Hyperpolarized 13 C magnetic resonance imaging for noninvasive assessment of tissue inflammation

Abstract

Inflammation is a central mechanism underlying numerous diseases and incorporates multiple known and potential future therapeutic targets. However, progress in developing novel immunomodulatory therapies has been slowed by a need for improvement in noninvasive biomarkers to accurately monitor the initiation, development and resolution of immune responses as well as their response to therapies. Hyperpolarized magnetic resonance imaging (MRI) is an emerging molecular imaging technique with the potential to assess immune cell responses by exploiting characteristic metabolic reprogramming in activated immune cells to support their function. Using specific metabolic tracers, hyperpolarized MRI can be used to produce detailed images of tissues producing lactate, a key metabolic signature in activated immune cells. This method has the potential to further our understanding of inflammatory processes across different diseases in human subjects as well as in preclinical models. This review discusses the application of hyperpolarized MRI to the imaging of inflammation, as well as the progress made towards the clinical translation of this emerging technique.

Keywords: hyperpolarized magnetic resonance imaging, inflammation.

FIGURE 1

A, Metabolic flux through glycolysis and into the tricarboxylic acid cycle, highlighting flux through lactate dehydrogenase (LDH) from the interconversion of hyperpolarized [1‐¹³C]pyruvate to [1‐¹³C]lactate. B, Spectrum generated in the heart from [1‐¹³C]pyruvate flux through LDH. C, Activation of immune cell in response to antigen receptor stimulation promoting the metabolic switch of pyruvate flux from the TCA to flux through glycolysis leading to increased production of lactate

FIGURE 2

A, in vitro activation of immune cells with pro‐inflammatory stimulus lipopolysaccharide (LPS) compared with quiescent immune cells given phosphate buffered saline (PBS). B, Hyperpolarized [1‐¹³C]pyruvate flux through LDH produces higher [1‐¹³C]lactate signals in LPS‐stimulated macrophages compared with control, unstimulated macrophages ⁵³

FIGURE 3

Hyperpolarized [1‐¹³C]lactate generation in a rodent model of cryoinfarction at 3 and 7 days postexperimental myocardial infarction ⁵³

FIGURE 4

Heatmaps of hyperpolarized [1‐¹³C]lactate, [1‐¹³C]pyruvate and [1‐¹³C]urea in rodent model of neuroinflammation induced by intracranial injection of lipopolysaccharide ⁸⁹