High-resolution diffusion-weighted brain MRI under motion

Magnetic resonance imaging is one of the fastest developing medical imaging techniques. It provides excellent soft tissue contrast and has been a leading tool for neuroradiology and neuroscience research over the last decades. One of the possible MR imaging contrasts is the ability to visualize diffusion processes. The method, referred to as diffusion-weighted imaging, is one of the most common clinical contrasts but is prone to artifacts and is challenging to acquire at high resolutions. This thesis aimed to improve the resolution of diffusion weighted imaging, both in a clinical and in a research context. While diffusion-weighted imaging traditionally has been considered a 2D technique the manuscripts and methods presented here explore 3D diffusion acquisitions with isotropic resolution. Acquiring multiple small 3D volumes, or slabs, which are combined into one full volume has been the method of choice in this work. The first paper presented explores a parallel imaging driven multi-echo EPI readout to enable high resolution with reduced geometric distortions. The work performed on diffusion phase correction lead to an understanding that was used for the subsequent multi-slab papers. The second and third papers introduce the diffusion-weighted 3D multi-slab echo-planar imaging technique and explore its advantages and performance. As the method requires a slightly increased acquisition time the need for prospective motion correction became apparent. The forth paper suggests a new motion navigator using the subcutaneous fat surrounding the skull for rigid body head motion estimation, dubbed FatNav. The spatially sparse representation of the fat signal allowed for high parallel imaging acceleration factors, short acquisition times, and reduced geometric distortions of the navigator. The fifth manuscript presents a combination of the high-resolution 3D multi-slab technique and a modified FatNav module. Unlike our first FatNav implementation, using a single sagittal slab, this modified navigator acquired orthogonal projections of the head using the fat signal alone. The combined use of both presented methods provides a promising start for a fully motion corrected high-resolution diffusion acquisition in a clinical setting

Doctor of Philosophy

dissertationMagnetic resonance imaging (MRI) techniques are widely applied in various disease diagnoses and scientific research projects as noninvasive methods. However, lower signal-to-noise ratio (SNR), B1 inhomogeneity, motion-related artifact, susceptibility artifact, chemical shift artifact and Gibbs ring still play a negative role in image quality improvement. Various techniques and methods were developed to minimize and remove the degradation of image quality originating from artifacts. In the first part of this dissertation, a motion artifact reduction technique based on a novel real time self-gated pulse sequence is presented. Diffusion weighted and diffusion tensor magnetic resonance imaging techniques are generally performed with signal averaging of multiple measurements to improve the signal-to-noise ratio and the accuracy of diffusion measurement. Any discrepancy in images between different averages causes errors that reduce the accuracy of diffusion MRI measurements. The new scheme is capable of detecting a subject's motion and reacquiring motion-corrupted data in real time and helps to improve the accuracy of diffusion MRI measurements. In the second part of this dissertation, a rapid T1 mapping technique (two dimensional singleshot spin echo stimulated echo planar image--2D ss-SESTEPI), which is an EPI-based singleshot imaging technique that simultaneously acquires a spin-EPI (SEPI) and a stimulated-EPI (STEPI) after a single RF excitation, is discussed. The magnitudes of SEPI and STEPI differ by T1 decay for perfect 90o RF pulses and can be used to rapidly measure the T1 relaxation time. However, the spatial variation of B1 amplitude induces uneven splitting of the transverse magnetization for SEPI and STEPI within the imaging FOV. Therefore, correction for B1 inhomogeneity is critical for 2D ss-SESTEPI to be used for T1 measurement. In general, the EPI-based pulse sequence suffers from geometric distortion around the boundary of air-tissue or bone tissue. In the third part of this dissertation, a novel pulse sequence is discussed, which was developed based on three dimensional singleshot diffusion weighted stimulated echo planar imaging (3D ss-DWSTEPI). A parallel imaging technique was combined with 3D ss-DWSTEPI to reduce the image distortion, and the secondary spin echo formed by three RF pulses (900-1800-900) is used to improve the SNR. Image quality is improved

Interleaved EPI based fMRI improved by multiplexed sensitivity encoding (MUSE) and simultaneous multi-band imaging

