Title: In-Vivo Three Dimensional Proton Hadamard Spectroscopic Imaging in the Human Brain
Description: Magnetic resonance spectroscopic imaging (MRSI) is a useful tool for obtaining information on the biochemical processes underlying various pathologies. A widely used multi-voxel localization method is chemical shift imaging (CSI) which uses gradients for phase encoding. Although simple to implement, low in specific absorption rate (SAR) and immune to chemical shift displacement (CSD), it also suffers from some well known drawbacks caused by its sinc-shaped point spread function (PSF). This results in loss of both signal-to-noise ratio (SNR) as well as localization, an effect that is exacerbated at low resolutions. In contrast, an alternative localization method, Hadamard spectroscopic imaging (HSI) benefits from a theoretically ideal PSF and consequently does not suffer from these drawbacks. In this work we exploit the theoretically ideal PSF of HSI encoding to develop a novel three dimensional (3D) multi-voxel MR localization method based on transverse HSI (T-HSI). The advantages of T HSI are that unlike gradient phase-encoding: (i) the volume of interest (VOI) does not need to be smaller than the field-of-view to prevent aliasing; (ii) the number of partitions in each direction can be small, 8, 4 or even 2 at no cost in PSF; (iii) the VOI does not have to be contiguous; and (iv) the voxel profile depends on the available B1 and pulse synthesis paradigm and can therefore, at least theoretically, approach "ideal" "1" inside and "0" elsewhere.

Clinical utility of the new method is shown by spectra obtained from the brain of a healthy volunteer. The benefits of T-HSI are demonstrated by a quantitative comparison to CSI of the SNR and localization in a phantom in both one and three dimensions at clinical resolutions. A novel matrix formalism is used to quantify the impact of non-ideal flip angles on T-HSI. The superior PSF of T-HSI is then used to demonstrate the feasibility of scanning regions near or on the skull while limiting the impact of lipid contamination and obtaining quantifiable spectra. A comparison to spectra obtained using CSI is shown for a healthy volunteer. The new method is also used in a clinical pathology: to scan multiple sclerosis (MS) lesions occurring near the skull. To maintain the benefits provided by the PSF of HSI at higher fields, despite its susceptibility to CSD, a additional hybrid sequence is also developed that limits both the SAR and the CSD, regardless of the size of the VOI. A comparison to CSI in a phantom and in-vivo is carried out and spectra obtained from the brain of a healthy volunteer at 3T are shown.

Finally, future research avenues involving extension of this research to ultra high fields (7T) are discussed and possible clinical uses are described.