Feasibility Analysis of Brain Perfusion Using Polyaspartic Acid Surface-Modified Superparamagnetic Contrast Agent

Abstract

This research was aimed to construct polyaspartic acid (PASP) surface-modified magnetic resonance imaging (MRI) contrast agent nanoparticles (NPs) and preliminarily demonstrate the feasibility of using the NPs for MRI cerebral perfusion. Ultrasmall superparamagnetic iron oxide (USPIO) NPs were fabricated by a one-step chemical coprecipitation methodology, and surface modification of USPIO NPs was performed using PASP as the surface modifier to prepare PASP-USPIO NPs. The physicochemical properties of the NPs were detected, and their specific structural ability with HUVECs was visualized by Prussian blue staining. With the contrast agent gadolinium-diethylene triamine pentaacetate (Gd-DTPA) as the control group, the intravenous bolus of USPIO and PASP-USPIO was analyzed and a brain MRI scan of New Zealand white rabbits was performed. The relative cerebral blood volume (rCBV) and maximum signal reduction ratio (SRRmax) values of cerebral gray matter and white matter were calculated based on the plotted time-signal intensity. The results showed that the USPIO and PASP-USPIO NPs were successfully prepared. The average particle sizes were 40.1±5.5 nm and 42.7±6.9 nm, respectively, and the specific saturation magnetization was 86.9 A m2 ·kg−1 and 51.3 A m2 ·kg−1, respectively. Relative to USPIO, human umbilical vein endothelial cells (HUVECs) stained with Prussian blue positively in vitro in the PASP-USPIO group were notably increased, while the rate of change in the signal-to-noise ratio of imaging in vivo was substantially decreased. The time-signal intensity curves were plotted, and it was found that the rCBV of gray matter, rCBV of white matter, SRRmax of gray matter, and SRRmax of white matter in the USPIO group and PASP-USPIO group were greatly increased relative to control group (P < 0.05), while the SRRmax ratio of gray matter to white matter was decreased (P < 0.05). Additionally, the rCBV in the gray matter and rCBV in the white matter of the PASP-USPIO group were drastically increased in contrast to the USPIO group (P < 0.05). In short, the constructed PASP surface-modified USPIO NPs can become a novel MRI contrast agent for monitoring hemodynamic changes in brain tissue.