The Mechanism Of Cerebral Oxygen Saturation Change And Its Influence On Prognosis After Acute Ischemic Stroke

PurposeTo quantitatively measure the volume of asymmetricclly prominent cortical veins（APCVs）to measure cerebral venous oxygen saturation（SvO₂）in patients with acute ischemic stroke（AIS）using quantitative susceptibility mapping（QSM）.To explore whether the quantitative measurement of APCVs volume is better than the traditional semi-quantitative analysis to observe the changes of cerebral oxygen metabolism in ischemic penumbra.To observe the quantitative changes of SvO₂in brain tissue before and after stroke treatment,to explore the mechanism of SvO₂changes with APCVs and its impact on clinical neurological prognosis.To analyze the dynamic changes of SvO₂and perfusion in brain tissue of APCVs area and their impact on acute cerebral infarction,to explore the independent predictors of infarct progression.Materials and MethodsPart one:85 patients with AIS within 12 hours were retrospectively analyzed.All patients underwent diffusion-weighted imaging（DWI）,susceptibility weighted imaging（SWI）and dynamic susceptibility contrast perfusion weighted imaging（DSC-PWI）and time-of-flight magnetic resonance angiography（TOF-MRA）.The APCVs was observed by two radiologists on SWI images.The quantitative volume measurement（SWI-volume）and Alberta stroke program early CT Score（ASPECT）semi-quantitative assessment（SWI-ASPECT）of APCVs were performed on QSM images,and the infarct core(ADC<620×10^-6mm²/s region)was measured on DWI.The volume of infarct core,Tmax>6s delayed perfusion volume,PWI-DWI mismatch volume and mismatch ratio were obtained by rapid processing of perfusion and diffusion（RAPID）software.SWI_volume-DWI mismatch and SWI_ASPECT-DWI mismatch were calculated by SWI-volume and infarct core.PWI-DWI mismatch was used as the reference of ischemic penumbra.Chi-square test was used to compare the diagnostic efficiency of quantitative and semi-quantitative methods for ischemic penumbra.Bland-Altman plots was used to analyze the consistency of SWI_volume-DWI mismatch and PWI-DWI mismatch,and the consistency of APCVs volume（SWI-volume）and Tmax>6s delayed perfusion volume.Pearson/Spearman correlation analysis was used to evaluate the correlation between SWI_volume-DWI mismatch,SWI_ASPECT-DWI mismatch and PWI-DWI mismatch,and their correlation with NIHSS score.The correlation between APCVs volume and Tmax>6s volume was also evaluated.Part two:53 patients with AIS within 24 hours were retrospectively analyzed.All patients underwent multi-modal MRI examination,including DWI,SWI,DSC-PWI and TOF-MRA at admission and within 2 weeks after standardized treatment.Two radiologists observed the presence or absence of APCVs on SWI images.The patients were divided into APCVs-positive group and APCVs-negative group according to the SWI image at admission.The SvO₂of APCVs region in infarcted side was calculated in all the patients.The differences of SvO₂,Tmax>6s delayed perfusion volume and NIHSS score between groups were analyzed by independent sample t test.The paired sample t test was used to analysis the above parameters before and after treatment.Pearson/Spearman correlation analysis was used to evaluate the relationship between SvO₂and hypoperfusion,NIHSS score and90-day m RS score.Independent sample t test was used to compare the differences of SvO₂between different prognosis subgroups and different 90-day outcome subgroups in APCVs-positive group.Part three:39 patients with AIS within 24 hours were retrospectively analyzed.All patients underwent multi-modal MRI examination（including DWI,SWI,DSC-PWI,TOF-MRA）at admission and within 2 weeks after receiving standardized treatment.SWI images of all the patients showed APCVs.According to the method of part one,the volume of APCVs was measured to calculate SWI_volume-DWI mismatch.According to the method of part two,the SvO₂of all the patients before and after treatment were calculated.The patients were divided into infarct progression group and infarct non progression group according to the DWI-ASPECT of baseline and FUP（follow-up）-ASPECT.Chi-square test,Fisher’s exact test,two independent samples t test or Mann Whitney U test were used to compare the differences of penumbra volume,baseline SvO₂,SvO₂change,baseline hypoperfusion area volume and hypoperfusion area change between the two groups.Univariate regression analysis and multivariate logistic regression analysis were used to obtain independent predictors of infarct progression.Receiver operating characteristic（ROC）curve analysis was used to evaluate the diagnostic efficacy of related indicators in predicting the progression of infarction.Pearson/Sperman correlation analysis was used to assess the correlation between baseline SvO₂and SWI_volume-DWI mismatch and PWI-DWI mismatch,as well as the correlation between the volume of penumbra,the change of SvO₂,the change of Tmax>6s delayed perfusion volume and the score of infarction