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This white paper discusses prospects for advancing hyperpolarization technology to better understand cancer metabolism, identify current obstacles to HP (hyperpolarized) 13C magnetic resonance imaging's (MRI's) widespread clinical use, and provide recommendations for overcoming them. Since the publication of the first NIH white paper on hyperpolarized 13C MRI in 2011, preclinical studies involving [1-13C]pyruvate as well a number of other 13C labeled metabolic substrates have demonstrated this technology's capacity to provide unique metabolic information. A dose-ranging study of HP [1-13C]pyruvate in patients with prostate cancer established safety and feasibility of this technique. Additional studies are ongoing in prostate, brain, breast, liver, cervical, and ovarian cancer. Technology for generating and delivering hyperpolarized agents has evolved, and new MR data acquisition sequences and improved MRI hardware have been developed. It will be important to continue investigation and development of existing and new probes in animal models. Improved polarization technology, efficient radiofrequency coils, and reliable pulse sequences are all important objectives to enable exploration of the technology in healthy control subjects and patient populations. It will be critical to determine how HP 13C MRI might fill existing needs in current clinical research and practice, and complement existing metabolic imaging modalities. Financial sponsorship and integration of academia, industry, and government efforts will be important factors in translating the technology for clinical research in oncology. This white paper is intended to provide recommendations with this goal in mind.

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi‐nuclear MRS and MRI techniques have the potential to provide a comprehensive non‐invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high‐fat diet feeding. This model was characterized using in vivo hyperpolarized [1‐13C]pyruvate and [2‐13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon‐like peptide‐1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high‐energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi‐nuclear MRS in the development of new therapies for obesity. [ABSTRACT FROM AUTHOR]

Purpose: To show that B0$$ {\mathrm{B}}_0 $$ variations through slice and slice profile effects are two major confounders affecting 2D dual angle B1+$$ {\mathrm{B}}_1^{+} $$ maps using gradient‐echo signals and thus need to be corrected to obtain accurate B1+$$ {\mathrm{B}}_1^{+} $$ maps. Methods: The 2D gradient‐echo transverse complex signal was Bloch‐simulated and integrated across the slice dimension including nonlinear variations in B0$$ {\mathrm{B}}_0 $$ inhomogeneities through slice. A nonlinear least squares fit was used to find the B1+$$ {\mathrm{B}}_1^{+} $$ factor corresponding to the best match between the two gradient‐echo signals experimental ratio and the Bloch‐simulated ratio. The correction was validated in phantom and in vivo at 3T. Results: For our RF excitation pulse, the error in the B1+$$ {\mathrm{B}}_1^{+} $$ factor scales by approximately 3.8% for every 10 Hz/cm variation in B0$$ {\mathrm{B}}_0 $$ along the slice direction. Higher accuracy phantom B1+$$ {\mathrm{B}}_1^{+} $$ maps were obtained after applying the proposed correction; the root mean square B1+$$ {\mathrm{B}}_1^{+} $$ error relative to the gold standard B1+$$ {\mathrm{B}}_1^{+} $$ decreased from 6.4% to 2.6%. In vivo whole‐liver T1$$ {\mathrm{T}}_1 $$ maps using the corrected B1+$$ {\mathrm{B}}_1^{+} $$ map registered a significant decrease in T1$$ {\mathrm{T}}_1 $$ gradient through slice. Conclusion: B0$$ {\mathrm{B}}_0 $$ inhomogeneities varying through slice were seen to have an impact on the accuracy of 2D double angle B1+$$ {\mathrm{B}}_1^{+} $$ maps using gradient‐echo sequences. Consideration of this confounder is crucial for research relying on accurate knowledge of the true excitation flip angles, as is the case of T1$$ {\mathrm{T}}_1 $$ mapping using a spoiled gradient recalled echo sequence. [ABSTRACT FROM AUTHOR]

Motivation: 31P magnetic resonance spectroscopic imaging (31P MRSI) is a powerful technique for investigating the metabolic effects of treatments for heart failure in vivo, allowing a better understanding of their mechanism of action in patient cohorts. Unfortunately, cardiac 31P MRSI is fundamentally limited by low SNR, which leads to compromises in acquisition, such as no cardiac or respiratory gating or low spatial resolution, in order to achieve reasonable scan times. Spectroscopy with linear algebra modeling (SLAM) reconstruction may be able to address these challenges and therefore improve repeatability by incorporating a segmented localizer into the reconstruction. Methods: Six healthy volunteers were scanned twice in a test-retest procedure to allow quantification of repeatability. Each scan consisted of anatomical localizers and two acquisition-weighted (AW) 31P MRSI acquisitions, which were acquired with and without cardiac gating. Five patients with heart failure with a preserved ejection fraction were then scanned with the same 31P MRSI sequence without cardiac gating. All 31P MRSI datasets were reconstructed with both conventional Fourier transform (FT)-based reconstruction and SLAM reconstruction, which were compared statistically. The effect of shifting the 31P MRSI acquisition field of view was also investigated. Results: In the healthy volunteer cohort, the spectral fit of the SLAM reconstructions had significantly improved Cramer-Rao lower bounds (CRLBs) compared to the FT-based reconstruction of non-cardiac gated data, as well as improved coefficients of variability and repeatability. The SLAM reconstruction found a significant difference in the PCr/ATP ratio between the healthy volunteer and patient cohorts, which the FT-based reconstruction did not find. Furthermore, the SLAM reconstruction was less influenced by the placement of the field of view (FOV) of the 31P MRSI acquisition in post hoc analysis. Discussion: The experimental benefits of the SLAM reconstruction for AW data were demonstrated by the improvements in fit confidence and repeatability seen in the healthy volunteer cohort and post hoc FOV analysis. The benefit of SLAM reconstruction of AW data for clinical studies was then illustrated by the patient cohort, which suggested improved sensitivity to clinically significant changes in the PCr/ATP ratio. [ABSTRACT FROM AUTHOR]

