UCSF

Purpose

The goal of this study was to combine a specialized acquisition method with a new quantification pipeline to accurately and efficiently probe the metabolism of hyperpolarized ¹³ C-labeled compounds in vivo. In this study, we tested our approach on [2-¹³ C]pyruvate and [1-¹³ C]α-ketoglutarate data in rat orthotopic brain tumor models at 3T.

Methods

We used a multiband metabolite-specific radiofrequency (RF) excitation in combination with a variable flip angle scheme to minimize substrate polarization loss and measure fast metabolic processes. We then applied spectral-temporal denoising using singular value decomposition to enhance spectral quality. This was combined with LCModel-based automatic ¹³ C spectral fitting and flip angle correction to separate overlapping signals and rapidly quantify the different metabolites.

Results

Denoising improved the metabolite signal-to-noise ratio (SNR) by approximately 5. It also improved the accuracy of metabolite quantification as evidenced by a significant reduction of the Cramer Rao lower bounds. Furthermore, the use of the automated and user-independent LCModel-based quantification approach could be performed rapidly, with the kinetic quantification of eight metabolite peaks in a 12-spectrum array achieved in less than 1 minute.

Conclusion

The specialized acquisition method combined with denoising and a new quantification pipeline using LCModel for the first time for hyperpolarized ¹³ C data enhanced our ability to monitor the metabolism of [2-¹³ C]pyruvate and [1-¹³ C]α-ketoglutarate in rat orthotopic brain tumor models in vivo. This approach could be broadly applicable to other hyperpolarized agents both preclinically and in the clinical setting.