Measurement of T1 of the ultrashort T2* components in white matter of the brain at 3T.

Recent research demonstrates that white matter of the brain contains not only long T2 components, but a minority of ultrashort T2* components. Adiabatic inversion recovery prepared dual echo ultrashort echo time (IR-dUTE) sequences can be used to selectively image the ultrashort T2* components in white matter of the brain using a clinical whole body scanner. The T2*s of the ultrashort T2* components can be quantified using mono-exponential decay fitting of the IR-dUTE signal at a series of different TEs. However, accurate T1 measurement of the ultrashort T2* components is technically challenging. Efficient suppression of the signal from the majority of long T2 components is essential for robust T1 measurement. In this paper we describe a novel approach to this problem based on the use of IR-dUTE data acquisitions with different TR and TI combinations to selectively detect the signal recovery of the ultrashort T2* components. Exponential recovery curve fitting provides efficient T1 estimation, with minimized contamination from the majority of long T2 components. A rubber phantom and a piece of bovine cortical bone were used for validation of this approach. Six healthy volunteers were studied. An averaged T2* of 0.32 ± 0.09 ms, and a short mean T1 of 226 ± 46 ms were demonstrated for the healthy volunteers at 3T

The UTE and ZTE Sequences at Ultra-High Magnetic Field Strengths: A Survey

UTE (Ultrashort Echo Time) and ZTE (Zero Echo Time) sequences have been developed to detect short T2 relaxation signals coming from regions that are unable to be detected by conventional MRI methods. Due to the high dipole-dipole interactions in solid and semi-solid tissues, the echo time generated is simply not enough to produce a signal using conventional imaging method, often leading to void signal coming from the discussed areas. By the application of these techniques, solid and semi-solid areas can be imaged which can have a profound impact in clinical imaging. High and Ultra-high field strength (UHF) provides a vital advantage in providing better sensitivity and specificity of MR imaging. When coupled with the UTE and ZTE sequences, the image can recover void signals as well as a much-improved signal quality. To further this strategy, secondary data from various research tools was obtained to further validate the research while addressing the drawbacks to this approach. It was found that UTE and ZTE sequences coupled with some techniques such as qualitative imaging and new trajectories are very crucial for accurate image depiction of the areas of the musculoskeletal system, neural system, lung imaging and dental imaging

Magnetic Resonance Imaging of Short-T2 Tissues with Applications for Quantifying Cortical Bone Water and Myelin

The human body contains a variety of tissue species with short T2 ranging from a few microseconds to hundreds of microseconds. Detection and quantification of these short-T2 species is of considerable clinical and scientific interest. Cortical bone water and myelin are two of the most important tissue constituents. Quantification of cortical bone water concentration allows for indirect estimation of bone pore volume and noninvasive assessment of bone quality. Myelin is essential for the proper functioning of the central nervous system (CNS). Direct assessment of myelin would reveal CNS abnormalities and enhance our understanding of neurological diseases. However, conventional MRI with echo times of several milliseconds or longer is unable to detect these short-lived MR signals. Recent advances in MRI technology and hardware have enabled development of a number of short-T2 imaging techniques, key among which are ultra-short echo time (UTE) imaging, zero echo time (ZTE) imaging, and sweep imaging with Fourier transform (SWIFT). While these pulse sequences are able to detect short-T2 species, they still suffer from signal interference between different T2 tissue constituents, image artifacts and excessive scan time. These are primary technical hurdles for application to whole-body clinical scanners. In this thesis research, new MRI techniques for improving short-T2 tissue imaging have been developed to address these challenges with a focus on direct detection and quantification of cortical bone water and myelin on a clinical MRI scanner. The first focus of this research was to optimize long-T2 suppression in UTE imaging. Saturation and adiabatic RF pulses were designed to achieve maximum long-T2 suppression while maximizing the signal from short-T2 species. The imaging protocols were optimized by Bloch equation simulations and were validated using phantom and in vivo experiments. The results show excellent short-T2 contrast with these optimized pulse sequences. The problem of blurring artifacts resulting from the inhomogeneous excitation profile of the rectangular pulses in ZTE imaging was addressed. The proposed approach involves quadratic phase-modulated RF excitation and iterative solution of an inverse problem formulated from the signal model of ZTE imaging and is shown to effectively remove the image artifacts. Subsequently image acquisition efficiency was improved in order to attain clinically-feasible scan times. To accelerate the acquisition speed in UTE and ZTE imaging, compressed sensing was applied with a hybrid 3D UTE sequence. Further, the pulse sequence and reconstruction procedure were modified to enable anisotropic field-of-view shape conforming to the geometry of the elongated imaged object. These enhanced acquisition techniques were applied to the detection and quantification of cortical bone water. A new biomarker, the suppression ratio (a ratio image derived from two UTE images, one without and the other with long-T2 suppression), was conceived as a surrogate measure of cortical bone porosity. Experimental data suggest the suppression ratio may be a more direct measure of porosity than previously measured total bone water concentration. Lastly, the feasibility of directly detecting and quantifying spatially-resolved myelin concentration with a clinical imager was explored, both theoretically and experimentally. Bloch equation simulations were conducted to investigate the intrinsic image resolution and the fraction of detectable myelin signal under current scanner hardware constraints. The feasibility of quantitative ZTE imaging of myelin extract and lamb spinal cord at 3T was demonstrated. The technological advances achieved in this dissertation research may facilitate translation of short-T2 MRI methods from the laboratory to the clinic

