Journal
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
Volume 68, Issue 5, Pages 1527-1535Publisher
IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
DOI: 10.1109/TBME.2020.3040079
Keywords
X-ray imaging; Imaging; Breast; Lipidomics; Detectors; Light sources; Iron; Contrast agents; microbubbles; synchrotron; X-ray in-line phase contrast
Categories
Funding
- Canadian Light Source, a national research facility of the University of Saskatchewan
- Canada Foundation for Innovation (CFI)
- Natural Sciences and Engineering Research Council (NSERC)
- National Research Council (NRC)
- Canadian Institutes of Health Research (CIHR)
- Government of Saskatchewan
- University of Saskatchewan
- NSERC [RGPIN-2018-06505]
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The study aimed to evaluate the feasibility of ultrasound microbubbles as a contrast agent for X-ray phase contrast imaging. Results suggest that lipid-MBs larger than 4 µm may be candidates for PCI, and a concentration of 5 x 10(6) MBs/ml could be the lowest suitable concentration for generating visible phase contrast in vivo.
Objective: X-ray phase contrast imaging generates contrast from refraction of X-rays, enhancing soft tissue contrast compared to conventional absorption-based imaging. Our goal is to develop a contrast agent for X-ray in-line phase contrast imaging (PCI) based on ultrasound microbubbles (MBs), by assessing size, shell material, and concentration. Methods: Polydisperse perfluorobutane-core lipid-shelled MBs were synthesized and size separated into five groups between 1 and 10 mu m. We generated two size populations of polyvinyl-alcohol (PVA)-MBs, 2-3 mu m and 3-4 mu m, whose shells were either coated or integrated with iron oxide nanoparticles (SPIONs). Microbubbles were then embedded in agar at three concentrations: 5 x 10(7), 5 x 10(6) and 5 x 10(5) MBs/ml. In-line phase contrast imaging was performed at the Canadian Light Source with filtered white beam micro-computed tomography. Phase contrast intensity was measured by both counting detectable MBs, and comparing mean pixel values (MPV) in minimum and maximum intensity projections of the overall samples. Results: Individual lipid-MBs 6-10 mu m, lipid-MBs 4-6 mu m and PVA-MBs coated with SPIONs were detectable at each concentration. At the highest concentration, lipid-MBs 6-10 mu m and 4-6 mu m showed an overall increase in positive contrast, whereas at a moderate concentration, only lipid-MBs 6-10 mu m displayed an increase. Negative contrast was also observed from two largest lipid-MBs at high concentration. Conclusion: These data indicate that lipid-MBs larger than 4 mu m are candidates for PCI, and 5 x 10(6) MBs/ml may be the lowest concentration suitable for generating visible phase contrast in vivo. Significance: Identifying a suitable MB for PCI may facilitate future clinical translation.
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