High-sensitivity deuterium metabolic MRI differentiates acute pancreatitis from pancreatic cancers in murine models

Abstract

Deuterium metabolic imaging (DMI) is a promising tool for investigating a tumor’s biology, and eventually contribute in cancer diagnosis and prognosis. In DMI, [6,6’-2H2]-glucose is taken up and metabolized by different tissues, resulting in the formation of HDO but also in an enhanced formation of [3,3’-2H2]-lactate at the tumor site as a result of the Warburg effect. Recent studies have shown DMI’s suitability to highlight pancreatic cancer in murine models by [3,3’-2H2]-lactate formation; an important question is whether DMI can also differentiate between these tumors and pancreatitis. This differentiation is critical, as these two diseases are hard to distinguish today radiologically, but have very different prognoses requiring distinctive treatments. Recent studies have shown the limitations that hyperpolarized MRI faces when trying to distinguish these pancreatic diseases by monitoring the [1-13C1]-pyruvate◊[1-13C1]-lactate conversion. In this work, we explore DMI’s capability to achieve such differentiation. Initial tests used a multi-echo (ME) SSFP sequence, to identify any metabolic differences between tumor and acute pancreatitis models that had been previously elicited very similar [1-13C1]-pyruvate◊[1-13C1]-lactate conversion rates. Although ME-SSFP provides approximately 5 times greater signal-to-noise ratio (SNR) than the standard chemical shift imaging (CSI) experiment used in DMI, no lactate signal was observed in the pancreatitis model. To enhance lactate sensitivity further, we developed a new, weighted-average, CSI-SSFP approach for DMI. Weighted-average CSI-SSFP improved DMI’s SNR by another factor of 4 over ME-SSFP –a sensitivity enhancement that sufficed to evidence natural abundance 2H fat in abdominal images, something that had escaped the previous approaches even at ultrahigh (15.2T) MRI fields. Despite these efforts to enhance DMI’s sensitivity, no lactate signal could be detected in acute pancreatitis models (n = 10; [3,3’-2H2]-lactate limit of detection < 100 µM; 15.2T). This leads to the conclusion that pancreatic tumors and acute pancreatitis may be clearly distinguished by DMI, based on their different abilities to generate deuterated lactate.