Segmentation-based blood flow parameter refinement in cerebrovascular structures using 4D arterial spin labeling MRA

Objective: Cerebrovascular diseases are one of the main global causes of death and disability in the adult population. The preferred imaging modality for the diagnostic routine is digital subtraction angiography, an invasive modality. Time-resolved three-dimensional arterial spin labeling magnetic resonance angiography (4D ASL MRA) is an alternative non-invasive modality, which captures morphological and blood flow data of the cerebrovascular system, with high spatial and temporal resolution. This work proposes advanced medical image processing methods that extract the anatomical and hemodynamic information contained in 4D ASL MRA datasets. Methods: A previously published segmentation method, which uses blood flow data to improve its accuracy, is extended to estimate blood flow parameters by fitting a mathematical model to the measured vascular signal. The estimated values are then refined using regression techniques within the cerebrovascular segmentation. The proposed method was evaluated using fifteen 4D ASL MRA phantoms, with ground-truth morphological and hemodynamic data, fifteen 4D ASL MRA datasets acquired from healthy volunteers, and two 4D ASL MRA datasets from patients with a stenosis. Results: The proposed method reached an average Dice similarity coefficient of 0.957 and 0.938 in the phantom and real dataset segmentation evaluations, respectively. The estimated blood flow parameter values are more similar to the ground-truth values after the refinement step, when using phantoms. A qualitative analysis showed that the refined blood flow estimation is more realistic compared to the raw hemodynamic parameters. Conclusion: The proposed method can provide accurate segmentations and blood flow parameter estimations in the cerebrovascular system using 4D ASL MRA datasets. Significance: The information obtained with the proposed method can help clinicians and researchers to study the cerebrovascular system non-invasively

New MRI Techniques for Nanoparticle Based Functional and Molecular Imaging

Although in clinical use for several decades, magnetic resonance imaging: MRI) is undergoing a transition from a qualitative anatomical imaging tool to a quantitative technique for evaluating myriad diseases. Furthermore, MRI has made great strides as a potential tool for molecular imaging of cellular and tissue biomarkers. Of the candidate contrast agents for molecular MRI, the excellent bio-compatibility and adaptability of perfluorocarbon nanoparticles: PFC NP) has established these agents as a potent targeted imaging agent and as a functional platform for non-invasive oxygen tension sensing. Direct readout and quantification of PFC NP can be achieved with fluorine: 19F) MRI because of the unique 19F signal emanating from the core PFC molecules. However, the signal is usually limited by the modest accumulated concentrations as well as several special NMR considerations for PFC NP, which renders 19F MRI technically challenging in terms of detection sensitivity, scan time, and image reconstruction. In the present dissertation, some of the pertinent NMR properties of PFC NP are investigated and new 19F MRI techniques developed to enhance their performance and expand the biomedical applications of 19F MRI with PFC NP. With the use of both theoretical and experimental methods, we evaluated J-coupling modulation, chemical shift and paramagnetic relaxation enhancement of PFC molecules in PFC NP. Our unique contribution to the technical improvement of 19F MRI of small animal involves:: 1) development of general strategies for RF 1H/19F coil design;: 2) design of novel MR pulse sequences for 19F T1 quantification; and: 3) optimization of imaging protocols for distinguishing and visualizing multiple PFC components: multi-chromatic 19F MRI). The first pre-clinical application of our novel 19F MRI techniques is blood vessel imaging and rapid blood oxygen tension measurement in vivo. Blood vessel anatomy and blood oxygen tension provide pivotal physiological information for routine diagnosis of cardiovascular disease. Using our novel Blood: flow)-Enhanced-Saturation-Recovery: BESR) sequence, we successfully visualized reduced flow caused by thrombosis in carotid arteries and jugular veins, and we quantified the oxygen tension in the cardiac ventricles of the mouse. The BESR sequence depicted the expected oxygenation difference between arterial and venous blood and accurately registered the response of blood oxygen tension to high oxygen concentration in 100% oxygen gas. This study demonstrated the potential application of PFC NP as a blood oxygen tension sensor and blood pool MR contrast agent for angiography. Another pre-clinical application investigated was functional kidney imaging with 19F MRI of circulating PFC NP. Conventional functional kidney imaging typically calls for the injection of small molecule contrast agents that may be nephrotoxic, which raises concerns for their clinical applications in patients with renal insufficiency. We demonstrated that our 19F MRI technique offers a promising alternative functional renal imaging approach that generates quantitative measurement of renal blood volume and intrarenal oxygenation. We successfully mapped the expected heterogeneous distribution of renal blood volume and confirmed the presence of an oxygenation gradient in healthy kidneys. We validated the diagnostic capability of 19F MRI in a mouse model of acute ischemia/reperfusion kidney injury. We also employed 19F MRI as a tool to test the therapeutic efficacy of a new nanoparticle-based drug, i. e. PPACK: D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone) PFC NP, which was postulated to inhibit microvascular coagulation during acute kidney injury. Based on our preliminary 19F MRI findings, we observed that PPACK PFC NP effectively reduced coagulation in our animal model, as evidenced by lesser accumulation of particles trapped by the clotting process. This finding suggests the potential for 19F MRI to be used as a drug monitoring tool as well in common medical emergencies such as acute kidney failure

