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Reduced Blood Flow and Preserved Vasoreactivity Characterize Oxygen Hypometabolism Due to Incomplete Infarction in Occlusive Carotid Artery Diseases

¹ Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan
² Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
³ Department of Tracer Kinetics, Hokkaido University Graduate School of Medicine, Sapporo, Japan

Recent studies have clarified that hemodynamically compromised patients are at high risk for subsequent stroke. The acetazolamide test is widely used to detect the patients with hemodynamic compromise due to occlusive carotid artery disease. Previous studies have suggested that patients with impaired reactivity to acetazolamide had an increased oxygen extraction fraction (OEF) on PET. However, the underlying pathophysiology has not been defined in patients with reduced blood flow and preserved reactivity to acetazolamide due to carotid occlusive diseases regardless of a normal appearance on MRI. This study aimed to clarify hemodynamic and metabolic parameters in such patients, using ¹⁵O gas and ¹¹C-flumazenil (FMZ) PET. Methods: Our study included 15 patients who had reduced cerebral blood flow (CBF) and preserved cerebrovascular reactivity (CVR) to acetazolamide in the ipsilateral middle cerebral artery territory due to occlusive carotid diseases on N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP) SPECT. We determined the CBF, cerebral metabolic rate for oxygen (CMRO₂), cerebral blood volume (CBV), and OEF using ¹⁵O gas PET. The binding potential for ¹¹C-FMZ was also measured in 5 patients. All patients were medically treated and followed-up during a mean period of 2.7 y. Results: ¹⁵O gas PET scans revealed that the ipsilateral CBF and CMRO₂ were reduced to 80% ± 11% (P < 0.0001) and 78% ± 8% (P < 0.0001) of the contralateral side, respectively. However, there was no significant side-to-side difference in the CBV and OEF. The ipsilateral binding potential for ¹¹C-FMZ was also significantly reduced to 82% ± 2% of the contralateral side (P < 0.05), being very similar to the asymmetry of the CBF and CMRO₂. No patients suffered further ischemic stroke in the ipsilateral hemisphere during the follow-up period. Conclusion: Our results strongly suggest that a reduced CBF and a normal CVR characterize oxygen hypometabolism probably due to ischemia-related neuronal loss—namely, incomplete infarction. Such an ischemic lesion is not hemodynamically compromised and is at very low risk for a subsequent ischemic stroke even if the patient is medically treated.

Key Words: acetazolamide • incomplete infarction • oxygen metabolism • PET • cerebral ischemia

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