Dynamic susceptibility contrast-enhanced MRI with USPIO in evaluating angiogenesis of the peri-infarction zones in subacute ischemic stroke in a permanent middle cerebral artery occlusion rat model
Restricted accessResearch articleFirst published online December, 2024
Dynamic susceptibility contrast-enhanced MRI with USPIO in evaluating angiogenesis of the peri-infarction zones in subacute ischemic stroke in a permanent middle cerebral artery occlusion rat model
Dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) can reflect the angiogenesis of ischemic stroke.
Purpose
To investigate the value of DSC-MRI with ultrasmall superparamagnetic particles of iron oxides (USPIO) in evaluating angiogenesis in the peri-infarction zones in subacute ischemic stroke in a permanent middle cerebral artery occlusion (pMCAO) rat model.
Material and Methods
A total of 21 Sprague–Dawley rats were randomly divided into the pMCAO and sham operation groups. Every rat in each group underwent DSC-MRI with USPIO at 3, 5, and 7 days. DSC-MRI parameters of the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT), and relative time to peak (rTTP) were measured, calculated, and compared among the different times. Sequential correlations were analyzed among the histopathological indexes with the microvascular density (MVD) and percentage of vascular area (%VA), the serum factors with vascular endothelial growth factor (VEGF), vascular cell adhesion molecule 1 (VCAM-1), and perfusion parameters, respectively.
Results
The rCBV and rCBF in the peri-infarction area of pMCAO rats were significantly higher on day 7 than on day 3, whereas no significant changes in rMTT and rTTP were observed at 3, 5, and 7 days. Significantly positive correlations were found between rCBV and MVD, %VA, VEGF, VCAM-1, between rCBF and MVD, %VA, VEGF, and VCAM-1 at 3, 5, and 7 days in the pMCAO group.
Conclusion
The rCBV and rCBF deriving from USPIO-DSC may be potentially useful for evaluating the angiogenesis of the peri-infarction zones in the subacute phase of ischemic stroke.
FeiginVLStarkBAJohnsonCO, et al.Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol2021;20:795–820.
2.
TsaoCWAdayAWAlmarzooqZI, et al.Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation2022;145:e153–e639.
3.
RinglebPASchellingerPDSchranzC, et al.Thrombolytic therapy within 3 to 6 hours after onset of ischemic stroke. Stroke2002;33:1437–1441.
4.
TsivgoulisGKatsanosAHSandsetEC, et al.Thrombolysis for acute ischaemic stroke: current status and future perspectives. Lancet Neurol2023;22:418–429.
5.
FangJWangZMiaoC. Angiogenesis after ischemic stroke. Acta Pharmacol Sin2023;44:1305–1321.
6.
LapiDColantuoniA. Remodeling of cerebral microcirculation after ischemia-reperfusion. J Vasc Res2015;52:22–31.
7.
YangYTorbeyMT. Angiogenesis and blood-brain barrier permeability in vascular remodeling after stroke. Curr Neuropharmacol2020;18:1250–1265.
8.
ZhuTWangLWangL, et al.Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: applications for natural compounds from medicinal herbs. Biomed Pharmacother2022;148:112719.
9.
LiuJWangYAkamatsuY, et al.Vascular remodeling after ischemic stroke: mechanisms and therapeutic potentials. Prog Neurobiol2014;115:138–156.
10.
BoeseACLeQ-SEPhamD, et al.Neural stem cell therapy for subacute and chronic ischemic stroke. Stem Cell Res Ther2018;9:154.
11.
DaiMGuiXJiaS, et al.Dl-3-n-butylphthalide promotes angiogenesis in ischemic stroke mice through upregulating autocrine and paracrine sonic hedgehog. Acta Pharmacol Sin2023;44:2404–2417.
12.
GuCLiYLiuJ, et al.Neural stem cell-derived exosomes-loaded adhesive hydrogel controlled-release promotes cerebral angiogenesis and neurological function in ischemic stroke. Exp Neurol2023;370:114547.
13.
XuSYangJWanH, et al.Combination of radix astragali and safflower promotes angiogenesis in rats with ischemic stroke via silencing PTGS2. IJMS2023;24:2126.
14.
LinC-YChangCCheungW-M, et al.Dynamic changes in vascular permeability, cerebral blood volume, vascular density, and size after transient focal cerebral ischemia in rats: evaluation with contrast-enhanced magnetic resonance imaging. J Cereb Blood Flow Metab2008;28:1491–1501.
15.
FuRSzidonyaLBarajasRF, et al.Diagnostic performance of DSC perfusion MRI to distinguish tumor progression and treatment-related changes: a systematic review and meta-analysis. Neurooncol Adv2022;4:vdac027.
16.
FranxBALebrunFChin Joe KieL, et al.Dynamics of cerebral blood volume during and after middle cerebral artery occlusion in rats – comparison between ultrafast ultrasound and dynamic susceptibility contrast-enhanced MRI measurements. J Cereb Blood Flow Metab2024;44:333–344.
17.
FuYZhaoWLinK, et al.USPIO-SWI shows fingolimod enhanced alteplase action on angiographic reperfusion in eMCAO rats. Magn Reson Imaging2022;55:1095–1106.
