Synopsis

Keywords: Contrast mechanisms: Hyperpolarized MR (Non-Gas), Contrast mechanisms: Hyperpolarization, Cross-organ: Cancer

Hyperpolarized (HP) imaging agents can produce signal that is five orders of magnitude stronger compared to normal thermal equilibrium, enabling rapid measurement of physiological characteristics that were previously inaccessible by MRI. The most widely studied HP imaging agent is [1-¹³C]-pyruvate which can be used to characterize tumor metabolism. HP [1-¹³C]-pyruvate MRI requires the use of coils, sequences, and workflow that are similar to traditional MRI but modified to accommodate the unique characteristics of HP MRI. Recent patient studies demonstrate continuing technical improvements as well as strong potential for this technology to provide new information to guide improved patient care.

Introduction

Magnetic resonance imaging (MRI) is unique among imaging modalities in its ability to provide high-resolution anatomic and functional imaging data with exquisite soft-tissue contrast, without the use of ionizing radiation. MR images are ultimately limited by noise; all optimized imaging sequences reflect a careful balance between image resolution, scan time, and the signal-to-noise ratio (SNR). Methods that fundamentally improve sensitivity can be leveraged to produce images with higher resolution, lower scan time, and/or higher SNR, and sometimes these methods can provide new insight into previously inaccessible characteristics of tissues and disease.

Recent advances in dissolution dynamic nuclear polarization (dDNP) (1, 2) can enhance the signal from key ¹³C-enriched imaging agents such as [1-¹³C]-pyruvate by 100,000-fold or more. Dynamic spectroscopic imaging of pyruvate that has been hyperpolarized by dDNP enables imaging of pyruvate and its metabolites in nearly real time. This application is particularly important in oncology because hyperpolarized (HP) pyruvate MRI provides a new method for assessing the altered metabolism that has been observed in many cancers.

Translational Research

Imaging of HP agents is challenging because the signal is non-renewable, constantly decaying due to T1 relaxation, and depleted by excitation pulses. These challenges have spawned a wide range of technical studies to develop improved methods for production and imaging of HP agents, and for analysis and quantification of dynamic HP MRI data. Preclinical studies have also demonstrated tremendous promise for HP [1-¹³C]-pyruvate MRI to provide early insight into response to therapy.

Ten years ago, Sarah Nelson and colleagues at the University of California in San Francisco demonstrated the safety and feasibility of HP [1-¹³C]-pyruvate MRI in patients with prostate cancer (3). Patient studies require coils, imaging sequences, and workflow that are similar to traditional MRI but adjusted to accommodate the unique characteristics of HP MRI. Patient studies also require careful coordination between physics, pharmacy, patient support, and imaging technologists. Since initial demonstration of safety and feasibility, more than 70 studies have been carried out involving patients with cancers of the prostate, brain, breast, kidney, liver, pancreas, thyroid, and metastases to refine techniques and explore the potential use of this technology to improve care for patients. Although most of these studies are limited in size and require further investigation, strong potential continues to be demonstrated for HP [1-¹³C]-pyruvate MRI to assess tumor aggressiveness (4-6) or provide early indications of response to therapy (7-9).

Future Directions

Although the vast majority of HP MRI studies have been carried out using [1-¹³C]-pyruvate, new agents that will probe other tumor characteristics are currently under development, with first-in-human scans using HP ¹³C-urea (10) and HP [1-¹³C]-alphaketoglutarate recently completed. Advances in instrumentation may reduce the cost and complexity of preparing HP imaging agents for use with human subjects, and streamline the workflow for acquisition of HP imaging data. Encouraging but still relatively preliminary studies supporting the use of HP [1-¹³C]-pyruvate MRI to improve care for patients will have to be demonstrated in larger, multi-center trials. Recent FDA approval of HP ¹²⁹Xe gas for imaging lung ventilation shows the true potential for clinical translation of these technologies.

Acknowledgements

No acknowledgement found.

References

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