Novel in-vivo magnetic resonance spectroscopy techniques for 3 T and 7 T

This thesis describes several novel in-vivo proton magnetic resonance spectroscopy (MRS) techniques used to study the human brain. By measuring brain metabolites non-invasively, MRS has provided seminal contributions to our fundamental understanding of the brain as well as a wide variety of clinical conditions. However, due to the relative insensitivity and low spectral resolution of MRS, many important brain metabolites cannot be accurately quantified under standard clinical conditions. One way of in- creasing both the sensitivity and spectral resolution of MRS is to increase the static magnetic field strength. Unfortunately, increasing the static magnetic field strength also creates new technical challenges that must be resolved before any gains associated with higher magnetic field strength can be achieved.
Due to increased shimming requirements and hardware limitations, many MRS experiments at higher magnetic fields are performed on a single voxel in the brain - thereby limiting any possible insight that may be shed by concurrent measurements in other regions of the brain. This thesis presents a pragmatic acquisition scheme for concurrent acquisition of high quality spectra from multiple brain regions at ultra-high field (7 Tesla). This is accomplished by dynamically updating the first order shims and flip angles and acquiring spectra in an alternating fashion. The dynamic acquisition protocol produced spectra similar to static single voxel measurements demonstrating that high spectral quality from two voxels can be acquired concurrently without specialized hardware.
This dynamic acquisition scheme was then used to investigate the time-course of metabolites in both motor cortices (M1) following application of a non-invasive brain stimulation technique called transcranial direct current stimulation (tDCS). When applied over the motor cortex, tDCS has been shown to increase or decrease neuronal excitability depending on current direction. However, the pathways by which specific neuro-chemicals might mediate the tDCS-induced changes are not fully under- stood. Concurrent measurement of the tDCS time-courses revealed that anodal stimulation reduced GABA in both the anode-targeted and non-stimulated M1s. Cathodal stimulation decreased GABA and glutamate in the non-stimulated M1, with no changes in the cathode-targeted M1. Bilateral stimulation reduced glutamate in both M1 and no change in GABA.
Another problem associated with in-vivo MRS is that most metabolite peaks are overlapped by broad, unwanted macromolecule and lipid signals. At higher magnetic field strengths this can introduce significant bias in metabolite measurements. One way of avoiding this potential source of quantification error is to delay signal acquisition until the broad, unwanted signals have relaxed leaving only the metabolite signals present. The main problem with waiting for these broad macromolecule signals to relax is that scalar coupled metabolites will now evolve under J-coupling - rendering them very difficult to quantify. The final project involved development of a new pulse sequence designed to suppress J-modulation. Results show that J-modulation was sufficiently suppressed at 3 T long enough for nearly all the macromolecule signal to relax (up to TE = 150 ms). This technique can also be used for straight forward T2 measurements of coupled metabolites.

Advisor: Jezzard, P
Emir, U