Robust gamma-aminobutyric acid and energy metabolism measurements by proton and phosphorus magnetic resonance spectroscopy and fingerprinting

Magnetic resonance spectroscopy (MRS) is the only technique that can detect endogenous metabolites directly and non-invasively in vivo. It allows to identify different metabolites and analyze the dynamic neurochemical processes in the brain, skeletal muscle, and other organs. In this thesis, new acquisition methods are developed in order to improve the robustness of data acquisition and to reduce the scanning duration in human at 7T. gamma-aminobutyric acid (GABA) is a primary inhibitory neurotransmitter which plays a key role to control brain activities associated with normal brain functions and the pathophysiology of disease. However, GABA signal is overlapped with more abundant metabolites, hindering its direct measurement. At ultra-high field, even with the improved SNR and spectral dispersion, it is still challenging to quantify GABA directly using a non-editing short echo time (TE) method. MEGA-sSPECIAL sequence is introduced for improved GABA measurement in the brain. The motor and medial prefrontal cortices were selected considering different GABA concentrations between the two areas. The test-retest reproducibility of the method was compared with that of short-TE measurement with the same localization.Knowledge of relaxation time is not only important for the optimization of acquisition parameters but also for the investigation of alterations in tissue microstructure integrity. Magnetic resonance fingerprinting (MRF) is a novel technique to acquire multi-parametric and quantitative data simultaneously by using varying flip angle, repetition time, and/or TE patterns. Although it has been successfully implemented in clinical studies, it has never been adapted for 31P metabolite acquisition at 7T in the human brain. Therefore, the feasibility of MRF application to T1 and T2 of 31P metabolites measurements is explored in the thesis. Phosphocreatine, Adenosine triphosphate (ATP), and creatine kinase (CK) play key roles in intracellular energy buffering and transport. The energy is needed for various processes in organisms and living cells including intracellular signaling, DNA and RNA synthesis, and muscle contraction. 31P MRS is a unique tool to measure the CK reaction rate constant (kCK) via magnetization transfer, providing important insight into energetics in the brain, muscle, and heart. However, it suffers from low SNR and long acquisition time. In order to overcome the challenges, a novel approach is suggested to acquire 3D CK exchange rate constants map using MRF. High spatial resolution with the minimum acquisition time was achieved using a stack-of-spiral trajectory. The preliminary results obtained from the skeletal muscle are presented in this thesis.In conclusion, the MEGA-sSPECIAL sequence showed more robust GABA quantification results in both of the brain regions than the short-TE method, suggesting a capability to detect small alterations in GABA levels. Fast and simultaneous measurements of T1 and T1 relaxation times of 31P metabolites were enabled by 31P MRF by shortening the acquisition time by 1.7-fold in comparison with inversion recovery and multi-TE techniques. Lastly, the feasibility of 3D kCK mapping by 31P MRF was investigated for the first time with accelerated spatial encoding, achieving 3 min 16 s of acquisition time in the skeletal muscle, paving the way for studying energy metabolism in future clinical and research studies.