Initial Experience on Hyperpolarized [1-C-13]Pyruvate MRI Multicenter Reproducibility-Are Multicenter Trials Feasible?

Background: Magnetic resonance imaging (MRI) with hyperpolarized [1-C-13]pyruvate allows real-time and pathway specific clinical detection of otherwise unimageable in vivo metabolism. However, the comparability between sites and protocols is unknown. Here, we provide initial experiences on the agreement of hyperpolarized MRI between sites and protocols by repeated imaging of same healthy volunteers in Europe and the US. Methods: Three healthy volunteers traveled for repeated multicenter brain MRI exams with hyperpolarized [1-C-13]pyruvate within one year. First, multisite agreement was assessed with the same echo-planar imaging protocol at both sites. Then, this was compared to a variable resolution echo-planar imaging protocol. In total, 12 examinations were performed. Common metrics of C-13-pyruvate to C-13-lactate conversion were calculated, including the k(PL), a model-based kinetic rate constant, and its model-free equivalents. Repeatability was evaluated with intraclass correlation coefficients (ICC) for absolute agreement computed using two-way random effects models. Results: The mean k(PL) across all examinations in the multisite comparison was 0.024 +/- 0.0016 s(-1). The ICC of the k(PL) was 0.83 (p = 0.14) between sites and 0.7 (p = 0.09) between examinations of the same volunteer at any of the two sites. For the model-free metrics, the lactate Z-score had similar site-to-site ICC, while it was considerably lower for the lactate-to-pyruvate ratio. Conclusions: Estimation of metabolic conversion from hyperpolarized [1-C-13]pyruvate to lactate using model-based metrics such as k(PL) suggests close agreement between sites and examinations in volunteers. Our initial results support harmonization of protocols, support multicenter studies, and inform their design.