ABSTRACT
PET hypoxia imaging can assess tissue viability in acute ischemic stroke (AIS). [18F]FMISO is an established tracer but requires substantial accumulation time, limiting its use in hyperacute AIS. [64Cu]CuATSM requires less accumulation time and has shown promise as a hypoxia tracer. We compared these tracers in a M2-occlusion model (M2CAO) with preserved collateral blood flow. Rats underwent M2CAO and [18F]FMISO (n = 12) or [64Cu]CuATSM (n = 6) examinations. [64Cu]CuATSM animals were also examined with MRI. Pimonidazole was used as a surrogate for [18F]FMISO in an immunofluorescence analysis employed to profile levels of hypoxia in neurons (NeuN) and astrocytes (GFAP). There was increased [18F]FMISO uptake in the M2CAO cortex. No increase in [64Cu]CuATSM activity was found. The pimonidazole intensity of neurons and astrocytes was increased in hypoxic regions. The pimonidazole intensity ratio was higher in neurons than in astrocytes. In the majority of animals, immunofluorescence revealed a loss of astrocytes within the core of regions with increased pimonidazole uptake. We conclude that [18F]FMISO is superior to [64Cu]CuATSM in detecting hypoxia in AIS, consistent with an earlier study. [18F]FMISO may provide efficient diagnostic imaging beyond the hyperacute phase. Results do not provide encouragement for the use of [64Cu]CuATSM in experimental AIS.
Subject(s)
Brain Ischemia/pathology , Misonidazole/analogs & derivatives , Organometallic Compounds/chemistry , Radiopharmaceuticals/chemistry , Thiosemicarbazones/chemistry , Animals , Astrocytes/chemistry , Astrocytes/metabolism , Autoradiography , Brain/diagnostic imaging , Brain Ischemia/metabolism , Cerebellar Cortex/chemistry , Cerebellar Cortex/diagnostic imaging , Cerebellar Cortex/pathology , Coordination Complexes , Copper Radioisotopes/chemistry , Disease Models, Animal , Fluorine Radioisotopes/chemistry , Hypoxia , Male , Misonidazole/chemical synthesis , Misonidazole/chemistry , Neurons/chemistry , Neurons/metabolism , Organometallic Compounds/chemical synthesis , Positron-Emission Tomography , Radiopharmaceuticals/chemical synthesis , Rats , Rats, Sprague-Dawley , Thiosemicarbazones/chemical synthesisABSTRACT
The penumbra is sustained by an increased extraction of oxygen (OEF) from blood to brain tissue. Metabolic imaging may improve penumbra specificity when examining stroke patients with wake-up stroke and a long time between admission and symptom onset. We used MRI to examine OEF, and compared the volume of regions with elevated OEF to the volume of regions with perfusion deficit in a M2 occlusion model (M2CAO) with preserved collateral blood flow. OEF was calculated from BOLD MRI examining tissue R2', with ASL perfusion imaging employed to determine cerebral blood flows (CBF) and volumes. Diffusion imaging was used to identify the ischemic core (IC). Examinations were performed during and after transient M2CAO in rats. The IC-OEF mismatch was significantly smaller than the IC-CBF mismatch during M2CAO. The penumbra OEF was significantly increased during M2CAO, and decreased significantly after reperfusion. The IC-OEF mismatch may provide increased penumbra specificity compared to IC-CBF mismatch regimens. Results strongly indicate the potential of metabolic MRI for thrombectomy patient selection in cases with a long time from symptom onset to admission. Results demonstrate the effectiveness of reperfusion in alleviating metabolic disturbances in ischemic regions, emphasizing fast treatment to achieve significant neurological recovery in stroke patients.
