Magnetic resonance imaging of glycogen using its magnetic coupling with water

Abstract

Glycogen plays a central role in glucose homeostasis and is abundant in several types of tissue. We report an MRI method for imaging glycogen noninvasively with enhanced detection sensitivity and high specificity, using the magnetic coupling between glycogen and water protons through the nuclear Overhauser enhancement (NOE). We show in vitro that the glycogen NOE (glycoNOE) signal is correlated linearly with glycogen concentration, while pH and temperature have little effect on its intensity. For validation, we imaged glycoNOE signal changes in mouse liver, both before and after fasting and during glucagon infusion. The glycoNOE signal was reduced by 88 ± 16% (n = 5) after 24 h of fasting and by 76 ± 22% (n = 5) at 1 h after intraperitoneal (i.p.) injection of glucagon, which is known to rapidly deplete hepatic glycogen. The ability to noninvasively image glycogen should allow assessment of diseases in which glucose metabolism or storage is altered, for instance, diabetes, cardiac disease, muscular disorders, cancer, and glycogen storage diseases.

Mechanism and quantitative assessment of saturation transfer for water‐based detection of the aliphatic protons in carbohydrate polymers

“…The Z-spectra for glycogen were fit to 4 Lorentzian line shapes 26 (centered at +1.2, +0.6, 0.0, and −1.0 ppm) 14,24 (…”

“…12 Quantifying the concentrations of sugar polymers in vivo is desirable for evaluating cellular metabolism and functions. 12,[40][41][42][43] These sugar polymers have been previously detected in vivo with signal enhancement using CEST MRI method, 11,12,14,24 opening up opportunities to study carbohydrate polymer metabolism at high spatial and temporal resolutions in vivo. Another carbohydrate polymer, dextran, has been assessed with CEST MRI to study tumor-based blood brain barrier permeability 44,45 and even tumor receptor binding.…”

“…Previous CEST MRI studies [11][12][13][14] on carbohydrate polymers such as glycogen and glycosaminoglycans reported strong magnetic connections between the aliphatic protons in these macromolecules and water protons. For CEST experiments on macromolecular carbohydrates, 12,14 the MT from an aliphatic proton to water can be achieved via 2 mechanisms 2,3,14,15 : (1) relayed NOE (rNOE), in which the NOE between an aliphatic proton and a neighboring labile (hydroxyl or amino) proton is relayed to water via chemical exchange; and (2) direct NOE between aliphatic protons and long-lived (>1 ns) bound water, which has been shown to exist in DNA, 16 RNA, 17 and protein interior space. 18 For both solid-like proteins 19 and large mobile proteins, 2,20,21 previous evidence in vitro and in vivo shows that the MT to water under physiological conditions is dominated by the rNOE mechanism.…”

MRI monitoring of energy storage in vivo using magnetization pathways

“…However, at present, none of the proposed methods has proven to be robust, reliable, or practical for routine use and translation to clinical practice. In PNAS, Zhou et al (5) introduce an MRI method for glycogen mapping relying only on endogenous molecules and manipulation of their magnetization via radiofrequency (RF) pulses. The approach has the potential to overcome limitations of previous technologies and become a game changer for the noninvasive mapping of glycogen in vivo.…”

“…In PNAS, Zhou et al (5) use the NOE mechanism to create MRI contrast weighted by glycogen. The method is dubbed glycoNOE.…”