High-resolution relaxometry-based calibrated fMRI in murine brain: Metabolic differences between awake and anesthetized states

Abstract

Functional magnetic resonance imaging (fMRI) techniques using the blood-oxygen level-dependent (BOLD) signal have shown great potential as clinical biomarkers of disease. Thus, using these techniques in preclinical rodent models is an urgent need. Calibrated fMRI is a promising technique that can provide high-resolution mapping of cerebral oxygen metabolism (CMRO2). However, calibrated fMRI is difficult to use in rodent models for several reasons: rodents are anesthetized, stimulation-induced changes are small, and gas challenges induce noisy CMRO2 predictions. We used, in mice, a relaxometry-based calibrated fMRI method which uses cerebral blood flow (CBF) and the BOLD-sensitive magnetic relaxation component, R2′, the same parameter derived in the deoxyhemoglobin-dilution model of calibrated fMRI. This method does not use any gas challenges, which we tested on mice in both awake and anesthetized states. As anesthesia induces a whole-brain change, our protocol allowed us to overcome the former limitations of rodent studies using calibrated fMRI. We revealed 1.5-2 times higher CMRO2, dependent upon brain region, in the awake state versus the anesthetized state. Our results agree with alternative measurements of whole-brain CMRO2 in the same mice and previous human anesthesia studies. The use of calibrated fMRI in rodents has much potential for preclinical fMRI.

Mapping oxidative metabolism in the human brain with calibrated fMRI in health and disease

“…The use of R 2 ′ mapping for estimating CMR O2 has been demonstrated in rat, mouse, and human brain calibrated fMRI studies. 41,117–120…”

Aerobic glycolysis imaging of epileptic foci during the inter-ictal period

“… 14 , and Xu et al. 11 which we have used previously to calculate CMR O2 in mice. 11 A summary of the theory is repeated in Supplementary Methods.…”

“… 11 which we have used previously to calculate CMR O2 in mice. 11 A summary of the theory is repeated in Supplementary Methods. The difference between relaxation rates R 2 * (or 1/T 2 *) and R 2 (or 1/T 2 ) is characterised by R 2 ' ( Eq.…”

“…Rather than the blood-oxygen level dependent (BOLD) signal measured by traditional fMRI, calibrated fMRI methods measure CMR O2 through a biophysical model for BOLD signal. While many calibrated fMRI methods require administering CO 2 , we used a method that was recently developed in rodents 11 that uses relaxometry instead of gas exposure. 10 , 12 , 13 , 14 As modern PET-MRI scanners allow simultaneous recording of both modalities, calibrated fMRI can be combined with FDG-PET to measure both oxygen and glucose and achieve OGI measurement in a single session.…”

Review on the Application of Hyperspectral Imaging Technology of the Exposed Cortex in Cerebral Surgery

“…Thanks to the invention of non-invasive imaging of the human brain, our understanding of the relationship between the brain and behaviors has undergone a major shift. Nowadays, a variety of imaging modalities are employed as guidance tools during the neurosurgeries e.g., computed tomography (CT) ( Paty et al, 1988 ; Hövels et al, 2008 ), magnetic resonance imaging (MRI) ( Dewenter et al, 2021 ; Xu et al, 2021 ) and fluorescent tumor markers (FTM) ( Ferraro et al, 2016 ). Nevertheless, these methods have some limitations.…”