Fast high-resolution metabolite mapping in the rat brain using 1H-FID-MRSI at 14.1T

Magnetic resonance spectroscopic imaging (MRSI) enables the simultaneous non-invasive acquisition of MR spectra from multiple spatial locations inside the brain. While 1H-MRSI is increasingly used in the human brain, it is not yet widely applied in the preclinical settings, mostly because of difficulties specifically related to very small nominal voxel size in the rodent brain and low concentration of brain metabolites, resulting in low signal-to-noise ratio SNR. In this context, we implemented a free induction decay 1H-MRSI sequence (1H-FID-MRSI) in the rat brain at 14.1T. We combined the advantages of 1H-FID-MRSI with the ultra-high magnetic field to achieve higher SNR, coverage and spatial resolution in the rodent brain, and developed a custom dedicated processing pipeline with a graphical user interface: MRS4Brain toolbox. LCModel fit, using the simulated metabolite basis-set and in-vivo measured MM, provided reliable fits for the data at acquisition delays of 1.3 and 0.94 ms. The resulting Cram\'er-Rao lower bounds were sufficiently low (<40%) for eight metabolites of interest, leading to highly reproducible metabolic maps. Similar spectral quality and metabolic maps were obtained between 1 and 2 averages, with slightly better contrast and brain coverage due to increased SNR in the latter case. Furthermore, the obtained metabolic maps were accurate enough to confirm the previously known brain regional distribution of some metabolites. The acquisitions proved high repeatability over time. We demonstrated that the increased SNR and spectral resolution at 14.1T can be translated into high spatial resolution in 1H-FID-MRSI of the rat brain in 13 minutes, using the sequence and processing pipeline described herein. High-resolution 1H-FID-MRSI at 14.1T provided reproducible and high-quality metabolic mapping of brain metabolites with significantly reduced technical limitations.Comment: Dunja Simicic and Brayan Alves are joint first author

In-Vivo Three Dimensional Proton Hadamard Spectroscopic Imaging in the Human Brain

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

ACCELERATING EDITED MAGNETIC RESONANCE SPECTROSCOPY AND SPECTROSCOPIC IMAGING OF THE HUMAN BRAIN AT 3T

Edited magnetic resonance spectroscopy is a method capable of probing biochemical processes non-invasively, but suffers from an inherently low signal-to-noise which results in long acquisition times. Increasing the efficiency of these scans would reduce these acquisition times and can increase the number of scans, and consequently the amount of information, that can be acquired within a time-limited scan session in clinical and research settings. This thesis addresses this need with methods to increase the number of metabolites and regions that can be detected within a single scan as well as a method to reduce the duration of the preparation pulses. In particular, we demonstrate the ability of two techniques to detected glutathione and lactate simultaneously. We then move on to introduce ‘Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy’ (HERMES) and demonstrate that it can detect two and three metabolites simultaneously. As an example of this method, a scheme for separately detecting N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) is presented. This scheme is then extended to separately edit Aspartate in addition to NAA and NAAG. All multi-metabolite editing schemes are shown to be capable of optimally detecting each metabolite separately in simulations, phantom, and in vivo experiments. Relative to separate acquisitions of each metabolite separately, multi-metabolite editing results in a scan time reduction of two-fold and three-fold for editing two metabolites and three metabolites respectively. This thesis then introduces and evaluates methods for multi-region editing. First, a new technique ‘Spatial Hadamard Editing and Reconstruction for Parallel Acquisition’ (SHERPA) is introduced and found to be capable of separating the GABA-edited spectra from two voxels. HERMES is then extended for use with magnetic resonance spectroscopic imaging (MRSI) and is found to be also introduced and is shown to decrease subtraction artifacts in GABA-edited spectra. Lastly, a short-duration water suppression technique compatible for use with fast editedMRSI sequences is introduced and is shown to suppress water better than VAPOR. Readers: Peter Barker, DPhil and Richard Edden, Ph

A Study of Prostate Cancer by Using Single-Voxel and Hadamard Multi-Voxel 2D Localized COSY and JPRESS MR Spectroscopy Techniques

