High-resolution diffusion-weighted imaging at 7 Tesla: single-shot readout trajectories and their impact on signal-to-noise ratio, spatial resolution and accuracy

Diffusion MRI (dMRI) is a valuable imaging technique to study the brain in vivo. However, the resolution of dMRI is limited by the low signal-to-noise ratio (SNR) of this technique. Various acquisition strategies have been developed to achieve high resolutions, but they require long scan times. Imaging at ultra-high fields (UHF) could further increase the SNR of single-shot dMRI; however, the shorter T2* and the greater field non-uniformities will degrade image quality. In this study, we investigated the trade-off between the SNR and resolution of different k-space trajectories, including echo planar imaging (EPI), partial Fourier EPI, and spiral, over a range of resolutions at 7T. The effective resolution, spatial specificity and sharpening effect were measured from the point spread function (PSF) of the simulated diffusion sequences for a nominal resolution range of 0.6-1.8 mm. In-vivo scans were acquired using the three readout trajectories. Field probes were used to measure dynamic magnetic fields up to the 3rd order of spherical harmonics. Using a static field map and the measured trajectories image artifacts were corrected, leaving T2* effects as the primary source of blurring. The effective resolution was examined in fractional anisotropy (FA) maps. In-vivo scans were acquired to calculate the SNR. EPI trajectories had the highest specificity, effective resolution, and image sharpening effect, but also had substantially lower SNR. Spirals had significantly higher SNR, but lower specificity. Line plots of the in-vivo scans in phase and frequency encode directions showed ~0.2 units difference in FA values between the different trajectories. The difference between the effective and nominal resolution is greater for spirals than for EPI. However, the higher SNR of spiral trajectories at UHFs allows us to achieve higher effective resolutions compared to EPI and PF-EPI trajectories

Single shot three-dimensional pulse sequence for hyperpolarized 13 C MRI.

PURPOSE: Metabolic imaging with hyperpolarized 13 C-labeled cell substrates is a promising technique for imaging tissue metabolism in vivo. However, the transient nature of the hyperpolarization, and its depletion following excitation, limits the imaging time and the number of excitation pulses that can be used. We describe here a single-shot three-dimensional (3D) imaging sequence and demonstrate its capability to generate 13 C MR images in tumor-bearing mice injected with hyperpolarized [1-13 C]pyruvate. METHODS: The pulse sequence acquires a stack-of-spirals at two spin echoes after a single excitation pulse and encodes the kz-dimension in an interleaved manner to enhance robustness to B0 inhomogeneity. Spectral-spatial pulses are used to acquire dynamic 3D images from selected hyperpolarized 13 C-labeled metabolites. RESULTS: A nominal spatial/temporal resolution of 1.25 × 1.25 × 2.5 mm3  × 2 s was achieved in tumor images of hyperpolarized [1-13 C]pyruvate and [1-13 C]lactate acquired in vivo. Higher resolution in the z-direction, with a different k-space trajectory, was demonstrated in measurements on a thermally polarized [1-13 C]lactate phantom. CONCLUSION: The pulse sequence is capable of imaging hyperpolarized 13 C-labeled substrates at relatively high spatial and temporal resolutions and is robust to moderate system imperfections. Magn Reson Med 77:740-752, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The work was supported by a Cancer Research UK Programme grant (17242) to KMB and by the CRUK-EPSRC Imaging Centre in Cambridge and Manchester (16465). JW was also supported, in part, by a grant from the Danish Strategic Research Council (LIFE-DNP: Hyperpolarized magnetic resonance for in vivo quantification of lipid, sugar and amino acid metabolism in lifestyle related diseases).This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/mrm.2616

Development of pulse sequences for hyperpolarized 13C magnetic resonance spectroscopic imaging of tumour metabolism

