Serial Changes in CT Cerebral Blood Volume and Flow after 4 Hours of Middle Cerebral Occlusion in an Animal Model of Embolic Cerebral Ischemia
B.D. Murphya,b,c,
X. Chena,b and
T.-Y. Leea,b,c
a Robarts Research Institute, London, Ontario, Canada
b Lawson Health Research Institute, London, Ontario, Canada
c Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada
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Fig 1. Time attenuation curves from CT perfusion study of a rabbit showing enhancement (above baseline value) of various regions over the 99 sequential images acquired. Arterial and venous time-attenuation curves (A) and tissue time-attenuation curves (B) for 9-mm2 regions of interest in the ischemic hemisphere and contralateral hemisphere.
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Fig 2. Serial CBF and CBV images from select time points (minutes poststroke on left) for 2 contiguous CT perfusion sections from 1 animal. Corresponding TTC staining shows infarcted tissue (white) corresponding to areas of decreased CBF and CBV, whereas viable tissue is stained red. CBF and CBV images are colored according to a "rainbow" color scale with red and blue representing high and low values, respectively: CBF, 0–150 mL · 100 g–1 · min–1; CBV, 0–10 mL · 100 g–1.
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Fig 3. Average values of CBF (A) and CBV (B) in infarcted (n = 32) and oligemic (n = 45) regions of interest at different times after embolization; error bars show SD. For comparison, CBF and CBV of contralateral tissue are also shown (error bars not shown for clarity).
A, CBF is significantly lower than baseline at every time point after embolization in both oligemic and infarct regions. Contralateral CBF is not significantly different from baseline at any time point.
B, CBV in infarcted regions is significantly lower (P < .05) than baseline at 60 minutes after embolization and at every subsequent time point (*). CBV for oligemic regions was significantly higher than baseline values at 30, 90, 120, 150, and 180 minutes after embolization (#). No significant differences in CBV between oligemic and contralateral regions were found at any time point.
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Fig 4. Scatter plot of cerebral blood volume (CBV) versus cerebral blood flow (CBF) in oligemic and infracted tissue. Dashed line, CBFxCBV = 31.1, defines the threshold of infarction for the CBFxCBV model. Data points above the line are classified as oligemic, and points below the line are classified as infarct. When the predicted group membership is compared with the true group membership (defined on the TTC-stained tissue sections), the specificity and sensitivity of the model for infarction are 93.3% and 90.6%, respectively.
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Fig 5. Mismatch between CBF and CBV at 4 hours after embolization. The CBF and CBV maps display the corresponding functional values according to a "rainbow" color scale with red and blue representing high and low values, respectively (CBF, 0–150 mL · 100 g–1 · min–1; CBV, 0–10 mL · 100 g–1). CBF map (A) shows ischemic areas (dashed arrows) and CBV map (B) shows normal to increased blood volume in ischemic area (solid arrow) relative to contralateral hemisphere.
C, Brain tissue segmented from skull in the nonenhanced CT image by a CT number threshold of 340 HU and further classified according to CBF: 0 < pink pixels  25 > green pixels < 100 mL · 100 g–1 · min–1.
D, A manually drawn region of interest around the ischemic area.
E, The ischemic region shown in D classified according to the logistic regression model (purple pixels = infarct; yellow pixels = oligemic). Most of the ischemic region in D is classified as penumbra, which agrees with the TTC-stained section (F).
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Fig 6. Matched decrease in CBF and CBV at 4 hours after embolization. The CBF and CBV maps display the corresponding functional values according to a "rainbow" color scale with red and blue representing high and low values, respectively (CBF, 0–150 mL · 100 g–1 · min–1; CBV, 0–10 mL · 100 g–1). CBF map (A) shows ischemic areas (dashed arrows) and CBV map (B) shows decreased blood volume in ischemic area (solid arrow) relative to contralateral hemisphere (C) brain tissue segmented from skull in the nonenhanced CT image by a CT number threshold of 340 HU and further classified according to CBF: 0 < pink pixels 25 > green pixels < 100 mL · 100 g–1 · min–1.
D, A manually drawn region of interest around the ischemic area.
E, The ischemic region shown in D classified according to the logistic regression model (purple pixels = infarct; yellow pixels = oligemic).
F, The corresponding TTC-stained tissue section shows an area of infarction that corresponds with pixels classified as infarct in E.
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Fig 7. Total volume of tissue classified as infarct by the CBFxCBV model with a threshold of CBFxCBV = 31.1 at multiple time points in the study and expressed as a percentage of final infarct volume on TTC-stained sections. Error bars show SD of the mean for each time point. Thresholds for infarction are probably time-dependent and are expected to increase with time from baseline. The assumed threshold at 4 hours after embolization applied at earlier time points is expected to overestimate the fraction of voxels destined to infarction. However, the extent of this overestimation at early time points was not investigated in this study.
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