An in vivo, MRI-integrated real-time model of active contrast extravasation in acute intracerebral hemorrhage.
OBJECTIVE
The "spot sign" or contrast extravasation is strongly associated with hematoma formation and growth. An animal model of contrast extravasation is important to test existing and novel therapeutic interventions to inform present and future clinical studies. The purpose of this study was to create an animal model of contrast extravasation in acute intracerebral hemorrhage.


METHODS
Twenty-eight hemispheres of Yorkshire male swine were insonated with an MR imaging-guided focused sonography system following lipid microsphere infusion and mean arterial pressure elevation. The rate of contrast leakage was quantified by using dynamic contrast-enhanced MR imaging and was classified as contrast extravasation or postcontrast leakage by using postcontrast T1. Hematoma volume was measured on gradient recalled-echo MR imaging performed 2 hours postprocedure. Following this procedure, sacrificed brain was subjected to histopathologic examination. Power level, burst length, and blood pressure elevation were correlated with leakage rate, hematoma size, and vessel abnormality extent.


RESULTS
Median (intracerebral hemorrhage) contrast extravasation leakage was higher than postcontrast leakage (11.3; 6.3-23.2 versus 2.4; 1.1-3.1 mL/min/100 g; P<.001). Increasing burst length, gradient recalled-echo hematoma (ρ=0.54; 95% CI, 0.2-0.8; P=.007), and permeability were correlated (ρ=0.55; 95% CI, 0.1-0.8; P=.02). Median permeability (P=.02), gradient recalled-echo hematoma (P=.02), and dynamic contrast-enhanced volumes (P=.02) were greater at 1000 ms than at 10 ms. Within each burst-length subgroup, incremental contrast leakage was seen with mean arterial pressure elevation (ρ=0.2-0.8).


CONCLUSIONS
We describe a novel MR imaging-integrated real-time swine intracerebral hemorrhage model of acute hematoma growth and contrast extravasation.
From the Department of Medical Imaging (T.H., R.I.A., R.L.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Medical Imaging (T.H., K.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada Richard.aviv@sunnybrook.ca.
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Aviv
From the Department of Medical Imaging (T.H., R.I.A., R.L.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada Medical Imaging (T.H., K.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada.
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Huynh
Imaging Research (Y.H., K.H.), Sunnybrook Research Institute, Toronto, Ontario, Canada.
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Huang
Department of Pathology (D.R.), London Health Sciences Centre, London, Ontario, Canada.
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Ramsay
The Centre for Proteomic Studies (D.D., P.V.S.).
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Van Slyke
Departments of Medical Biophysics (K.H., D.D., R.A., P.A.) The Centre for Proteomic Studies (D.D., P.V.S.).
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Dumont
Departments of Medical Biophysics (K.H., D.D., R.A., P.A.).
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Asmah
Departments of Medical Biophysics (K.H., D.D., R.A., P.A.).
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Alkins
From the Department of Medical Imaging (T.H., R.I.A., R.L.), Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
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Liu
Departments of Medical Biophysics (K.H., D.D., R.A., P.A.) Medical Imaging (T.H., K.H., R.I.A.), University of Toronto, Toronto, Ontario, Canada Imaging Research (Y.H., K.H.), Sunnybrook Research Institute, Toronto, Ontario, Canada.
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Hynynen
D000818:Animals; D002533:Cerebral Angiography / Q000379:methods; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000209:etiology; D004195:Disease Models, Animal; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000175:diagnosis* / Q000209:etiology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D013552:Swine