UCSF

Magnetic resonance imaging using hyperpolarized ¹³C-labeled small molecules has emerged as an extremely powerful tool for the in vivo monitoring of perfusion and metabolism. This work presents methods for improved imaging, parameter mapping, and image contrast generation for in vivo hyperpolarized ¹³C MRI. Angiography using hyperpolarized urea was greatly improved with a highly T₂-weighted acquisition in combination with ¹⁵N labeling of the urea amide groups. This is due to the fact that the T₂ of [¹³C]urea is strongly limited by the scalar coupling to the neighboring quadrupolar ¹⁴N. The long in vivo T₂ values of [¹³C,¹⁵N2]urea were utilized for sub-millimeter projection angiography using a contrast agent that could be safely injected in concentrations of 10-100 mM while still tolerated in patients with renal insufficiency. This study also presented the first method for in vivo T₂ mapping of hyperpolarized ¹³C compounds. The in vivo T₂ of urea was short in the blood and long within the kidneys. This persistent signal component was isolated to the renal filtrate, thus enabling for the first time direct detection of an imaging contrast agent undergoing glomerular filtration. While highly T₂-weighted acquisitions select for molecules with short rotational correlation times, high diffusion weighting selects for those with the long translational correlation times. A specialized spin-echo EPI sequence was developed in order to generate highly diffusion-weighted hyperpolarized ¹³C images on a clinical MRI system operating within clinical peak- RF and gradient amplitude constraints. Low power adiabatic spin echo pulses were developed in order to generate a sufficiently large refocused bandwidth while maintaining low nominal power. This diffusion weighted acquisition gave enhanced tumor contrast-to-noise ratio when imaging [1-¹³C]lactate after infusion of [1-¹³C]pyruvate. Finally, the first in-man hyperpolarized 13C MRI clinical trial is discussed.