Simultaneous Multiagent Hyperpolarized ¹³C Perfusion Imaging

Purpose: To demonstrate simultaneous hyperpolarization and imaging of three ¹³C-labeled perfusion MRI contrast agents with dissimilar molecular structures ([¹³C]urea, [¹³C]hydroxymethyl cyclopropane, and [¹³C]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. Methods: Rapid 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. Results: Dynamic 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. Conclusion: Tripolarized perfusion MRI provides new molecular imaging measures for specifically monitoring permeability, perfusion, and transport simultaneously in vivo.