Quantifying metabolism in vivo using PET/MRI with hyperpolarized compounds and development of MRI pulse sequences

Magnetic resonance spectroscopic imaging (MRSI) has been used to study biochemical processes non-invasively, although it suffers from a low sensitivity and requires long scan times. The invention of hyperpolarization (HP) techniques has shifted these limits, allowing signal enhancements of 13C-labelled metabolites by more than five orders of magnitude. However, hyperpolarized signals decay with the spin-lattice relaxation time (T1) which is on the order of a few tens of seconds, limiting the time available for signal acquisition and requiring fast signal acquisition.

Hyperpolarized [1-13C]pyruvate is most often used in vivo, because of its key role in glucose metabolism, its fast metabolic conversion to lactate, its high achievable polarization level and a relatively long T1. Tumors readily internalize and metabolize pyruvate to lactate by lactate dehydrogenase (LDH-A). The expression of LDH-A is upregulated in many tumors, which results in an increased pyruvate-to-lactate conversion that can be quantified with MRSI.

We attempt to assess the flux of glucose through the glycolytic pathway simultaneously with both FDG-PET and pyruvate imaging. In a recent study, we established and validated a workflow at a clinical whole-body PET/MR for the multiparametric characterization of the glycolytic flux in a pre-clinical MAT-B-III breast cancer model. We analyzed the in vivo correlation of FDG uptake with pyruvate-to-lactate conversion and performed a longitudinal study with a group of tumor-bearing rats to study the effect of changing tumor cellularity on metabolic PET and MRSI data (see Figure 1).

In this study, single-frequency bSSFP (without multi-echoes) was used for consecutively imaging individual hyperpolarized metabolites in vitro and in vivo. The Warburg effect was imaged by observing the exchange of [1-13C]pyruvate and [1-13C]lactate. In a recent study, we investigated multi-echo-bSSFP-IDEAL at 3T. Compared to previous results, the spatial and temporal resolution was substantially improved such that observation of the metabolic conversion in one slice or 3D metabolite mapping became possible (see Figure 2).