Towards in vivo g-ratio mapping using MRI: unifying myelin and diffusion imaging

The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. This is the second review on the topic of g-ratio mapping using MRI. As such, it summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. Using simulations based on recently published data, this review demonstrates the relevance of the calibration step for three myelin-markers (macromolecular tissue volume, myelin water fraction, and bound pool fraction). It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the potential of many novel techniques yet to be investigated.Comment: Will be published as a review article in Journal of Neuroscience Methods as parf of the Special Issue with Hu Cheng and Vince Calhoun as Guest Editor

Joint T1 and T2 Mapping with Tiny Dictionaries and Subspace-Constrained Reconstruction

Purpose: To develop a method that adaptively generates tiny dictionaries for joint T1-T2 mapping. Theory: This work breaks the bond between dictionary size and representation accuracy (i) by approximating the Bloch-response manifold by piece-wise linear functions and (ii) by adaptively refining the sampling grid depending on the locally-linear approximation error. Methods: Data acquisition was accomplished with use of an 2D radially sampled Inversion-Recovery Hybrid-State Free Precession sequence. Adaptive dictionaries are generated with different error tolerances and compared to a heuristically designed dictionary. Based on simulation results, tiny dictionaries were used for T1-T2 mapping in phantom and in vivo studies. Reconstruction and parameter mapping were performed entirely in subspace. Results: All experiments demonstrated excellent agreement between the proposed mapping technique and template matching using heuristic dictionaries. Conclusion: Adaptive dictionaries in combination with manifold projection allow to reduce the necessary dictionary sizes by one to two orders of magnitude

Fast Absolute Quantification of In Vivo Water and Fat Content with Magnetic Resonance Imaging

Quantitative water fat imaging offers a non-invasive method for monitoring and staging diseases associated with changes in either water or fat content in tissue. In this work absolute water and fat mass density measurement with in vivo Magnetic Resonance Imaging (MRI) is demonstrated. T1 independent, T2* corrected chemical shift based water-fat separated images are acquired. By placing a phantom with known mass density in the field of view for signal intensity calibration, absolute water or fat mass density can be computed, assuming the B1+ (transmit) and B1- (receive) fields can be measured. Phantom experiments with known water fat concentration were conducted to validate the feasibility of proposed method and in vivo data was collected from healthy volunteers. Results show good agreement with known values of in vivo water density. Each measurement was within one breath hold. Fast absolute quantification of water and fat with MRI is feasible in the abdomen

On the track of the brain's microstructure : myelin water imaging using quantitative MRI

Conventional quantitative magnetic resonance imaging (MRI), for example monoexponential determination of the relaxation times T1 and T2, is sensitive to the various pathologies of myelinated tissue in the brain. However, it gives relatively unspecific information about the underlying nature of the disease. A parameter that directly correlates with the integrity of the myelin sheath is the so-called myelin water fraction (MWF). Based on multi-component analysis of non-invasive quantitative MRI measurements, mapping of the MWF becomes feasible and proved to be useful for studying demyelination and remyelination processes in the course of multiple sclerosis (MS) and other myelin related pathologies. Common myelin water imaging techniques often suffer from a lack of volume coverage due to their 2D acquisition schemes. This thesis focuses on the development of new myelin water mapping procedures, especially on fast 3D MRI measurements that provide whole brain coverage. In chapter 2, an MWF mapping technique based on balanced steady-state free precession (bSSFP) sequences is introduced. An extended bSSFP signal equation, which is based on a two-pool water model describing brain tissue, is derived to determine typical multi-compartment parameters, including the MWF, of healthy subjects. Possible influences of magnetization transfer effects, infinite radiofrequency pulses and B0/B1 inhomogeneities are discussed extensively. Chapter 3 introduces a 3D acquisition scheme based on multi-gradient-echo (mGRE) pulse sequences that is applied for sampling multi-component T2* decays in the human brain of healthy volunteers and MS patients. Quantitative myelin water maps are generated based on analysis of T2* spectra. Chapter 4 discusses possible adaptations and modifications of the proposed procedure from chapter 3 when moving to higher main magnetic field strengths. The effects of B0 inhomogeneities on the data sets and possible correction methods are additionally covered in this part of the thesis. Finally, the crucial role of accurate B1 and B0 imaging and the influences on myelin water imaging are revisited in chapter 5. A solution to simultaneous mapping of B1 and B0 is presented that might help to overcome systematic error sources in MWF mapping in the future

Simultaneous multislice acquisition with multi-contrast segmented EPI for separation of signal contributions in dynamic contrast-enhanced imaging

