Hypoxic viable tissue in human chronic cerebral ischemia because of unilateral major cerebral artery steno-occlusive disease.

Abstract

Positron emission tomography (PET) with radiolabeled 2-nitroimidazoles directly detects hypoxic but viable tissue present in an acute ischemic area in the human brain. This study using PET with 1-(2-(18)F-fluoro-1-[hydroxymethyl]ethoxy) methyl-2-nitroimidazole ((18)F-FRP170) aimed to determine whether tissue with an abnormally elevated uptake of (18)F-FRP170 exists in human chronic cerebral ischemia because of unilateral atherosclerotic major cerebral artery steno-occlusive disease. (18)F-FRP170 PET was performed, and cerebral blood flow and metabolism were assessed using (15)O-gas PET in 20 healthy subjects and 52 patients. A region of interest (ROI) was automatically placed in 3 segments of the middle cerebral artery territory in both cerebral hemispheres with a 3-dimensional stereotaxic ROI template using SPM2, and each PET value was determined in each ROI. The ratio of values in the affected versus contralateral hemispheres was calculated for the (18)F-FRP170 PET image. A significant correlation was observed between oxygen extraction fraction and (18)F-FRP170 ratios (ρ=0.509; P<0.0001) in a total of 156 ROIs in 52 patients. The specificity and positive-predictive value for a combination of an elevated oxygen extraction fraction and a moderately reduced cerebral oxygen metabolism for detection of an abnormally elevated (18)F-FRP170 ratio (19 ROIs: 12%) were significantly greater than those for the individual categories (elevated oxygen extraction fraction, moderately reduced cerebral oxygen metabolism, or reduced cerebral blood flow). Tissues with abnormally elevated uptake of (18)F-FRP170 exist in human chronic cerebral ischemia characterized by a combination of misery perfusion and moderately reduced oxygen metabolism because of unilateral atherosclerotic major cerebral artery steno-occlusive disease.