Hyperoxia-Induced ΔR(1): MRI Biomarker of Histological Infarction in Acute Cerebral Stroke

OBJECTIVE: To evaluate whether hyperoxia-induced ΔR(1) (hyperO(2)ΔR(1)) can accurately identify histological infarction in an acute cerebral stroke model. MATERIALS AND METHODS: In 18 rats, MRI parameters, including hyperO(2)ΔR(1), apparent diffusion coefficient (ADC), cerebral blood flow and volume, and (18)F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and non-ischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO(2)ΔR(1) and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO(2)ΔR(1)-derived infarction and histological cell death was evaluated. RESULTS: HyperO(2)ΔR(1) increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO(2)ΔR(1) sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO(2)ΔR(1) value of 0.04 s(-1) was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO(2)ΔR(1) higher than 0.04 s(-1) on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). CONCLUSION: HyperO(2)ΔR(1) may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.