Label-Free Assessment of Mannitol Accumulation Following Osmotic Blood–Brain Barrier Opening Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging
Jing Liu,
Chengyan Chu,
Jia Zhang,
Chongxue Bie,
Lin Chen,
Safiya Aafreen,
Jiadi Xu,
David O. Kamson,
Peter C. M. van Zijl,
Piotr Walczak,
Miroslaw Janowski,
Guanshu Liu
Affiliations
Jing Liu
Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510230, China
Chengyan Chu
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD 21201, USA
Jia Zhang
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chongxue Bie
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Lin Chen
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Safiya Aafreen
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
Jiadi Xu
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
David O. Kamson
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21218, USA
Peter C. M. van Zijl
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Piotr Walczak
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD 21201, USA
Miroslaw Janowski
Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD 21201, USA
Guanshu Liu
Russell H. Morgan Department of Radiology and Radiological Sciences, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Purpose: Mannitol is a hyperosmolar agent for reducing intracranial pressure and inducing osmotic blood–brain barrier opening (OBBBO). There is a great clinical need for a non-invasive method to optimize the safety of mannitol dosing. The aim of this study was to develop a label-free Chemical Exchange Saturation Transfer (CEST)-based MRI approach for detecting intracranial accumulation of mannitol following OBBBO. Methods: In vitro MRI was conducted to measure the CEST properties of D-mannitol of different concentrations and pH. In vivo MRI and MRS measurements were conducted on Sprague-Dawley rats using a Biospec 11.7T horizontal MRI scanner. Rats were catheterized at the internal carotid artery (ICA) and randomly grouped to receive either 1 mL or 3 mL D-mannitol. CEST MR images were acquired before and at 20 min after the infusion. Results: In vitro MRI showed that mannitol has a strong, broad CEST contrast at around 0.8 ppm with a mM CEST MRI detectability. In vivo studies showed that CEST MRI could effectively detect mannitol in the brain. The low dose mannitol treatment led to OBBBO but no significant mannitol accumulation, whereas the high dose regimen resulted in both OBBBO and mannitol accumulation. The CEST MRI findings were consistent with 1H-MRS and Gd-enhanced MRI assessments. Conclusion: We demonstrated that CEST MRI can be used for non-invasive, label-free detection of mannitol accumulation in the brain following BBBO treatment. This method may be useful as a rapid imaging tool to optimize the dosing of mannitol-based OBBBO and improve its safety and efficacy.
