Theranostics 2021; 11(13):6240-6250. doi:10.7150/thno.55953 This issue Cite

Research Paper

Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention

Lin Chen1,2*, Jing Liu3,2*, Chengyan Chu4*, Zheng Han2,5*, Nirhbay Yadav2,5, Jiadi Xu2,5, Renyuan Bai6, Verena Staedtke7, Monica Pearl2, Piotr Walczak4, Peter van Zijl2,5, Miroslaw Janowski4, Guanshu Liu2,5✉

1. Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, School of Electronic Science and Engineering, National Model Microelectronics College, Xiamen University, Xiamen, Fujian, China.
2. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3. The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
4. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, USA.
5. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
6. Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.
7. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA.
* These authors contributed equally.

Citation:
Chen L, Liu J, Chu C, Han Z, Yadav N, Xu J, Bai R, Staedtke V, Pearl M, Walczak P, van Zijl P, Janowski M, Liu G. Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention. Theranostics 2021; 11(13):6240-6250. doi:10.7150/thno.55953. https://www.thno.org/v11p6240.htm
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Abstract

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Rationale: 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.

Keywords: deuterium oxide, MRI contrast medium, intra-arterial hyperosmotic blood brain barrier (BBB) opening, endovascular neurointervention, MRI guidance.


Citation styles

APA
Chen, L., Liu, J., Chu, C., Han, Z., Yadav, N., Xu, J., Bai, R., Staedtke, V., Pearl, M., Walczak, P., van Zijl, P., Janowski, M., Liu, G. (2021). Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention. Theranostics, 11(13), 6240-6250. https://doi.org/10.7150/thno.55953.

ACS
Chen, L.; Liu, J.; Chu, C.; Han, Z.; Yadav, N.; Xu, J.; Bai, R.; Staedtke, V.; Pearl, M.; Walczak, P.; van Zijl, P.; Janowski, M.; Liu, G. Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention. Theranostics 2021, 11 (13), 6240-6250. DOI: 10.7150/thno.55953.

NLM
Chen L, Liu J, Chu C, Han Z, Yadav N, Xu J, Bai R, Staedtke V, Pearl M, Walczak P, van Zijl P, Janowski M, Liu G. Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention. Theranostics 2021; 11(13):6240-6250. doi:10.7150/thno.55953. https://www.thno.org/v11p6240.htm

CSE
Chen L, Liu J, Chu C, Han Z, Yadav N, Xu J, Bai R, Staedtke V, Pearl M, Walczak P, van Zijl P, Janowski M, Liu G. 2021. Deuterium oxide as a contrast medium for real-time MRI-guided endovascular neurointervention. Theranostics. 11(13):6240-6250.

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