Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion

Xiaolei Song; Piotr Walczak; Xiaowei He; Xing Yang; Monica Pearl; Jeff W M Bulte; Martin G Pomper; Michael T McMahon; Mirosław Janowski

doi:10.1177/0271678X16637882

Salicylic acid analogues as chemical exchange saturation transfer MRI contrast agents for the assessment of brain perfusion territory and blood-brain barrier opening after intra-arterial infusion

J Cereb Blood Flow Metab. 2016 Jul;36(7):1186-94. doi: 10.1177/0271678X16637882. Epub 2016 Mar 15.

Authors

Xiaolei Song¹, Piotr Walczak², Xiaowei He³, Xing Yang⁴, Monica Pearl⁴, Jeff W M Bulte⁵, Martin G Pomper⁴, Michael T McMahon¹, Mirosław Janowski⁶

Affiliations

¹ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
² Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Department of Radiology, Faculty of Medical Sciences, University of Warmia and Mazury, Olsztyn, Poland.
³ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA School of Information Sciences and Technology, Northwest University, Xi'an, P. R. China.
⁴ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA.
⁵ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltmore, MD, USA Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA NeuroRepair Department, MMRC, PAS, Warsaw, Poland Department of Neurosurgery, MMRC, PAS, Warsaw, Poland mjanows1@jhmi.edu mcmahon@mri.jhu.edu.

Abstract

The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Predicted, focal opening of the BBB through intra-arterial infusion of hyperosmolar mannitol is feasible, but there is a need to facilitate imaging techniques (e.g. MRI) to guide interventional procedures and assess the outcomes. Here, we show that salicylic acid analogues (SAA) can depict the brain territory supplied by the catheter and detect the BBB opening, through chemical exchange saturation transfer (CEST) MRI. Hyperosmolar SAA solutions themselves are also capable of opening the BBB, and, when multiple SAA agents were co-injected, their locoregional perfusion could be differentiated.

Keywords: BBB opening; CEST MRI; Salicylic acid analogues; perfusion territory.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / diagnostic imaging*
Blood-Brain Barrier / metabolism
Brain / blood supply
Brain / diagnostic imaging
Contrast Media / administration & dosage
Contrast Media / chemistry*
Hydroxybenzoates / administration & dosage
Hydroxybenzoates / chemistry
Infusions, Intra-Arterial
Magnetic Resonance Imaging, Interventional / methods*
Osmolar Concentration
Perfusion
Perfusion Imaging / methods*
Phthalic Acids / administration & dosage
Phthalic Acids / chemistry
Rats, Sprague-Dawley
Salicylic Acid / administration & dosage
Salicylic Acid / chemistry*
Sodium Salicylate / administration & dosage
Sodium Salicylate / chemistry
Solutions

Substances

2,5-dihydroxyterephthalic acid
Contrast Media
Hydroxybenzoates
Phthalic Acids
Solutions
beta-resorcylic acid
Salicylic Acid
Sodium Salicylate

Abstract

Publication types

MeSH terms

Substances

Grants and funding