Ultrasensitive ¹²⁹Xe Magnetic Resonance Imaging: From Clinical Monitoring to Molecular Sensing

Abstract Magnetic resonance imaging (MRI) is a cornerstone technology in clinical diagnostics and in vivo research, offering unparalleled visualization capabilities. Despite significant advancements in the past century, traditional ¹H MRI still faces sensitivity limitations that hinder its further development. To overcome this challenge, hyperpolarization methods have been introduced, disrupting the thermal equilibrium of nuclear spins and leading to an increased proportion of hyperpolarized spins, thereby enhancing sensitivity by hundreds to tens of thousands of times. Among these methods, hyperpolarized (HP) ¹²⁹Xe MRI, also known as ultrasensitive ¹²⁹Xe MRI, stands out for achieving the highest polarization enhancement and has recently received clinical approval. It effectively tackles the challenge of weak MRI signals from low proton density in the lungs. HP ¹²⁹Xe MRI is valuable for assessing structural and functional changes in lung physiology during pulmonary disease progression, tracking cells, and detecting target molecules at pico‐molar concentrations. This review summarizes recent developments in HP ¹²⁹Xe MRI, including its physical principles, manufacturing methods, in vivo characteristics, and diverse applications in biomedical, chemical, and material sciences. In addition, it carefully discusses potential technical improvements and future prospects for enhancing its utility in these fields, further establishing HP ¹²⁹Xe MRI's importance in advancing medical imaging and research.