Dynamic metabolic imaging of copolarized [2-13C]pyruvate and [1,4-13C2]fumarate using 3D-spiral CSI with alternate spectral band excitation

Purpose: Developing a method for simultaneous metabolic imaging of copolarized [2-C-13]pyruvate and [1,4-C-13(2)]fumarate without chemical shift displacement artifacts that also permits different excitation flip angles for substrates and their metabolic products. Methods: The proposed pulse sequence consists of 2 frequency-selective radiofrequency pulses to alternatingly excite 2 spectral sub-bands each one followed by a fast 3D spiral CSI (3D-spCSI) readout. Spectrally selective radiofrequency pulses were designed to excite differential flip angles on substrates and products in each spectral sub-band. Number of signal averages analysis was used to determine a spectral width suitable to resolve the metabolites of interest in each of the sub-bands. Results: Phantom experiments verified the copolarization strategy and radiofrequency pulse design following differential flip angle used in our method. The signal behavior of the resonances in each sub-band was unaffected by the excitation of the respective alternate frequency band. Dynamic 3D C-13 CSI data demonstrated the ability of the sequence to image metabolites like pyruvate-hydrate, lactate, alanine, fumarate, and malate simultaneously and detect metabolic changes in the liver in a rat model of carbon tetrachloride-induced liver damage. Conclusion: The presented method allows the dynamic CSI of a mixture of [2-C-13] pyruvate and [1,4-C-13(2)]fumarate without chemical shift displacement artifacts while also permitting the use of different flip angles for substrate and product signals. The method is potentially useful for combined in vivo imaging of inflammation and cell necrosis.