Zhou Chi-Heng, Zhu Yi-Cheng
Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Brain Sci. 2025 Aug 29;15(9):944. doi: 10.3390/brainsci15090944.
Iron is critical for brain development, metabolism, and function; however, dysregulated iron disposition contributes to neurological diseases. Many neuroimaging techniques have enabled detection of iron susceptibility, and quantitative susceptibility mapping (QSM) offers a sensitive magnetic resonance imaging (MRI) technique for quantifying brain iron. To elucidate the functional role of cerebral iron and clarify the utility of QSM in establishing iron as a potential biomarker, this review synthesizes cellular and regional behaviours of iron from physiological aging to disease conditions, with a focus on neurodegeneration such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS), as well as cerebral small vessel disease (CSVD) as cerebrovascular manifestation. Distinct patterns of iron distribution in deep gray matter and selective cortical regions are associated with motor and cognitive impairment, while the interaction between iron, vascular integrity, and glial function further stresses its pathological relevance. QSM of iron may, thereby, serve as a marker to monitor iron-related disease progression and facilitate intervention. Temporal dynamics of iron in brain pathology remain underexplored, and we emphasized the need for longitudinal mapping and multi-modality biomarker integration. Establishing iron as a clinically relevant imaging biomarker requires continued investigation into its topographical, molecular, and functional correlates across aging and disease trajectories.
铁对大脑发育、新陈代谢及功能至关重要;然而,铁代谢失调会引发神经疾病。许多神经成像技术已能够检测铁的易感性,而定量易感性图谱(QSM)提供了一种用于量化脑铁的灵敏磁共振成像(MRI)技术。为阐明脑铁的功能作用并明确QSM在将铁确立为潜在生物标志物方面的效用,本综述综合了从生理衰老到疾病状态下铁的细胞和区域行为,重点关注神经退行性疾病,如阿尔茨海默病(AD)、帕金森病(PD)和多发性硬化症(MS),以及作为脑血管表现的脑小血管病(CSVD)。深部灰质和选择性皮质区域中铁分布的不同模式与运动和认知障碍相关,而铁、血管完整性和神经胶质功能之间的相互作用进一步凸显了其病理相关性。因此,铁的QSM可能作为监测铁相关疾病进展及促进干预的标志物。脑病理学中铁的时间动态仍未得到充分研究,我们强调了纵向图谱绘制和多模态生物标志物整合的必要性。将铁确立为临床相关的成像生物标志物需要持续研究其在衰老和疾病轨迹中的地形、分子和功能相关性。