Absolute Cerebral Blood Flow Infarction Threshold for 3-Hour Ischemia Time Determined with CT Perfusion and ¹⁸F-FFMZ-PET Imaging in a Porcine Model of Cerebral Ischemia

<div><p>CT Perfusion (CTP) derived cerebral blood flow (CBF) thresholds have been proposed as the optimal parameter for distinguishing the infarct core prior to reperfusion. Previous threshold-derivation studies have been limited by uncertainties introduced by infarct expansion between the acute phase of stroke and follow-up imaging, or DWI lesion reversibility. In this study a model is proposed for determining infarction CBF thresholds at 3hr ischemia time by comparing contemporaneously acquired CTP derived CBF maps to ¹⁸F-FFMZ-PET imaging, with the objective of deriving a CBF threshold for infarction after 3 hours of ischemia. Endothelin-1 (ET-1) was injected into the brain of Duroc-Cross pigs (n = 11) through a burr hole in the skull. CTP images were acquired 10 and 30 minutes post ET-1 injection and then every 30 minutes for 150 minutes. 370 MBq of ¹⁸F-FFMZ was injected ~120 minutes post ET-1 injection and PET images were acquired for 25 minutes starting ~155–180 minutes post ET-1 injection. CBF maps from each CTP acquisition were co-registered and converted into a median CBF map. The median CBF map was co-registered to blood volume maps for vessel exclusion, an average CT image for grey/white matter segmentation, and ¹⁸F-FFMZ-PET images for infarct delineation. Logistic regression and ROC analysis were performed on infarcted and non-infarcted pixel CBF values for each animal that developed infarct. Six of the eleven animals developed infarction. The mean CBF value corresponding to the optimal operating point of the ROC curves for the 6 animals was 12.6 ± 2.8 mL·min^-1·100g^-1 for infarction after 3 hours of ischemia. The porcine ET-1 model of cerebral ischemia is easier to implement then other large animal models of stroke, and performs similarly as long as CBF is monitored using CTP to prevent reperfusion.</p></div

ROC Parameters for Each Animal.

<p>ROC Parameters for Each Animal.</p

ROC Curve with Optimal Operating Point.

<p>ROC curves plotted for each of the 6 animals. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0158157#pone.0158157.t001" target="_blank">Table 1</a> lists the CBF threshold derived from the optimal operating point of the ROC curve for each animal, and the corresponding sensitivity, specificity, accuracy, and AUC.</p

Predicted Probability of Infarction vs. CBF.

<p>Predicted probability of infarction from logistic regression plotted against CBF for each animal. The average of the CBF values that corresponded to a 75% predicted probability of infarction was approximately 4.5 ± 2.6 mL·min^-1·100g^-1.</p

Average Relative CBF of Infarct ROIs.

<p>Average rCBF value from the infarct regions of the 6 animals at each time point. Error bars indicate standard error.</p

Image Analysis Method.

<p>Infarct (pink) was identified on a PET image (top left) acquired 160-185min after ET-1 injection as pixels in the affected side ROI with signal below the infarction threshold derived from the contralateral ROI. Pixels with signal above this threshold were classified as non-infarct (yellow). The average image (top right) was used to segment out white matter. Blood vessels were identified on the BV map (bottom left) using a threshold derived from the affected side ROI (see text). Grey matter, vessel-less infarct and non-infarct ROIs were then superimposed onto the median CBF map (bottom right).</p