Dynamic Imaging of Glucose and Lactate Metabolism by ¹³C-MRS without Hyperpolarization

Metabolic reprogramming is one of the defining features of cancer and abnormal metabolism is associated with many other pathologies. Molecular imaging techniques capable of detecting such changes have become essential for cancer diagnosis, treatment planning, and surveillance. In particular, ¹⁸F-FDG (fluorodeoxyglucose) PET has emerged as an essential imaging modality for cancer because of its unique ability to detect a disturbed molecular pathway through measurements of glucose uptake. However, FDG-PET has limitations that restrict its usefulness in certain situations and the information gained is limited to glucose uptake only.¹³C magnetic resonance spectroscopy theoretically has certain advantages over FDG-PET, but its inherent low sensitivity has restricted its use mostly to single voxel measurements unless dissolution dynamic nuclear polarization (dDNP) is used to increase the signal, which brings additional complications for clinical use. We show here a new method of imaging glucose metabolism in vivo by MRI chemical shift imaging (CSI) experiments that relies on a simple, but robust and efficient, post-processing procedure by the higher dimensional analog of singular value decomposition, tensor decomposition. Using this procedure, we achieve an order of magnitude increase in signal to noise in both dDNP and non-hyperpolarized non-localized experiments without sacrificing accuracy. In CSI experiments an approximately 30-fold increase was observed, enough that the glucose to lactate conversion indicative of the Warburg effect can be imaged without hyper-polarization with a time resolution of 12s and an overall spatial resolution that compares favorably to ¹⁸F-FDG PET.