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Novel, highly sensitive, specific, and low-toxicity contrast agents for MRI and MDCT are the need of the hour in clinics. For MRI, manganese-containing contrast agents would be most suitable as they can demonstrate calcium metabolism that is inherent in disease processes in the inner ear [115–118]. Nanoparticle-based GdC carrier are an effective MRI T1 contrast agent and have been used in high resolution MRI for tracing apoptosis and gene transcription in animal models of cerebral ischemia and brain tumors [119, 120]. A novel, super-paramagnetic iron oxide nanoparticle (SPION) that is water soluble, a characteristic that can be invaluable for medical applications, has been designed (Fig. 7) [121, 122]. It is constructed from iron oxide nanoparticle cores with a hierarchical coating consisting of a surface layer of Pluornic® F127 copolymer (PF127, approved by the Food and Drug Administration) that overlays a layer of oleic acid on the surface of the iron oxide nanoparticles (POA@SPIONs). POA@SPIONs is a promising T2-negative contrast agent that is detectable within the inner ear by MRI [123]. Functionalization of POA@SPIONs can be performed that make it a target for inflammatory cytokines in the inner ear; however, they were found not to enter the inner ear efficiently after the transtympanic injection [106]. Another novel, highly hydrophilic, anti-aggregative super-paramagnetic maghemite (γ-Fe₂O₃) nanoparticle (NP) was developed using ceric ammonium nitrate (CAN)-mediated oxidation of starting magnetite (Fe₃O₄) NPs (CAN-γ-Fe₂O₃ NPs), which were highly stable aqueous suspensions/ferrofluids due to a unique ultrasound-mediated doping process of the Fe₃O₄ NP surface using lanthanide Ce^3/4+ cations [124]. Zou et al. [125] have also demonstrated that the novel CAN-γ-Fe₂O₃ NPs is a strong T₂ MRI contrast agent that penetrates both round and oval windows, and has potential applications in molecular imaging of the inner ear [125].

Fig. 7. Super-paramagnetic iron oxide nanoparticles (SPION) contrasted inner ear in a rat. The SPION administered into the perilymph will extinguish the signal from the perilymph and only endolymphatic spaces are visible on MRI. Reprinted with permission of Europ J nanomed [122]. Cochlea, vestibule and the semicircular canals are shown.

By developing a novel nanomaterial to be used as contrasting agent, for example, encapsulation of metals and metal clusters in fullerenes (endohedral metallofullerenes) opens additional vistas for inner ear imaging [126–128]. The carbon cage has inherent advantages because of its high stability and characteristic resistance to any potential metabolic cage-opening process. This prevents the release of toxic metal ions from endohedral metallofullerenes into surrounding tissue, serum, and other biologic components [126]. Water-soluble endohedral gadolinium-lutetium fullerene is generating considerable interest because of the possibility of using these novel nanomaterials as both MRI and MDCT imaging contrast agents. It is possible that specific molecular MRI and MDCT imaging can be performed after single injection of the targetable dual contrast agent in future.