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Purpose: This study aims to show the viability of conducting three‐dimensional (3D) myocardial perfusion quantification covering the entire heart using both GRE and bSSFP sequences with hyperpolarized HP001. Methods: A GRE sequence and a bSSFP sequence, both with a stack‐of‐spirals readout, were designed and applied to three pigs. The images were reconstructed using 13$$ {}^{13} $$C coil sensitivity maps measured in a phantom experiment. Perfusion was quantified using a constrained decomposition method, and the estimated rest/stress perfusion values from 13$$ {}^{13} $$C GRE/bSSFP and Dynamic contrast‐enhanced MRI (DCE‐MRI) were individually analyzed through histograms and the mean perfusion values were compared with reference values obtained from PET(15$$ {}^{15} $$O‐water). The Myocardial Perfusion Reserve Index (MPRI) was estimated for 13$$ {}^{13} $$C GRE/bSSFP and DCE‐MRI and compared with the reference values. Results: Perfusion values, estimated by both DCE and 13$$ {}^{13} $$C MRI, were found to be lower than reference values. However, DCE‐MRI's estimated perfusion values were closer to the reference values than those obtained from 13$$ {}^{13} $$C MRI. In the case of MPRI estimation, the 13$$ {}^{13} $$C estimated MPRI values (GRE/bSSFP: 2.3/2.0) more closely align with the literature value (around 3) than the DCE estimated MPRI value (1.6). Conclusion: This study demonstrated the feasibility of 3D whole‐heart myocardial perfusion quantification using hyperpolarized HP001 with both GRE and bSSFP sequences. The 13$$ {}^{13} $$C perfusion measurements underestimated perfusion values compared to the 15$$ {}^{15} $$O PET literature value, while the 13$$ {}^{13} $$C estimated MPRI value aligned better with the literature. This preliminary result indicates 13$$ {}^{13} $$C imaging may more accurately estimate MPRI values compared to DCE‐MRI. [ABSTRACT FROM AUTHOR]

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.

PurposeTo demonstrate simultaneous hyperpolarization and imaging of three (13)C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([(13)C]urea, [(13)C]hydroxymethyl cyclopropane, and [(13)C]t-butanol) and correspondingly variable chemical shifts and physiological characteristics, and to exploit their varying diffusibility for simultaneous measurement of vascular permeability and perfusion in initial preclinical studies.MethodsRapid and efficient dynamic multislice imaging was enabled by a novel pulse sequence incorporating balanced steady state free precession excitation and spectral-spatial readout by multiband frequency encoding, designed for the wide, regular spectral separation of these compounds. We exploited the varying bilayer permeability of these tracers to quantify vascular permeability and perfusion parameters simultaneously, using perfusion modeling methods that were investigated in simulations. "Tripolarized" perfusion MRI methods were applied to initial preclinical studies with differential conditions of vascular permeability, in normal mouse tissues and advanced transgenic mouse prostate tumors.ResultsDynamic imaging revealed clear differences among the individual tracer distributions. Computed permeability maps demonstrated differential permeability of brain tissue among the tracers, and tumor perfusion and permeability were both elevated over values expected for normal tissues.ConclusionTripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.

Purpose: Water freely diffuses across cell membranes, making it suitable for measuring absolute tissue perfusion. In this study, we introduce an imaging method for conducting coronary artery angiography and quantifying myocardial perfusion across the entire heart using hyperpolarized water. Methods: 1H was hyperpolarized using dissolution dynamic nuclear polarization (dDNP) with UV-generated radicals. Submillimeter resolution coronary artery images were acquired as 2D projections using a spoiled GRE (SPGRE) sequence gated on diastole. Dynamic perfusion images were obtained with a multi-slice SPGRE with diastole gating, covering the entire heart. Perfusion values were analyzed through histograms, and the most frequent estimated perfusion value (the mode of the distribution), was compared with the average values for 15O water PET from the literature. Results: A liquid state polarization of 10% at the time of the injection and a 30 s T1 in D2O TRIS buffer were measured. Both coronary artery and dynamic perfusion images exhibited good quality. The main and small coronary artery branches were well resolved. The most frequent estimated perfusion value is around 0.6 mL/g/min, which is lower than the average values obtained from the literature for 15O-water PET (around 1.1 and 1.5 mL/g/min). Conclusions: The study successfully demonstrated the feasibility of achieving high-resolution, motion-free coronary artery angiography and 3D whole-heart quantitative myocardial perfusion using hyperpolarized water. [ABSTRACT FROM AUTHOR]

