Considering whole-body metabolism in hyperpolarized MRI through 13 C breath analysis-An alternative way to quantification and normalization?

Abstract

Purpose: Hyperpolarized [1-¹³ C]pyruvate MRI is an emerging clinical tool for metabolic imaging. It has the potential for absolute quantitative metabolic imaging. However, the method itself is not quantitative, limiting comparison of images across both time and between individuals. Here, we propose a simple signal normalization to the whole-body oxidative metabolism to overcome this limitation.

Theory and methods: A simple extension of the model-free ratiometric analysis of hyperpolarized [1-¹³ C]pyruvate MRI is presented, using the expired ¹³ CO₂ in breath for normalization. The proposed framework was investigated in two porcine cohorts (N = 11) subjected to local renal hypoperfusion defects and subsequent [1-¹³ C]pyruvate MRI. A breath sample was taken before the [1-¹³ C]pyruvate injection and 5 min after. The raw MR signal from both the healthy and intervened kidney in the two cohorts was normalized using the ¹³ CO₂ in the expired air.

Results: ¹³ CO₂ content in the expired air was significantly different between the two cohorts. Normalization to this reduced the coefficients of variance in the aerobic metabolic sensitive pathways by 25% for the alanine/pyruvate ratio, and numerical changes were observed in the bicarbonate/pyruvate ratio. The lactate/pyruvate ratio was largely unaltered (<2%).

Conclusion: Our results indicate that normalizing the hyperpolarized ¹³ C-signal ratios by the ¹³ CO₂ content in expired air can reduce variation as well as improve specificity of the method by normalizing the metabolic readout to the overall metabolic status of the individual. The method is a simple and cheap extension to the hyperpolarized ¹³ C exam.

Keywords: MRI; carbon-13; hyperpolarization; ischemia; metabolism; pyruvate.