Synopsis

The goal of this educational session is to provide understanding of the basic principles of generating hyperpolarization and hyperpolarized MR imaging strategies, which have enabled novel in vivo imaging studies of metabolism, perfusion, pH, ventilation, redox state, and more. This talk will cover hyperpolarization methods, including those used in clinical trials, and imaging strategies that efficiently use the non-recoverable magnetization.

Highlights

• Hyperpolarization provides substantial sensitivity enhancements
• Enables novel in vivo imaging of metabolism, perfusion, pH, redox state, and more
• Description of hyperpolarization methods, including methods used in clinical trials
• Description of hyperpolarized imaging strategies that efficiently use the non-recoverable magnetization
• Slides will be posted at: http://radiology.ucsf.edu/research/labs/larson/educational-materials

Target Audience

Outcomes/Objectives

Purpose

Methods

Experiment

A hyperpolarized MRI experiment typically consists of

1. Preparation of the agent
2. Hyperpolarization of the agent
3. Administration to the subject
4. Imaging acquisition

This presentation will focus on the hyperpolarization and acquisition components.

Hyperpolarization

There are several approaches that can provide hyperpolarization, each with their own unique requirements and tradeoffs. This talk will focus on dissolution dynamic nuclear polarization (dDNP), which is currently in human metabolic imaging studies at multiple sites, and will also discuss other approaches:

• Dissolution dynamic nuclear polarization (dDNP) [1, 2]: In this approach, a sample containing the agent and an electron spin source is irradiated with microwaves to transfer the electron polarization to the nuclear spins. This is typically done at low temperatures (down to <1K) to further increase the polarizations. Since the sample is frozen, it must be rapidly dissolved prior to administration and imaging. The most common use of dDNP is for hyperpolarization of ¹³C nuclei for metabolic imaging.
• Parahydrogen induced polarization (PHIP) [3]: These methods exploit the spin order of the parahydrogen (pH2) singlet state, which can be transferred to nuclei of interest including ¹³C and ¹⁵N. PHIP methods are typically fast and cheap relative to dDNP, but the range of polarizable compounds of in vivo interest is currently limited. New methods including SABRE [4] and SABRE-SHEATH [5] have greatly expanded the capabilities of PHIP.
• Optical Pumping: Spin-exchange optical pumping [6] has been used to hyperpolarize ³He and ¹²⁹Xe gasses, both of which have been translated into human pulmonary imaging studies [7]. Circularly polarized laser light is used to excite electrons in an alkali metal, which transfers polarization to the nuclei.

Imaging Methods

MR with hyperpolarized agents require specialized imaging method that address the unique challenges of hyperpolarized agents, including non-recoverable and rapid signal decay, rapid uptake, and metabolic conversion [8]. For example, hyperpolarized [1-¹³C]pyruvate experiments must be completed within approximately 1-2 minutes due to T1 decay, and must separately resolve metabolic products of lactate, alanine, and bicarbonate based on their chemical shift.

1. RF pulse strategies: RF pulses for hyperpolarized MR should be designed to efficiently use the limited available magnetization and, if needed, for selective excitation of different metabolites.

• Variable flip angles: The RF flip angles are typically increased during the experiment to compensate for the effect of the preceding RF pulses T1 decay and metabolic conversion [9].
• Multiband strategies: In the presence of metabolic conversion, lower excitation flip angles of the hyperpolarized substrate preserve magnetization and improve the SNR of metabolic products [10].
• Spectral-spatial RF pulses: These pulses can achieve both spatial localization and spectral selectively of various hyperpolarized compounds [11].

2. Acquisition strategies: Acquisition methods must capture the rapid dynamics of administered hyperpolarized agents, which are rapidly modulated (on the order of seconds) due to uptake, conversion, and T1 decay. They also must often capture spectral information to resolve various hyperpolarized compounds.

• MRSI: Rapid MRSI methods, such as echo-planar spectroscopic imaging (EPSI) [12] and spiral CSI [13] are useful to provide spectral coverage.
• Model-based approaches: With known chemical shifts, model-based approaches such as IDEAL [14 ]are faster than MRSI.
• Fast Imaging methods: Single resonance experiments can use fast imaging methods, such as spirals or EPI. With sparse chemical shifts, these fast imaging techniques can be used in combination with metabolite-specific spectral-spatial excitations [15].
• Acceleration methods: Parallel imaging [16–18] and compressed sensing [19] have been shown to provide beneficial accelerations for hyperpolarized MRI for either more rapid imaging or increased spatial coverage.

3. Data Analysis: Many hyperpolarized MR experiments use kinetic models for quantification of metabolic conversion, uptake, and perfusion [20–25].

Discussion

Acknowledgements

References

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