This first-in-man imaging study evaluated the safety and feasibility of hyperpolarized [1-¹³C]pyruvate as an agent for noninvasively characterizing alterations in tumor metabolism for patients with prostate cancer. Imaging living systems with hyperpolarized agents can result in more than 10,000-fold enhancement in signal relative to conventional magnetic resonance (MR) imaging. When combined with the rapid acquisition of in vivo ¹³C MR data, it is possible to evaluate the distribution of agents such as [1-¹³C]pyruvate and its metabolic products lactate, alanine, and bicarbonate in a matter of seconds. Preclinical studies in cancer models have detected elevated levels of hyperpolarized [1-¹³C]lactate in tumor, with the ratio of [1-¹³C]lactate/[1-¹³C]pyruvate being increased in high-grade tumors and decreased after successful treatment. Translation of this technology into humans was achieved by modifying the instrument that generates the hyperpolarized agent, constructing specialized radio frequency coils to detect ¹³C nuclei, and developing new pulse sequences to efficiently capture the signal. The study population comprised patients with biopsy-proven prostate cancer, with 31 subjects being injected with hyperpolarized [1-¹³C]pyruvate. The median time to deliver the agent was 66 s, and uptake was observed about 20 s after injection. No dose-limiting toxicities were observed, and the highest dose (0.43 ml/kg of 230 mM agent) gave the best signal-to-noise ratio for hyperpolarized [1-¹³C]pyruvate. The results were extremely promising in not only confirming the safety of the agent but also showing elevated [1-¹³C]lactate/[1-¹³C]pyruvate in regions of biopsy-proven cancer. These findings will be valuable for noninvasive cancer diagnosis and treatment monitoring in future clinical trials.

Hyperpolarized carbon‐13 labeled compounds are increasingly being used in medical MR imaging (MRI) and MR imaging (MRI) and spectroscopy (MRS) research, due to its ability to monitor tissue and cell metabolism in real‐time. Although radiological biomarkers are increasingly being considered as clinical indicators, biopsies are still considered the gold standard for a large variety of indications. Bioreactor systems can play an important role in biopsy examinations because of their ability to provide a physiochemical environment that is conducive for therapeutic response monitoring ex vivo. We demonstrate here a proof‐of‐concept bioreactor and microcoil receive array setup that allows for ex vivo preservation and metabolic NMR spectroscopy on up to three biopsy samples simultaneously, creating an easy‐to‐use and robust way to simultaneously run multisample carbon‐13 hyperpolarization experiments. Experiments using hyperpolarized [1‐13C]pyruvate on ML‐1 leukemic cells in the bioreactor setup were performed and the kinetic pyruvate‐to‐lactate rate constants (kPL) extracted. The coefficient of variation of the experimentally found kPLs for five repeated experiments was CV=35%. With this statistical power, treatment effects of 30%–40% change in lactate production could be easily differentiable with only a few hyperpolarization dissolutions on this setup. Furthermore, longitudinal experiments showed preservation of ML‐1 cells in the bioreactor setup for at least 6 h. Rat brain tissue slices were also seen to be preserved within the bioreactor for at least 1 h. This validation serves as the basis for further optimization and upscaling of the setup, which undoubtedly has huge potential in high‐throughput studies with various biomarkers and tissue types. [ABSTRACT FROM AUTHOR]