© 2014 Chang et al. Functional magnetic resonance imaging (fMRI) is a non-invasive and powerful imaging tool for detecting brain activities. The majority of fMRI studies are performed with single-shot echo-planar imaging (EPI) due to its high temporal resolution. Recent studies have demonstrated that, by increasing the spatial-resolution of fMRI, previously unidentified neuronal networks can be measured. However, it is challenging to improve the spatial resolution of conventional single-shot EPI based fMRI. Although multi-shot interleaved EPI is superior to single-shot EPI in terms of the improved spatial-resolution, reduced geometric distortions, and sharper point spread function (PSF), interleaved EPI based fMRI has two main limitations: 1) the imaging throughput is lower in interleaved EPI; 2) the magnitude and phase signal variations among EPI segments (due to physiological noise, subject motion, and B0 drift) are translated to significant in-plane aliasing artifact across the field of view (FOV). Here we report a method that integrates multiple approaches to address the technical limitations of interleaved EPI-based fMRI. Firstly, the multiplexed sensitivity-encoding (MUSE) post-processing algorithm is used to suppress in-plane aliasing artifacts resulting from time-domain signal instabilities during dynamic scans. Secondly, a simultaneous multi-band interleaved EPI pulse sequence, with a controlled aliasing scheme incorporated, is implemented to increase the imaging throughput. Thirdly, the MUSE algorithm is then generalized to accommodate fMRI data obtained with our multi-band interleaved EPI pulse sequence, suppressing both in-plane and through-plane aliasing artifacts. The blood-oxygenation-level-dependent (BOLD) signal detectability and the scan throughput can be significantly improved for interleaved EPI-based fMRI. Our human fMRI data obtained from 3 Tesla systems demonstrate the effectiveness of the developed methods. It is expected that future fMRI studies requiring high spatial-resolvability and fidelity will largely benefit from the reported techniques.published_or_final_versio

Impacts of Simultaneous Multislice Acquisition on Sensitivity and Specificity in fMRI

Simultaneous multislice (SMS) imaging can be used to decrease the time between acquisition of fMRI volumes, which can increase sensitivity by facilitating the removal of higher-frequency artifacts and boosting effective sample size. The technique requires an additional processing step in which the slices are separated, or unaliased, to recover the whole brain volume. However, this may result in signal “leakage” between aliased locations, i.e., slice “leakage,” and lead to spurious activation (decreased specificity). SMS can also lead to noise amplification, which can reduce the benefits of decreased repetition time. In this study, we evaluate the original slice-GRAPPA (no leak block) reconstruction algorithmand acceleration factor (AF = 8) used in the fMRI data in the young adult Human Connectome Project (HCP). We also evaluate split slice-GRAPPA (leak block), which can reduce slice leakage. We use simulations to disentangle higher test statistics into true positives (sensitivity) and false positives (decreased specificity). Slice leakage was greatly decreased by split slice-GRAPPA. Noise amplification was decreased by using moderate acceleration factors (AF = 4). We examined slice leakage in unprocessed fMRI motor task data from the HCP. When data were smoothed, we found evidence of slice leakage in some, but not all, subjects. We also found evidence of SMS noise amplification in unprocessed task and processed resting-state HCP data

Development of Methodologies for Diffusion-weighted Magnetic Resonance Imaging at High Field Strength

Diffusion-weighted imaging of small animals at high field strengths is a challenging prospect due to its extreme sensitivity to motion. Periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) was introduced at 9.4T as an imaging method that is robust to motion and distortion. Proton density (PD)-weighted and T2-weighted PROPELLER data were generally superior to that acquired with single-shot, Cartesian and echo planar imaging-based methods in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio and resistance to artifacts. Simulations and experiments revealed that PROPELLER image quality was dependent on the field strength and echo times specified. In particular, PD-weighted imaging at high field led to artifacts that reduced image contrast. In PROPELLER, data are acquired in progressively rotated blades in k-space and combined on a Cartesian grid. PROPELLER with echo truncation at low spatial frequencies (PETALS) was conceived as a postprocessing method that improved contrast by reducing the overlap of k-space data from different blades with different echo times. Where the addition of diffusion weighting gradients typically leads to catastrophic motion artifacts in multi-shot sequences, diffusion-weighted PROPELLER enabled the acquisition of high quality, motion-robust data. Applications in the healthy mouse brain and abdomen at 9.4T and in stroke patients at 3T are presented. PROPELLER increases the minimum scan time by approximately 50%. Consequently, methods were explored to reduce the acquisition time. Two k-space undersampling regimes were investigated by examining image fidelity as a function of degree of undersampling. Undersampling by acquiring fewer k-space blades was shown to be more robust to motion and artifacts than undersampling by expanding the distance between successive phase encoding steps. To improve the consistency of undersampled data, the non-uniform fast Fourier transform was employed. It was found that acceleration factors of up to two could be used with minimal visual impact on image fidelity. To reduce the number of scans required for isotropic diffusion weighting, the use of rotating diffusion gradients was investigated, exploiting the rotational symmetry of the PROPELLER acquisition. Fixing the diffusion weighting direction to the individual rotating blades yielded geometry and anisotropy-dependent diffusion measurements. However, alternating the orientations of diffusion weighting with successive blades led to more accurate measurements of the apparent diffusion coefficient while halving the overall acquisition time. Optimized strategies are proposed for the use of PROPELLER in rapid high resolution imaging at high field strength