Metabolic imaging with hyperpolarized 13C-labeled cell substrates is a promising technique for imaging tissue metabolism in vivo. However, the transient nature of the hyperpolarization - and its depletion following excitation - limits the imaging time and the number of excitation pulses that can be used. A single-shot 3D imaging sequence has been developed and it is shown in this thesis to generate 13C MR images in tumour-bearing mice injected with hyperpolarized [1-13C]pyruvate. The pulse sequence acquires a stack-of-spirals at two spin echoes after a single excitation pulse and encodes the kz-dimension in an interleaved manner to enhance robustness to B0 inhomogeneity. Spectral-spatial pulses are used to acquire dynamic 3D images from selected hyperpolarized 13C-labeled metabolites. A nominal spatial/temporal resolution of 1.25 x 1.25 x 2.5 $mm^3$ x 2 s was achieved in tumour images of hyperpolarized [1-13C]pyruvate and [1-13C]lactate acquired in vivo. An advanced sequence is also described in this thesis in a later study to acquire higher resolution images with isotropic voxels (1.25 x 1.25 x 1.25 $mm^3$) at no cost of temporal resolution. EPI is a sequence widely used in hyperpolarized 13C MRI because images can be acquired rapidly with limited RF exposure. However, EPI suffers from Nyquist ghosting, which is normally corrected for by acquiring a reference scan. In this thesis a workflow for hyperpolarized 13C EPI is proposed that requires no reference scan and, therefore, that does not sacrifice a time point in the dynamic monitoring of tissue metabolism. To date, most of the hyperpolarized MRI on metabolism are based on 13C imaging, while 1H is a better imaging target for its 4 times higher gyromagnetic ratio and hence 16 times signal. In this thesis the world’s first dynamic 1H imaging in vivo of hyperpolarized [1-13C]lactate is presented, via a novel double-dual-spin-echo INEPT sequence that transfers the hyperpolarization from 13C to 1H, achieving a spatial resolution of 1.25 x 1.25 $mm^2$

High efficiency, low distortion 3D diffusion tensor imaging with variable density spiral fast spin echoes (3D DW VDS RARE)

We present an acquisition and reconstruction method designed to acquire high resolution 3D fast spin echo diffusion tensor images while mitigating the major sources of artifacts in DTI-field distortions, eddy currents and motion. The resulting images, being 3D, are of high SNR, and being fast spin echoes, exhibit greatly reduced field distortions. This sequence utilizes variable density spiral acquisition gradients, which allow for the implementation of a self-navigation scheme by which both eddy current and motion artifacts are removed. The result is that high resolution 3D DTI images are produced without the need for eddy current compensating gradients or B_0 field correction. In addition, a novel method for fast and accurate reconstruction of the non-Cartesian data is employed. Results are demonstrated in the brains of normal human volunteers

Detecting diverse types of cardiovascular brain pulses in Alzheimer’s disease simultaneously with fNIRS and MREG

Abstract. One of the risk factors for Alzheimer’s disease is hypertension. Hypertension alters the brain’s blood vessel structure due to increased arterial pressure. Structural changes in the blood vessels are seen in the cardiovascular pulse, which is formed by blood velocity, blood flow rate, blood pressure, and infrequently blood flow. By simultaneously applying magnetic resonance encephalography (MREG) and functional near-infrared spectroscopy (fNIRS), this study discovered cardiovascular brain pulses from the blood flow within patients with Alzheimer’s disease and healthy controls. This study detects specific parameters within diverse types of cardiovascular brain pulses. The results detected changes in parameters for diverse types of cardiovascular brain pulses in patients with Alzheimer’s disease within MREG and fNIRS. In addition, the results present an alternative method for finding cardiovascular brain pulse from the blood flow, which might reflect the structural changes of a blood vessel in patients with Alzheimer’s disease. In conclusion, diverse types of cardiovascular brain pulses represent an approximation of arterial, venous, and tissue pulses, which is beneficial for distinguishing the effect of venous and arterial hypertension in Alzheimer’s disease. Furthermore, altered blood flow may potentially be associated with the impaired glymphatic system in Alzheimer’s disease

