Quantitative rotating frame relaxometry methods in MRI

Macromolecular degeneration and biochemical changes in tissue can be quantified using rotating frame relaxometry in MRI. It has been shown in several studies that the rotating frame longitudinal relaxation rate constant (R1ρ) and the rotating frame transverse relaxation rate constant (R2ρ) are sensitive biomarkers of phenomena at the cellular level. In this comprehensive review, existing MRI methods for probing the biophysical mechanisms that affect the rotating frame relaxation rates of the tissue (i.e. R1ρ and R2ρ) are presented. Long acquisition times and high radiofrequency (RF) energy deposition into tissue during the process of spin-locking in rotating frame relaxometry are the major barriers to the establishment of these relaxation contrasts at high magnetic fields. Therefore, clinical applications of R1ρ and R2ρ MRI using on- or off-resonance RF excitation methods remain challenging. Accordingly, this review describes the theoretical and experimental approaches to the design of hard RF pulse cluster- and adiabatic RF pulse-based excitation schemes for accurate and precise measurements of R1ρ and R2ρ. The merits and drawbacks of different MRI acquisition strategies for quantitative relaxation rate measurement in the rotating frame regime are reviewed. In addition, this review summarizes current clinical applications of rotating frame MRI sequences. © 2016 John Wiley & Sons, Ltd

Pulse sequences for measuring exchange rates between proton species: From unlocalised NMR spectroscopy to chemical exchange saturation transfer imaging

Within the field of NMR spectroscopy, the study of chemical exchange processes through saturation transfer techniques has a long history. In the context of MRI, chemical exchange techniques have been adapted to increase the sensitivity of imaging to small fractions of exchangeable protons, including the labile protons of amines, amides and hydroxyls. The MR contrast is generated by frequency-selective irradiation of the labile protons, which results in a reduction of the water signal associated with transfer of the labile protons’ saturated magnetization to the protons of the surrounding free water. The signal intensity depends on the rate of chemical exchange and the concentration of labile protons as well as on the properties of the irradiation field. This methodology is referred to as CEST (chemical exchange saturation transfer) imaging. Applications of CEST include imaging of molecules with short transverse relaxation times and mapping of physiological parameters such as pH, temperature, buffer concentration and chemical composition due to the dependency of this chemical exchange effect on all these parameters. This article aims to describe these effects both theoretically and experimentally. In depth analysis and mathematical modelling are provided for all pulse sequences designed to date to measure the chemical exchange rate. Importantly, it has become clear that the background signal from semi-solid protons and the presence of the Nuclear Overhauser Effect (NOE), either through direct dipole-dipole mechanisms or through exchange-relayed signals, complicates the analysis of CEST effects. Therefore, advanced methods to suppress these confounding factors have been developed, and these are also reviewed. Finally, the experimental work conducted both in vitro and in vivo is discussed and the progress of CEST imaging towards clinical practice is presented

Magnetisation transfer effects at ultra high field MRI

Increased signal to noise ratio in ultra high field Magnetic Resonance Imaging (MRI) has allowed the development of quantitative imaging techniques and new contrast mechanisms, such as Chemical Exchange Saturation Transfer (CEST) to be probed. The development of CEST contrast imaging has involved overcoming a number of technical challenges associated with ultra high field MRI. The B1 transmit field was, and still is, a major challenge. Presented in this thesis, the B1 transmit field in regions of low B1 are improved with the use of dielectric pads and a simulation study shows that the overall B1 transmit field homogeneity is significantly improved when multi-transmit slice-selective RF spokes pulse sequences are used. Multiple methods have been developed to quantify the chemical exchange from slow exchanging proton pools seen in CEST contrast imaging. However, magnetisation transfer (MT) from the macromolecular bound pool contaminates current quantification methods, and presented in this thesis is a method whereby the CEST and MT are simultaneously saturated using dual frequency saturation pulses, allowing the CEST contrast in z-spectra to be separated from the MT and to enhance visualisation of the CEST effects. Despite the considerable interest in CEST, only one study has probed the CEST effects in blood, and interestingly high levels of CEST signals can be observed from the superior sagittal sinus. To investigate these effects, z-spectra from ex vivo blood samples considering the effects of oxygenation, haematocrit levels and cell structure were quantified. Quantification shows that the main source of the CEST signals was from the cells within the blood

