Calcium 45 autoradiography and dual-isotope single-photon emission CT in a canine model of cerebral ischemia and middle cerebral artery occlusion

PURPOSE: To determine whether transient ischemia can be separated from permanent ischemia via calcium 45 autoradiography and to assess the applicability of dual isotope single-photon emission CT (SPECT) in the evaluation of cerebral blood flow. METHODS: We examined calcium influx in 12 dogs (group A) by using whole-brain calcium 45 autoradiography: Animals received 250 μCi/kg 24 hours after 30-minute (n = 6) or permanent (n = 6) middle cerebral artery (MCA) occlusion. Forty-eight hours after MCA occlusion, 5-mm coronal brain sections were fixed for either autoradiography or pathologic examination. In a separate study, 9 mongrel dogs (group B) were given 250 μCi/kg calcium 45 and a mean dose of 700 μCi/kg technetium Tc 99m hexamethyl-propyleneamine oxime intravenously. A silicone plug was then injected into the internal carotid artery and angiography was performed to verify MCA occlusion. A 10th (control) animal did not undergo occlusion. In an 11th animal, placement of the plug could not be achieved and a slurry of microfibrillar collagen was injected into the carotid artery. No angiography was performed in animals 10 and 11. After occlusion, each animal was injected with a mean dose of 126 μCi/kg ¹²³I-iodoamphetamine. The control animal was also injected. SPECT was performed using a simultaneous acquisition for technetium 99m and ¹²³I-iodoamphetamine. RESULTS: In group A, all animals who had permanent MCA occlusion showed infarction and increased calcium 45 uptake in infarcted territories. None of the animals who had 30-minute occlusion had either increased calcium 45 uptake or infarction at 48 hours. In group B, 7 of 10 dogs had SPECT findings that were consistent with the calcium autoradiographic marker for ischemia. One animal died during the procedure and 1 dog served as a control. CONCLUSION: Calcium 45 autoradiography allowed distinction between areas of temporary and permanent occlusion. Iodoamphetamine imaging was not consistently sensitive to that level of ischemia. Timing of calcium influx may lead to insight that could impact timing of pharmacologic or endovascular intervention.