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

Abstract

The purpose of this study was to directly compare two isotopic metabolic imaging approaches, hyperpolarized (HP) 13 C MRI and deuterium metabolic imaging (DMI), for imaging specific closely related segments of cerebral glucose metabolism at 4.7 T. Methods: Comparative HP-13 C and DMI neuroimaging experiments were conducted consecutively in normal rats during the same scanning session. Localized conversions of [1-13 C]pyruvate and [6,6-2 H 2 ]glucose to their respective downstream metabolic products were measured by spectroscopic imaging, using an identical 2D-CSI sequence with parameters optimized for the respective experiments. To facilitate direct comparison, a pair of substantially equivalent 2.5-cm double-tuned X/ 1 H RF surface coils was developed. For improved results, multidimensional low-rank reconstruction was applied to denoise the raw DMI data. Results: Localized conversion of HP [1-13 C]pyruvate to [1-13 C]lactate, and [6,6-2 H 2 ]glucose to [3,3-2 H 2 ]lactate and Glx-d (glutamate and glutamine), was detected in rat brain by spectroscopic imaging at 4.7 T. The SNR and spatial resolution of HP-13 C MRI was superior to DMI but limited to a short time window, whereas the lengthy DMI acquisition yielded maps of not only lactate, but also Glx production, albeit with relatively poor spectral discrimination between metabolites at this field strength. Across the individual rats, there was an apparent inverse correlation between cerebral production of HP [1-13 C]lactate and Glx-d, along with a trend toward increased [3,3-2 H 2 ]lactate. Conclusion: The HP-13 C MRI and DMI methods are both feasible at 4.7 T and have significant potential for metabolic imaging of specific segments of glucose metabolism. K E Y W O R D S brain, dynamic nuclear polarization, imaging, stable isotopes 1796 | von MoRZE Et al. How to cite this article: von Morze C, Engelbach JA, Blazey T, et al. Comparison of hyperpolarized 13 C and non-hyperpolarized deuterium MRI approaches for imaging cerebral glucose metabolism at 4.7 T.

Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

“…Moreover, its chemical shift spread enables an easier signal resolution. However, the longer acquisition time of DMI allows to observe not only the lactate but also Glx (glutamine and glutamate) production, thus creating metabolic map for both oxidative and non-oxidative pathways of glucose metabolism [ 61 ]. A variety of other analogous methods have been used relying on bioconversion of an administered probe including hyperpolarized 15 N MRI, as well as studies at thermal equilibrium using 13 C, 15 N, 19 F, and 31 P [ 62 , 63 , 64 , 65 , 66 ].…”

“…Straathof et al showed glucose metabolism after ischemic stroke in rats by presenting a significant increase in lactate formation in the diseased animals [ 98 ]. Furthermore, a recent publication compered DMI and HP [1- 13 C] pyruvate in imaging of cerebral metabolism, showing that they are both feasible methods at 4.7 T [ 61 ]. An alternate approach, described recently in Mahar et al, was to assess cerebral glucose metabolism by administering [ 2 H 7 ] glucose by looking at the HDO as the metabolic product, bypassing the need for lower resonance products such as lactate and Glx and showing that HDO can indeed serve as a biomarker of [ 2 H 7 ] glucose, lactate, and Glx metabolism [ 99 ].…”

Deuterium MRSI characterizations of glucose metabolism in orthotopic pancreatic cancer mouse models

“…MR spectroscopy (MRS) and spectroscopic imaging (MRSI), following the administration of deuterated metabolites, have recently been introduced and applied to image tissue metabolism 25–34 . Exogenously administered 2 H 6,6′ ‐glucose was found to originate 2 H 4,4′ ‐glutamate and 2 H 4,4′ ‐glutamine peaks in healthy brains, as well as a 2 H 3,3′ ‐lactate signature in tumors; a significant production of 2 H‐water was also detected in all the tissues.…”

Proton/Deuterium Magnetic Resonance Imaging of Rodents at 9.4T Using Birdcage Coils

“…However, PET imaging has disadvantages such as (1) using radioactive contrast agents which risk human health; (2) having limited applications for expectant mothers, children, and infants; (3) labeling agents with 18 F (e.g., 2‐ 18 F‐fluoro‐2‐deoxy‐ d ‐glucose, 18 FDG) as being unable to participate in downstream reactions, thus not being able to provide intact and complete metabolic information. Hyperpolarized 13 C magnetic resonance imaging (MRI) performs satisfactorily in both signal‐to‐noise ratios (SNRs) and spatial resolution [Merritt et al, 2007; von Morze et al, 2021], but the demanding polarization process and its short half‐life restrict the applications. A technique called deuterium metabolic imaging (DMI), which is based on deuterium magnetic resonance spectroscopy (MRS), has been developed recently to overcome these disadvantages [De Feyter et al, 2018, 2021; De Graaf et al, 2021; Hesse et al, 2021; Kreis et al, 2020; Lu et al, 2017].…”