Quantitative pulsed CEST MR imaging

Chemical Exchange Saturation Transfer (CEST) experiments enable the indirect detection of small metabolites, e.g. creatine, and proteins in living tissue by means of magnetic resonance imaging. Selective RF saturation of solute protons in chemical exchange with water leads to an accumulation of saturation in the water magnetization. The resulting reduction of the water signal depends on physiological properties, e.g. pH, temperature and solute concentration, but also on the saturation scheme. In a clinical setup, the latter is limited to a series of short RF-pulses to obey safety regulations. Pulsed saturation is diffcult to describe theoretically, thus, the quantitative determination of physiological parameters via CEST experiments is a challenging task. In this thesis, a new analytical model for CEST is proposed, which extends a former interleaved saturation-relaxation approach. This model enables the analytical calculation of Z-spectra yielding deeper insight into the physics of pulsed CEST experiments. Furthermore, it enables for the first time in the case of pulsed saturation the separate and independent determination of the exchange rate k and the relative proton concentration f. The validity of this approach was tested by simulations and verified in measurements of model solutions containing creatine on a 7-Tesla whole-body MR tomograph. Finally, the obtained knowledge was used to quantitatively investigate pH and absolute creatine concentration in the human calf muscle under resting conditions and during exercise

Magnetisation transfer effects at ultra high field MRI

Increased signal to noise ratio in ultra high field Magnetic Resonance Imaging (MRI) has allowed the development of quantitative imaging techniques and new contrast mechanisms, such as Chemical Exchange Saturation Transfer (CEST) to be probed. The development of CEST contrast imaging has involved overcoming a number of technical challenges associated with ultra high field MRI. The B1 transmit field was, and still is, a major challenge. Presented in this thesis, the B1 transmit field in regions of low B1 are improved with the use of dielectric pads and a simulation study shows that the overall B1 transmit field homogeneity is significantly improved when multi-transmit slice-selective RF spokes pulse sequences are used. Multiple methods have been developed to quantify the chemical exchange from slow exchanging proton pools seen in CEST contrast imaging. However, magnetisation transfer (MT) from the macromolecular bound pool contaminates current quantification methods, and presented in this thesis is a method whereby the CEST and MT are simultaneously saturated using dual frequency saturation pulses, allowing the CEST contrast in z-spectra to be separated from the MT and to enhance visualisation of the CEST effects. Despite the considerable interest in CEST, only one study has probed the CEST effects in blood, and interestingly high levels of CEST signals can be observed from the superior sagittal sinus. To investigate these effects, z-spectra from ex vivo blood samples considering the effects of oxygenation, haematocrit levels and cell structure were quantified. Quantification shows that the main source of the CEST signals was from the cells within the blood

Quantitative methods in magnetization transfer and chemical exchange saturation transfer at 7T

Ultra-High field (7T) MRI provides high sensitivity which allows for new qualitative and quantitative methodologies to be developed, that provide clinically useful information. The work presented in this thesis is focussed on developing a quick and reliable quantitative MT and CEST methodology, taking account of the difficulties encountered at high field. The method developed here has been tested on various studies, in both healthy and diseased brain, in an effort to aid the understanding of myelination in the human brain. The work in this thesis uses the quantitative measure of MT as a marker for myelination, and it shows strong correlations between MT-based myelination and functional connectivity, as well as very strong correlation between MT and NOE. These findings showcase the potential of NOE as a myelin marker as well, as long as the MT vs. NOE relationship remains the same in pathology. Myelination is investigated (via MT and NOE) in Multiple Sclerosis (MS) and Glioma, showing a strong coupling between the two exists even in pathology. Amide Proton Transfer (APT) is also investigated in Glioma, showing similar trends to MT and NOE. High resolution anatomical images can provide valuable information on the extend of the pathology, but quantitative information of the NMR properties of tissue (like MT, NOE and APT) has the potential to detect earlier abnormalities, and give a quantitative measure of healing or degeneration caused by pathology