Temporal evolution of cerebral metabolic rate of oxygen utilization using MRI in a middle cerebral artery occlusion stroke

Abstract

The balance between cerebral blood flow (CBF) and oxygen extraction fraction (OEF) is important in determining the status of tissue viability during acute cerebral ischemia 1, 2. After ischemic onset, CBF decreases, accompanied by an increase in OEF in order to maintain cerebral oxygen cerebral metabolic rate of oxygen utilization (CMRO2). A persisted or further reduced CBF results in a decline of CMRO2, leading to neural cell death. In this study, a T2* (T2') approach 3 and a dynamic tracer method 4 are used to obtain OEF and CBF, respectively, which in turn allows the estimates of MR_CMRO2, in a middle cerebral artery occlusion (MCAO) rat model. The temporal evolution of cerebral haemodynamic changes is examined. In total, three male Long Evans rats were studied. Cerebral ischemia was induced using the suture model inside the magnet bore with approved animal protocols. All images were acquired on a Siemens 3 T Allegra scanner. A 2D multi-echo gradient echo/spin echo sequence (MEGESE) was utilized to obtain OEF 3. Apparent diffusion coefficient (ADC) maps was obtained from segmented EPI diffusion weighted images (DWI). MEGESE and DWI images were acquired prior to MCAO and continued up to three hours post MCAO. A tracer dynamic perfusion weighted imaging (PWI) was utilized to obtain CBF at the end of the entire study so as to avoid the contamination of contrast agent induced susceptibility for the oxygenation measurements. CBF is assumed to remain constant throughout the entire post MCAO period in a permanent MCAO. MR_CMRO2 was calculated by multiplying OEF and CBF. ROIs were defined in both ipsilateral and contralateral hemisphere to obtain ADC, OEF, CBF and CMRO2 changes. Before MCA occlusion, ADC, OEF were not statistically different in the ipsilateral and contralateral hemisphere ROIs. Immediately after MCAO, ADC reduced, while OEF increased. As lesion progressed, the initially elevated OEF returned to or below the baseline, while the ADC might have little change. In addition, CMRO2 showed a moderate decrease to 30–55% followed by a severe reduction to 9–20% of that of normal tissue. The time period of moderate reduction of CMRO2 depends on the severity of CBF. In one rat, a 14% of CBF reduction corresponded to a 40 minutes moderate CMRO2 reduction followed by severe CMRO2 reduction. In another rat, a 21% CBF reduction allows a moderate CMRO2 reduction for about 90 minutes. With a MCAO rat model, our results demonstrate the temporal biphasic behavior of OEF with an initial increase and followed by a returning baseline values. In addition, the temporal evolution of CMRO2 agree with the reported results in the literature using PET 5. In conclusion, non-invasive methods to assess cerebral oxygenation status in vivo may provide us more insight into the ischemic tissue viability.