Doctor of Philosophy

dissertationThe gold standard for evaluation of arterial disease using MR continues to be contrast-enhanced MR angiography (MRA) with gadolinium-based contrast agents (Gd-MRA). There has been a recent resurgence in interest in methods that do not rely on gadolinium for enhancement of blood vessels due to associations Gd-MRA has with nephrogenic systemic fibrosis (NSF) in patients with impaired renal function. The risk due to NSF has been shown to be minimized when selecting the appropriate contrast type and dose. Even though the risk of NSF has been shown to be minimized, demand for noncontrast MRA has continued to rise to reduce examination cost, and improve patient comfort and ability to repeat scans. Several methods have been proposed and used to perform angiography of the aorta and peripheral arteries without the use of gadolinium. These techniques have had limitations in transmit radiofrequency field (B1+) inhomogeneities, acquisition time, and specific hardware requirements, which have stunted the utility of noncontrast enhanced MRA. In this work feasibility of noncontrast (NC) MRA at 3T of the femoral arteries using dielectric padding, and using 3D radial stack of stars and compressed sensing to accelerate acquisitions in the abdomen and thorax were tested. Imaging was performed on 13 subjects in the pelvis and thighs using high permittivity padding, and 11 in the abdomen and 19 in the thorax using 3D radial stack of stars with tiny golden angle using gold standards or previously published techniques. Qualitative scores for each study were determined by radiologists who were blinded to acquisition type. Vessel conspicuity in the thigh and pelvis showed significant increase when high permittivity padding was used in the acquisition. No significant difference in image quality was observed in the abdomen and thorax when using undersampling, except for the descending aorta in thoracic imaging. All image quality scores were determined to be of diagnostic quality. In this work it is shown that NC-MRA can be improved through the use of high permittivity dielectric padding and acquisition time can be decreased through the use of 3D radial stack of stars acquisitions

NONINVASIVE IMAGING OF BRAIN VASCULATURE WITH HIGH RESOLUTION BLOOD OXYGENATION LEVEL-DEPENDENT VENOGRAPHY IN MAGNETIC RESONANCE IMAGING: APPLICATIONS TO FUNCTIONAL AND CLINICAL STUDIES

BOLD techniques have been used in a vast range of applications including functional MRI (fMRI) and clinical MR venography of brain vasculature. Despite the immense success of BOLD fMRI applications, our understanding of complex neuronal and hemodynamic processes associated with BOLD techniques is limited. An experimental investigation with BOLD MR venography may allow us to expand our knowledge in hemodynamic process involved in BOLD fMRI. BOLD techniques are also clinically useful. In clinical brain imaging studies, imaging both time-of-flight (TOF) MR angiogram (MRA) and BOLD MR venogram (MRV) is often desirable, because they complement the depiction of vascular pathologies. Nevertheless, MRV is usually not acquired to minimize the image acquisition time. It will be highly beneficial if we can acquire MRV while imaging MRA without increasing scan time. Thus, the objective of our study was to develop and assess BOLD MRV techniques for both functional and clinical applications. For the experimental evaluation of BOLD MRV, we used a rat brain model at 9.4T. The scan condition for BOLD MRV was optimized and the venous origin of hypointense vasculature was investigated with modulation of oxygenation. Detailed venules of ˜16-30μm diameter were detected in the resulting in vivo images with 78μm isotropic scan resolution, verified with in vivo two-photon microscopy and computer simulation data. Activation foci of high-resolution BOLD fMRI maps were correlated with relatively large intracortical veins detected with high-resolution BOLD MRV, indicating that detectability of conventional BOLD fMRI is limited by density of these intracortical veins (˜1.5 vessels/mm²). For the clinical application of BOLD MRV, we developed and tested a compatible dual-echo arteriovenography (CODEA) technique for simultaneous acquisition of TOF MRA and BOLD MRV at a 3T human system. Image quality of the CODEA technique acquired in a single session was comparable to conventional TOF MRA and BOLD MRV separately acquired in two sessions. The CODEA technique was applied to chronic stroke studies. Detailed vascular structures including arterial occlusions and venous abnormalities were depicted. The CODEA technique appears valuable to other clinical applications, particularly for those requiring efficient MRA/MRV imaging with limited scan time such as acute stroke studies

