Mapping Trabecular Bone Fabric Tensor by in Vivo Magnetic Resonance Imaging

The mechanical competence of bone depends upon its quantity, structural arrangement, and chemical composition. Assessment of these factors is important for the evaluation of bone integrity, particularly as the skeleton remodels according to external (e.g. mechanical loading) and internal (e.g. hormonal changes) stimuli. Micro magnetic resonance imaging (µMRI) has emerged as a non-invasive and non-ionizing method well-suited for the repeated measurements necessary for monitoring changes in bone integrity. However, in vivo image-based directional dependence of trabecular bone (TB) has not been linked to mechanical competence or fracture risk despite the existence of convincing ex vivo evidence. The objective of this dissertation research was to develop a means of capturing the directional dependence of TB by assessing a fabric tensor on the basis of in vivo µMRI. To accomplish this objective, a novel approach for calculating the TB fabric tensor based on the spatial autocorrelation function was developed and evaluated in the presence of common limitations to in vivo µMRI. Comparisons were made to the standard technique of mean-intercept-length (MIL). Relative to MIL, ACF was identified as computationally faster by over an order of magnitude and more robust within the range of the resolutions and SNRs achievable in vivo. The potential for improved sensitivity afforded by isotropic resolution was also investigated in an improved µMR imaging protocol at 3T. Measures of reproducibility and reliability indicate the potential of images with isotropic resolution to provide enhanced sensitivity to orientation-dependent measures of TB, however overall reproducibility suffered from the sacrifice in SNR. Finally, the image-derived TB fabric tensor was validated through its relationship with TB mechanical competence in specimen and in vivo µMR images. The inclusion of trabecular bone fabric measures significantly improved the bone volume fraction-based prediction of elastic constants calculated by micro-finite element analysis. This research established a method for detecting TB fabric tensor in vivo and identified the directional dependence of TB as an important determinant of TB mechanical competence

Doctor of Philosophy

dissertationEach year in the United States, a quarter million cases of stroke are caused directly by atherosclerotic disease of the cervical carotid artery. This represents a significant portion of health care costs that could be avoided if high-risk carotid artery lesions could be detected early on in disease progression. There is mounting evidence that Magnetic Resonance Imaging of the carotid artery can better classify subjects who would benefit from interventions. Turbo Spin Echo sequences are a class of Magnetic Resonance Imaging sequences that provide a variety of tissue contrasts. While high resolution Turbo Spin Echo images have demonstrated important details of carotid artery morphology, it is evident that pulsatile blood and wall motion related to the cardiac cycle are still significant sources of image degradation. In addition, patient motion artifacts due to the relatively long scan times of Turbo Spin Echo sequences result in an unacceptable fraction of noninterpretable studies. This dissertation presents work done to detect and correct for types of voluntary and physiological patient motion

Blind Retrospective Motion Correction of MR Images

Die Bewegung des Patienten während einer MRI Untersuchung kann die Bildqualität stark verringern. Eine Verschiebung des abzubildenden Objektes von nur ein Paar Millimetern ist genug um Bewegungsartefakte zu erzeugen und der Scan unbrauchbar für die medizinische Diagnostik zu machen. Obwohl in den letzten 20 Jahren mehrere Verfahren entwickelt wurden, ist die Bewegungskorrektur immer noch ein ungelöstes Problem. Wir schlagen einen neuen retrospektiven Bewegungskorrekturalgorithmus vor, mit dem man die Qualität von 3D MR Bildern verbessern kann. Mit diesem Verfahren ist es möglich sowohl starre als auch nicht starre Körperbewegungen zu korrigieren. Der wichtigste Aspekt unserer Algorithmen ist, dass keine Informationen über die Bewegungstrajektorie, z. B. von Kameras, nötig sind um die Bewegungskorrektur durchzuführen. Unsere Verfahren verwenden die RAW-Dateien von normalen MRT-Sequenzen und brauchen keinerlei Anderungen im Scanablauf. Wir benutzen Grafikprozessoren um die Bewegungskorrektur zu beschleunigen – im Fall von starren Körperbewegungen sind nur wenige Sekunden erforderlich, bei nicht starrer Körperbewegung nur einige Minuten Unser Bewegungskorrekturalgorithmus für starre Körper basiert auf der Minimierung einer Kostenfunktion, die die objektive Qualit ̈at des korrigierten Bildes abschätzt. Die Hauptidee ist, durch Optimierung eine Bewegungstrajektorie zu finden, die den kleinsten Betrag der Kostenfunktion liefert. Wir verwenden die Entropie der Bildgradienten als Bildqualitätsfunktion. Um nicht starre Körperbewegungen zu korrigieren, erweitern wir unser mathematisches Modell von Bewegungseffekten. Wir approximieren nicht starre Körperbewegungen als mehrere lokale starre Körperbewegungen. Um solche Bewegungen zu korrigieren, entwickeln wir ein neues annealing-basiert Optimierungsverfahren. Während der Optimierung wechseln wir zwei Schritte ab - die Kostenfunktionsminimierung durch Bild- und Bewegungsparameter. Wir haben mehrere Simulationen sowie in vivo Versuche am Menschen durchgeführt – beide lieferten wesentliche Bildqualitätsverbesserungen

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

Quantitative Analysis of Three-Dimensional Cone-Beam Computed Tomography Using Image Quality Phantoms

In the clinical setting, weight-bearing static 2D radiographic imaging and supine 3D radiographic imaging modalities are used to evaluate radiographic changes such as, joint space narrowing, subchondral sclerosis, and osteophyte formation. These respective imaging modalities cannot distinguish between tissues with similar densities (2D imaging), and do not accurately represent functional joint loading (supine 3D imaging). Recent advances in cone-beam CT (CBCT) have allowed for scanner designs that can obtain weight-bearing 3D volumetric scans. The purpose of this thesis was to analyze, design, and implement advanced imaging techniques to quantify image quality parameters of reconstructed image volumes generated by a commercially-available CBCT scanner, and a novel ceiling-mounted CBCT scanner. In addition, imperfections during rotation of the novel ceiling-mounted CBCT scanner were characterized using a 3D printed calibration object with a modification to the single marker bead method, and prospective geometric calibration matrices

Anatomo-functional magnetic resonance imaging of the spinal cord and its application to the characterization of spinal lesions in cats

Les lésions de la moelle épinière ont un impact significatif sur la qualité de la vie car elles peuvent induire des déficits moteurs (paralysie) et sensoriels. Ces déficits évoluent dans le temps à mesure que le système nerveux central se réorganise, en impliquant des mécanismes physiologiques et neurochimiques encore mal connus. L'ampleur de ces déficits ainsi que le processus de réhabilitation dépendent fortement des voies anatomiques qui ont été altérées dans la moelle épinière. Il est donc crucial de pouvoir attester l'intégrité de la matière blanche après une lésion spinale et évaluer quantitativement l'état fonctionnel des neurones spinaux. Un grand intérêt de l'imagerie par résonance magnétique (IRM) est qu'elle permet d'imager de façon non invasive les propriétés fonctionnelles et anatomiques du système nerveux central. Le premier objectif de ce projet de thèse a été de développer l'IRM de diffusion afin d'évaluer l'intégrité des axones de la matière blanche après une lésion médullaire. Le deuxième objectif a été d'évaluer dans quelle mesure l'IRM fonctionnelle permet de mesurer l'activité des neurones de la moelle épinière. Bien que largement appliquées au cerveau, l'IRM de diffusion et l'IRM fonctionnelle de la moelle épinière sont plus problématiques. Les difficultés associées à l'IRM de la moelle épinière relèvent de sa fine géométrie (environ 1 cm de diamètre chez l'humain), de la présence de mouvements d'origine physiologique (cardiaques et respiratoires) et de la présence d'artefacts de susceptibilité magnétique induits par les inhomogénéités de champ, notamment au niveau des disques intervertébraux et des poumons. L'objectif principal de cette thèse a donc été de développer des méthodes permettant de contourner ces difficultés. Ce développement a notamment reposé sur l'optimisation des paramètres d'acquisition d'images anatomiques, d'images pondérées en diffusion et de données fonctionnelles chez le chat et chez l'humain sur un IRM à 3 Tesla. En outre, diverses stratégies ont été étudiées afin de corriger les distorsions d'images induites par les artefacts de susceptibilité magnétique, et une étude a été menée sur la sensibilité et la spécificité de l'IRM fonctionnelle de la moelle épinière. Les résultats de ces études démontrent la faisabilité d'acquérir des images pondérées en diffusion de haute qualité, et d'évaluer l'intégrité de voies spinales spécifiques après lésion complète et partielle. De plus, l'activité des neurones spinaux a pu être détectée par IRM fonctionnelle chez des chats anesthésiés. Bien qu'encourageants, ces résultats mettent en lumière la nécessité de développer davantage ces nouvelles techniques. L'existence d'un outil de neuroimagerie fiable et robuste, capable de confirmer les paramètres cliniques, permettrait d'améliorer le diagnostic et le pronostic chez les patients atteints de lésions médullaires. Un des enjeux majeurs serait de suivre et de valider l'effet de diverses stratégies thérapeutiques. De telles outils représentent un espoir immense pour nombre de personnes souffrant de traumatismes et de maladies neurodégénératives telles que les lésions de la moelle épinière, les tumeurs spinales, la sclérose en plaques et la sclérose latérale amyotrophique.Spinal cord injury has a significant impact on quality of life since it can lead to motor (paralysis) and sensory deficits. These deficits evolve in time as reorganisation of the central nervous system occurs, involving physiological and neurochemical mechanisms that are still not fully understood. Given that both the severity of the deficit and the successful rehabilitation process depend on the anatomical pathways that have been altered in the spinal cord, it may be of great interest to assess white matter integrity after a spinal lesion and to evaluate quantitatively the functional state of spinal neurons. The great potential of magnetic resonance imaging (MRI) lies in its ability to investigate both anatomical and functional properties of the central nervous system non invasively. To address the problem of spinal cord injury, this project aimed to evaluate the benefits of diffusion-weighted MRI to assess the integrity of white matter axons that remain after spinal cord injury. The second objective was to evaluate to what extent functional MRI can measure the activity of neurons in the spinal cord. Although widely applied to the brain, diffusion-weighted MRI and functional MRI of the spinal cord are not straightforward. Various issues arise from the small cross-section width of the cord, the presence of cardiac and respiratory motions, and from magnetic field inhomogeneities in the spinal region. The main purpose of the present thesis was therefore to develop methodologies to circumvent these issues. This development notably focused on the optimization of acquisition parameters to image anatomical, diffusion-weighted and functional data in cats and humans at 3T using standard coils and pulse sequences. Moreover, various strategies to correct for susceptibility-induced distortions were investigated and the sensitivity and specificity in spinal cord functional MRI was studied. As a result, acquisition of high spatial and angular diffusion-weighted images and evaluation of the integrity of specific spinal pathways following spinal cord injury was achieved. Moreover, functional activations in the spinal cord of anaesthetized cats was detected. Although encouraging, these results highlight the need for further technical and methodological development in the near-future. Being able to develop a reliable neuroimaging tool for confirming clinical parameters would improve diagnostic and prognosis. It would also enable to monitor the effect of various therapeutic strategies. This would certainly bring hope to a large number of people suffering from trauma and neurodegenerative diseases such as spinal cord injury, tumours, multiple sclerosis and amyotrophic lateral sclerosis

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

Development and Validation of Mechatronic Systems for Image-Guided Needle Interventions and Point-of-Care Breast Cancer Screening with Ultrasound (2D and 3D) and Positron Emission Mammography

The successful intervention of breast cancer relies on effective early detection and definitive diagnosis. While conventional screening mammography has substantially reduced breast cancer-related mortalities, substantial challenges persist in women with dense breasts. Additionally, complex interrelated risk factors and healthcare disparities contribute to breast cancer-related inequities, which restrict accessibility, impose cost constraints, and reduce inclusivity to high-quality healthcare. These limitations predominantly stem from the inadequate sensitivity and clinical utility of currently available approaches in increased-risk populations, including those with dense breasts, underserved and vulnerable populations. This PhD dissertation aims to describe the development and validation of alternative, cost-effective, robust, and high-resolution systems for point-of-care (POC) breast cancer screening and image-guided needle interventions. Specifically, 2D and 3D ultrasound (US) and positron emission mammography (PEM) were employed to improve detection, independent of breast density, in conjunction with mechatronic and automated approaches for accurate image acquisition and precise interventional workflow. First, a mechatronic guidance system for US-guided biopsy under high-resolution PEM localization was developed to improve spatial sampling of early-stage breast cancers. Validation and phantom studies showed accurate needle positioning and 3D spatial sampling under simulated PEM localization. Subsequently, a whole-breast spatially-tracked 3DUS system for point-of-care screening was developed, optimized, and validated within a clinically-relevant workspace and healthy volunteer studies. To improve robust image acquisition and adaptability to diverse patient populations, an alternative, cost-effective, portable, and patient-dedicated 3D automated breast (AB) US system for point-of-care screening was developed. Validation showed accurate geometric reconstruction, feasible clinical workflow, and proof-of-concept utility across healthy volunteers and acquisition conditions. Lastly, an orthogonal acquisition and 3D complementary breast (CB) US generation approach were described and experimentally validated to improve spatial resolution uniformity by recovering poor out-of-plane resolution. These systems developed and described throughout this dissertation show promise as alternative, cost-effective, robust, and high-resolution approaches for improving early detection and definitive diagnosis. Consequently, these contributions may advance breast cancer-related equities and improve outcomes in increased-risk populations and limited-resource settings