Influence of 100% and 40% oxygen on penumbral blood flow, oxygen level, and T2*-weighted MRI in a rat stroke model

Abstract

Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T(2)(*) magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O(2) induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T(2)(*) signal. Therefore, we investigated replacing 100% O(2) OC with 40% O(2) OC (5 minutes 40% O(2) versus 100% O(2)) and determined the effects on blood pressure (BP), CBF, tissue pO(2), and T(2)(*) signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded pO(2) and CBF during 40% O(2) (n=6) or 100% O(2) (n=8) OC. In a separate MRI study, T(2)(*) signal change to 40% O(2) (n=6) and 100% O(2) (n=5) OC was compared. Oxygen challenge (40% and 100% O(2)) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra pO(2) levels by 80% and 144%, respectively. T(2)(*) signal significantly increased by 4.56% ± 1.61% and 8.65% ± 3.66% in penumbra compared with 2.98% ± 1.56% and 2.79% ± 0.66% in contralateral cortex and 1.09% ± 0.82% and -0.32% ± 0.67% in ischemic core, respectively. For diagnostic imaging, 40% O(2) OC could provide sufficient T(2)(*) signal change to detect penumbra with limited influence in BP and CBF.

Figure 1

(A) Representative composite magnetic resonance imaging (MRI) image revealing position of optodes in relation to penumbra (black). Ischemic injury (diffusion-weighted imaging (DWI), white) superimposed onto perfusion deficit (perfusion-weighted imaging (PWI), black) reveals PWI/DWI mismatch (presumed penumbra) ∼90 minutes post-middle cerebral artery occlusion (MCAO); baseline tissue p₂ (B) and relative cerebral blood flow (rCBF) (C) in ipsilateral (Ipsi) and contralateral (Contra) cortices of sham (n=14) and MCAO (n=14) rats before oxygen challenge (OC). Data from all groups are pooled and presented as mean±s.d. ^*P<0.05, ^**P<0.0005 versus MCAO contra, Student's paired t-test. BPU, blood perfusion units.

Figure 2

(A) Representative traces of mean arterial blood pressure (MABP), presumed penumbra (ipsilateral) and contralateral cortex p₂ and relative cerebral blood flow (rCBF) from a middle cerebral artery occlusion (MCAO) rat during oxygen challenge (OC) (shaded box); (B) percentage increase in cortex p₂; and (C) percentage increase in rCBF, in presumed penumbra (MCAO ipsi) and contralateral cortex of sham and MCAO rats breathing either 40% or 100% O₂. Data (n=6 to 8) are presented as mean±s.d. ^#P<0.05, paired Student's t-test; ^*P<0.001, ^**P⩽0.0005, 100% O₂ versus 40% O₂ (unpaired Student's t-test). Contra, contralateral; Ipsi, ipsilateral; BPU, blood perfusion units. The color reproduction of this figure is available on the html full text version of the manuscript.

Figure 3

(A) Representative trace of time course of T₂^* signal change in penumbra, ischemic core, equivalent contralateral cortex, and contralateral caudate nucleus during oxygen challenge (OC). (B) T₂^* percentage signal change to OC (40% O₂ or 100%, O₂) in middle cerebral artery occlusion (MCAO) rats (n=6). Data are expressed as mean±s.d. ^*P<0.05 versus 40% O₂ inhalation (unpaired Student's t-test), ^#P<0.005 versus equivalent ischemic core, $P<0.05 versus equivalent contralateral cortex (paired Student's t-test). Contra, contralateral. (C) Representative thresholded T₂^* percentage signal change maps for 100% O₂ OC and 40% O₂ (top row) with the equivalent perfusion-weighted/diffusion-weighted imaging (PWI/DWI) mismatch maps (bottom row) where ischemic injury (DWI, white) superimposed onto perfusion deficit (PWI, red) reveals penumbra as PWI/DWI mismatch (P denotes OC-defined penumbra and IC denotes ADC-defined ischemic core). ADC, apparent diffusion coefficient.