Real-Time MRI Guidance for Reproducible Hyperosmolar Opening of the Blood-Brain Barrier in Mice

Chengyan Chu; Chengyan Chu; Chengyan Chu; Guanshu Liu; Guanshu Liu; Miroslaw Janowski; Miroslaw Janowski; Miroslaw Janowski; Miroslaw Janowski; Jeff W. M. Bulte; Jeff W. M. Bulte; Shen Li; Shen Li; Shen Li; Monica Pearl; Piotr Walczak; Piotr Walczak; Piotr Walczak

doi:10.3389/fneur.2018.00921

Frontiers in Neurology (Oct 2018)

Real-Time MRI Guidance for Reproducible Hyperosmolar Opening of the Blood-Brain Barrier in Mice

Chengyan Chu,
Chengyan Chu,
Chengyan Chu,
Guanshu Liu,
Guanshu Liu,
Miroslaw Janowski,
Miroslaw Janowski,
Miroslaw Janowski,
Miroslaw Janowski,
Jeff W. M. Bulte,
Jeff W. M. Bulte,
Shen Li,
Shen Li,
Shen Li,
Monica Pearl,
Piotr Walczak,
Piotr Walczak,
Piotr Walczak

Affiliations

Chengyan Chu: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Chengyan Chu: Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Chengyan Chu: Neurology Department, Dalian Municipal Central Hospital Affiliated with Dalian Medical University, Dalian, China
Guanshu Liu: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Guanshu Liu: F. M. Kirby Research Center, Kennedy Krieger Research Institute, Baltimore, MD, , United States
Miroslaw Janowski: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Miroslaw Janowski: Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Miroslaw Janowski: NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
Miroslaw Janowski: Department of Neurosurgery, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
Jeff W. M. Bulte: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Jeff W. M. Bulte: Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Shen Li: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Shen Li: Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Shen Li: Neurology Department, Dalian Municipal Central Hospital Affiliated with Dalian Medical University, Dalian, China
Monica Pearl: Division of Interventional Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Piotr Walczak: Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Piotr Walczak: Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
Piotr Walczak: Department of Neurology and Neurosurgery, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland

DOI: https://doi.org/10.3389/fneur.2018.00921
Journal volume & issue: Vol. 9

Abstract

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The blood-brain barrier (BBB) prevents effective delivery of most therapeutic agents to the brain. Intra-arterial (IA) infusion of hyperosmotic mannitol has been widely used to open the BBB and improve parenchymal targeting, but the extent of BBB disruption has varied widely with therapeutic outcomes often being unpredictable. In this work, we show that real-time MRI can enable fine-tuning of the infusion rate to adjust and predict effective and local brain perfusion in mice, and thereby can be allowed for achieving the targeted and localized BBB opening (BBBO). Both the reproducibility and safety are validated by MRI and histology. The reliable and reproducible BBBO we developed in mice will allow cost-effective studies on the biology of the BBB and drug delivery to the brain. In addition, the IA route for BBBO also permits subsequent IA delivery of a specific drug during the same procedure and obtains high targeting efficiency of the therapeutic agent in the targeted tissue, which has great potential for future clinical translation in neuro-oncology, regenerative medicine and other neurological applications.

Published in Frontiers in Neurology

ISSN: 1664-2295 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry: Neurology. Diseases of the nervous system
Website: https://www.frontiersin.org/journals/neurology/

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