1. ^*Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical Center, Worcester, Massachusetts, U.S.A.
2. ^†Center for Comparative NeuroImaging, Department of Neurology, University of Massachusetts Medical Center, Worcester, Massachusetts, U.S.A.
3. ^#Programs in Neuroscience, Biomedical Engineering & Medical Physics, University of Massachusetts Medical Center, Worcester, Massachusetts, U.S.A.
4. ^‡Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts, U.S.A.

Correspondence: Timothy Q Duong, Center for Comparative NeuroImaging, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, MA 01655, U.S.A.; e-mail: timothy.duong@umassmed.edu

Received 26 June 2003; Revised 19 September 2003; Accepted 23 September 2003.

Abstract

Pixel-by-pixel spatiotemporal progression of focal ischemia (permanent occlusion) in rats was investigated using quantitative perfusion and diffusion magnetic resonance imaging every 30 minutes for 3 hours. The normal left-hemisphere apparent diffusion coefficient (ADC) was 0.76 0.03 10^-3 mm²/s and CBF was 0.7 0.3 mL g^-1 min^-1 (mean SD, n=5). The ADC and CBF viability thresholds yielding the lesion volumes (LV) at 3 hours that best approximated the 2,3,5-triphenyltetrazolium chloride (TTC) infarct volumes (200 30 mm³) at 24 hours were 0.53 0.02 10^-3 mm²/s (30% 2% reduction) and 0.30 0.09 mL g^-1 min^-1 (57% 11% reduction), respectively. Temporal evolution of the ADC- and CBF-defined LV showed a significant "perfusion-diffusion mismatch" up to 2 hours (P < 0.05, n = 11), a potential therapeutic window. Based on the viability thresholds, three pixel clusters were identified on the CBF-ADC scatterplots: (1) a "normal" cluster with normal CBF and ADC, (2) an "ischemic core" cluster with markedly reduced CBF and ADC, and (3) a "mismatch" cluster with reduced CBF but slightly reduced ADC. These clusters were color-coded and mapped onto the image and CBF-ADC spaces. Lesions grew peripheral and medial to the initial ADC abnormality. In contrast to the CBF distribution, the ADC distribution in the ischemic hemisphere was bimodal; the relatively time-invariant bimodal-ADC minima were 0.57 0.02 10^-3 mm²/s (corresponding CBF 0.35 0.04 mL g^-1 min^-1), surprisingly similar to the TTC-derived thresholds. Together, these results illustrate an analysis approach to systemically track the pixel-by-pixel spatiotemporal progression of acute ischemic brain injury.