Dipolar coupling and ordering effects observed in magnetic resonance spectra of skeletal muscle

Abstract

Skeletal muscle is a biological structure with a high degree of organization at different spatial levels. This order influences magnetic resonance (MR) in vivo-in particular 1 H-spectra-by a series of effects that have very distinct physical sources and biomedical applications: (a) bulk fat (extramyocellular lipids, EMCL) along fasciae forms macroscopic plates, changing the susceptibility within these structures compared to the spherical droplets that contain intra-myocellular lipids (IMCL); this effect leads to a separation of the signals from EMCL and IMCL; (b) dipolar coupling effects due to anisotropic motional averaging have been shown for 1 H-resonances of creatine, taurine, and lactate; (c) aromatic protons of carnosine show orientation-dependent effects that can be explained by dipolar coupling, chemical shift anisotropy or by relaxation anisotropy; (d) limited rotational freedom and/or compartmentation may explain differences of 1 H-MR-visibility of the creatine/phosphocreatine resonances; (e) lactate 1 H-MR resonances are reported to reveal information on tissue compartmentation; (f) transverse relaxation of water and metabolites show multiple components, indicative of intra-, extracellular and/or macromolecular-bound pools, and in addition dipolar or J-coupling lead to a modulation of the signal decay, hindering straightforward interpretation; (g) diffusion weighted 31 P-MRS has shown restricted diffusion of phosphocreatine; (h) magnetization transfer (MT) indicates that there is a motionally restricted proton pool in spin-exchange with free creatine; reduced availability or restricted motion of creatine is particularly important for an estimation of ADP from 31 P-MR spectra, and in addition MT effects may alter the signal intensity of creatine 1 H-resonances following water-suppression pulses; (i) transcytolemmal water-exchange can be studied in 1 H-MRS by contrast-agents applied to the extracellular space; (k) transport of glucose across the cell membrane has been studied in diabetes patients using a combination of 13 C-and 31 P-MRS; and (l) residual quadrupolar interaction in 23 Na MR spectra from human skeletal muscle suggest that sodium ions are bound to ordered muscular structures.

Role of proton MR for the study of muscle lipid metabolism

“…The tumbling of the molecules and the subsequent modulation of the magnetic field allows a spin to interact with the lattice (T 1 relaxation) and leads to a dephasing of the spins in the transversal plane (T 2 relaxation). This tumbling of water molecules or metabolites can be anisotropic in ordered tissues; however, it would go far beyond the scope of this overview to review anisotropic relaxation effects in MRI and MRS (73,81).…”

“…In muscle spectra the line width of the extramyocellular lipid signal (EMCL) is particularly affected by susceptibility-induced magnetic field distribution, as mentioned before. This may limit the advantages of the better separation of the resonances in some muscles, depending on the orientation of the fibers ['pennation angle' (73)] relative to the main magnetic field. Figure 11 shows spectra of two muscles with different pennation angles from a 26-year-old male volunteer recorded at 1.5 and 3.0 T. Experimentally, the SNR is elevated by a factor of 1.7 to 1.8 at 3.0 T as compared with 1.5 T. While fibers of the tibialis anterior muscle are almost parallel to the main magnetic field, the fibers of the soleus muscle (SOL) are tilted such that the angle between fibers and main field is close to the magic angle (4,73) where dipolar coupling of the metabolites, in particular creatine-CH 2 is canceled and the doublet at 3.96 ppm degenerates to a singlet.…”

“…This may limit the advantages of the better separation of the resonances in some muscles, depending on the orientation of the fibers ['pennation angle' (73)] relative to the main magnetic field. Figure 11 shows spectra of two muscles with different pennation angles from a 26-year-old male volunteer recorded at 1.5 and 3.0 T. Experimentally, the SNR is elevated by a factor of 1.7 to 1.8 at 3.0 T as compared with 1.5 T. While fibers of the tibialis anterior muscle are almost parallel to the main magnetic field, the fibers of the soleus muscle (SOL) are tilted such that the angle between fibers and main field is close to the magic angle (4,73) where dipolar coupling of the metabolites, in particular creatine-CH 2 is canceled and the doublet at 3.96 ppm degenerates to a singlet. Spectra were recorded from the same voxel with identical measurement parameters for 1.5 and 3.0 T. At the higher field strength, the separation of IMCL-CH 2 and EMCL-CH 2 is clearly improved, in particular in the soleus spectrum where the lines are inherently less separated than in the tibialis anterior.…”

Inductively coupled helmholtz coil on a dedicated imaging platform for the in vivo1H‐MRS measurement of intramyocellular lipids in the hind leg of rats

“…Because muscles are characterized by having a highly anisotropic environment that induces an orientation-dependence of chemical shifts in the MR spectra, it is important to reproducibly align the muscle fibers along the axis of the static magnetic field. By doing so, one obtains fully featured and undistorted MR spectra with a good separation of IMCL and EMCL resonances (10,11).…”

Significant differences in proton trimethyl ammonium signals between human gastrocnemius and soleus muscle

“…In vivo proton spectroscopy of muscles can directly monitor creatine (4,5), carnitine (6,7), extramyocelluar lipid (EMCL), intramyocellular lipid (IMCL) (8 -11), pH-sensitive imidazole protons of histidine (12), and deoxymyoglobin (13). Because of the discovery of the effect of fiber orientation on 1 H metabolites (14,15), in vivo 1 H MRS of skeletal muscle offers the potential to investigate both physical changes and biochemical changes induced by a diseased process or physiological activity. Despite enormous achievement, however, the progress of in vivo proton MRS of neuromuscular disorders has been slow.…”