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dc.contributor.authorChen, Lin
dc.contributor.authorLiu, Jing
dc.contributor.authorChu, Chengyan
dc.contributor.authorHan, Zheng
dc.contributor.authorYadav, Nirhbay
dc.contributor.authorXu, Jiadi
dc.contributor.authorBai, Renyuan
dc.contributor.authorStaedtke, Verena
dc.contributor.authorPearl, Monica
dc.contributor.authorWalczak, Piotr
dc.contributor.authorvan Zijl, Peter
dc.contributor.authorJanowski, Miroslaw
dc.contributor.authorLiu, Guanshu
dc.date.accessioned2021-05-13T15:04:19Z
dc.date.available2021-05-13T15:04:19Z
dc.date.issued2021-04-15
dc.identifier.urihttp://hdl.handle.net/10713/15647
dc.description.abstractRationale: Endovascular intervention plays an important role in the treatment of various diseases, in which MRI-guidance can potentially improve precision. However, the clinical applications of currently available contrast media, including Gadolinium-based contrast agents and superparamagnetic iron oxide particles (SPIO), are hindered by safety concerns. In the present study, we sought to develop D2O as a novel contrast agent for guiding endovascular neurointervention. Methods: Animal studies were approved by institutional ACUC and conducted using an 11.7 T Bruker Biospec system and a 3T Siemens Trio clinical scanner for rodent and canine imaging, respectively. The locally selective blood brain barrier opening (BBBO) in rat brains was obtained by intraarterial (IA) injection of mannitol. The dynamic T2w* EPI MRI sequence was used to study the trans-catheter perfusion territory by IA administered SPIO before mannitol administration, whereas a dynamic T1w FLASH sequence was used to acquire Gd contrast-enhanced MRI for assessing BBBO after injection of mannitol. The contrast generated by D2O assessed by either EPI or FLASH methods was compared with the corresponding results assessed by SPIO or Gd. The utility of D2O MRI was also demonstrated to guide drug delivery to glioma in a mouse model. Finally, the clinical utility of D2O-MRI was demonstrated in a canine model. Results: Our study has shown that the contrast generated by D2O can be used to precisely delineate trans-catheter perfusion territory in both small and large animals. The perfusion territories determined by D2O-MRI show moderate correlation with those by SPIO-MRI (Spearman coefficient r = 0.5234, P < 0.001). Moreover, our results show that the perfusion territory determined by D2O-MRI can successfully predict the areas with BBBO after mannitol treatment similar to that assessed by Gd-MRI (Spearman coefficient r = 0.6923, P < 0.001). Using D2O-MRI as imaging guidance, the optimal infusion rate in the mouse brain was determined to be 150 µL/min to maximize the delivery efficacy to the tumor without serious off-target delivery to the brain parenchyma. The enhanced drug delivery of antibodies to the brain tumor was confirmed by fluorescence imaging. Conclusion: Our study demonstrated that D2O can be used as a negative MRI contrast medium to guide endovascular neurointervention. The established D2O -MRI method is safe and quantitative, without the concern of contrast accumulation. These qualities make it an attempting approach for a variety of endovascular procedures. © The author(s).en_US
dc.description.sponsorshipNational Multiple Sclerosis Societyen_US
dc.description.urihttps://doi.org/10.7150/thno.55953en_US
dc.language.isoenen_US
dc.publisherIvyspring International Publisheren_US
dc.relation.ispartofTheranosticsen_US
dc.subjectDeuterium oxideen_US
dc.subjectEndovascular neurointerventionen_US
dc.subjectIntra-arterial hyperosmotic blood brain barrier (BBB) openingen_US
dc.subjectMRI contrast mediumen_US
dc.subjectMRI guidanceen_US
dc.titleDeuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointerventionen_US
dc.typeArticleen_US
dc.identifier.doi10.7150/thno.55953
dc.source.volume11
dc.source.issue13
dc.source.beginpage6240
dc.source.endpage6250


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