Parallel transit methods for arterial spin labelling magnetic resonance imaging

Vessel selective arterial spin labelling (ASL) is a magnetic resonance imaging technique which permits the visualisation and assessment of the perfusion territory of a specific set of feeding arteries. It is of clinical importance in both acute and chronic cerebrovascular disease, and the mapping of blood supplied to tumours. Continuous ASL is capable of providing the highest signal-to-noise (SNR) ratio of the various ASL methods. However on clinical systems it suffers from high hardware demands, and the control of systematic errors decreases perfusion sensitivity. A separate labelling coil avoids these problems, enabling high labelling efficiency and subsequent high SNR, and vessel specificity can be localised to one carotid artery. However this relies on the careful and accurate positioning of the labelling coil over the common carotid arteries in the neck. It is proposed to combine parallel transmission (multiple transmit coils, each transmitting with different amplitudes and phases) to spatially tailor the labelling field, removing the reliance on coil location for optimal labelling efficiency, and enabling robust vessel selective labelling with a high degree of specificity. Presented is the application of parallel transmission methods to continuous ASL, requiring the development of an ASL labelling coil array, and a two channel transmitter system. Coil safety testing was performed using a novel MRI temperature mapping technique to accurately measure small temperature changes on the order of 0.1 ⁰C. A perfusion phantom with distinct vascular territories was constructed for sequence testing and development. Phantom and in-vivo testing of parallel transmit CASL using a 3D-GRASE acquisition showed an improvement of up to 35% in vessel specificity when compared with using a single labelling coil, whilst retaining the high labelling efficiency and associated SNR of separate coil CASL methods

Proceedings Virtual Imaging Trials in Medicine 2024

This submission comprises the proceedings of the 1st Virtual Imaging Trials in Medicine conference, organized by Duke University on April 22-24, 2024. The listed authors serve as the program directors for this conference. The VITM conference is a pioneering summit uniting experts from academia, industry and government in the fields of medical imaging and therapy to explore the transformative potential of in silico virtual trials and digital twins in revolutionizing healthcare. The proceedings are categorized by the respective days of the conference: Monday presentations, Tuesday presentations, Wednesday presentations, followed by the abstracts for the posters presented on Monday and Tuesday

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Preclinical MRI of the kidney : methods and protocols

This Open Access volume provides readers with an open access protocol collection and wide-ranging recommendations for preclinical renal MRI used in translational research. The chapters in this book are interdisciplinary in nature and bridge the gaps between physics, physiology, and medicine. They are designed to enhance training in renal MRI sciences and improve the reproducibility of renal imaging research. Chapters provide guidance for exploring, using and developing small animal renal MRI in your laboratory as a unique tool for advanced in vivo phenotyping, diagnostic imaging, and research into potential new therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and thorough, Preclinical MRI of the Kidney: Methods and Protocols is a valuable resource and will be of importance to anyone interested in the preclinical aspect of renal and cardiorenal diseases in the fields of physiology, nephrology, radiology, and cardiology. This publication is based upon work from COST Action PARENCHIMA, supported by European Cooperation in Science and Technology (COST). COST (www.cost.eu) is a funding agency for research and innovation networks. COST Actions help connect research initiatives across Europe and enable scientists to grow their ideas by sharing them with their peers. This boosts their research, career and innovation. PARENCHIMA (renalmri.org) is a community-driven Action in the COST program of the European Union, which unites more than 200 experts in renal MRI from 30 countries with the aim to improve the reproducibility and standardization of renal MRI biomarkers

Streamlining the Design and Use of Array Coils for In Vivo Magnetic Resonance Imaging of Small Animals

Small-animal models such as rodents and non-human primates play an important pre-clinical role in the study of human disease, with particular application to cancer, cardiovascular, and neuroscience models. To study these animal models, magnetic resonance imaging (MRI) is advantageous as a non-invasive technique due to its versatile contrast mechanisms, large and flexible field of view, and straightforward comparison/translation to human applications. However, signal-to-noise ratio (SNR) limits the practicality of achieving the high-resolution necessary to image the smaller features of animals in an amount of time suitable for in vivo animal MRI. In human MRI, it is standard to achieve an increase in SNR through the use of array coils; however, the design, construction, and use of array coils for animal imaging remains challenging due to copper-loss related issues from small array elements and design complexities of incorporating multiple elements and associated array hardware in a limited space. In this work, a streamlined strategy for animal coil array design, construction, and use is presented and the use for multiple animal models is demonstrated. New matching network circuits, materials, assembly techniques, body-restraining systems and integrated mechanical designs are demonstrated for streamlining high-resolution MRI of both anesthetized and awake animals. The increased SNR achieved with the arrays is shown to enable high-resolution in vivo imaging of mice and common marmosets with a reduced time for experimental setup