Introduction

MRI measures mostly protons in water molecule and offers information in the macroscopic scale, while MR spectroscopy offers the measurement of many other nuclei (e.g.¹³C, ³¹P, ¹⁵N, ¹⁹F, ¹⁷O, ²H, etc.) and molecules in a scale of four orders of magnitude smaller. 1H MRS can offer the measurement of a large number of metabolites such as N‐acetylaspartate, creatine, glutamate, choline, γ–aminobutyric acid. The administration of ¹³C labelled substrates together with ¹³C MRS allows us to track the fate of the infused substrate in its metabolic pathway and to measure metabolic fluxes through a mathematic model. ³¹P MRS allows the noninvasive measurement of phosphorylated metabolites such as phosphocreatine, adenosine triphosphate (ATP), inorganic phosphate, membrane metabolites, physiological parameters (pH, [Mg²⁺]) and enzyme activities of ATP production and utilization together with magnetization transfer. This course will start with showing some typical ¹H, ¹³C or ³¹P MR spectra and then introduce the basic physics behind them.

MR spectral characteristics (chemical shift and J-coupling)

Nuclei of the same element were found to be precessing at different frequencies depending on the chemical environment. For example, the protons in the CH₃ groups of creatine experience a different local magnetic field than those in the CH₂ groups. This kind of chemical environment dependent frequency shift is called chemical shift. It is caused by the shielding of nuclei by their surrounding electrons in a magnetic field. The static field B0 induces currents in the orbital electrons, which in turn generate a field that is ∼ 10⁻⁶ times smaller than the main magnetic field. Therefore, the nuclear spins experience both B₀ and the induced local magnetic field. In addition, splitting of MR peaks into multiplets can often be observed, which is referred as the coupling between nuclear spins through the bonding electrons (spin-spin coupling or J-coupling).
In MR spectra, most molecules of interest are complex J-coupled systems. This usually results in complex spectral patterns, which act as a “fingerprint” for identifying these biochemical compounds. MR spectral characteristics also depends on the applied pulse sequence, B0, relaxation times and field inhomogeneity. Predicting the behavior of the spectral pattern and intensity based on density matrix formalism allows us to design new pulse sequences for a specific purpose, or to choose the most appropriate sequence and inter-pulse delays for optimizing signal detection. For example, spectral editing methods based on J-modulation of coupled spin system are developed for the detection of less resolved metabolites such as γ–aminobutyric acid.

Water and lipid suppression

¹H MRS provides the highest sensitivity among all MR visible nuclei due to its high gyromagnetic ratio and natural abundance. However, it also faces several challenges, such as an intense water signal and lipid signal contamination. The intensive water signal will cause baseline distortions or spurious signal, which in turn affects the measurements of the resonances of interest. Therefore, a water suppression module is usually necessary in ¹H localized MRS. VAPOR is a relaxation based technique that commonly used and it contains seven frequency selective RF pulses (CHESS, CHEmical Shift Selective) with different power and optimized pulse intervals to achieve ∼ zero longitudinal magnetization of water prior to the localization sequence. Lipid suppression could be achieved by placing Outer Volume Suppression bands covering the extracranial lipids.

Localization

When using in vivo MRS, one is usually interested in obtaining information from a specific region of the body by using localization methods. This can be achieved by using a surface coil specified for the volume of interest, or using pulse sequences with frequency selective RF pulses and magnetic field gradients based on the basic concepts of MRI. There are two main types of localized MR spectroscopy, i.e. single voxel and multi-volume MR spectroscopy. It should be note that the chemical shift difference between different resonances will lead to differences in localized positions of these resonances, which is referred as chemical shift displacement error (CSDE). Sufficiently strong gradient strength and RF pulse bandwidth can be used to reduce CSDE.The commonly used single voxel localization techniques are Outer Volume Suppression (OVS), Stimulated Echo Acquisition Mode (STEAM), Point RESolved Spectroscopy (PRESS), Image Selected In vivo Spectroscopy (ISIS), LASER(localization by adiabatic selective refocusing), sLASER, SPECIAL(spin echo full intensity acquired localized spectroscopy) and sSPECIAL. Recommended localization pulse sequences for ¹H, ³¹P or ¹³C MRS will be discussed.

Decoupling and NOE

The heteronuclear coupling e.g. between ¹³C and its attached ¹Hs results in muliplets, which leads to complicated ¹³C or ³¹P spectra and further degrades the measurement sensitivity. In order to simplify MR spectra and improve the sensitivity, ¹H decoupling (applying a RF field at the Larmor frequency of ¹H) is generally employed during X-nuclei (¹³C or ³¹P) acquisition to collapse the multiplets into singlets. The application of a weak RF field at the Larmor frequency of ¹H for a sufficient period could further enhance the signal intensity of ¹³C or ³¹P, which is known as Nuclear Overhauser Effect (NOE).

Fundamentals of 13C MRS

¹³C MR spectrum has wide chemical shift dispersion (∼ 200 ppm) which allows the detection of a large number of ¹³C metabolites. However, it has low sensitivity due to low natural abundance of ¹³C and small gyromagnetic ratio. Direct ¹³C localization methods employ both NOE and ¹H decoupling to enhance the signal intensity and to increase the spectral simplicity. However, it faces severe CSDE due to its wide chemical shift range. Therefore, for those resonances which have a sufficiently long T₂, heteronuclear polarization transfer (DEPT: Distortionless Enhancement by Polarization Transfer or INEPT: Insensitive Nuclei Enhanced by Polarization Transfer) is an alternative to achieve signal enhancement by a factor of four [γ(¹H)/γ(¹³C)]. It also allows the performance of localization with 1H magnetizations, of which the chemical shift range is narrow, to significantly reduce CSDE. Based on the heteronuclear coupling between ¹³C and ¹H, indirect detection of ¹³C through the more sensitive ¹H nucleus is another alternative to enhance sensitivity, albeit at the expense of a lower spectral resolution in ¹H.

Acknowledgements

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References

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