Self-Confirming “AND” Logic Nanoparticles for Fault-Free MRI

Abstract

Achieving high accuracy in the imaging of biological targets is a challenging issue. For MRI, to enhance imaging accuracy, two different imaging modes with specific contrast agents are used; one is T1 type for a "positive" MRI signal and the other is T2 type for a "negative" signal. Conventional contrast agents response only in a single imaging mode and frequently encounter ambiguities in the MR images. Here, we propose a "magnetically decoupled" core-shell design concept to develop a dual mode nanoparticle contrast agent (DMCA). This DMCA not only possesses superior MR contrast effects, but also has the unique capability of displaying "AND" logic signals in both the T1 and T2 modes. The latter enables self-confirmation of images and leads to a greater diagnostic accuracy. A variety of novel DMCAs are possible and the use of DMCAs can potentially bring the accuracy of MR imaging of diseases to a higher level.By combining complementary information obtained from various imaging methods, including magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT) and optical microscopy, multi-modal imaging techniques have been devised to increase the accuracy of disease diagnosis. 1 However, even when multimodal techniques are employed, inherent problems still exist. For example, image matching difficulties caused by relocating biological samples and the discrepancies resulting from different depth penetrations and spatial/time resolutions of multiple imaging devices can lead to inaccuracies. 1a,b Therefore, the development of dual imaging strategies that employ a single instrumental system is another important approach.MRI is a powerful technique for tomographic images of biological targets in a non-invasive manner with a high spatial resolution. In MRI, relaxation time of protons of water in the sample is measured. Contrast agents are employed to greatly change proton relaxation rates and to enhance visualization of the differences between normal and disease tissues. T1 contrast agents, comprised typically of paramagnetic materials such as Gd complexes and Mn oxide nanoparticles, facilitate spin-lattice relaxation of protons causing a positive (or bright) MR image. 2,3 On the other hand, T2 contrast agents that commonly consist of superparamagnetic nanoparticles (e.g. iron oxide) cause protons in their vicinity to undergo spin-spin relaxation which gives rise to negative (or dark) MR images. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptA dual mode strategy for MRI, where two different T1 and T2 imaging modes are utilized simultaneously, can potentially give highly sensitive and accurate information. For such purposes, ultra small superparamagnetic iron oxide (USPIO), which displays enhanced T1 contrast effects, has been developed, but their T2 contrast effects are weak. 6 Although a system comprised of FeCo nanoparticles is the only one reported thus far that exhibits high T1 and T2 contrast effects, 7 an understanding of the mechanism by which this...

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