A New Nanotechnology for Imaging the Juxta-Articular Intraosseous Vasculature-Canal Complex and Related Clinical Pilot Studies.

Abstract

Objective: The objective of this study is to achieve distinct visualization of juxta-articular intraosseous microvessels, a novel nanoimaging methodology in which superparamagnetic iron oxide nanoparticles and meglumine diatrizoate (MD) are used cooperatively was implemented.

Methods: A newly created composite of MD and Fe₃O₄ nanoparticles (MD-Fe₃O₄ NPs) was prepared as a contrast agent to achieve efficacious imaging of the juxta-articular intraosseous vasculature-canal complex (JIVCC). Scanning electron microscopy (SEM) and energy dispersive spectrum (EDS) were employed to observe the structural characteristics and binding stability of the MD-Fe₃O₄ NPs. In 20 rabbits that received an injection of MD-Fe₃O₄ NPs, 1-mm-thick computed tomography (CT) scanning was performed for radiographic assessment. Hematoxylin-eosin- and potassium ferrocyanide-stained sections from 10 sacrificed rabbits were used to observe the histological characteristics of JIVCC with MD-Fe₃O₄ NPs, and the remaining 10 rabbits were utilized for a systemic safety evaluation. After a healthy volunteer received an MD-Fe₃O₄ NP injection, we also performed CT scanning and related safety evaluations.

Results: When the MD nanoparticles and amino-Fe₃O₄ nanoparticles were mixed together, they aggregated into a stable compound structure according to microscopic observations and SEM-EDS verification. In 20 rabbits receiving MD-Fe₃O₄ injections, 1-mm slice CT imaging demonstrated significantly enhanced visualization of the JIVCCs in magnet-placed knees compared to contralateral limbs (tibial JIVCC: p < 0.001; femoral JIVCC: p < 0.001), confirming MD-Fe₃O₄ NPs as the efficacious magnetic contrast enhancer. The histological characteristics of MD-Fe₃O₄ NPs in JIVCC were revealed. The levels of serum iron before and 4 and 72 h after MD-Fe₃O₄ NP injection were 23.9 ± 2.13 μmol/L, 26.2 ± 2.30 μmol/L, and 24.9 ± 2.33 μmol/L, respectively, indicating that there was no significant difference in safety (p = 0.092). After a volunteer received MD-Fe₃O₄ NPs via intravenous administration, the JIVCC was clearly visualized, laboratory tests of serum iron levels were normal, and no injection-related complications occurred.

Conclusions: A novel compound nanoparticle, which achieved satisfactory overall outcomes, was implemented as an appropriate alternative for the discernible visualization of juxta-articular intraosseous microvessels. The nanotechnology utilized in this study may augment the clinical imaging methodology for the osseous vascular system.