Aivojen unenaikaiset pulsaatiot

Tiivistelmä. Työtarkoitus: Tutkielman tarkoituksena oli selvittää miten aivojen pulsaatiot eroavat toisistaan unessa ja hereillä eri taajuuskaistoilla (Todella matalat taajuudet (VLF), hengityskaista, sykekaista) mitattuna todella nopealla fMRI sekvenssillä. MREG:llä. VLF-kaista oli 0.0098–0.10 Hz, hengityskaista 0.110–0.439 Hz ja sykekaista 0.522–1.599 Hz. MREG:n näytteenottotaajuus 10 Hz on korkeampi kuin perinteisen BOLD fMRI:n (blood oxygen-level-dependent functional magnetic resonance imaging), joten tulokset antavat entistä tarkempaa tietoa aivojen unenaikaisten pulsaatioiden toiminnasta. Menetelmät: MREG datalle tehtiin aluksi perinteinen fMRI-esikäsittely, jonka jälkeen AFNI:n 3dPeriodogram komennolla saatiin FFT tehospektrit koko pään alueelle. Tämän jälkeen halutut vokselit lajiteltiin maskeilla kolmeksi ROI:ksi (region of interest), jotka olivat harmaa aine, valkoinen aine ja kaikki ventrikkelit. 4 ventrikkelin ROI saatiin etsimällä kirkkain vokseli sen alueelta ja muodostettua sen ympärille pieni ROI. Unen ja valvetilan vertailu toteutettiin työtä varten luodulla MATLAB-skriptillä, joka jakoi ROI:den datan edellä mainittuihin taajuuskaistoihin laskien keskiarvot ja keskihajonnat niiden mukaan. Tulokset: MREG:llä kerätty data tuki vahvasti aiempien tutkimusten tuloksia aivojen unenaikaisista pulsaatioista. Päälöydös oli VLF-taajuuskaistan tehospektrin selkeä unen aikainen voimistuminen kaikissa ROI:ssa verrattuna valvetilaan. Johtopäätökset: MREG:n korkeampi näytteenottotaajuus on voinut poistaa hengityselimistön ja sydämen taajuuskaistojen laskostumisen, jonka seurauksena tulokset ovat tarkempia selkäydinnesteen unenaikaisten pulsaatioiden tutkimisessa.Pulsations of brain during sleep. Abstract. Objective: The objective of this thesis was to study how physiological brain pulsations (very low frequency (VLF), respiratory, cardiac) power differ in sleep compared to wakefulness measured with ultrafast MREG (Magnetic resonance encephalography). VLF-band was 0.0098–0.1 Hz, respiratory band 0.110–0.439 Hz and cardiac band 0.522–1.599Hz. MREG has a higher 10 Hz sampling rate so the results could be more accurate compared to data collected with traditional BOLD fMRI (Blood oxygen-level-dependent functional magnetic resonance imaging). Methods: MREG data was preprocessed the way fMRI data usually is. Then AFNI’s 3dPeriodogram-command was used to generate FFT power spectrum for the whole brain. Masks were used to split the data into 3 different ROI’s (region of interest) that which were white matter, gray matter, and all ventricles. Brightest voxel was then searched from the region of 4th ventricle to generate ROI for analyzing 4th ventricle. Comparison between sleep and awake was performed by MATLAB-script that also divided the data into three frequency spectrums. The script also calculated means and standard deviations for every spectrum of every ROI. Results: MREG-data seemed to follow the results of previous studies and theories regarding pulsations of the brain during sleep. The main discovery was VLF-frequency band’s greater power spectrum during sleep in every ROI compared to awake. Conclusion: Higher sampling rate achieved by MREG prevented aliasing with respiratory and cardiac frequencies and gave more accurate results regarding CSF-pulsations during sleep

Development of a 3D radial MR Imaging sequence to be used for (self) navigation during the scanning of the fetal brain in utero

Imaging the fetal brain in utero is challenging due to the unpredictable motion of the fetus. Although ultra-fast MRI sequences are able to image a 2D slice in under a second, thus limiting the time in which fetal motion can corrupt images, Cartesian sampling makes these sequences sensitive to signal misregistration and motion-corruption. Corruption of a single 2D slice renders it impossible to reconstruct 3D volumes from these slices without complex slice-to-volume registration. There is a need for motion-robust sequences that can produce high-resolution 3D volumes of the fetal brain. The Siemens Cardiovascular sequence was edited to produce a new radial readout that sampled a 3D spherical volume of k-space with successive diametric spokes. The diameter end points map a spiral trajectory on the surface of a sphere. The trajectory was modified so that multiple sub-volumes of data are sampled during a single acquisition where M is the number of sub-spirals and N is the number of diametric spokes per sub-spiral. This allows reconstruction of individual sub-volumes of data to produce a series of low-resolution navigator images that can be co-registered to provide information on motion during the acquisition. In this way, a segmented sequence suited to self-navigation was developed. Imaging parameters for the 3D radial sequence were optimised based on theoretical calculations and scans performed in adult brains and abdomens. Optimum values for M and N needed to be determined. Increasing M for a constant total number of projections improves the temporal accuracy of motion tracking at the expense of decreased signal to noise ratio in the navigator images. The effects of breathing and rigid body motion on image quality were also compared between 3D radial and equivalent 3D Cartesian acquisitions. Custom reconstruction code was written to separate the incoming scan data according to the sub-spiral trajectories described within the sequence such that individual navigator images could be reconstructed. Successive sub-spiral images were co-registered to the first navigator image to quantify motion during the acquisition. The resulting transformation matrices were then applied to each sub-spiral image after reconstruction and co-registered sub-spiral images combined in image space to generate the final 3D volume. To improve the quality of navigator images, a method is presented to perform navigator image reconstruction at a lower base resolution, thus reducing streaking artifacts and improving the accuracy of image co-registrations. Finally, the methods developed were applied to two fetal scans. The radial sequence was shown to be more motion-robust than an equivalent Cartesian sequence. The minimum number of diametric spokes that provided navigator images that could be accurately co-registered when scanning an adult brain was N=256, which could be acquired in 1.25 s. For abdominal scans, the minimum number of spokes was N=1024, which could be acquired in about 6 s when water excitation is applied. However, the latter could potentially be reduced by reconstructing navigator images at a lower base resolution. Although fetal scans demonstrated poor image contrast, navigator images were able to track motion during the acquisition demonstrating the potential use of this method for self-navigation. In conclusion, a motion-robust radial sequence is presented with potential applications for prospective navigation during fetal MRI

