Measuring Tumor Glycolytic Flux in Vivo by Using Fast Deuterium MRI

Abstract

Background: Tumor cells frequently show high rates of aerobic glycolysis, which provides the glycolytic intermediates needed for the increased biosynthetic demands of rapid cell growth and proliferation. Existing clinical methods (fluorodeoxyglucose PET and carbon 13 MRI and spectroscopy) do not allow quantitative images of glycolytic flux. Purpose: To evaluate the use of deuterium (hydrogen 2 [ 2 H]) MR spectroscopic imaging for quantitative mapping of tumor glycolytic flux and to assess response to chemotherapy. Materials and Methods: A fast three-dimensional 2 H MR spectroscopic imaging pulse sequence, with a time resolution of 10 minutes, was used to image glycolytic flux in a murine tumor model after bolus injection of D-[6,6'-2 H 2 ]glucose before and 48 hours after treatment with a chemotherapeutic agent. Tumor lactate labeling, expressed as the lactate-to-water and lactate-to-glucose signal ratios, was also assessed in localized 2 H MR spectra. Statistical significance was tested with a one-sided paired t test. Results: 2 H MR spectroscopic imaging showed heterogeneity in glycolytic flux across the tumor and an early decrease in flux following treatment with a chemotherapeutic drug. Spectroscopy measurements on five animals showed a decrease in the lactate-to-water signal ratio, from 0.33 6 0.10 to 0.089 6 0.039 (P = .005), and in the lactate-to-glucose ratio, from 0.27 6 0.12 to 0.12 6 0.06 (P = .04), following drug treatment. Conclusion: Rapidly acquired deuterium (hydrogen 2) MR spectroscopic images can provide quantitative and spatially resolved measurements of glycolytic flux in tumors that can be used to assess treatment response. Published under a CC BY 4.0 license.

Comparison of hyperpolarized 13C and non‐hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T

“…Additional studies are needed to verify these findings, probably better conducted in a range of normal and abnormal tissues with wider differences in their metabolic activities. In addition to some overlapping potential, HP 13 C and DMI also have many complementary features, particularly in terms of the possibility for absolute metabolic rate quantitation through DMI, 5,8 as compared with higher sensitivity and potential for higher-resolution imaging through HP 13 C. For example, spatially coarse metabolic rate maps acquired using DMI could be augmented with higher-resolution mapping of lactate pools using HP 13 C, providing enhanced tumor localization together with quantitative metabolic readouts.…”

“…Natural abundance background HDO signal (~10 mM) is also detectable in DMI, facilitating absolute concentration referencing. Enrichment of this peak is known to occur during the glucose DMI experiment, likely through multiple pathways, 26 and there is evidence that this enrichment may be largely due to nonspecific inflow of HDO 5 . Although there have been some successful efforts toward HP [ 13 C]glucose imaging, 27,28 its T 1 s are much shorter than [1‐ 13 C]pyruvate, even with deuteration, and consequently this approach has not found widespread application for in vivo metabolic imaging studies.…”

“…This low-rank approach is very similar to two recent studies that applied low-rank denoising with similar compression factors for improved dynamic spectroscopic imaging of [U- 13 C] glucose and [6,6-2 H 2 ]glucose, respectively. 5,36 Although also potentially applicable for denoising HP- 13 C data, 37 low-rank analysis was applied only for the DMI data because of its intrinsically lower SNR. The DMI imaging data were oversampled by a factor of two along both spatial dimensions, to match the resolution of the HP-13 C acquisition.…”

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 .…”

In vitro singlet state and zero-quantum encoded magnetic resonance spectroscopy: Illustration with N-acetyl-aspartate

“…2 H-enriched, nonradioactive molecules like 2 H-glucose are used to obtain background-free spectra in vivo. Valuable insights into biochemistry were gained by this approach [ 8 – 10 ]. However, because of the limited amount of substrate that can be administered in conjunction with the low magnetogyric ratio of 2 H, the signal remains low and does not allow routine high-resolution imaging.…”