고산소 유도 하 R1의 변화: 급성 뇌졸중에서 비가역적 뇌 손상의 자기공명영상 바이오마커

Abstract

Purpose: Accurate and reliable measurement of irreversibly damaged area is an important diagnostic task in acute stroke, particularly for helping development of neuroprotective treatment. This study was performed to validate hyperoxia-induced ΔR1 (hyperO2ΔR1) as a useful imaging biomarker for identifying irreversible ischemic damage in stroke. Materials and Methods: In cross-sectional experiment (12 rats, transient occlusion of middle-cerebral artery), hyperO2ΔR1, apparent diffusion coefficient (ADC), 18F-fluorodeoxyglucose uptake on positron emission tomography, cerebral blood flow and cerebral blood volumes were measured 2.5, 4.5, and 6.5 hours after stroke initiation. They were compared among infarct area, non-infarct ischemia and non-ischemic area on the criteria of histology and ADC. The levels of hyperO2ΔR1 and ADC were voxel-wisely measured from the infarct core to the non-ischemic area. In longitudinal experiment (n=9), time-dependent changes of hyperO2ΔR1 and ADC were analyzed at 3, 6, and 24 hours after initiation of transient stroke. Results: In cross sectional study, hyperO2ΔR1 increased exclusively in infarct area at all time points. In contrast, ADC gradually decreased from non-ischemic to infarct areas, and the other parameters did not show consistent patterns. HyperO2ΔR1 showed a sharp decline from the core to the border of infarct areas and a plateaued level in non-infarct areas. Most voxels in infarct area showed hyperO2ΔR1 > 0.04 s-1. There was no noticeable difference of ADC at the border between infarct and non-infarct areas. In longitudinal study, hyperO2ΔR1 was not reverted to normal level once having gone higher than 0.04 s-1, and the area with hyperO2ΔR1 higher than 0.04 s-1 continuously increased over time. ADC in infarct area showed inconsistent temporal changes in each rat. Conclusion: HyperO2ΔR1 can be used as an accurate and reliable biomarker for identifying irreversible ischemic damage in stroke.