18.
ChenCGeJGaoY, et al.Ultrasmall superparamagnetic iron oxide nanoparticles: a next generation contrast agent for magnetic resonance imaging. WIRES Nanomed Nanobiotechnol2022;14:e1740.
19.
WeiHHuYWangJ, et al.Superparamagnetic iron oxide nanoparticles: cytotoxicity, metabolism, and cellular behavior in biomedicine applications. Int J Nanomedicine2021;16:6097–6113.
20.
PucciCDegl’InnocentiABelenli GümüşM, et al.Superparamagnetic iron oxide nanoparticles for magnetic hyperthermia: recent advancements, molecular effects, and future directions in the omics era. Biomater Sci2022;10:2103–2121.
21.
LiYLiuBZhaoT, et al.Comparative study of extracellular vesicles derived from mesenchymal stem cells and brain endothelial cells attenuating blood–brain barrier permeability via regulating caveolin-1-dependent ZO-1 and claudin-5 endocytosis in acute ischemic stroke. J Nanobiotechnol2023;21:70.
22.
XuTWangXMaC, et al.Identification of potential regulating effect of baicalin on NFκB/CCL2/CCR2 signaling pathway in rats with cerebral ischemia by antibody-based array and bioinformatics analysis. J Ethnopharmacol2022;284:114773.
23.
ChenBYiJXuY, et al.Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu decoction in the treatment of cerebral ischemia. Biomed Pharmacother2022;145:112445.
24.
YangSLinJLuF, et al.Use of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging and mean vessel density imaging to monitor antiangiogenic effects of sorafenib on experimental hepatocellular carcinoma. Contrast Media Mol Imaging2017;2017:9265098.
25.
YangDYeQWilliamsM, et al.USPIO-enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys. Magnetic Resonance in Med2001;46:1152–1163.
26.
AllkemperTBremerCMatuszewskiL, et al.Contrast-enhanced blood-pool MR angiography with optimized iron oxides: effect of size and dose on vascular contrast enhancement in rabbits. Radiology2002;223:432–438.
27.
ZaidatOOYooAJKhatriP, et al.Recommendations on angiographic revascularization grading standards for acute ischemic stroke. Stroke2013;44:2650–2663.
28.
SavitzSIBaronJ-CYenariMA, et al.Reconsidering neuroprotection in the reperfusion era. Stroke2017;48:3413–3419.
29.
CopenWASchaeferPWWuO. MR perfusion imaging in acute ischemic stroke. Neuroimaging Clin N Am2011;21:259–283.
30.
CarmelietP. Mechanisms of angiogenesis and arteriogenesis. Nat Med2000;6:389–395.
31.
BoxermanJLSchmaindaKMWeisskoffRM. Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. AJNR Am J Neuroradiol2006;27:859–867.
32.
GkagkanasiouMPloussiAGazouliM, et al.USPIO-enhanced MRI neuroimaging: a review. J Neuroimaging2016;26:161–168.
33.
SimonsenCZStergaardLVestergaard-PoulsenP, et al.CBF and CBV measurements by USPIO bolus tracking: reproducibility and comparison with Gd-based values. J Magn Reson Imaging1999;9:342–347.
34.
KimJKimEEucedaLR, et al.Multiparametric characterization of response to anti-angiogenic therapy using USPIO contrast-enhanced MRI in combination with dynamic contrast-enhanced MRI. Magn Reson Imaging2018;47:1589–1600.
35.
WuTDingXSuB, et al.Magnetic resonance imaging of tumor angiogenesis using dual-targeting RGD10–NGR9 ultrasmall superparamagnetic iron oxide nanoparticles. Clin Transl Oncol2018;20:599–606.
36.
BurrellJSWalker-SamuelSBakerLCJ, et al.Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the antiangiogenic effects of cediranib (AZD2171) in rat C6 gliomas. Int J Cancer2012;131:1854–1862.
37.
WangHRanHYinY, et al.Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling. Acta Pharmacol Sin2022;43:1670–1685.
38.
MartiHJHBernaudinMBellailA, et al.Hypoxia-Induced vascular endothelial growth factor expression precedes neovascularization after cerebral ischemia. Am J Pathol2000;156: 965–976.
39.
GeiselerSJMorlandC. The Janus face of VEGF in stroke. Int J Mol Sci2018;19:1362.
40.
LiYMaTZhuX, et al.Zinc improves neurological recovery by promoting angiogenesis via the astrocyte-mediated HIF-1α/VEGF signaling pathway in experimental stroke. CNS Neurosci Ther2022;28:1790–1799.
41.
LiuYLongLZhangF, et al.Microneedle-mediated vascular endothelial growth factor delivery promotes angiogenesis and functional recovery after stroke. J Control Release2021;338:610–622.
42.
UsmanovaGRakhimbaevaG. The significance of some biomarkers of neuroinflammation and angiogenesis in strokes. World Bull Public Health2022;11:40–47.
43.
ZhangXWangLHanZ, et al.KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke. J Neuroinflammation2020;17:107.
