Microfluidic preparation of liposomal hydrogel microbeads containing CT agents (CT-lipobeads) to longitudinally monitor pH using CEST MRI
Peng Xiao1, Jianpan Huang1, Xiongqi Han1, Jacinth Wing-Sum Cheu2, Joseph Lai1, Lok Hin Law1, Carmen Chak-Lui Wong2,3, and Kannie Wai Yan Chan1,4,5
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, 2Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong, 3State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, Hong Kong, 4City University of Hong Kong Shenzhen Research Institute, Shen Zhen, China, 5Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States
CT-lipobeads were prepared using microfluidics. It generates ~10% CEST contrast at 4.2ppm with pH dependency.
CEST contrast remains constant over a week in vivo at 3T.
Figure 1 Microfluidic preparation of alginate
microbeads incorporated with Iopamiro or Iohexol-loaded liposome. (a) Microfluidics
design for preparation of microbeads. 1, 2, 3 were inlets for water phase, oil
phase and oil/acid phase, respectively, and 4 was outlet. (b) Schematic
of liposomal hydrogel beads, i.e. alginate microbeads containing liposomes
loaded with CT contrast agent (CT-lipobead). Prepared lipobeads(c). Chemical
structure of Iohexol (d) and Iopamiro (e), and protons that can
be detected by CEST are in red circles.
Figure 2 Power optimization and pH dependency for CT-lipobeads showing that CEST contrast at 4.2ppm
reach the highest value at 1.6uT and 2.0uT for both beads and capability to
distinguish HM from NM. CEST contrast for Iopamiro liposome beads and Iohexol
liposome beads at different B1 at neutral pH(a). CEST contrast at 4.2ppm in
saline with different pH at 1.6 uT(b). CEST contrast at 4.2ppm in Iopamiro lipobeads
in HM, NM and FM at 1.6 uT (c) and corresponded CEST map(d). pH of HM, NM and
FM are 6.8, 7.1 and 7.2, respectively. HM: Hypoxic medium. NM: Normoxic medium.
FM: Fresh medium