UCSF

Hyperpolarized ¹³C magnetic resonance imaging has become a powerful tool for investigating metabolism and perfusion in vivo for a variety of diseases, such as cancer and diabetes. Recent phase II human studies in prostate, brain, and liver cancer have shown the ability to probe pyruvate metabolism in a rapid, noninvasive, and safe fashion. However, with the short lifetime of the hyperpolarized ¹³C magnetization, rapid sequences need to be developed to efficiently use all the magnetization. The goal of my work presented here was to develop the balanced steady-state free precession (bSSFP) sequence for high spatiotemporal resolution imaging of both metabolically active compounds, such as pyruvate and lactate, and perfusion compounds, such as urea. Initial in vivo studies showed the capability of both 1 mm² in-plane T₂ mapping and 1.5 mm 3D isotropic imaging of multiple probes, including [1-¹³C]pyruvate, [2-¹³C]pyruvate, [1-¹³C]lactate, and [¹³C,¹⁵N₂]urea. Differences in T₂ values as well as biodistribution and uptake of each compound were detected within healthy rat kidneys, liver, and heart, as well as tumors within tumor-bearing mice. To improve dynamic imaging at these high spatial resolutions, a local low rank plus sparse (LLR+S) reconstruction was employed, which allowed for 3D dynamic imaging at 1.5 mm isotropic resolution, as well as sub-millimeter and 3D 1 mm isotropic T₂ mapping, with each image acquired in <1 s. The LLR+S reconstruction enforced both low rank and sparse constraints via iterative soft thresholding on singular values and sparse coefficients to reconstruct undersampled dynamic MRI. Additionally, the bSSFP approach was further developed for simultaneous acquisition of multiple hyperpolarized probes, such as [1-¹³C]pyruvate and produced [1-¹³C]lactate, as well as [2-¹³C]pyruvate, [1-¹³C]lactate, and [¹³C,¹⁵N₂]urea. This metabolite-specific imaging was accomplished via an optimization of the RF pulse design, width, and time-bandwidth, as well as repetition time, and incorporation of spectral suppression pulses for the case of [1-¹³C]pyruvate/[1-¹³C]lactate imaging. The techniques developed were designed to have significant biomedical and clinical benefits, and can potentially provide high spatiotemporal assessment of multiple anatomical structures and disease progression.