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It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities. <jats:italic>In vivo<\/jats:italic> MRI of rats injected intravenously with MIO@SiO<jats:sub>2<\/jats:sub>\u2010RITC nanoparticles exhibited enhancement of the <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> contrast in brain tissue, in particular a time\u2010delayed enhancement in the hippocampus, pituitary gland, striatum and cerebellum. This is attributable to the gradual degradation of MIO@SiO<jats:sub>2<\/jats:sub>\u2010RITC nanoparticles in the liver, resulting in the slow release of manganese(II) [Mn(II)] into the blood pool and, subsequently, accumulation in the brain tissue. Thus, <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>\u2010weighted contrast enhancement was clearly detected in the anatomic structure of the brain as time progressed. In addition, <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub>*\u2010weighted images of the liver showed a gradual darkening effect. Here, we demonstrate the concept of the slow release of Mn(II) for neuroimaging. This new nanoparticle\u2010based manganese contrast agent allows one simple intravenous injection (rather than multiple infusions) of Mn(II) precursor, and results in delineation of the detailed anatomic neuroarchitecture in MRI; hence, this provides the advantage of the long\u2010term study of neural function. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/nbm.2932","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T02:42:20Z","timestamp":1364006540000},"page":"1176-1185","source":"Crossref","is-referenced-by-count":18,"title":["Manganese\u2010enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica\u2010encapsulated Mn<i><sub>x<\/sub><\/i>Fe<sub>1\u2013<i>x<\/i><\/sub>O nanoparticles"],"prefix":"10.1002","volume":"26","author":[{"given":"Wei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Chemistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemistry National Taiwan University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao\u2010Chi 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