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Evaluation of Delayed Appearance of Acetazolamide Effect in Patients with Chronic Cerebrovascular Ischemic Disease: Feasibility and Usefulness of SPECT Method Using Triple Injection of ECD

¹ Department of Neurosurgery, Cerebrovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan
² Department of Neurology, Cerebrovascular Center, Saiseikai Kumamoto Hospital, Kumamoto, Japan
³ Market Planning Department, Clinical Application Technology Group, Daiichi Radioisotope Laboratories Ltd., Tokyo, Japan
⁴ Department of Neurology, Kumamoto University School of Medicine, Kumamoto, Japan
⁵ Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan

The purpose of this study was to verify the feasibility and usefulness of a new SPECT method, called triple injection of ^99mTc-ethylcysteinate dimer (TIE), in evaluation of the delayed or poor appearance of acetazolamide (ACZ) effects in patients with chronic cerebral ischemic disease. Methods: Three equal-volume splits of ^99mTc-ethylcysteinate dimer were intravenously administered, and 1,000 mg ACZ were used as a vasodilator. A middle cerebral artery territory in the lateral ventricle was used as a region of interest. The data at rest and at 7.5 and 20 min after ACZ challenge (ACZ 7.5 and ACZ 20, respectively) were obtained by dynamic SPECT, and a time response curve to ACZ was obtained through the relative ratio of regional counts to the data at rest, not through regional cerebral blood flow. Nine cases of complete occlusion of the internal carotid artery (IC) and 6 cases of severe IC stenosis were analyzed. Results: In 12 healthy volunteers (24 cerebral hemispheres) using a placebo (negative control), the values at rest and at rest 7.5 and rest 20 (corresponding to ACZ 7.5 and ACZ 20, respectively) were 100%, 100.4% ± 2.8%, and 99.6% ± 3.6%, respectively, indicating the accuracy of the TIE method. In a positive control using 24 normal cerebral hemispheres, prompt maximal vasoreactivity at ACZ 7.5 (124.5% ± 8.0%) was confirmed, as was continuous vasoreactivity until ACZ 20 (130.1% ± 12.8%). The values between ACZ 7.5 and ACZ 20 were not statistically different. Patients with complete IC occlusion exhibited a poor response at ACZ 7.5 despite a normal response at ACZ 20 (delayed response). Furthermore, in patients with severe IC stenosis, restoration of cerebrovascular reactivity after carotid endarterectomy was confirmed not only at ACZ 20 but also at ACZ 7.5. Conclusion: The TIE method using SPECT may be a potentially useful and sensitive strategy in clinical evaluation of the delayed or poor appearance of ACZ effects in patients with chronic cerebrovascular ischemic disease.

Key Words: acetazolamide • ^99mTc-ECD • triple-injection protocol • cerebral perfusion reserve • internal carotid artery