[1‐¹³C] glucose MRS in chronic hepatic encephalopathy in man

Abstract

[1-13 C]-labeled glucose was infused intravenously in a single dose of 0.2 g/kg body weight over 15 min in six patients with chronic hepatic encephalopathy, and three controls. Serial 13 C MR spectra of the brain were acquired. Patients exhibited the following characteristics relative to normal controls: 1) Cerebral glutamine concentration was increased (12.6 ؎ 3.8 vs. 6.5 ؎ 1.9 mmol/kg, P < 0.006) and glutamate was reduced (8.2 ؎ 1.0 vs. 9.9 ؎ 0.6 mmol/kg, P < 0.02). 2)

Clinical experience with 13C MRS in vivo

“…[10][11][12][13][14][15][16][17][18][19] The following topics will be considered: R f coil design; proton-decoupling and safety; nuclear-Overhauser effects; peak assignments; quantitative analysis; 13 C substrate preparation; practicable i.v. infusion protocols; interpretation of metabolic models; experimental design and metabolic modeling to yield meaningful results; and clinical experience.…”

“…Correction factors were then applied for the quantification of clinical 13 C spectra (Table 1). 10,15,19 Peak assignments Broad-band excitation and proton-decoupling over the entire 4 kHz range results in excitation and assignment of all of five carbon atoms of glutamate and glutamine [ Fig. 3(A)], and many other interesting brain metabolites besides.…”

“…Nevertheless, it has been of value to have quantifiable data, even if the experimental range is rather broad. 15,17,18 Myoinositol, which appears in 1 H and 13 C MR spectra ( Fig. 4) and is not enriched during several hours of (1-13 C) glucose infusion, provides a robust internal reference from which all 13 C signals can be derived in mmol/unit brain volume.…”

“…26 Fortunately, with the more limited goal of finding clinically meaningful differences between patients and controls, our less rigorous approach has proved effective. 15,27 The arguments against 13 C glucose-insulin clamp are three: (a) cost-a total of 40-50 g of (1-13 C) glucose is typically infused to achieve and maintain steady state; we were able to reduce the cost of (1-13 C) glucose by 80% in our simpler protocol; (b) FDA concerns-somatostatin, the hormone which is used to prevent reactive insulin release during the glucose clamp, is not approved for use in children; (c) duration of the study-while achieving steady state can take several hours, 120 min in the MR scanner is already excessive. In future, it is probable that 13 C administered to the patient outside the MR scanner, with brief data acquisition at a pre-determined time, will provide a practical solution.…”

MR spectroscopy: its potential role for drug development for the treatment of psychiatric diseases

“…A second approach overcomes some of the low sensitivity of 13 C MRS while maintaining the high spectral resolution, and that is achieved by measuring concentrations of 13 C-labeled glutamate and glutamine after an infusion of [1-13 C]glucose. This approach has been used successfully to relate labeled quantities of glutamine with disease grade in hepatic encephalopathy (155). Of note is that NAA labeling in the patients was much lower than in the healthy controls, demonstrating that reduced NAA turnover rates can be detected in some conditions of neuronal compromise.…”