Analysis of glycogen storage disease by in vivo¹³C NMR comparison of normal volunteers with a patient

Abstract

Broadband proton-decoupled natural abundance 13C spectra of the human calf, liver, and head were obtained from normal volunteers and a patient with glycogen type IIIA storage disease. Two concentric and coplanar surface coils of diameters 8.0 cm and 13.0 cm were used for 13C (at 16.0 MHz) and 1H (at 63.6 MHz), respectively. A WALTZ-8 sequence lead to homogeneous decoupling over a large volume. In addition to lipid resonances a variety of other metabolite resonances could be resolved. The glycogen concentration in the muscle and the liver of normal volunteers varied considerably depending on dietary preparation and physical exercise. The glycogen level in the liver and the calf of a patient with glycogen type IIIA storage disease was increased by a factor of 2-3 compared to normal, well-trained volunteers. Proton-decoupled 13C spectra of human head are reported for the first time. The spectra are dominated by lipid resonances but an additional resonance at 54.0 ppm is clearly visible. The proton-decoupled 13C head spectrum of a patient with glycogen type IIIA storage disease revealed additional resonances between 71.0 and 85.0 ppm.

Progress towards in vivo brain 13C-MRS in mice: Metabolic flux analysis in small tissue volumes

“…Metabolic steady state is usually assumed, which means that total concentrations of the metabolic pools as well as metabolic fluxes are constant throughout the infusion experiment. Studies tracking the time evolution of the pool sizes, as possible with 1 …”

“…Given the limitations in 13 C detection in vivo in small volumes, 13 C MRS in mice was at first applied to tissue brain extracts with indirect detection [95]: these results gave a quantitative appreciation of neuroglial metabolism with their respective regional differences and distinction of GABAergic and glutamatergic neurotransmission. A first proof of concept of the feasibility of in vivo detection was made at 7 Tesla with a direct detection sequence applying 1 H polarization transfer to 13 C, combined to 1 H broadband localization [50] in a volume of interest of 175 mL [27].…”

“…Although most of the early 13 C MRS human studies were based on detection of natural abundance signals [1,2,5,6,8], the technique met its wider success with the combined injection of 13 C-enriched substrates like glucose and acetate, as single or multiple substrate intravenous administration. These substrates in their different isotopically labelled forms enabled specific insights on compartmentalized cerebral metabolism in the healthy brain and in various brain diseases in human and animal models when combined with 13 C metabolic flux analysis (MFA).…”

A Half-Volume Coil for Efficient Proton Decoupling in Humans at 4 Tesla

“…The calcuwhich compares favorably with the 21:1 SNR reported for lated maximal SAR local (Eq. [3]) is within the FDA guide-5 min measurements at 4.7 T using a 3.5 cm 13 C coil (15). lines for local power deposition.…”

“…Despite these drawbacks, conin that 1 H decoupling can increase spectral resolution, especially in the PME and PDE resonances at low magnetic centric coil design was not prohibitive for some clinical applications using small coils at 4.7 T (14) as well as at fields (1), and improved signal-to-noise ratio (SNR) can be obtained by NOE generation. These heteronuclear tech-1.5-2.1 T (15,16). However, for the volumes needed for human applications at 4 T, we found that the performance niques use relatively long and intense RF irradiation at the 1 H frequency, which can make it difficult to achieve decou-of the proton coil in a double concentric arrangement was not sufficient for decoupling within FDA guidelines.…”