Design of a Transceive Coil Array for Parallel Imaging at 9.4T

The main goal of this thesis is to design and develop a transmit/receive (transceive) coil array for small animal imaging at 9.4T. The goal is achieved by following basic RF design principles with a methodical construction approach and demonstrating viable applications. As operational frequencies increase linearly with higher static fields, the wavelength approaches the size of the sample being imaged. The resulting standing wave mode deteriorates image homogeneity. Fortunately, with multi-channel coil arrays, the produced Bi field can be tailored to produce a homogeneous excitation in the region of interest, thus overcoming the so called dielectric resonance effect. We examined a solution to achieve a higher level of Bx homogeneity and we compared the improvement of RF wavelength effects reduction against the results obtained with a similar-sized conventional birdcage coil. An additional benefit of this design lies in the fact that the use of multiple receiving coil elements is necessary for the implementation of fast imaging acquisition techniques such as parallel imaging. This is possible because the distinct element sensitivities are used to reconstruct conventional images from undersampled (or accelerated) data. The greatest advantage of parallel imaging is thus the reduction of total acquisition time. In functional MRI (fMRI), single-shot EPI is one of the standard imaging technique. Unfortunately, EPI suffers from significant limitations, precisely because all of the data is acquired following a single RF excitation. As a result EPI images can manifest artifacts and blurring due to susceptibility mismatch, off-resonance effects and reduced signal at the edges of k-space. Fortunately, parallel imaging can be used to decrease such unwanted effects by reducing the total k-space data acquired. Presented in this thesis is the logical progression of the construction of a transceive coil from surface coil fundamentals to high field applications such as field focusing and parallel imaging techniques

Myocardial tagging by Cardiovascular Magnetic Resonance: evolution of techniques--pulse sequences, analysis algorithms, and applications

Cardiovascular magnetic resonance (CMR) tagging has been established as an essential technique for measuring regional myocardial function. It allows quantification of local intramyocardial motion measures, e.g. strain and strain rate. The invention of CMR tagging came in the late eighties, where the technique allowed for the first time for visualizing transmural myocardial movement without having to implant physical markers. This new idea opened the door for a series of developments and improvements that continue up to the present time. Different tagging techniques are currently available that are more extensive, improved, and sophisticated than they were twenty years ago. Each of these techniques has different versions for improved resolution, signal-to-noise ratio (SNR), scan time, anatomical coverage, three-dimensional capability, and image quality. The tagging techniques covered in this article can be broadly divided into two main categories: 1) Basic techniques, which include magnetization saturation, spatial modulation of magnetization (SPAMM), delay alternating with nutations for tailored excitation (DANTE), and complementary SPAMM (CSPAMM); and 2) Advanced techniques, which include harmonic phase (HARP), displacement encoding with stimulated echoes (DENSE), and strain encoding (SENC). Although most of these techniques were developed by separate groups and evolved from different backgrounds, they are in fact closely related to each other, and they can be interpreted from more than one perspective. Some of these techniques even followed parallel paths of developments, as illustrated in the article. As each technique has its own advantages, some efforts have been made to combine different techniques together for improved image quality or composite information acquisition. In this review, different developments in pulse sequences and related image processing techniques are described along with the necessities that led to their invention, which makes this article easy to read and the covered techniques easy to follow. Major studies that applied CMR tagging for studying myocardial mechanics are also summarized. Finally, the current article includes a plethora of ideas and techniques with over 300 references that motivate the reader to think about the future of CMR tagging

Double volumetric navigators for real-time simultaneous shim and motion measurement and correction in Glycogen Chemical Exchange Saturation Transfer (GlycoCEST) MRI