High Resolution Fast MRI and MRSI using Spiral Data Acquisition

In this thesis, spiral k-space sampling was configured differently for two applications in Magnetic Resonance Spectroscopic Imaging (MRSI) and time resolved 3D Magnetic Resonance Imaging (MRI). Selective Multiple Quantum Coherence Transfer (Sel-MQC) technique was implemented in in vivo MRSI in combination with Spiral data acquisition. The Spiral Sel-MQC technique enabled fast mapping of Polyunsaturated Fatty Acids (PUFA) in human breast in vivo compared to Chemical Shift Imaging (CSI). The Sel-MQC technique utilizes a scalar coupling to excite PUFA signal while suppressing other resonances in lipid and water. An in vivo 2D Sel- MQC sequence was first implemented to optimize the performance of the Sel-MQC excitation and to investigate the compositions of PUFA as well as Monounsaturated Fatty Acids (MUFA). Spiral data acquisition was then implemented to image PUFA signal exclusively. An image can be acquired in 1-2 min with 16 or 32 scans. Time resolved 3D MRI was also developed with high spatial and temporal resolutions with spiral data acquisition. Off-resonance correction was performed using inhomogeneity field maps. View sharing and sliding window reconstruction were utilized to generate high temporal resolution. High resolution 3D angiograms were generated at 1-2 seconds per frame in vivo. A quantitative method was developed to evaluate the performance of spiral parameters in these applications. This method approximates spiral imaging as a process of linear estimation. The optimal spiral parameters can be determined by finding the least estimation error. Two in vivo applications of spiral data acquisition discussed in this thesis shows that spiral data acquisition can shorten scan times by a factor of up to 10. It can, therefore, enable clinics to include advanced MR techniques such as Sel-MQC and time resolved 3D MRI to enhance diagnosis of cancer or vascular diseases

Analysis and Mitigation of the Effect of Magnetic Field Inhomogeneities and Undersampling Artifacts on Magnetic Resonance Fingerprinting