Prostate cancer is the most common cancer among men in the western countries. It grows indolently and can take more than 10 years to turn deadly. Currently no imaging methods can provide both high sensitivity and specificity for prostate cancer detection and characterization. 1H Magnetic Resonance Spectroscopy (MRS) is a non-invasive technique, which can provide biochemical information of the prostate gland. (Choline + Creatine)/ Citrate ratio is widely used as a criterion for the diagnosis of prostate cancer. The specificity of multi-voxel 1D* 1H MRS is still limited due to the severe overlap of 1D* 1H MRS spectrum and voxel bleeding artifacts. Two-dimensional 1H MRS, which spreads the metabolite resonance peaks on a two-spectral dimensional surface, can help to differentiate most of the overlapping resonance peaks compared to conventional 1D* MRS spectrum. In the present study, a Hadamard multi-voxel 2D* localized COrrelated SpectroscopY (COSY) MRS technique was developed and implemented on a whole-body 4T MR system. The combination of localized 2D* 1H MR correlation spectroscopy and Hadamard encoding enables the simultaneous acquisition of multiple volumes of interest with the benefits of improved spectral resolution, increased SNR without an increase in the experimental duration, and with limited voxel bleeding compared to 1D* CSI acquisition. Most of the metabolites were measured without contamination of other resonances. The developed technique solves the severe resonances overlap problem in 1D* 1H MR spectra and offers multi-regional analysis of MRS due to the multi-focal and heterogeneous nature of prostate adeno-carcinoma, which can be easily overlooked by a single-voxel based MR spectroscopy method. By using this technique, more metabolites can be identified and additional information about the metabolites can be gained from the extended 2D* MRS spectra. This offers an opportunity to accurately follow up the metabolism in vivo. New biomarker of prostate cancer -polyamine spermine resonances are very well-resolved in 2D* L-COSY spectra and can be traced longitudinally by its cross-peaks for chemoprevention research of prostate cancer. 2D* Localized J-resolved Pointed RESolved Spectroscopy (JPRESS) MRS technique was also implemented to compare it with the 2D* L-COSY technique. The advantages and disadvantages of both techniques are thoroughly investigated

Compressed Sensing Accelerated Magnetic Resonance Spectroscopic Imaging

abstract: Magnetic resonance spectroscopic imaging (MRSI) is a valuable technique for assessing the in vivo spatial profiles of metabolites like N-acetylaspartate (NAA), creatine, choline, and lactate. Changes in metabolite concentrations can help identify tissue heterogeneity, providing prognostic and diagnostic information to the clinician. The increased uptake of glucose by solid tumors as compared to normal tissues and its conversion to lactate can be exploited for tumor diagnostics, anti-cancer therapy, and in the detection of metastasis. Lactate levels in cancer cells are suggestive of altered metabolism, tumor recurrence, and poor outcome. A dedicated technique like MRSI could contribute to an improved assessment of metabolic abnormalities in the clinical setting, and introduce the possibility of employing non-invasive lactate imaging as a powerful prognostic marker. However, the long acquisition time in MRSI is a deterrent to its inclusion in clinical protocols due to associated costs, patient discomfort (especially in pediatric patients under anesthesia), and higher susceptibility to motion artifacts. Acceleration strategies like compressed sensing (CS) permit faithful reconstructions even when the k-space is undersampled well below the Nyquist limit. CS is apt for MRSI as spectroscopic data are inherently sparse in multiple dimensions of space and frequency in an appropriate transform domain, for e.g. the wavelet domain. The objective of this research was three-fold: firstly on the preclinical front, to prospectively speed-up spectrally-edited MRSI using CS for rapid mapping of lactate and capture associated changes in response to therapy. Secondly, to retrospectively evaluate CS-MRSI in pediatric patients scanned for various brain-related concerns. Thirdly, to implement prospective CS-MRSI acquisitions on a clinical magnetic resonance imaging (MRI) scanner for fast spectroscopic imaging studies. Both phantom and in vivo results demonstrated a reduction in the scan time by up to 80%, with the accelerated CS-MRSI reconstructions maintaining high spectral fidelity and statistically insignificant errors as compared to the fully sampled reference dataset. Optimization of CS parameters involved identifying an optimal sampling mask for CS-MRSI at each acceleration factor. It is envisioned that time-efficient MRSI realized with optimized CS acceleration would facilitate the clinical acceptance of routine MRSI exams for a quantitative mapping of important biomarkers.Dissertation/ThesisDoctoral Dissertation Bioengineering 201

Key clinical benefits of neuroimaging at 7 T

The growing interest in ultra-high field MRI, with more than 35.000 MR examinations already performed at 7 T, is related to improved clinical results with regard to morphological as well as functional and metabolic capabilities. Since the signal-to-noise ratio increases with the field strength of the MR scanner, the most evident application at 7 T is to gain higher spatial resolution in the brain compared to 3 T. Of specific clinical interest for neuro applications is the cerebral cortex at 7 T, for the detection of changes in cortical structure, like the visualization of cortical microinfarcts and cortical plaques in Multiple Sclerosis. In imaging of the hippocampus, even subfields of the internal hippocampal anatomy and pathology may be visualized with excellent spatial resolution. Using Susceptibility Weighted Imaging, the plaque-vessel relationship and iron accumulations in Multiple Sclerosis can be visualized, which may provide a prognostic factor of disease. Vascular imaging is a highly promising field for 7 T which is dealt with in a separate dedicated article in this special issue. The static and dynamic blood oxygenation level-dependent contrast also increases with the field strength, which significantly improves the accuracy of pre-surgical evaluation of vital brain areas before tumor removal. Improvement in acquisition and hardware technology have also resulted in an increasing number of MR spectroscopic imaging studies in patients at 7 T. More recent parallel imaging and short-TR acquisition approaches have overcome the limitations of scan time and spatial resolution, thereby allowing imaging matrix sizes of up to 128×128. The benefits of these acquisition approaches for investigation of brain tumors and Multiple Sclerosis have been shown recently. Together, these possibilities demonstrate the feasibility and advantages of conducting routine diagnostic imaging and clinical research at 7 T