1. Department of Biomedical Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong;
2. City University of Hong Kong Shenzhen Research Institute, Shenzhen, China;
3. Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, USA;
4. Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong.
5. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, USA.
Adjuvant treatment using local drug delivery is applied in treating glioblastoma multiforme (GBM) after tumor resection. However, there are no non-invasive imaging techniques available for tracking the compositional changes of hydrogel-based drug treatment.
Methods: We developed Chemical Exchange Saturation Transfer Magnetic Resonance Imaging (CEST MRI) detectable and injectable liposomal hydrogel to monitor these events in vivo at 3T clinical field. Mechanical attributes of these hydrogels and their in vitro and in vivo CEST imaging properties were systematically studied.
Results: The MRI detectable hydrogels were capable of generating multiparametric readouts for monitoring specific components of the hydrogel matrix simultaneously and independently. Herein, we report, for the first time, CEST contrast at -3.4 ppm provides an estimated number of liposomes and CEST contrast at 5 ppm provides an estimated amount of encapsulated drug. CEST contrast decreased by 1.57% at 5 ppm, while the contrast at -3.4 ppm remained constant over 3 d in vivo, demonstrating different release kinetics of these components from the hydrogel matrix. Furthermore, histology analysis confirmed that the CEST contrast at -3.4 ppm was associated with liposome concentrations.
Conclusion: This multiparametric CEST imaging of individual compositional changes in liposomal hydrogels, formulated with clinical-grade materials at 3T and described in this study, has the potential to facilitate the refinement of adjuvant treatment for GBM.
Keywords: CEST MRI, hydrogel, liposome, glioblastoma