Magnetic resonance imaging (MRI) is largely limited to producing qualitative contrast images instead of quantitative maps of tissue characteristics. A novel framework for quantitative MRI termed Magnetic Resonance Fingerprinting (MRF) to map tissue parameters such as the relaxation times T1 and T2 has recently been introduced. In MRF, tissue signals are generated by applying a pseudo-randomly varying MRI acquisition, acquired using highly undersampled trajectories and matched to a database of simulated tissue signals. The aim of this thesis is to investigate hypotheses underlying MRF regarding its susceptibility to undersampling artifacts and magnetic field inhomogeneities and develop countermeasures. Since MRF can be implemented in various ways, one of the most popular implementations based on the FISP (Fast Imaging with Steady State Precession) sequence was chosen for analysis and as a basis for further developments. The single shot spiral trajectories employed lead to substantial undersampling artifacts. In this work, the temporal variation of the spiral sampling patterns was examined and optimized. The results show that the originally proposed temporal order yields artifacts of similar frequencies as the signal responses from tissues, which leads to spatially dependent misestimations of parameters. To resolve those, an optimized temporal order was developed in simulations and proven in in-vivo experiments. The following chapter is dedicated to the influence of magnetic field inhomogeneities on MRF. Here it is shown that different local amplitudes of the radio frequency (RF) field B1+ can lead to misestimations of parameters by up to 50%, which can be resolved by measuring a B1+ map and integrating the information in the pattern match. Another newly developed strategy in this work is to mitigate the influence of B1+ by the introduction of acquisition segments that are particularly sensitive to B1+. Two approaches were developed and evaluated, one including FLASH (Fast Low-Angle Shot) and one using two 90° phase shifted pulses. Here, tissue parameter maps and B1+ maps were simultaneously generated, thereby resolving interdependencies. Furthermore, in this work it was found that the static magnetic field B0 can also have an impact on FISP-MRF. The dependency was analyzed and related to the relative phase difference between spin ensembles and RF pulses. A technique to mitigate the dependency by additionally dephasing spins before RF pulses was developed. The chapter is concluded with the presentation of the novel development of MRFF (Magnetic Resonance Field Fingerprinting). By replacing some FISP segments with TrueFISP and FLASH segments, B0 and B1+ dependent information was added, which enabled the simultaneous generation of T1, T2, B0, B1+ and intravoxel phase dispersion maps. In the last chapter, the in-vivo reproducibility of FISP-MRF with the newly developed improvements described in the previous chapters was evaluated by scanning ten volunteers on ten scanners. T1 and T2 values varied less than 8.0% in brain compartments across scanners.Die Magnetresonanztomographie (MRT) beschränkt sich weitgehend auf die Erzeugung qualitativer Kontrastbilder anstelle von quantitativen Karten von Gewebeeigenschaften. Kürzlich wurde ein neuartiges Framework für quantitative MRT, Magnetic Resonance Fingerprinting (MRF) zur direkten Abbildung von Gewebeparametern wie der Relaxationszeiten T1 und T2 präsentiert. Bei MRF werden Gewebesignale mittels einer pseudozufällig variierenden MRT-Sequenz generiert, die unter Verwendung stark unterabgetasteter Trajektorien aufgenommen werden und daraufhin mit einer Datenbank simulierter Gewebesignale zum Zweck der Identifikation von Gewebeparametern verglichen werden. Ziel dieser Arbeit ist es, die Anfälligkeit von MRF für Unterabtastungsartefakte und Magnetfeldinhomogenitäten zu untersuchen und entsprechende Gegenmaßnahmen zu entwickeln. Da MRF auf verschiedene Arten implementiert werden kann, wurde die bis dato am häufigsten verwendete Implementierung basierend auf der FISP (Fast Imaging with Steady State Precession) Sequenz zur Analyse und als Grundlage für weitere Entwicklungen ausgewählt. Die in FISP-MRF verwendeten Einzelschuss-Spiraltrajektorien führen zu erheblichen Unterabtastungsartefakten im Bildraum. In dieser Arbeit wird deren zeitliche Variation untersucht und optimiert. Die Resultate zeigen, dass die ursprünglich vorgeschlagene Abfolge Artefakte mit ähnlichen Frequenzen wie die der Signalantworten von Geweben ergibt, was zu ortsabhängigen Parameterfehlern führt. Eine optimierte Abfolge wurde in Simulationen gefunden, die in in-vivo Experimenten bestätigt wurde. Das folgende Kapitel befasst sich mit dem Einfluss von Magnetfeldinhomogenitäten auf FISP-MRF. Hier wird gezeigt, dass variierende lokale Amplituden des HF-Feldes B1+ zu Parameterfehlern von bis zu 50% führen können, die sich durch die Messung einer B1+ Karte und Integrieren der Informationen in den Musterabgleich beheben lassen können. Eine weitere in dieser Arbeit entwickelte Strategie ist die Einführung von Akquisitionssegmenten, die gegenüber B1+ besonders sensitiv sind. Zwei Ansätze, einer mit FLASH (Fast Low-Angle Shot) und einer mit zwei um 90° phasenverschobenen Hochfrequenz-Pulsen pro TR wurden in dieser Arbeit entwickelt. Hier werden gleichzeitig Gewebeparameter- und B1+ -Karten erzeugt, wodurch gegenseitige Abhängigkeiten aufgelöst werden. In dieser Arbeit wurde auch gezeigt, dass Inhomogenitäten des statischen Magnetfelds B0 sich auf FISP-MRF auswirken können. Diese Abhängigkeit wurde analysiert und mit der relativen Phasendifferenz zwischen Spin-Ensembles und HF-Pulsen in Beziehung gesetzt. Wie in dieser Arbeit gezeigt, kann durch zusätzliches Dephasieren von Spin-Ensembles vor einem HF-Impuls der Einfluss von B0 stark vermindert werden. Im letzten Abschnitt dieses Kapitels wird die neue eigene Entwicklung MRFF (Magnetic Resonance Field Fingerprinting) präsentiert. Durch Ersetzen einiger FISP-Segmente durch TrueFISP- und FLASH-Segmente werden B0 und B1+ abhängige Informationen hinzugefügt, wodurch die gleichzeitige Erzeugung von T1, T2, B0, B1+ sowie Suszeptibilitätskarten möglich wird. Im fünften Kapitel wurde die in-vivo Reproduzierbarkeit und Wiederholbarkeit von FISP-MRF mit den in den vorhergehenden Kapiteln beschriebenen Verbesserungen durch Messungen von zehn Probanden auf insgesamt zehn Scannern evaluiert. Die T1- und T2-Werte variierten zwischen den Scannern in den Gehirnkompartimenten um weniger als 8,0%

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD