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Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has intrinsic advantage in safety compared with radiotracer and optical imaging modalities. However, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually clinical used Gd-based complexes MRI-T 1 contrast agents are toxic. Therefore, demand for nontoxic novel T 1 -weighted MRI potential candidate with ultrasensitive imaging and advanced functionality is very high. In this research, silica coated ultra small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via thermal decomposition method which demonstrated high performance T 1 -weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses.Transmission electron microscopy (TEM) results have illustrated that the diameter of SPIONPs was in the range of 4nm and the average size of Fe 3 O 4 @SiO 2 was about 30~40nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the purity in phase of the prepared SPIONPs. These magnetite nanoparticles exhibited weak magnetic moment at room temperature because of spin-canting effect which escorted high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica coated ultra small (4nm-sized) magnetite nanoparticles exhibited a good r 1 relaxivity of 1.2mM -1 s -1 and low r 2 /r 1 ratio of 6.5 mM -1 s -1 . In vivo T 1 -weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of as-synthesized magnetite nanoparticles. These results reveal silica coated SPIONPs as a promising candidate for T 1 contrast agent with extraordinary capability to enhance MR images.

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Magnetic resonance imaging (MRI) has received significant attention as the noninvasive diagnostic technique for complex diseases. Image-guided therapeutic strategy for diseases such as cancer has also been at the front line of biomedical research, thanks to the innovative MRI, enhanced by the prior delivery of contrast agents (CAs) into patients' bodies through injection. These CAs have contributed a great deal to the clinical utility of MRI but have been based on metal-containing compounds such as gadolinium, manganese, and iron oxide. Some of these CAs have led to cytotoxicities such as the incurable Nephrogenic Systemic Fibrosis (NSF), resulting in their removal from the market. On the other hand, CAs based on organic nitroxide radicals, by virtue of their structural composition, are metal free and without the aforementioned drawbacks. They also have improved biocompatibility, ease of functionalization, and long blood circulation times, and have been proven to offer tissue contrast enhancement with longitudinal relaxivities comparable with those for the metal-containing CAs. Thus, this Review highlights the recent progress in metal-based CAs and their shortcomings. In addition, the remarkable goals achieved by the organic nitroxide radical CAs in the enhancement of MR images have also been discussed extensively. The focal point of this Review is to emphasize or demonstrate the crucial need for transition into the use of organic nitroxide radicalsmetal-free CAsas against the metal-containing CAs, with the aim of achieving safer application of MRI for early disease diagnosis and image-guided therapy.