ABSTRACT
OBJECTIVES: This work aimed to refine a large animal in minimally invasive reversible middle cerebral artery (MCA) occlusion (MCAO) model to account for leptomeningeal collateral formation. MATERIALS AND METHODS: An angiographically based methodology allowed for transient MCA and carotid terminus occlusion in 12 mongrel dogs and assessment of pial collateral recruitment. Outcome measures included 1- and 24-hour magnetic resonance imaging-based infarct volume calculation, a behavioral scale and histopathologic sections. RESULTS: MCAO succeeded in 8 of 12 dogs (67% efficiency). One-hour postreperfusion infarct volume predicted 24-hour postreperfusion infarct volume (r = 0.997, P < 0.0001). Pial collateral recruitment varied with time and reproducibly assessed predicted infarct volume on 1-hour postreperfusion mean diffusivity maps (P < 0.0001; r = 0.946) and 24-hour fluid-attenuated inversion recovery FLAIR magnetic resonance imaging (P = 0.0033; r = 0.961). The canine stroke scale score correlated with infarct volumes and pial collateral score. CONCLUSION: This canine MCAO model produces defined cerebral infarct lesions whose volumes correlate with leptomeningeal collateral formation and canine behavior.
Subject(s)
Brain Ischemia/diagnosis , Carotid Arteries/pathology , Infarction, Middle Cerebral Artery/diagnosis , Middle Cerebral Artery/pathology , Angiography , Animals , Anticoagulants/therapeutic use , Brain Ischemia/pathology , Brain Ischemia/therapy , Clopidogrel , Disease Models, Animal , Dogs , Feasibility Studies , Heparin/therapeutic use , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/therapy , Multivariate Analysis , Platelet Aggregation Inhibitors/therapeutic use , Statistics as Topic , Ticlopidine/analogs & derivatives , Ticlopidine/therapeutic useABSTRACT
OBJECTIVES: This study assessed whether ultra-small particles of iron oxide (USPIO) intravascular contrast agent could enhance visualization of tumor microvascularity in F98 glioma bearing rats by means of ultra high field (UHF) high-resolution gradient echo (GRE) magnetic resonance imaging (MRI). In an effort to explain differences in visualization of microvascularity before and after USPIO administration, hypoxia and vessel diameters were assessed on corresponding histopathologic sections. MATERIALS AND METHODS: F98 glioma cells were implanted stereotactically into the brains of syngeneic Fischer rats. Based on clinical criteria, rats were imaged 1 to 2 days before their death with and without USPIO contrast on an 8 Tesla MRI. To identify hypoxic regions of the brain tumor by immunohistochemical staining, a subset of animals also received a nitroimidazole-based hypoxia marker, EF5, before euthanasia. These sections then were compared with noncontrast enhanced MR images. The relative caliber of tumor microvasculature, compared with that of normal brain, was analyzed in a third group of animals. RESULTS: After USPIO administration, UHF high-resolution GRE MRI consistently predicted increased microvascular density relative to normal gray matter when correlated with histopathology. The in-plane visibility of glioma microvascularity in 22 rats increased by an average of 115% and signal intensity within the tumor decreased by 13% relative to normal brain. Tumor microvascularity identified on noncontrast MR images matched hypoxic regions identified by immunohistochemical staining with a sensitivity of 83% and specificity of 89%. UHF GRE MRI was able to resolve microvessels less than 20 micro in diameter, although differences in tumor vessel size did not consistently account for differences in visualization of microvascularity. CONCLUSIONS: USPIO administration significantly enhanced visualization of tumor microvascularity on gradient echo 8 T MRI and significantly improved visualization of tumor microvascularity. Microvascularity identified on precontrast images is suspected to be partly associated with hypoxia.
