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

Abstract

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, 18 F-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. 13 C 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 18 F-FDG PET.

Measuring Tumor Glycolytic Flux in Vivo by Using Fast Deuterium MRI

“…Furthermore, it was not possible to make a quantitative estimate of glycolytic flux from these data. More recently, Brender et al (30) showed that dynamic images of tumor glucose consumption and lactate production could be acquired with nonhyperpolarized 13 C-labeled glucose by using tensor decomposition, which effectively uses all of the signal collected during 90 minutes of data acquisition, to denoise the images and to generate a time series of individual images. However, again there was no quantitative estimate of the glycolytic rate.…”

1H magnetic resonance spectroscopy of 2H-to-1H exchange quantifies the dynamics of cellular metabolism in vivo

“…Given ongoing efforts to establish robust acquisition and analysis methodologies for clinical 1 H MRS 27 , we expect that qMRS will be easily implemented on 3T and 7T clinical scanners, making it relatively straight-forward to translate to clinical use. It is also possible to further improve qMRS by applying spectral denoising strategies [28][29][30] ( Fig. S6).…”

Glycolytic metabolism of pathogenic T cells enables early detection of GvHD by13C-MRI

“…Wide clinical implementation of hyperpolarized metabolic imaging may be currently limited by the logistics and cost of equipment, but active clinical studies testing methodological modifications are currently being conducted and could facilitate wider application of metabolic MRI 30,64 . Furthermore, recent improvements in data processing have enabled omission of hyperpolarization for metabolic imaging and could be tested in the setting of GvHD 65,66 .…”