Glycogen is the primary glucose storage mechanism in in living systems and plays a central role in systemic glucose homeostasis. The study of muscle glycogen concentrations in vivo still largely relies on tissue sampling methods via needle biopsy. However, muscle biopsies are invasive and limit the frequency of measurements and the number of sites that can be assessed. Non-invasive methods for quantifying glycogen in vivo are therefore desirable in order to understand the pathophysiology of common diseases with dysregulated glycogen metabolism such as obesity, insulin resistance, and diabetes, as well as glycogen metabolism in sports physiology. Chemical Exchange Saturation Transfer (CEST) MRI has emerged as a non-invasive contrast enhancement technique that enables detection of molecules, like glycogen, whose concentrations are too low to impact the contrast of standard MR imaging. CEST imaging is performed by selectively saturating hydrogen nuclei of the metabolites that are in chemical exchange with those of water molecules and detecting a reduction in MRI signal in the water pool resulting from continuous chemical exchange. However, CEST signal can easily be compromised by artifacts. Since CEST is based on chemical shift, it is very sensitive to field inhomogeneity which may arise from poor initial shimming, subject respiration, heating of shim iron, mechanical vibrations or subject motion. This is a particular problem for molecules that resonate close to water, such as - OH protons in glycogen, where small variations in chemical shift cause misinterpretation of CEST data. The purpose of this thesis was to optimize the CEST MRI sequence for glycogen detection and implement a real-time simultaneous motion and shim correction and measurement method. First, analytical solution of the Bloch-McConnell equations was used to find optimal continuous wave RF pulse parameters for glycogen detection, and results were validated on a phantom with varying glycogen concentrations and in vivo on human calf muscle. Next, the CEST sequence was modified with double volumetric navigators (DvNavs) to measure pose changes and update field of view and zero- and first-order shim parameters. Finally, the impact of B0 field fluctuations on the scan-rescan reproducibility of CEST was evaluated in vivo in 9 volunteers across 10 different scans. Simulation results showed an optimal RF saturation power of 1.5µT and duration of 1s for glycoCEST. These parameters were validated experimentally in vivo and the ability to detect varying glycogen concentrations was demonstrated in a phantom. Phantom data showed that the DvNav-CEST sequence accurately estimates system frequency and linear shim gradient changes due to motion and corrects resulting image distortions. In addition, DvNav-CEST was shown to yield improved CEST quantification in vivo in the presence of motion and motion-induced field inhomogeneity. B0 field fluctuations were found to lower the reproducibility of CEST measures: the mean coefficient of variation (CoV) for repeated scans was 83.70 ± 70.79 % without shim correction. However, the DvNav-CEST sequence was able to measure and correct B0 variations, reducing the CoV to 2.6 ± 1.37 %. The study confirms the possibility of detecting glycogen using CEST MRI at 3 T and shows the potential of the real-time shim and motion navigated CEST sequence for producing repeatable results in vivo by reducing the effect of B0 field fluctuations

Functional MRI of Awake Behaving Macaques Using Standard Equipment

status: publishe

Methods for cleaning the BOLD fMRI signal

Available online 9 December 2016 http://www.sciencedirect.com/science/article/pii/S1053811916307418?via%3Dihubhttp://www.sciencedirect.com/science/article/pii/S1053811916307418?via%3DihubBlood oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI) has rapidly become a popular technique for the investigation of brain function in healthy individuals, patients as well as in animal studies. However, the BOLD signal arises from a complex mixture of neuronal, metabolic and vascular processes, being therefore an indirect measure of neuronal activity, which is further severely corrupted by multiple non-neuronal fluctuations of instrumental, physiological or subject-specific origin. This review aims to provide a comprehensive summary of existing methods for cleaning the BOLD fMRI signal. The description is given from a methodological point of view, focusing on the operation of the different techniques in addition to pointing out the advantages and limitations in their application. Since motion-related and physiological noise fluctuations are two of the main noise components of the signal, techniques targeting their removal are primarily addressed, including both data-driven approaches and using external recordings. Data-driven approaches, which are less specific in the assumed model and can simultaneously reduce multiple noise fluctuations, are mainly based on data decomposition techniques such as principal and independent component analysis. Importantly, the usefulness of strategies that benefit from the information available in the phase component of the signal, or in multiple signal echoes is also highlighted. The use of global signal regression for denoising is also addressed. Finally, practical recommendations regarding the optimization of the preprocessing pipeline for the purpose of denoising and future venues of research are indicated. Through the review, we summarize the importance of signal denoising as an essential step in the analysis pipeline of task-based and resting state fMRI studies.This work was supported by the Spanish Ministry of Economy and Competitiveness [Grant PSI 2013–42343 Neuroimagen Multimodal], the Severo Ochoa Programme for Centres/Units of Excellence in R & D [SEV-2015-490], and the research and writing of the paper were supported by the NIMH and NINDS Intramural Research Programs (ZICMH002888) of the NIH/HHS