Quantitative magnetic resonance mapping of the myelin bilayer reflects pathology in multiple sclerosis brain tissue

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by loss of myelin (demyelination) and, to a certain extent, subsequent myelin repair (remyelination). To better understand the pathomechanisms underlying de- and remyelination and to monitor the efficacy of treatments aimed at regenerating myelin, techniques offering noninvasive visualizations of myelin are warranted. Magnetic resonance (MR) imaging has long been at the forefront of efforts to visualize myelin, but it has only recently become feasible to access the rapidly decaying resonance signals stemming from the myelin lipid-protein bilayer itself. Here, we show that direct MR mapping of the bilayer yields highly specific myelin maps in brain tissue from patients with MS. Furthermore, examination of the bilayer signal behavior is found to reveal pathological alterations in normal-appearing white and gray matter. These results indicate promise for in vivo implementations of the myelin bilayer mapping technique, with prospective applications in basic research, diagnostics, disease monitoring, and drug development

Quantitative MRI in leukodystrophies

Leukodystrophies constitute a large and heterogeneous group of genetic diseases primarily affecting the white matter of the central nervous system. Different disorders target different white matter structural components. Leukodystrophies are most often progressive and fatal. In recent years, novel therapies are emerging and for an increasing number of leukodystrophies trials are being developed. Objective and quantitative metrics are needed to serve as outcome measures in trials. Quantitative MRI yields information on microstructural properties, such as myelin or axonal content and condition, and on the chemical composition of white matter, in a noninvasive fashion. By providing information on white matter microstructural involvement, quantitative MRI may contribute to the evaluation and monitoring of leukodystrophies. Many distinct MR techniques are available at different stages of development. While some are already clinically applicable, others are less far developed and have only or mainly been applied in healthy subjects. In this review, we explore the background, current status, potential and challenges of available quantitative MR techniques in the context of leukodystrophies

