Perfluorocarbons enhance a T2*-based MRI technique for identifying the penumbra in a rat model of acute ischemic stroke

Abstract

Accurate imaging of ischemic penumbra is crucial for improving the management of acute stroke patients. T2* magnetic resonance imaging (MRI) combined with a T2*oxygen challenge (T2*OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. Using 100% O2, T2*OC-defined penumbra exhibits ongoing glucose metabolism and tissue recovery on reperfusion. However, potential limitations in translating this technique include a sinus artefact in human scans with delivery of 100% OC and relatively small signal changes. Here we investigate whether an oxygen-carrying perfluorocarbon (PFC) emulsion can enhance the sensitivity of the technique, enabling penumbra detection with lower levels of inspired oxygen. Stroke was induced in male Sprague-Dawley rats (n=17) with ischemic injury and perfusion deficit determined by diffusion and perfusion MRI, respectively. T2* signal change was measured in regions of interest (ROIs) located within ischemic core, T2*OC-defined penumbra and equivalent contralateral areas during 40% O2±prior PFC injection. Region of interest analyses between groups showed that PFC significantly enhanced the T2* response to 40% O2 in T2*-defined penumbra (mean increase of 10.6±2.3% compared to 5.6±1.5% with 40% O2, P<0.001). This enhancement was specific to the penumbra ROI. Perfluorocarbon emulsions therefore enhances the translational potential of the T2*OC technique for identifying penumbra in acute stroke patients.

Figure 1

Detection of the penumbra (P) using T₂* oxygen challenge OC with a 0.4 fraction of inspired oxygen (FiO₂) (A) or 0.4 FiO₂ following 1.5 ml perfluorocarbon (PFC) intravenous (B). (i) Apparent diffusion coefficient (ADC) map prior to OC; (ii) T₂* % signal change map; (iii) the corresponding thresholded image; (iv) ADC map with selected regions of interests (ROIs) superimposed (green, T₂* P; blue, contralateral cortex; purple, ischemic core; and orange, equivalent contralateral ROI); (v) quantitative cerebral blood flow (CBF) map for the same slice measured at baseline prior to PFC injection and OC; and (vi) the thresholded diffusion-weighted image (DWI) lesion (white shading) and perfusion image-DWI mismatch (red shading) with the four ROIs superimposed.

Figure 2

Graphs showing mean time course data (n=7 per group) of T₂* signal change to 0.4 fraction of inspired oxygen (FiO₂) (A) or perfluorocarbon (PFC) +0.4 FiO₂ (B) in the four regions of interests (ROIs); blue shading indicates the period of oxygen challenge (OC) with 0.4 FiO₂. (C) Peak T₂* signal changes to 0.4 FiO₂ with and without prior administration of PFC in the four ROIs. Horizontal bars indicate means. *indicates significantly greater signal change in T₂*-defined penumbra (P) compared to all other ROIs. ^#indicates significantly enhanced T₂* response in the P to 40% oxygen following PFC when compared to 40% oxygen alone.

Figure 3

(A) (i) Detection of the penumbra (P) from the T₂* % signal change map using 0.4 fraction of inspired oxygen (FiO₂) following 1.5 mL perfluorocarbon (PFC) intravenous; (ii) the corresponding thresholded image; (iii) detection of the P in the same animal from the T₂* % signal change map following an increase in FiO₂ to 1.0; (iv) the corresponding thresholded image. (B) Graph showing mean (n=3) time course of T₂* signal change in regions of interests (ROIs) to 0.4 FiO₂ (light blue shaded area) and 1.0 FiO₂ (darker blue shaded area) following administration of PFC. (C) Peak T₂* signal change in ROIs to 0.4 and 1.0 FiO₂ following administration of PFC. Dotted lines indicate further increase in T₂* within the P ROI on increasing FiO₂ from 0.4 to 1.0 following PFC. Horizontal bars indicate means.

Figure 4

Standard hemoglobin dissociation curve (black line) for Sprague-Dawley rats (modified from Cartheuser ) where arterial hemoglobin saturation (SaO₂%) is plotted against partial pressure of oxygen in arterial blood (PaO₂). Brain tissue pO₂ data have been superimposed from one of our earlier studies (brain tissue pO₂ was measured simultaneously in the presumed penumbra (P) and corresponding contralateral cortex using implanted Oxyflo/Oxylite probes) to emphasize the expected SaO₂ changes associated with 40% O₂ oxygen challenge (OC) and perfluorocarbon (PFC)+40% O₂ in the contralateral cortex and P.