Using Permeability Imaging To Evaluate Collateral Flow In Patients With Acute Ischemic Stroke

Background:The cerebral collateral circulation is a network of blood vessels designed to preserve cerebral blood flow when primary routes fail.Collateral circulation plays a key role in the occurrence, evolution, treatment and prognosis of ischemic stroke. The beneficial influence of collateral flow has now gained significant attention because of widely available, rapid multimodal CT, MRI and angiographic techniques.Collateral imaging has become a cornerstone in the evaluation of patients with acute and chronic cerebral ischemia.DSA has become the gold standard among these techniques, but it is limited in clinical study because of its invasiveness and complication. Conventional MRA and CTA can provide accurate delination to collateral circulation of grade Ⅰ, but they can’t give more information about grade Ⅱand Ⅲ.4D-CTA has shortcoming in the evaluation of collateral circulation of grade Ⅲ and it also can’t assess collaterals quantitatively, though it has promising future.Collateral circulation of grade Ⅲ means angiogenesis, which occurs at some time after ischemia. The structure of angiogenesis is immature; as a result its permeability is high. Permeability imaging can determine the blood-brain barrier permeability quickly and quantitatively. And this technique has been used to predict hemorrhagic transformation after ischemic stroke.We used permeability imaging to evaluate the cerebral collateral circulation of patients in clinical study and rats in experimental study. We compared the permeability imaging with other image techniques in the collateral flow score(CFS) of patients with ischemic stroke. In experimental study, we compared the permeability imaging with pathology in the CFS of MCAO rats. We aimed to find an imaging marker based on permeability imaging which can assess cerebral collateral circulation of grade Ⅱand Ⅲ accurately and quantitatively.Section one Using permeability imaging to evaluate leptomeningeal collateral flow in patients with severe intracranial arterial stenosis or occlusionBackground:Different methods of angiography are of great clinical utili ty; however, it still remains unstandardized as which method would be suitable to determine cerebral collateral circulation. The study aims to determine whether volume transfer constant(Ktrans) maps calculated from DCE-MR data are a biomarker of cerebral collateral circulation in patients with severe intracranial arterial stenosis.Methods:Here we compared digital subtraction angiography(DSA), computer tomography angiography(CTA) and dynamic contrast-enhanced T1-weighted imaging magnetic resonance imaging(MRI) findings in twenty-one patients with severe intracranial arterial stenosis, and determine whether volume transfer constant(Ktrans) maps of permeability imaging could be used as the biomarkers of cerebral collateral circulation. We retrospectively reviewed twenty-one adult patients with severe intracranial arterial stenosis or occlusion with a complete parenchymal and vascular imaging work-up. DSA, CTA source imaging(CTA-SI), arterial spin labeling(ASL), and Ktrans maps were used to assess their collateral flow. Cohen’s Kappa coefficient was calculated to test the consistency of their collateral scores.Results:A reasonable agreement was found between DSA and Ktrans maps(Kappa = 0.502, P<0.001) when all 15 regional vascular sites were included, and a better agreement found after exclusion of perforating artery territories(N=10 sites, Kappa = 0.766, P<0.001). The agreement between CTA-SI and DSA was moderate on all 15 sites(Kappa = 0.413, P<0.001) and 10 sites(Kappa = 0.329, P<0.001). The agreement between ASL and DSA was least favorable, no matter for all 15 sites(Kappa = 0.270, P<0.001) or 10 sites(Kappa = 0.205, P = 0.002).Conclusions:Ktrans maps are useful and promising for leptomeningeal collateral assessment, when compared to CTA-SI or ASL. Further studies are required for verify its validity in a large registry of patients.Section Two Using standard first-pass perfusion Computed Tomographic data to evaluate collateral flow in acute ischemic strokeBackground:The study aims to determine whether volume transfer constant(Ktrans) maps calculated from first-pass perfusion computed tomographic data are a biomarker of cerebral collateral circulation and predict the clinical outcome in acute ischemic stroke caused by proximal arterial occlusion.Methods:Consecutive patients with acute occlusion of the middle cerebral artery who received endovascular treatment were enrolled. Digital subtraction angiography, computed tomographic angiography with maximum intensity projection, and Ktrans maps were used to assess their collateral circulation. Agreement between different methods was evaluated using the χ2 tests. The correlations of various radiological and clinical outcomes with the collateral flow score, as determined from Ktrans maps, were calculated.Results:Seventy-five patients were included, comprising 39 women and 36 men, with a mean age of 65.3±14.6 years. Collateral flow score on Ktrans maps had the highest correlation with digital subtraction angiography(Kappa=0.8101; P=0.9796). Twenty-five patients had poor collateral circulation on Ktrans maps, 25 had intermediate collateral flow, 20 had good collateral flow, and 5 had excellent collateral flow. Better collateral circulation was associated with better clinical outcome(P<0.0001).Conclusions:Ktrans maps extracted from standard first-pass perfusion computed tomography are correlated with collateral circulation status after acute proximal arterial occlusion and predictive of outcome.Section Three Using permeability imaging to evaluate collateral flow in rats with middle cerebral artery occlusionPurpose:The study aims to determine the correlation between various parameters of permeability MR and the intensity and size of vascular in the focal ischemic cortex of the rats with middle cerebral artery occlusion. And we also want to use these permeability parameters to assess the collateral circulation of grade Ⅲ quantitatively.Methods:Here we set the models of rats with middle cerebral artery occlusion. The models were simulated different ischemic status and intervene. The collateral circulation in the ischemic cortex was degraded by the use of multi-model MR. The rat brain slices were stained with immunohistological analysis before a confocal microscope was used to capture fluorescent images. The intensity of microvessels and capillary was degraded. The correlation of collateral circulation and vascular intens ity grades were compared.Results:BBBP of MCAO rats observed in the Ktrans map and IAUC map declined than the sham group at 24 h after ischemia, rised at 3d and reached the peak at 7d. The BBBP value in the outer cortex layers rose remarkably. The Ktrans value and intensity of capillary declined at 24 h.The Ktrans value and intensity of microvessels and capillary all rose obviously at 3d and 7d compared with the sham group. We found that SWI can better assess microvessels; IAUC and Ktrans map has better ability to evaluate capillary; IAUC can assess both capillary and microvessels. Ktrans value had better correlation with intensity of capillary(Kappa=0.764, P<0.001) and SWI had better correlation with intensity of microvessels(Kappa=0.715,P<0.001) at 4.5h. SWI had better correlation with intensity of microvessels(Kappa=0.719, P<0.001) at 3d.IAUC had better correlation with intensity of capillary(Kappa=0.725,P<0.001) at 7d.Conclusions:IAUC is a semiquantitative parameter with low Signal to Noise Ratio(SNR), stable effect and clear image. The permeability of vascular can be observed visually in the IAUC. The Ktransmap can assess the angiogenesis that is collateral circulation of grade Ⅲ quantitatively. The changes of BBBP can be observed visually and quantitatively from the IAUC and the Ktransmap.