Advancements, challenges, and future prospects in clinical hyperpolarized magnetic resonance imaging: A comprehensive review

Abstract

Hyperpolarized (HP) magnetic resonance imaging (MRI) is a groundbreaking imaging platform advancing from research to clinical practice, offering new possibilities for real-time, non-invasive metabolic imaging. This review explores the latest advancements, challenges, and future directions of HP MRI, emphasizing its transformative impact on both translational research and clinical applications. By employing techniques such as dissolution Dynamic Nuclear Polarization (dDNP), Parahydrogen-Induced Polarization (PHIP), Signal Amplification by Reversible Exchange (SABRE), and Spin-Exchange Optical Pumping (SEOP), HP MRI achieves enhanced nuclear spin polarization, enabling in vivo visualization of metabolic pathways with exceptional sensitivity. Current challenges, such as limited imaging windows, complex pre-scan protocols, and data processing difficulties, are addressed through innovative solutions like advanced pulse sequences, bolus tracking, and kinetic modeling. We highlight the evolution of HP MRI technology, focusing on its potential to revolutionize disease diagnosis and monitoring by revealing metabolic processes beyond the reach of conventional MRI and positron emission tomography (PET). Key advancements include the development of novel tracers like [2-¹³C]pyruvate and [1-¹³C]-alpha-ketoglutarate and improved data analysis techniques, broadening the scope of clinical metabolic imaging. Future prospects emphasize integrating artificial intelligence, standardizing imaging protocols, and developing new hyperpolarized agents to enhance reproducibility and expand clinical capabilities particularly in oncology, cardiology, and neurology. Ultimately, we envisioned HP MRI as a standardized modality for dynamic metabolic imaging in clinical practice.

Keywords: Carbon-13; Dynamic nuclear polarization; Hyperpolarization; Magnetic resonance imaging; Magnetic resonance spectroscopy.

Graphical abstract

Fig. 1

The flow of 13C substrate preparation, HP 13C polarization, MRI acquisition, and images. This diagram delineates the comprehensive process of employing HP 13C substrates, like pyruvate, to visualize downstream metabolites—lactate, alanine, and bicarbonate—in the glycolysis pathway through MRI. Initially, the 13C substrate undergoes preparation in a sterile environment, setting the stage for its transformation into a highly informative metabolic tracer (A). Subsequently, the substrate is subject to polarization via the DNP technique such as GE SPINlab (B).

Fig. 2

Challenges in HP 13C imaging acquisition and data analysis. This diagram vividly depicts the dynamic nature and inherent challenges of HP 13C imaging, focusing on the temporal progression of HP 13C pyruvate (red) and its metabolite lactate (blue) signals from injection up to 200 s, when signals diminish into the noise threshold. The depiction underscores the unique attribute of flux in HP 13C imaging, where the degrading metabolic signals over time highlight critical obstacles. The primary challenge illustrated is the limited imaging window, constrained to less than 200 s, demanding precise timing for optimal signal capture. The second challenge involves determining the optimal acquisition time within this narrow window to maximize data quality and relevance. Thirdly, the diagram points to the complexity of defining the pyruvate flow function, a pivotal component in the kinetic model necessary for estimating apparent exchange rate constants, crucial for accurate metabolic analysis. Lastly, the rapid degradation of the hyperpolarized state presents a significant hurdle, leading to a decreased signal-to-noise ratio (SNR) towards the end of the acquisition period. These challenges highlight the technical and temporal intricacies of HP 13C imaging, underscoring the need for precise timing and sophisticated modeling to harness its full diagnostic potential.