Magnetic barcode imaging for contrast agents.

PURPOSE: To demonstrate a new MR imaging approach that unambiguously identifies and quantitates contrast agents based on intrinsic agent properties such as r1 , r2 , r2*, and magnetic susceptibility. The approach is referred to as magnetic barcode imaging (MBI). METHODS: Targeted and bioresponsive contrast agents were imaged in agarose phantoms to generate T1 , T2 , T2*, and quantitative susceptibility maps. The parameter maps were processed by a machine learning algorithm that is trained to recognize the contrast agents based on these parameters. The output is a quantitative map of contrast agent concentration, identity, and functional state. RESULTS: MBI allowed the quantitative interpretation of intensities, removed confounding backgrounds, enabled contrast agent multiplexing, and unambiguously detected the activation and binding states of bioresponsive and targeted contrast agents. CONCLUSION: MBI has the potential to overcome significant limitations in the interpretation, quantitation, and multiplexing of contrast enhancement by MR imaging probes. Magn Reson Med 77:970-978, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging.

Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.

A multimeric MR-optical contrast agent for multimodal imaging.

We describe the design, synthesis and in vitro evaluation of a multimodal and multimeric contrast agent. The agent consists of three macrocyclic Gd(III) chelates conjugated to a fluorophore and possesses high relaxivity, water solubility, and is nontoxic. The modular synthesis is amenable for the incorporation of a variety of fluorophores to generate molecular constructs for a number of applications.

A modular system for the synthesis of multiplexed magnetic resonance probes.

We have developed a modular architecture for preparing high-relaxivity multiplexed probes utilizing click chemistry. Our system incorporates azide bearing Gd(III) chelates and a trialkyne scaffold with a functional group for subsequent modification. In optimizing the relaxivity of this new complex, we undertook a study of the linker length between a chelate and the scaffold to determine its effect on relaxivity. The results show a strong dependence on flexibility between the individual chelates and the scaffold with decreasing linker length leading to significant increases in relaxivity. Nuclear magnetic resonance dispersion (NMRD) spectra were obtained to confirm a 10-fold increase in the rotational correlation time from 0.049 to 0.60 ns at 310 K. We have additionally obtained a crystal structure demonstrating that modification with an azide does not impact the coordination of the lanthanide. The resulting multinuclear center has a 500% increase in per Gd (or ionic) relaxivity at 1.41 T versus small molecule contrast agents and a 170% increase in relaxivity at 9.4 T.