Hyperpolarized (13)C Magnetic Resonance Imaging Can Detect Metabolic Changes Characteristic of Penumbra in Ischemic Stroke

Magnetic resonance imaging (MRI) is increasingly the method of choice for rapid stroke assessment in patients and for guiding patient selection in clinical trials. The underlying metabolic status during stroke and following treatment is recognized as an important prognostic factor; thus, new methods are required to monitor local biochemistry following cerebral infarction, rapidly and in vivo. Hyperpolarized MRI with the tracer [1-(13)C]pyruvate enables rapid detection of localized [1-(13)C]lactate production, which has recently been shown in patients, supporting its translation to assess clinical stroke. Here we show the ability of hyperpolarized (13)C MRI to detect the metabolic alterations characteristic of endothelin-1-induced ischemic stroke in rodents. In the region of penumbra, determined via T2-weighted (1)H MRI, both [1-(13)C]pyruvate delivery and [1-(13)C]pyruvate cellular uptake independently increased. Furthermore, we observed a 33% increase in absolute [1-(13)C]lactate signal in the penumbra, and we determined that half of this increase was due to increased intracellular [1-(13)C]pyruvate supply and half was mediated by enhanced lactate dehydrogenase-mediated [1-(13)C]lactate production. Future work to characterize the kinetics of delivery, uptake, and enzymatic conversions of hyperpolarized tracers following ischemic stroke could position hyperpolarized (13)C MRI as an ideal technology for rapid assessment of the penumbra during the critical time window following ischemic stroke in patients.