Robust Magnetic Resonance Imaging of Short T2 Tissues

Tissues with short transverse relaxation times are defined as ‘short T2 tissues’, and short T2 tissues often appear dark on images generated by conventional magnetic resonance imaging techniques. Common short T2 tissues include tendons, meniscus, and cortical bone. Ultrashort Echo Time (UTE) pulse sequences can provide morphologic contrasts and quantitative maps for short T2 tissues by reducing time-of-echo to the system minimum (e.g., less than 100 us). Therefore, UTE sequences have become a powerful imaging tool for visualizing and quantifying short T2 tissues in many applications. In this work, we developed a new Flexible Ultra Short time Echo (FUSE) pulse sequence employing a total of thirteen acquisition features with adjustable parameters, including optimized radiofrequency pulses, trajectories, choice of two or three dimensions, and multiple long-T2 suppression techniques. Together with the FUSE sequence, an improved analytical density correction and an auto-deblurring algorithm were incorporated as part of a novel reconstruction pipeline for reducing imaging artifacts. Firstly, we evaluated the FUSE sequence using a phantom containing short T2 components. The results demonstrated that differing UTE acquisition methods, improving the density correction functions and improving the deblurring algorithm could reduce the various artifacts, improve the overall signal, and enhance short T2 contrast. Secondly, we applied the FUSE sequence in bovine stifle joints (similar to the human knee) for morphologic imaging and quantitative assessment. The results showed that it was feasible to use the FUSE sequence to create morphologic images that isolate signals from the various knee joint tissues and carry out comprehensive quantitative assessments, using the meniscus as a model, including the mappings of longitudinal relaxation (T1) times, quantitative magnetization transfer parameters, and effective transverse relaxation (T2*) times. Lastly, we utilized the FUSE sequence to image the human skull for evaluating its feasibility in synthetic computed tomography (CT) generation and radiation treatment planning. The results demonstrated that the radiation treatment plans created using the FUSE-based synthetic CT and traditional CT data were able to present comparable dose calculations with the dose difference of mean less than a percent. In summary, this thesis clearly demonstrated the need for the FUSE sequence and its potential for robustly imaging short T2 tissues in various applications

Variable echo time imaging for detecting the short T2* components of the sciatic nerve: a validation study

OBJECTIVE: The aim of this study was to develop and validate an MRI protocol based on a variable echo time (vTE) sensitive to the short T2* components of the sciatic nerve. MATERIALS AND METHODS: 15 healthy subjects (M/F: 9/6; age: 21-62) were scanned at 3T targeting the sciatic nerve at the thigh bilaterally, using a dual echo variable echo time (vTE) sequence (based on a spoiled gradient echo acquisition) with echo times of 0.98/5.37 ms. Apparent T2* (aT2*) values of the sciatic nerves were calculated with a mono-exponential fit and used for data comparison. RESULTS: There were no significant differences in aT2* related to side, sex, age, and BMI, even though small differences for side were reported. Good-to-excellent repeatability and reproducibility were found for geometry of ROIs (Dice indices: intra-rater 0.68-0.7; inter-rater 0.70-0.72) and the related aT2* measures (intra-inter reader ICC 0.95-0.97; 0.66-0.85) from two different operators. Side-related signal-to-noise-ratio non-significant differences were reported, while contrast-to-noise-ratio measures were excellent both for side and echo. DISCUSSION: Our study introduces a novel MR sequence sensitive to the short T2* components of the sciatic nerve and may be used for the study of peripheral nerve disorders

Myelin bilayer mapping in the human brain in vivo

PURPOSE To quantitatively map the myelin lipid-protein bilayer in the live human brain. METHODS This goal was pursued by integrating a multi-TE acquisition approach targeting ultrashort T$_{2}$ signals with voxel-wise fitting to a three-component signal model. Imaging was performed at 3 T in two healthy volunteers using high-performance RF and gradient hardware and the HYFI sequence. The design of a suitable imaging protocol faced substantial constraints concerning SNR, imaging volume, scan time, and RF power deposition. Model fitting to data acquired using the proposed protocol was made feasible through simulation-based optimization, and filtering was used to condition noise presentation and overall depiction fidelity. RESULTS A multi-TE protocol (11 TEs of 20-780 μs) for in vivo brain imaging was developed in adherence with applicable safety regulations and practical scan time limits. Data acquired using this protocol produced accurate model fitting results, validating the suitability of the protocol for this purpose. Structured, grainy texture of myelin bilayer maps was observed and determined to be a manifestation of correlated image noise resulting from the employed acquisition strategy. Map quality was significantly improved by filtering to uniformize the k-space noise distribution and simultaneously extending the k-space support. The final myelin bilayer maps provided selective depiction of myelin, reconciling competitive resolution (1.4 mm) with adequate SNR and benign noise texture. CONCLUSION Using the proposed technique, quantitative maps of the myelin bilayer can be obtained in vivo. These maps offer unique information content with potential applications in basic research, diagnosis, disease monitoring, and drug development