Background: Magnetic resonance imaging (MRI) with hyperpolarized [1-¹³C]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 [1-¹³C]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 ¹³C-pyruvate to ¹³C-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 [1-¹³C]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.

Dental plaque formation occurs in a systematic manner, with early bacterial colonizers creating a favorable environment for secondary colonizers.¹ In the transition from early colonizers to secondary colonizers, the dental plaque microbiome shifts to include a complex mixture of acidogenic (acid-producers) and aciduric (acid-tolerant) species.^{1 – 3} Plaque bacterial metabolism of dietary sugar and carbohydrates^4,5 produces lactic and other organic acids as by-products. The pH of dental plaques drop following a sucrose rinse and is restored back to baseline pH (now known as the Stephan curve), and repeated time spent below critical pH ($\sim 5.5$)⁶ leads to demineralization of enamel.⁷ Organic acids produced by these bacteria, specifically lactic and acetic acid, have been shown to cause enamel demineralization.^3,4 This demineralization may progress to the clinical diagnosis of dental caries or breakdown of the tooth enamel surface.⁸