Acute‐stage MRI cerebral oxygen consumption biomarkers predict 24‐hour neurological outcome in a rat cardiac arrest model

Abstract

Brain injury following cardiac arrest (CA) is thought to be caused by a sudden loss of blood flow resulting in disruption in oxygen delivery, neural function and metabolism. However, temporal trajectories of the brain's physiology in the first few hours following CA have not been fully characterized. Furthermore, the extent to which these early measures can predict future neurological outcomes has not been determined. The present study sought to perform dynamic measurements of cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2) with MRI in the first 3 hours following the return of spontaneous circulation (ROSC) in a rat CA model. It was found that CBF, OEF and CMRO 2 all revealed a time-dependent increase during the first 3 hours after the ROSC. Furthermore, the temporal trajectories of CBF and CMRO 2 , but not OEF, were different across rats and related to neurologic outcomes at a later time (24 hours after the ROSC) (P < .001). Rats who manifested better outcomes revealed faster increases in CBF and CMRO 2 during the acute stage. When investigating physiological parameters measured at a single time point, CBF (ρ = 0.82, P = .004) and CMRO 2 (ρ = 0.80, P = .006) measured at $ 3 hours post-ROSC were positively associated with neurologic outcome scores at 24 hours. These findings shed light on brain physiological changes following CA, and suggest that MRI measures of brain perfusion and metabolism may provide a potential biomarker to guide post-CA management. K E Y W O R D S cardiac arrest, cerebral blood flow, cerebral metabolic rate of oxygen, MRI, neurologic deficit score, oxygen consumption, phase contrast, TRUST 1 | INTRODUCTION Cardiac arrest (CA) carries a low survival rate ($10%) and unfavorable outcomes. 1,2 Poor functional outcomes and mortality in CA are primarily driven by brain injury that occurs from a sudden loss of blood supply to the brain. The lack of blood flow leads to rapid changes in intracellular and extracellular ion concentrations with the development of intracellular acidosis. Furthermore, the failure of maintaining ionic balance results in membrane disruption, irreversible neuronal injury and, eventually, cell death. 3 As a critical management strategy for CA, effective cardiopulmonary

Cerebral oxygen extraction fractionMRI: Techniques and applications

“…The two modalities also revealed a correlation (intraclass correlation coefficient = 0.90) in OEF measures 41 . In addition to human studies, TRUST has also been implemented on animal MR imaging systems for OEF assessment in mice and rats 50–53 …”

“…41 In addition to human studies, TRUST has also been implemented on animal MR imaging systems for OEF assessment in mice and rats. [50][51][52][53] Other interesting technical work on global T 2 assessment includes the use of high-spatial-resolution echo-planar or turbo-field-echo acquisition to obtain pure blood voxels, 54,55 the combination of a T 2 -preparation sequence with inversion recovery to simultaneously measure blood T 1 , 56,57 and the integration of flow measurement in the sequence to allow CMRO 2 measurement from a single sequence. 58 While global OEF estimation has the obvious limitation of a lack of spatial information, these techniques tend to have a high reproducibility with a short scan duration, which makes them easy to incorporate into the workflow of clinical or research imaging.…”

Hyperacute autonomic and cortical function recovery following cardiac arrest resuscitation in a rodent model

“…Ten adult Wistar male rats (400–450 g; 11–12 weeks old; Charles River, Wilmington, MA) were subjected to 7‐min ACA. Our prior study disclosed that a minimum of five rats (male) per group was adequate to detect the difference in brain injury induced by our ACA model 25,27 . All animals were pair‐housed in a quiet environment with 12‐h day/night cycles and free access to food and water.…”

Brain metabolism in tau and amyloid mouse models of Alzheimer's disease: An MRI study

“…The arterial oxygenation (Y a ) is generally characterized by a narrow dynamic range and is close to unity (assumed to be 0.99) 26,27 . Global venous oxygenation (Y v ) was assessed by a TRUST MRI technique, which was first developed on human scanners, 28,29 and was recently optimized and utilized on animal MRI systems 30–32 . Specifically, an axial time‐of‐flight (TOF) sequence was first performed to visualize the confluence of sagittal sinuses, with the following parameters: TR/TE = 20/2.6 ms, field of view (FOV) = 16 × 16 mm 2 , matrix size = 256 × 256, 35 axial slices, slice thickness = 0.5 mm, and scan duration = 2.2 min.…”