke intervention efficacy, suggesting clinical translatability for patients with insufficient collateral circulation.
ABBREVIATIONS BACKGROUND
NEH= Norepinephrine and Hydralazine; RSN= Resting-State Network; ICA = Independent Component Analysis; rsfMRI = resting-state Functional Magnetic Resonance Imaging; MCAO = Middle Cerebral Artery Occlusion; TFCE = Threshold-Free Cluster Enhancement.

Identifiants

pubmed: 38684318
pii: ajnr.A8320
doi: 10.3174/ajnr.A8320
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024 by American Journal of Neuroradiology.

Déclaration de conflit d'intérêts

The authors declare no conflicts of interest related to the content of this article.

Auteurs

Chisondi S Warioba (CS)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Mira Liu (M)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Sagada Penano (S)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Sean Foxley (S)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Gregory A Christoforidis (GA)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Timothy J Carroll (TJ)

Department of Radiology (C.S.W., S.P., M.L., S.F., T.J.C), The University of Chicago, Chicago, IL, USA; Department of Neurology (G.A.C.), Mount Carmel Health Systems, Columbus, Ohio, USA.

Classifications MeSH