Investigation in to the Effect of Spin Locking on Contrast Agent Relaxivity

Abstract

The current trend in magnetic resonance imaging (MRI) is towards higher external magnetic field strengths (B0) to take advantage of increased sensitivity and signal to noise ratio (SNR). Unfortunately, as B0 increases the effectiveness (relaxivity) of clinical gadolinium (Gd 3+)-based contrast agents (CAs) administered to enhance image contrast is significantly reduced. Excellent soft tissue contrast can be generated with current agents despite their non-optimum relaxivities but necessitates large doses. The limits of detection of a CA at high B0 fields can be lowered by recovering the lost relaxivity and is a prerequisite to the goal of molecular imaging in which CAs are bound to biomarkers of pathology that exist at very low concentrations. Traditional methods for increasing the detectability of CAs have focused on optimizing critical parameters identified from the Solomon-Bloembergen-Morgan (SBM) theory that affect relaxivity. Gains in relaxivity with these methods to date have been modest and are far from the theoretical maximum possible. Although researchers continue to investigate novel complexes that provide improved relaxivities, any such complex would require a lengthy and costly approval process with the U.S. Food and Drug Administration (FDA). Therefore, a method that affords improved relaxivities of current clinically approved CAs, particularly at high B0 fields, that could be adopted into clinical practice rapidly, is of great interest. Spin locking is a nuclear magnetic resonance (NMR) technique that was introduced for imaging in 1985, but has received very little attention in combination with Gd 3+-based CAs. The technique employs a low power long duration radiofrequency (RF) pulse (B1) I would like to take this opportunity to thank the following: Prof. Mark Woods for all his support, encouragement and assistance throughout the course of this research.

LDL-mimetic lipid nanoparticles prepared by surface KAT ligation forin vivoMRI of atherosclerosis

“…This was much higher than those of small molecule MRI-CAs, such as ProHance® (Bracco Spa, Milano, Italy) with r 1 ¼ 4.0 s À1 mM À1 (1.4 T/60 MHz). 40 It is known that the r 1 relaxivity value is related to the rotational correlation time of the Gd(III)-chelate and a slowed rate causes higher r 1 in comparison to the freely rotating small molecule Gd(III)-chelate especially at a lower magnitude. 41 This is commonly observed by linking the Gd(III)-chelate molecules to macromolecules, polymers, and nanoparticles.…”