Purpose: The spoiled gradient recalled echo (SPGR) sequence with variable flip angles (FAs) enables whole liver T1$$ {T}_1 $$ mapping at high spatial resolutions but is strongly affected by B1+$$ {B}_1^{+} $$ inhomogeneities. The aim of this work was to study how the precision of acquired T1$$ {T}_1 $$ maps is affected by the T1$$ {T}_1 $$ and B1+$$ {B}_1^{+} $$ ranges observed in the liver at 3T, as well as how noise propagates from the acquired signals into the resulting T1$$ {T}_1 $$ map. Theory: The T1$$ {T}_1 $$ variance was estimated through the Fisher information matrix with a total noise variance including, for the first time, the B1+$$ {B}_1^{+} $$ map noise as well as contributions from the SPGR noise. Methods: Simulations were used to find the optimal FAs for both the B1+$$ {B}_1^{+} $$ mapping and T1$$ {T}_1 $$ mapping. The simulations results were validated in 10 volunteers. Results: Four optimized SPGR FAs of 2°, 2°, 15°, and 15° (TR = 4.1 ms) and B1+$$ {B}_1^{+} $$ map FAs of 65° and 130° achieved a T1$$ {T}_1 $$ coefficient of variation of 6.2 ± 1.7% across 10 volunteers and validated our theoretical model. Four optimal FAs outperformed five uniformly spaced FAs, saving the patient one breath‐hold. For the liver B1+$$ {B}_1^{+} $$ and T1$$ {T}_1 $$ parameter space at 3T, a higher return in T1$$ {T}_1 $$ precision was obtained by investing FAs in the SPGR acquisition rather than in the B1+$$ {B}_1^{+} $$ map. Conclusion: A novel framework was developed and validated to calculate the SPGR T1$$ {T}_1 $$ variance. This framework efficiently identifies optimal FA values and determines the total number of SPGR and B1+$$ {B}_1^{+} $$ measurements needed to achieve a desired T1$$ {T}_1 $$ precision. [ABSTRACT FROM AUTHOR]

Even at 7 T, cardiac 31P magnetic resonance spectroscopic imaging (MRSI) is fundamentally limited by low signal‐to‐noise ratio (SNR), leading to long scan times and poor temporal and spatial resolutions. Compartment‐based reconstruction algorithms such as magnetic resonance spectroscopy with linear algebraic modeling (SLAM) and spectral localization by imaging (SLIM) may improve SNR or reduce scan time without changes to acquisition. Here, we compare the repeatability and SNR performance of these compartment‐based methods, applied to three different acquisition schemes at 7 T. Twelve healthy volunteers were scanned twice. Each scan session consisted of a 6.5‐min 3D acquisition‐weighted (AW) cardiac 31P phase encode‐based MRSI acquisition and two 6.5‐min truncated k‐space acquisitions with increased averaging (4 × 4 × 4 central k‐space phase encodes and fractional SLAM [fSLAM] optimized k‐space phase encodes). Spectra were reconstructed using (i) AW Fourier reconstruction; (ii) AW SLAM; (iii) AW SLIM; (iv) 4 × 4 × 4 SLAM; (v) 4 × 4 × 4 SLIM; and (vi) fSLAM acquisition–reconstruction combinations. The phosphocreatine‐to‐adenosine triphosphate (PCr/ATP) ratio, the PCr SNR, and spatial response functions were computed, in addition to coefficients of reproducibility and variability. Using the compartment‐based reconstruction algorithms with the AW 31P acquisition resulted in a significant increase in SNR compared with previously published Fourier‐based MRSI reconstruction methods while maintaining the measured PCr/ATP ratio and improving interscan reproducibility. The alternative acquisition strategies with truncated k‐space performed no better than the common AW approach. Compartment‐based spectroscopy approaches provide an attractive reconstruction method for cardiac 31P spectroscopy at 7 T, improving reproducibility and SNR without the need for a dedicated k‐space sampling strategy. [ABSTRACT FROM AUTHOR]