Technical Development of Hyperpolarized [1-13C]Pyruvate Imaging for Clinical Translation
Magnetic resonance imaging with hyperpolarized [1-13C]pyruvate is an emerging tool for assessing in vivo metabolism noninvasively. Over the past few years since the first clinical study with prostate cancer patients, translational studies using this imaging technique have been focused on demonstrating the feasibility of applying to healthy subjects and patients under several pathophysiological conditions. However, there are multiple remaining technical limitations to overcome for translating the technique to clinics. In this study, I made three technical advances in imaging hyperpolarized [1-13C]pyruvate and products in humans. First, I measured in vivo T2* of hyperpolarized signals, one of the key parameters that directly affect 13C acquisition methods and image quality. Measuring the in vivo T2*'s can be useful for optimizing the acquisition parameters and improving the signal-to-noise ratio. I proposed a dynamic 13C metabolite-selective multi-echo spiral imaging sequence for the T2* measurement of hyperpolarized 13C-labeled metabolites. The feasibility and reproducibility of the method were confirmed by phantom and rat studies. Moreover, from healthy volunteers, in vivo T2*s of hyperpolarized [1-13C]pyruvate, [1-13C]lactate and [13C]bicarbonate were measured from cardiac tissue compartments using the sequence. Second, I developed a cardiac-gated multi-phase 13C imaging sequence for the human heart. To demonstrate cyclic changes in cardiac metabolic profiles seen by hyperpolarized signals, dual-phase cardiac imaging of hyperpolarized [1-13C]pyruvate, [1-13C]lactate, [1-13C]alanine and [13C]bicarbonate was conducted at end-systole (ES) and end-diastole (ED) on the short-axis and vertical long-axis planes. Significantly smaller myocardial signal of [13C]bicarbonate relative to [1-13C]lactate was observed at ED compared to that at ES (p < 0.05). Third, a patch-based algorithm (PA) was developed to improve spatial resolution of hyperpolarized 13C images by exploiting the co-registered high-resolution 1H images. The spatial resolution of hyperpolarized 13C imaging is genuinely poor, compromising the overall image conspicuity and limiting accurate assessment of the hyperpolarized 13C metabolites. The PA was validated in simulation and phantom studies, and was further applied to low-resolution human brain metabolite maps of hyperpolarized [1-13C]pyruvate and [1-13C]lactate with three compartment segmentation (grey matter, white matter and cerebrospinal fluid). The results demonstrated that the PA can enhance low-resolution hyperpolarized 13C images in terms of spatial resolution and contrast while preserving quantification accuracy and intra-compartment signal inhomogeneity.