Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T₂ CA and its new application for different modality of MRI, such as T₁ imaging, simultaneous T₂/T₁ or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T₂ and T₁ modal based on quantum mechanical outer sphere and Solomon–Bloembergen–Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r₂ or r₁ values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.

氧化铁纳米粒子（IONP）具有独特的磁性和高生物相容性，长期以来被广泛用作磁共振成像（MRI）造影剂（CA）。然而，一篇综述全面总结了 IONP 作为传统T ₂ CA 的最新发展及其在不同形式的 MRI 中的新应用，例如T ₁成像、同时T ₂ / T ₁或 MRI/其他成像模式，以及环境响应CA很少见。本综述首先研究T ₂和T ₁中高性能 MRI CA 的发展方向基于量子力学外球和 Solomon-Bloembergen-Morgan (SBM) 理论的模态。总结了最近通过调整关键参数来增加IONP MRI对比度的合理尝试，包括磁化强度、尺寸、有效半径、周围产生的磁场的不均匀性、晶相、水的配位数、电子弛豫时间和表面改性。除了提高r ₂或r ₁值的策略，增加体内IONP的对比效率从三个不同方面进行了回顾，即引入第二成像模式以提高成像精度，赋予IONP环境响应能力以提高病灶与正常组织之间的信号差异，优化界面结构以改善积累病灶中 IONP 的量。这篇详细的回顾提供了对基于高性能 IONP 的 MRI CA 开发的最新研究的深入理解。希望引发对下一代 MRI CA 设计的深入思考，以进行早期和准确的诊断。