The Role of 3 Tesla MRA in the Detection of Intracranial Aneurysms

Intracranial aneurysms constitute a common pathological entity, affecting approximately 1–8% of the general population. Their early detection is essential for their prompt treatment. Digital subtraction angiography is considered the imaging method of choice. However, other noninvasive methodologies such as CTA and MRA have been employed in the investigation of patients with suspected aneurysms. MRA is a noninvasive angiographic modality requiring no radiation exposure. However, its sensitivity and diagnostic accuracy were initially inadequate. Several MRA techniques have been developed for overcoming all these drawbacks and for improving its sensitivity. 3D TOF MRA and contrast-enhanced MRA are the most commonly employed techniques. The introduction of 3 T magnetic field further increased MRA's sensitivity, allowing detection of aneurysms smaller than 3 mm. The development of newer MRA techniques may provide valuable information regarding the flow characteristics of an aneurysm. Meticulous knowledge of MRA's limitations and pitfalls is of paramount importance for avoiding any erroneous interpretation of its findings

MRI of the kidney—state of the art

Ultrasound and computed tomography (CT) are modalities of first choice in renal imaging. Until now, magnetic resonance imaging (MRI) has mainly been used as a problem-solving technique. MRI has the advantage of superior soft-tissue contrast, which provides a powerful tool in the detection and characterization of renal lesions. The MRI features of common and less common renal lesions are discussed as well as the evaluation of the spread of malignant lesions and preoperative assessment. MR urography technique and applications are discussed as well as the role of MRI in the evaluation of potential kidney donors. Furthermore the advances in functional MRI of the kidney are highlighted

Neuroimaging at 7 Tesla: a pictorial narrative review

Neuroimaging using the 7-Tesla (7T) human magnetic resonance (MR) system is rapidly gaining popularity after being approved for clinical use in the European Union and the USA. This trend is the same for functional MR imaging (MRI). The primary advantages of 7T over lower magnetic fields are its higher signal-to-noise and contrast-to-noise ratios, which provide high-resolution acquisitions and better contrast, making it easier to detect lesions and structural changes in brain disorders. Another advantage is the capability to measure a greater number of neurochemicals by virtue of the increased spectral resolution. Many structural and functional studies using 7T have been conducted to visualize details in the white matter and layers of the cortex and hippocampus, the subnucleus or regions of the putamen, the globus pallidus, thalamus and substantia nigra, and in small structures, such as the subthalamic nucleus, habenula, perforating arteries, and the perivascular space, that are difficult to observe at lower magnetic field strengths. The target disorders for 7T neuroimaging range from tumoral diseases to vascular, neurodegenerative, and psychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy, major depressive disorder, and schizophrenia. MR spectroscopy has also been used for research because of its increased chemical shift that separates overlapping peaks and resolves neurochemicals more effectively at 7T than a lower magnetic field. This paper presents a narrative review of these topics and an illustrative presentation of images obtained at 7T. We expect 7T neuroimaging to provide a new imaging biomarker of various brain disorders

Coronary MR angiography at 3T: fat suppression versus water-fat separation

Objectives: To compare Dixon water-fat suppression with spectral pre-saturation with inversion recovery (SPIR) at 3T for coronary magnetic resonance angiography (MRA) and to demonstrate the feasibility of fat suppressed coronary MRA at 3T without administration of a contrast agent. Materials and methods: Coronary MRA with Dixon water-fat separation or with SPIR fat suppression was compared on a 3T scanner equipped with a 32-channel cardiac receiver coil. Eight healthy volunteers were examined. Contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), right coronary artery (RCA), and left anterior descending (LAD) coronary artery sharpness and length were measured and statistically compared. Two experienced cardiologists graded the visual image quality of reformatted Dixon and SPIR images (1: poor quality to 5: excellent quality). Results: Coronary MRA images in healthy volunteers showed improved contrast with the Dixon technique compared to SPIR (CNR blood-fat: Dixon = 14.9 ± 2.9 and SPIR = 13.9 ± 2.1; p = 0.08, CNR blood-myocardium: Dixon = 10.2 ± 2.7 and SPIR = 9.11 ± 2.6; p = 0.1). The Dixon method led to similar fat suppression (fat SNR with Dixon: 2.1 ± 0.5 vs. SPIR: 2.4 ± 1.2, p = 0.3), but resulted in significantly increased SNR of blood (blood SNR with Dixon: 19.9 ± 4.5 vs. SPIR: 15.5 ± 3.1, p < 0.05). This means the residual fat signal is slightly lower with the Dixon compared to the SIPR technique (although not significant), while the SNR of blood is significantly higher with the Dixon technique. Vessel sharpness of the RCA was similar for Dixon and SPIR (57 ± 7 % vs. 56 ± 9 %, p = 0.2), while the RCA visualized vessel length was increased compared to SPIR fat suppression (107 ± 21 vs. 101 ± 21 mm, p < 0.001). For the LAD, vessel sharpness (50 ± 13 % vs. 50 ± 7 %, p = 0.4) and vessel length (92 ± 46 vs. 90 ± 47 mm, p = 0.4) were similar with both techniques. Consequently, the Dixon technique resulted in an improved visual score of the coronary arteries in the water fat separated images of healthy subjects (RCA: 4.6 ± 0.5 vs. 4.1 ± 0.7, p = 0.01, LAD: 4.1 ± 0.7 vs. 3.5 ± 0.8, p = 0.007). Conclusions: Dixon water-fat separation can significantly improve coronary artery image quality without the use of a contrast agent at 3T

Absolute Quantitation for MR Molecular Imaging of Angiogenesis

Medical imaging is undergoing a transition from an art that is used to make static images of human physiology into a scientific tool that employs advanced techniques to measure clinically relevant data. Recently, the role of magnetic resonance imaging in cardiovascular and oncological research has grown, largely due to the implementation of new quantitative techniques in the clinic. Magnetic resonance imaging (MRI) and spectroscopy (MRS) are particularly rich in their capability to quantify both physiology and disease via biomarker detection. While this is true for many applications of MRI in cardiovascular and oncological research, 19F MR molecular imaging is particularly useful when coupled to the use of emerging site-targeted molecular imaging agents for diagnosis and therapy, such as αvβ3 integrin-targeted perfluorocarbon (PFC) nanoparticle (NP) emulsions. Unfortunately, the radiological world is realizing that although image quality may be consistently high, the absolute quantitative values being calculated vary widely across time, techniques, laboratories, and imaging platforms. The overall objective of this work is to advance the state of the art for 19F MR molecular imaging of perfluorocarbon nanoparticle emulsion contrast agents. To reach this objective, three specific aims have been identified: (1) to create new tools and techniques for 19F MR molecular imaging of PFC nanoparticles, (2) to develop translatable procedures for absolute quantification of 19F nuclei with MR molecular imaging, and (3) to evaluate the potential for clinical translation with ex vivo and in vivo preclinical experiments. Robust, standardized techniques are developed in this work to improve the accuracy of in vivo quantitative 19F MR molecular imaging, validate system performance, calibrate measurements to ensure repeatability of these quantitative metrics, and evaluate the potential for clinical translation. As these quantitative metrics become routine in medical imaging procedures, these standardized calibrations and techniques are expected to be critical for accurate interpretation of underlying pathophysiology. This will also impact the development of new therapies and diagnostic techniques/agents by reducing the variability of image-based measurements, thereby increasing the impact of the studies and reducing the overall time and cost to translate new technologies into the clinic

Steady-state anatomical and quantitative magnetic resonance imaging of the heart using RF-frequencymodulated techniques

Cardiovascular disease (CVD) is the leading cause of death in the United States and Europe and generates healthcare costs of hundreds of billions of dollars annually. Conventional methods of diagnosing CVD are often invasive and carry risks for the patient. For example, the gold standard for diagnosing coronary artery disease, a major class of CVD, is x-ray coronary angiography, which has the disadvantages of being invasive, being expensive, using ionizing radiation, and having a ris k of complications. Conversely, coronary MR angiography (MRA) does not use ionizing radiation, can effectively visualize tissues without the need for exogenous contrast agents, and benefits from an adaptable temporal resolution. However, the acquisition time of cardiac MRI is far longer than the temporal scales of cardiac and respiratory motion, necessitating some method of compensating for this motion. The free-running framework is a novel development in our lab, benefitting from advances over the past three decades, that attempts to address disadvantages of previous cardiac MRI approaches: it provides fully self-gated 5D cardiac MRI with a simplified workflow, improved ease-of-use, reduced operator dependence, and automatic patient-specific motion detection. Free-running imaging increases the amount of information available to the clinician and is flexible enough to be translated to different app lications within cardiac MRI. Moreover, the self-gating of the free-running framework decoupled the acquisition from the motion compensation and thereby opened up cardiac MRI to the wider class of steady-state-based techniques utilizing balanced steady-state free precession (bSSFP) sequences, which have the benefits of practical simplicity and high signal-to-noise ratio. The focus of this thesis was therefore on the application of steady- state techniques to cardiac MRI. The first part addressed the long acquisition time of the current free-running framework and focused on anatomical coronary imaging. The published protocol of the free- running framework used an interrupted bSSFP acquisition where CHESS fat saturation modules were inserted to provide blood-fat contrast, as they suppress the signal of fat tissue surrounding the coronary arteries, and were followed by ramp-up pulses to reduce artefacts arising from the return to steady-state. This interrupted acquisition, however, suffered from an interrupted steady-state, reduced time efficiency, and higher specific absorption rate (SAR). Using novel lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses developed in our lab, the first project showed that LIBRE pulses incorporated into an uninterrupted free-running bSSFP sequence could be successfully used for 5D cardiac MRI at 1.5T. The free-running LIBRE approach reduced the acquisition time and SAR relative to the previous interrupted approach while maintaining image quality and vessel conspicuity. Furthermore, this had been the first successful use of a fat-suppressing RF excitation pulse in an uninterrupted bSSFP sequence for cardiac imaging, demonstrating that uninterrupted bSSFP can be used for cardiac MRI and addressing the problem of clinical sequence availability. Inspired by the feasibility of uninterrupted bSSFP for cardiac MRI, the second part investigated the potential of PLANET, a novel 3D multiparametric mapping technique, for free-running 5D myocardial mapping. PLANET utilizes a phase-cycled bSSFP acquisition and a direct ellipse-fitting algorithm to calculate T1 and T2 relaxation times, which suggested that it could be readily integrated into the free-running framework without interrupting the steady-state. After initially calibrating the acquisition, the possibility of accelerating the static PLANET acquisition was explored prior to applying it to the moving heart. It was shown that PLANET accuracy and precision could be maintained with two-fold acceleration with a 3D Cartesian spiral trajectory, suggesting that PLANET for myocardial mapping with the free-running 5D radial acquisition is feasible. Further work should investigate optimizing the reconstruction scheme, improving the coil sensitivity estimate, and examining the use of the radial trajectory with a view to implementing free-running 5D myocardial T1 and T2 mapping. This thesis presents two approaches utilizing RF-frequency-modulated steady-state techniques for cardiac MRI. The first approach involved the novel application of an uninterrupted bSSFP acquisition with off-resonant RF excitation for anatomical coronary imaging. The second approach investigated the use of phase-cycled bSSFP for free-running 5D myocardial T1 and T2 mapping. Both methods addressed the challenge of clinical availability of sequences in cardiac MRI, by showing that a common and simple sequence like bSSFP can be used for acquisition while the steps of motion compensation and reconstruction can be handled offline, and thus have the potential to improve adoption of cardiac MRI. -- Les maladies cardiovasculaires (MCV) représentent la principale cause de décès aux États-Unis et en Europe et génèrent des coûts de santé de plusieurs centaines de milliards de dollars par an. Les méthodes conventionnelles de diagnostic des MCV sont souvent invasives et comportent des risques pour le patient. Par exemple, la méthode de référence pour le diagnostic de la maladie coronarienne, une catégorie majeure de MCV, est la coronarographie par rayons X qui a comme inconvénients son caractère invasif, son coût, l’utilisation de rayonnements ionisants et le risque de complications. A l’inverse, l'angiographie coronarienne par résonance magnétique (ARM) n'utilise pas de rayonnements ionisants, permet de visualiser efficacement les tissus sans avoir recours à des agents de contraste exogènes et bénéficie d'une résolution temporelle ajustable. Cependant, le temps d'acquisition en IRM cardiaque est bien plus long que les échelles temporelles des mouvements cardiaques et respiratoires en jeu, ce qui rend la compensation de ces mouvements indispensable. Le cadre dit de « free -running » est un nouveau développement de notre laboratoire qui bénéficie des progrès réalisés au cours des trois dernières décennies et tente de remédier aux inconvénients des approches précédentes pour l'IRM cardiaque : il fournit une IRM cardiaque en cinq dimensions (5D) complètement « self-gated » , c’est-à-dire capable de détecter les mouvements cardiaques et respiratoires, forte d’une implémentation simplifiée, d’une plus grande facilité d'utilisation, d’une dépendance réduite vis-à-vis de l'opérateur et d’une détection automatique des mouvements spécifiques du patient. L'imagerie « free- running » augmente la quantité d'informations à disposition du clinicien et est suffisamment flexible pour être appliquée à différents domaines de l'IRM cardiaque. De plus, le « self-gating » du cadre « free-running » a découplé l'acquisition de la compensation de mouvement et a ainsi ouvert l'IRM cardiaque à la classe plus large des techniques basées sur l'état stationnaire utilisant des séquences de précession libre équilibrée en état stationnaire (bSSFP), qui se distinguent par leur simplicité d’utilisation et leur rapport signal sur bruit élevé. Le thème de cette thèse est donc l'application des techniques basées sur l'état stationnaire à l'IRM cardiaque. La première partie porte sur le long temps d'acquisition de l'actuel cadre « free-running» et se concentre sur l'imagerie anatomique coronaire. Le protocole publié utilise une acquisition bSSFP interrompue où des modules de saturation de graisse (CHESS) sont insérés de façon à fournir un contraste sang-graisse puisqu’ils suppriment le signal du tissu graisseux entourant les artères coronaires, et sont suivis par des impulsions en rampe pour réduire les artefacts résultant du retour à l'état stable. Cette acquisition interrompue souffre cependant d'un état d'équilibre interrompu, d'une efficacité temporelle réduite et d'un débit d'absorption spécifique (DAS) plus élevé. En utilisant les nouvelles impulsions d'excitation radiofréquence (RF) binomiales hors -résonance insensibles aux lipides (LIBRE) développées dans notre laboratoi re, ce premier projet montre que les impulsions LIBRE incorporées dans une séquence bSSFP ininterrompue et « free-running » peuvent être utilisées avec succès pour l'IRM cardiaque 5D à 1,5 T. L'approche « free-running LIBRE » permet de réduire le temps d'acquisition et le DAS par rapport à l'approche interrompue précédente, tout en maintenant la perceptibilité des artères coronariennes. En outre, il s'agit de la première utilisation réussie d'une impulsion d'excitation RF supprimant la graisse dans une séquence bSSFP ininterrompue pour l'imagerie cardiaque, ce qui démontre le potentiel d’utilisation de la séquence bSSFP ininterrompue pour l'IRM cardiaque et résout le problème de la disponibilité de la séquence en clinique. Inspirée par la faisabilité d’utilisation de la séquence bSSFP ininterrompue pour l'IRM cardiaque, la deuxième partie étudie le potentiel de PLANET, une nouvelle technique de cartographie 3D multiparamétrique, pour la cartographie 5D du myocarde via l’imagerie « free-running ». PLANET utilise une acquisition bSSFP à cycle de phase et un algorithme d'ajustement d'ellipse direct pour calculer les temps de relaxation T1 et T2, ce qui suggère que cette méthode pourrait être facilement intégrée au cadre « free - running » sans interruption de l’état d'équilibre. Après calibration de l'acquisition, nous explorons la possibilité d'accélérer l'acquisition statique de PLANET pour l'appliquer au cœur. Nous démontrons que l'exactitude et la précision de PLANET peuvent être maintenues pour une accélération double avec une trajectoire 3D cartésienne en spirale, ce qui suggère que PLANET est réalisable pour la cartographie du myocarde avec une acquisition radiale 5D « free-running ». D'autres travaux devraient porter sur l'optimisation du schéma de reconstruction, l'amélioration de l'estimation de la sensibilité de l’antenne et l'examen de l'utilisation de la trajectoire radiale en vue de la mise en œuvre de la cartographie 5D « free-running » T1 et T2 du myocarde. Cette thèse présente deux approches utilisant des techniques de modulation de fréquence radio en état stationnaire pour l'IRM cardiaque. La première approche implique l'application nouvelle d'une acquisition bSSFP ininterrompue avec une excitation RF hors résonance pour l'imagerie anatomique coronaire. La seconde approche porte sur l'utilisation d’une séquence bSSFP à cycle de phase pour la cartographie 5D T1 et T2 du myocarde. Ces deux méthodes permettent de répondre au défi posé par la disponibilité des séquences en IRM cardiaque en montrant qu'une séquence commune et simple comme la bSSFP peut être utilisée pour l'acquisition, tandis que les étapes de compensation du mouvement et de reconstruction peuvent être traitées hors ligne. Ainsi, ces méthodes ont le potentiel de favoriser l'adoption de l'IRM cardiaque