Cerebrovascular reactivity mapping using resting-state BOLD fMRI in First Episode Psychosis
Poster No:
2106
Submission Type:
Abstract Submission
Authors:
Thomas Prud'homme1, Olivier Percie du Sert1, Zacharie Potvin-Jutras2, Claudine Gauthier2, Mallar Chakravarty3, Katie Lavigne1, Martin Lepage1, Delphine Raucher-Chéné1
Institutions:
1McGill University, Montreal, Quebec, 2Concordia University, Montreal, Quebec, 3McGill University, Montréal, QC
First Author:
Co-Author(s):
Introduction:
Cerebrovascular reactivity (CVR) is a key marker of brain vascular health, reflecting the ability of cerebral vessels to dilate or constrict, respond to metabolic demands and regulate cerebral blood flow (CBF). Abnormal CBF is consistently observed in psychotic disorders, yet its underlying causes remain unclear. Distinct patterns of cortical hypoperfusion and subcortical hyperperfusion have been reported, with apparent associations to clinical symptoms (Percie du Sert, 2023).
Despite its potential to explain CBF alterations, CVR research in psychiatric populations is limited due to technical challenges. Traditional CVR mapping requieres physiological vasoactive challenges, such as breath-hold tasks or CO₂ inhalation. Breath-hold depend heavily on participants' adherence to protocol, introducing variability. On the other hand, CO2 inhalation requires specialized equipment and expertise. In both case, hypercapnia excludes participants with respiratory disorders, may feel invasive, anxiety-inducing, and be poorly tolerated (Liu, 2019, Urback 2017). These limitations hinder the broader clinical and research applicability of CVR mapping, particularly in psychiatry.
To address these challenges, alternative methods leveraging natural physiological fluctuations during resting-state functional MRI (rs-fMRI) have emerged. Liu et al. (2017) demonstrated that spontaneous arterial CO₂ fluctuations derived from global BOLD signals can serve as a proxy for CVR mapping, demonstrating its feasibility, reproducibility, and comparability to gas-inhalation-based method. However, no studies have applied rs-fMRI-based CVR mapping to psychotic disorders. This study aims to bridge this gap by utilizing rs-fMRI data to extrapolate CVR in individuals with first-episode psychosis (FEP).
Despite its potential to explain CBF alterations, CVR research in psychiatric populations is limited due to technical challenges. Traditional CVR mapping requieres physiological vasoactive challenges, such as breath-hold tasks or CO₂ inhalation. Breath-hold depend heavily on participants' adherence to protocol, introducing variability. On the other hand, CO2 inhalation requires specialized equipment and expertise. In both case, hypercapnia excludes participants with respiratory disorders, may feel invasive, anxiety-inducing, and be poorly tolerated (Liu, 2019, Urback 2017). These limitations hinder the broader clinical and research applicability of CVR mapping, particularly in psychiatry.
To address these challenges, alternative methods leveraging natural physiological fluctuations during resting-state functional MRI (rs-fMRI) have emerged. Liu et al. (2017) demonstrated that spontaneous arterial CO₂ fluctuations derived from global BOLD signals can serve as a proxy for CVR mapping, demonstrating its feasibility, reproducibility, and comparability to gas-inhalation-based method. However, no studies have applied rs-fMRI-based CVR mapping to psychotic disorders. This study aims to bridge this gap by utilizing rs-fMRI data to extrapolate CVR in individuals with first-episode psychosis (FEP).
Methods:
We recruited 100 individuals aged 18–35 years with FEP and minimal antipsychotic exposure (<30d) from the Prevention and Early Intervention Program for Psychoses at the Douglas Mental Health University Institute, Montreal. Sixty non-clinical controls were matched on age, sex, and parental education. Exclusion criteria included IQ < 70, neurological disorders, head injury, and MRI contraindications. Imaging was conducted using a 3T Siemens Prisma Fit MRI scanner. A 5-minute rs-fMRI scan (TR = 928 ms, TE = 31 ms, flip angle = 60°, FOV = 225 mm, voxel size = 2.5 mm³) and a T1-weighted MPRAGE sequence were acquired. Data were organized using the BIDS framework, visually inspected for artifacts, and preprocessed with fMRIPrep. CVR maps were generated by smoothing (FWHM = 8 mm) and domain-filtering (0–0.1164 Hz) the BOLD signal, which was then included as a regressor in a general linear model. CVR index maps were normalized to the whole-brain average to obtain relative CVR maps (Figure1; Potvin-Jutras, 2024). Brain-wide voxel-wise t-contrasts between groups were computed in SPM with family-wise error correction (FEW: p<0.001).
Results:
Preliminary analyses revealed significant group differences in CVR. FEP participants exhibited decreased CVR in a parietal lobe cluster compared to controls (P < 0.001, FWE corrected), with a trend-level increase observed in the prefrontal cortex.
Conclusions:
Our findings support the feasibility of deriving relative CVR maps from rs-fMRI data in psychiatric populations. This non-invasive, cost-effective approach leverages existing rs-fMRI datasets, potentially expanding the research and clinical utility of CVR mapping. The observed regional CVR alterations align with prior reports of hemodynamic dysfunction in psychosis and suggest a vascular contribution to brain pathophysiology. Future analyses should explore associations with clinical variables and validate findings against inhalation-based CVR measures. CVR holds promise as a novel biomarker for understanding the pathophysiology of psychosis and its vascular underpinnings.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Physiology, Metabolism and Neurotransmission:
Cerebral Metabolism and Hemodynamics 1
Keywords:
Cerebral Blood Flow
FUNCTIONAL MRI
Other - cerebrovascular reactivity; psychosis
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Was this research conducted in the United States?
Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.
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Provide references using APA citation style.
Liu, P. (2019). Cerebrovascular reactivity (CVR) MRI with CO2 challenge: A technical review. NeuroImage, 187, 104-115.
Percie du Sert, O. (2023). Cerebral blood flow in schizophrenia: A systematic review and meta-analysis of MRI-based studies. Progress in Neuropsychopharmacoly & Biological Psychiatry, 121, 110669.
Potvin-Jutras, Z. (2024). Sex-specific effects of intensity and dose of physical activity on BOLD-fMRI cerebrovascular reactivity and cerebral pulsatility. Cold Spring Harbor Laboratory. Biorxiv preprint.
Urback, A. L. (2017). Cerebrovascular reactivity measured by functional magnetic resonance imaging during breath-hold challenge: A systematic review. Neuroscience & Biobehavioral Reviews, 79, 27-47.