Abstract
Cerebral ischemic diseases remain a significant clinical challenge, necessitating advancements in imaging technologies to improve diagnosis and therapeutic monitoring. This review highlights the limitations of gadolinium-based contrast agents (GBCAs), particularly their nephrotoxicity and limited specificity, and explores the emerging role of manganese- and iron-based MRI contrast agents as promising alternatives. Manganese-based agents demonstrate exceptional sensitivity to neuronal activity and metabolic changes, making them highly effective for assessing functional and cellular dynamics. Meanwhile, iron-based agents leverage their superparamagnetic properties to enhance ischemic lesion detection, particularly in T(2)-weighted imaging. However, the clinical translation of these novel agents faces significant challenges, including biosafety concerns, suboptimal targeting efficiency, and the need for multimodal integration to improve diagnostic precision. Future research should focus on the development of low-toxicity, biodegradable contrast agents with enhanced targeting capabilities, the application of artificial intelligence for probe optimization, and the creation of theranostic nanoprobes that combine imaging with targeted therapy. Additionally, rigorous clinical validation and the establishment of standardized protocols will be critical for integrating these agents into routine practice. These advancements hold the potential to revolutionize ischemic stroke diagnosis and enable precision neuroimaging, driving the broader adoption of novel MRI contrast agents in clinical workflows.