Temporal Evolution of Average Apparent Diffusion Coefficient Threshold to Define Ischemic Abnormalities in a Rat Permanent Occlusion Model Fuhai Li, MD, Richard A. D. Carano, PhD, Katsumi Irie, MD, Christopher H. Sotak, PhD, and Marc Fisher, MD We examined average apparent diffusion coefficient (ADC~v) thresholds to define ischemic lesion size and characterized the temporal evolution of the ADC~v thresh- olds. Thirteen Sprague-Dawley rats underwent permanent middle cerebral artery occlusion in the magnetic resonance imaging unit. Diffusion-weighted imaging was acquired before occlusion and 25, 60, 90, 150, 210, and 270 minutes after occlusion. Absolute ADCav values from 0.46 to 0.62 • 10 3 mm2/s and the percentage of the decline of ADC.,v values from -32% to -16% compared with the baseline values were used to define the percentage of hemispheric lesion volume (%HLV) at each time point. Twenty-four hours after occlusion, the rats were killed, and 2,3,5- triphenyltetrazolium chloride (TTC) staining was used to calculate the percentage of hemispheric infarction volume (%HIV), which was then used as the "gold standard" to determine ADCav thresholds. The ADCa,.-derived %HLV was identical to and best correlated with the TTC-derived %HIV when the absolute ADC~,, threshold was 0.62, 0.60, 0.54, 0.52, 0.50, and 0.50 • 10 3 mm2/s and the percentage of ADCa,. threshold was 16%, -18%, -24%, -28%, -30%, and -30% at 25, 60, 90, 150, 210, and 270 minutes after occlusion, respectively. Our results suggest that both the absolute values and the percentage of ADCav thresholds can define the final lesion volume as early as 25 minutes and that these thresholds decrease over time and become constant 210 minutes after occlusion throughout the observation period. Key Words: Apparent diffusion coefficient--Experimental stroke--Ischemic lesion volume--Magnetic resonance imaging--Middle cerebral artery occlusion--Rats. Diffusion-weighted magnetic resonance imaging (DWI) can detect abnormalities within minutes after the onset of focal brain ischemia, 1,2 and the ischemic changes can be quantitatively evaluated by using apparent diffusion coefficient (ADC) maps. 3 Furthermore, ADC maps can From the Departments of Neurologyand Radiology,UMassMemo- rial Health Care and University of Massachusetts Medical School, Worcester, MA; and the Departments of BiomedicalEngineeringand Chemistry & Biochemistry,Worcester PolytechnicInstitute, Worces- ter, MA. Received March 22, 1999;accepted August 14,1999. Address reprint requests to Fuhai Li, MD, Department of NeuroL ogy, UMass Memorial Health Care, 119 Belmont St, Worcester, MA 01605. Copyright 9 2000by National Stroke Association 1052-3057/00/0901-000153.00/0 monitor the rapid spatial expansion of the ischemic lesion,4 providing the potential to define the ultimate extent of the ischemic lesion at early-time points after ischemia. Previously, ADC thresholds were chosen to evaluate the volume of the ischemic lesion.3-s A single ADC threshold, however, may not accurately evaluate ischemic abnormalities because the ADC values in the ischemic regions vary over time. Furthermore, ADC values acquired along only i of the 3 axes (x, y, or z) may not accurately delineate the volume of the ischemic lesion because of the anisotropy of water diffusion.6,7 A recent study has shown that the average ADC (ADCav), which is obtained from all 3 orthogonal planes, is a better indicator of the extent of ischemic injury. 8 Little is known, however, about the temporal evolution of ADCav thresholds to define the final extent of the ischemic lesion. We hypoth- Journal of Stroke and Cerebrovascular Diseases, Vol. 9, No. 1 (January-February), 2000: pp 1-7 1