We present a method to efficiently separate signal in magnetic resonance imaging (MRI) into a base signal S0, representing the mainly T1-weighted component without T2*-relaxation, and its T2*-weighted counterpart by the rapid acquisition of multiple contrasts for advanced pharmacokinetic modelling. This is achieved by incorporating simultaneous multislice (SMS) imaging into a multi-contrast, segmented echo planar imaging (EPI) sequence to allow extended spatial coverage, which covers larger body regions without time penalty. Simultaneous acquisition of four slices was combined with segmented EPI for fast imaging with three gradient echo times in a preclinical perfusion study. Six female domestic pigs, German-landrace or hybrid-form, were scanned for 11 minutes respectively during administration of gadolinium-based contrast agent. Influences of reconstruction methods and training data were investigated. The separation into T1- and T2*-dependent signal contributions was achieved by fitting a standard analytical model to the acquired multi-echo data. The application of SMS yielded sufficient temporal resolution for the detection of the arterial input function in major vessels, while anatomical coverage allowed perfusion analysis of muscle tissue. The separation of the MR signal into T1- and T2*-dependent components allowed the correction of susceptibility related changes. We demonstrate a novel sequence for dynamic contrast-enhanced MRI that meets the requirements of temporal resolution (Δt < 1.5 s) and image quality. The incorporation of SMS into multi-contrast, segmented EPI can overcome existing limitations of dynamic contrast enhancement and dynamic susceptibility contrast methods, when applied separately. The new approach allows both techniques to be combined in a single acquisition with a large spatial coverage

Imperfect spoiling in variable flip angle T1 mapping at 7T: Quantifying and minimizing impact

PURPOSE: The variable flip angle (VFA) approach to T1 mapping assumes perfectly spoiled transverse magnetisation at the end of each repetition time (TR). Despite radiofrequency (RF) and gradient spoiling, this condition is rarely met, leading to erroneous T1 estimates ( T 1 app ). Theoretical corrections can be applied but make assumptions about tissue properties, for example, a global T2 time. Here, we investigate the effect of imperfect spoiling at 7T and the interaction between the RF and gradient spoiling conditions, additionally accounting for diffusion. We provide guidance on the optimal approach to maximise the accuracy of the T1 estimate in the context of 3D multi-echo acquisitions. METHODS: The impact of the spoiling regime was investigated through numerical simulations, phantom and in vivo experiments. RESULTS: The predicted dependence of T 1 app on tissue properties, system settings, and spoiling conditions was observed in both phantom and in vivo experiments. Diffusion effects modulated the dependence of T 1 app on both B 1 + efficiency and T2 times. CONCLUSION: Error in T 1 app can be minimized by using an RF spoiling increment and gradient spoiler moment combination that minimizes T2 -dependence and safeguards image quality. Although the diffusion effect was comparatively small at 7T, correction factors accounting for this effect are recommended

Rapid parametric mapping of the longitudinal relaxation time t1 using two-dimensional variable flip angle magnetic resonance imaging at 1.5 Tesla, 3 Tesla, and 7 Tesla

INTRODUCTION: Visual but subjective reading of longitudinal relaxation time (T1) weighted magnetic resonance images is commonly used for the detection of brain pathologies. For this non-quantitative measure, diagnostic quality depends on hardware configuration, imaging parameters, radio frequency transmission field (B1+) uniformity, as well as observer experience. Parametric quantification of the tissue T1 relaxation parameter offsets the propensity for these effects, but is typically time consuming. For this reason, this study examines the feasibility of rapid 2D T1 quantification using a variable flip angles (VFA) approach at magnetic field strengths of 1.5 Tesla, 3 Tesla, and 7 Tesla. These efforts include validation in phantom experiments and application for brain T1 mapping. METHODS: T1 quantification included simulations of the Bloch equations to correct for slice profile imperfections, and a correction for B1+. Fast gradient echo acquisitions were conducted using three adjusted flip angles for the proposed T1 quantification approach that was benchmarked against slice profile uncorrected 2D VFA and an inversion-recovery spin-echo based reference method. Brain T1 mapping was performed in six healthy subjects, one multiple sclerosis patient, and one stroke patient. RESULTS: Phantom experiments showed a mean T1 estimation error of (-63±1.5)% for slice profile uncorrected 2D VFA and (0.2±1.4)% for the proposed approach compared to the reference method. Scan time for single slice T1 mapping including B1+ mapping could be reduced to 5 seconds using an in-plane resolution of (2×2) mm2, which equals a scan time reduction of more than 99% compared to the reference method. CONCLUSION: Our results demonstrate that rapid 2D T1 quantification using a variable flip angle approach is feasible at 1.5T/3T/7T. It represents a valuable alternative for rapid T1 mapping due to the gain in speed versus conventional approaches. This progress may serve to enhance the capabilities of parametric MR based lesion detection and brain tissue characterization