Current methods for hyperpolarized [1-13C]pyruvate MRI human studies

Abstract

MRI with hyperpolarized (HP) ¹³C agents, also known as HP ¹³C MRI, can measure processes such as localized metabolism that is altered in numerous cancers, liver, heart, kidney diseases, and more. It has been translated into human studies during the past 10 years, with recent rapid growth in studies largely based on increasing availability of HP agent preparation methods suitable for use in humans. This paper aims to capture the current successful practices for HP MRI human studies with [1-¹³C]pyruvate-by far the most commonly used agent, which sits at a key metabolic junction in glycolysis. The paper is divided into four major topic areas: (1) HP ¹³C-pyruvate preparation; (2) MRI system setup and calibrations; (3) data acquisition and image reconstruction; and (4) data analysis and quantification. In each area, we identified the key components for a successful study, summarized both published studies and current practices, and discuss evidence gaps, strengths, and limitations. This paper is the output of the "HP ¹³C MRI Consensus Group" as well as the ISMRM Hyperpolarized Media MR and Hyperpolarized Methods and Equipment study groups. It further aims to provide a comprehensive reference for future consensus, building as the field continues to advance human studies with this metabolic imaging modality.

Keywords: carbon‐13; dissolution dynamic nuclear polarization; hyperpolarized MRI; metabolic imaging; pyruvate.

Figure 1:

Illustration of the HP ¹³C MRI human study process, including the 4 major areas covered in this paper: Hyperpolarized ¹³C-pyruvate preparation, MRI system setup and calibration, Acquisition and Reconstruction, and Data Analysis and Quantification.

Figure 2:

Anatomical targets of HP [1-¹³C]pyruvate MRI human studies published up to September 2022.

Figure 3:

Hyperpolarized agent preparation methods reported by sites currently performing HP ¹³C MRI human studies

Figure 4:

Examples of RF coil configurations used for human HP [1-¹³C]pyruvate brain studies. (A,B) ¹³C Clamshell TX (Helmholz pair) and 2× 4-channel paddle RX arrays. (C) ¹³C Birdcage volume TX and 32-channel RX array (RX array slides into TX coil). (D) ¹³C Birdcage volume TX and 24-channel RX array, combined with a ¹H 8-channel RX array. Image reproduced with permission from Ref (16).

Figure 5:

Acquisition methods used in published HP [1-¹³C]pyruvate human studies published up to September 2022, classified into: MR spectroscopy and spectroscopy imaging (MRS/I); chemical shift encoding methods, such as IDEAL, that use multiple TEs and model-based reconstructions; and metabolite-specific imaging methods that use spectrally-selective excitation to image a single resonance at a time.

Figure 6:

Temporal acquisition characteristics reported in HP [1-¹³C]pyruvate human studies published up to September 2022. (a) Reported referencing of acquisition start times. (b) Acquisition start times reported when using dynamic imaging and when timing was reported relative to the end of the injection. (c) Temporal resolutions. “Not Applicable” indicates dynamic imaging was not used.

Figure 7:

HP [1-¹³C]pyruvate raw data (A) have typically been quantified using four categories of metrics depending on the acquisition. Data acquired as a single time point are often quantified using normalized metabolite images or metabolite ratios (B). Dynamic data can be quantified using normalized metabolite images or metabolite ratios (B), or with metabolite timings such as time-to-peak (TTP) or pharmacokinetic (PK) models (C). The latter two require the data to be time-resolved. [1-¹³C]alanine and ¹³C-bicarbonate are analyzed similarly to [1-¹³C]lactate but omitted here for display.

Figure 8:

Reported metrics used for analysis in HP [1-¹³C]pyruvate human studies published up to September 2022.

Figure 9:

Examples of different parameters, color schemes and anatomical reference used to visualize HP ¹³C MRI: (A) cardiac study showing each metabolite (SNR) on one monochromatic grayscale image and separate anatomic reference, no overlays (2); (B) preclinical cardiac study showing one image per metabolite in monochrome (red / blue) on outlines of anatomy, and additional annotated anatomical image in separate panel (108); (C) brain study where each metabolite AUC (multicolor) was fused with an anatomic image, plus one anatomical image (28); (D) prostate study showing k_PL as multicolor overlay on anatomic image (26).