Hypoxic Viable Tissue in Human Chronic Cerebral Ischemia Because of Unilateral Major Cerebral Artery Steno-Occlusive Disease

Abstract

Background and Purpose— 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. Methods— 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. Results— 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). Conclusions— 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.

Reduced Hypoxic Tissue and Cognitive Improvement after Revascularization Surgery for Chronic Cerebral Ischemia

“…18 F-FRP170 was synthesized using on-column alkaline hydrolysis according to previously described methods [6,12]. The final formulation for injection was prepared in normal saline containing 2.5% v/v ethanol using solidphase extraction techniques.…”

“…The final formulation for injection was prepared in normal saline containing 2.5% v/v ethanol using solidphase extraction techniques. Sixty minutes after an intravenous injection of approximately 370 MBq 18 F-FRP170, data were collected for 10 min [6,13].…”

“…Restoration of perfusion may lead to improvement in cerebral metabolism, resulting in cognitive improvement [4,5]. These findings suggest that functionally impaired but structurally intact tissue may exist in areas of chronic cerebral ischemia with reduced cerebral metabolism and that such tissue may be viable in hypoxic conditions [6].…”

“…A recent study using positron emission tomography (PET) with 15 O-gas and a new radiolabeled compound, 2-nitroimidazole, 1-(2-18 F-fluoro-1-[hydroxymethyl] ethoxy) methyl-2-nitroimidazole ( 18 F-FRP170), demonstrated that tissues with abnormally elevated uptake of 18 F-FRP170, a direct marker of hypoxic but viable tissue, are present in patients with chronic cerebral ischemia with a combination of misery perfusion and moderately reduced oxygen metabolism due to major cerebral artery steno-occlusive disease [6]. One hypothesis is that oxygen metabolism may decrease in the late stages of misery perfusion due to chronic cerebral ischemia, leading to hypoxia in that cerebral region [6].…”

“…One hypothesis is that oxygen metabolism may decrease in the late stages of misery perfusion due to chronic cerebral ischemia, leading to hypoxia in that cerebral region [6]. Several questions follow from this idea [6]. When cerebral perfusion is restored after revascularization surgery, does the hypoxic tissue remain?…”