change.ResultsPart one:85 patients with AIS were included in the study.The average age was71±12 years old,including 62 males and 23 females.44 cases were divided into APCVs-positive group and 41 cases into APCVs-negative group.There were significant differences in the infarct core,hypoperfusion and NIHSS score between the two groups（all p<0.001）.The infarct core and hypoperfusion area of APCVs-positive group were larger,and the clinical symptoms were more severe.In44 cases of APCVs-positive patients,41 cases showed PWI-DWI mismatch positive.In 41 cases of APCVs-negative patients,only 1 case showed PWI-DWI mismatch positive.In the APCVs-positive group,SWI_volume-DWI mismatch and PWI-DWI mismatch were both positive in 41 cases and negative in 2 cases;SWI_ASPECT-DWI mismatch and PWI-DWI mismatch were both positive in 22 cases and negative in 2cases.The sensitivity,negative predictive value and accuracy of SWI_volume-DWI mismatch was significantly higher than SWI_ASPECT-DWI mismatch（100%vs 53.7%,100%vs 9.5%,97.7%vs 54.5%,respectively）,and the specificity was the same（66.7%）.In 40 cases with APCVs and PWI-DWI mismatch（one case was excluded due to excessive perfusion on Tmax map）,SWI_volume-DWI mismatch and PWI-DWI mismatch volume showed good consistency and high correlation（r=0.691,p<0.001）;SWI_volume-DWI mismatch and SWI_ASPECT-DWI mismatch were negatively correlated with NIHSS score（r=-0.360,p=0.022;r=-0.499,p<0.001）.In 43 cases of APCVs-positive patients（one case was excluded due to excessive perfusion on Tmax map,as above）,SWI-volume and Tmax>6s volume showed good consistency and high correlation（r=0.786,p<0.001）.Part two:53 patients with AIS were included in the study,with an average age of71±10 years,including 39 males and 14 females.32 patients were divided into APCVs-positive group and 21 patients into APCVs-negative group.In the APCVs-positive group,28 cases disappeared after treatment.There was significant difference in SvO₂of infarct side in patients with APCVs before and after treatment（p<0.05）.The average SvO₂after treatment was higher than that before treatment（the average value increased from 34.01±6.07%to 63.88±10.99%）.There was no significant difference in SvO₂of infarct side in patients without APCVs before and after treatment（p>0.05）.In the APCVs-positive group,SvO₂was negatively correlated with Tmax>6s volume change,NIHSS score change and 90-day m RS（r=-0.388,p=0.028;r=-0.384,p=0.030;r_s=-0.420,p=0.017）,which was higher in 28patients with APCVs disappearance（r=-0.422,p=0.025;r=-0.405,p=0.033;r_s=-0.632,p<0.001）.It was found that the change of SvO₂in good prognosis group was significantly higher than that in poor prognosis group（37.03±5.57%vs 29.21±6.62%,p=0.003）.Part three:39 patients with AIS were included in the study,with an average age of 70±10 years,including 27 males and 12 females.They were divided into progressive infarction group（n=27）and non progressive infarction group（n=12）.Both the SWI_volume-DWI mismatch and PWI-DWI mismatch were positive in all the patients.The clinical symptoms at admission and discharge in the progressive infarction group were more severe than those in the non progressive infarction group（p=0.042,0.016,respectively）.There was no significant difference in baseline infarct volume,SvO₂,penumbra volume,hypoperfusion area and dynamic changes of hypoperfusion area between the two groups（all p>0.05）.There was significant difference in SvO₂between the two groups after treatment（35.45±6.14%vs26.80±10.93%,p=0.015）.Baseline NIHSS was an independent risk factor for infarct progression（OR=1.248,95%CI=1.042-1.494,p=0.016）.The change of SvO₂was an independent protective factor for infarct progression（OR=0.814,95%CI=0.688-0.964,p=0.017）.Baseline SvO₂was negatively correlated with hypoxic penumbra（r=-0.338,p=0.036）.The change of SvO₂was positively correlated with the change of infarction（r=0.425,p=0.007）,the change of penumbra volume and Tmax>6s volume were not correlated with the change of infarction（p>0.05）.Conclusions1.The quantitative SWI_volume-DWI mismatch measured by QSM is more effective than the semi-quantitative analysis of ASPECT in the diagnosis of ischemic penumbra.Cerebral ischemia and hypoxia occur simultaneously after AIS.The quantitative evaluation method of APCVs can reflect the changes of oxygen metabolism in ischemic penumbra.2.The dynamic changes of APCVs before and after the treatment of AIS can reflect oxygenation regulation ability of brain tissue.The improvement of SvO₂after the treatment of stroke can predict good neurological function prognosis and clinical prognosis.3.The dynamic changes of SvO₂ after AIS treatment can predict the progress of acute infarction.The more increases of SvO₂after treatment,the more conducive to delay the progress of infarction.It is proved that oxygen recovery is beneficial to maintain the function of nerve cells,which may be an important reason for the high oxygen saturation is conducive to the prognosis of nerve function.