1,093 research outputs found

    4D FLOW CMR in congenital heart disease

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    This thesis showed that the use of a cloud-based reconstruction applicationwith advanced eddy currents correction, integrated with interactiveimaging evaluation tools allowed for remote visualization and interpretationof 4D flow data and that was sufficient for gross visualizationof aortic valve regurgitation. Further, this thesis demonstrated that bulkflow and pulmonary regurgitation can be accurately quantified using 4Dflow imaging analyzed. Peak systolic velocity over the pulmonary valvemay be underestimated. However, the measurement of peak systolicvelocity can be optimized if measured at the level of highest velocity inthe pulmonary artery. Also correlated against invasive measurements (inan animal model), this thesis shows that aorta flow and pulmonary flowcan be accurately and simultaneously measured by 4D flow MRI.When applied in clinical practice, 4D flow has extra advantages, of beingable to visualize flow pattern, vorticity and to predict aortic growth. InASD patients it can measure shunt volume directly following the septumframe by frame. In Fontan patients in can visualize better than standardMRI the Fontan circuit and it can measure flow at multiple points alongthe Fontan circuit. We observed in our Fontan population that shunt lesionswere very common, most of the time via veno-venous collaterals.Further using advanced computations, we showed that WSS angle wasthe only independent predictor of aortic growth in BAV patients. We alsoshowed the feasibility of GLS analysis on 4D flow MRI and presented anintegrative approach in which flow and functional data are acquired inone sequence.From the technical point of view, 4D flow MRI has proved to complementthe traditional components of the standard cardiac MR exams, enablingin-depth insights into hemodynamics. At this moment it proved its addedvalue, but in most of the cases it is not able yet to replace the standardexam. This is still due to long scanning times and relatively longpost-processing times.<br/

    Novel 129Xe Magnetic Resonance Imaging and Spectroscopy Measurements of Pulmonary Gas-Exchange

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    Gas-exchange is the primary function of the lungs and involves removing carbon dioxide from the body and exchanging it within the alveoli for inhaled oxygen. Several different pulmonary, cardiac and cardiovascular abnormalities have negative effects on pulmonary gas-exchange. Unfortunately, clinical tests do not always pinpoint the problem; sensitive and specific measurements are needed to probe the individual components participating in gas-exchange for a better understanding of pathophysiology, disease progression and response to therapy. In vivo Xenon-129 gas-exchange magnetic resonance imaging (129Xe gas-exchange MRI) has the potential to overcome these challenges. When participants inhale hyperpolarized 129Xe gas, it has different MR spectral properties as a gas, as it diffuses through the alveolar membrane and as it binds to red-blood-cells. 129Xe MR spectroscopy and imaging provides a way to tease out the different anatomic components of gas-exchange simultaneously and provides spatial information about where abnormalities may occur. In this thesis, I developed and applied 129Xe MR spectroscopy and imaging to measure gas-exchange in the lungs alongside other clinical and imaging measurements. I measured 129Xe gas-exchange in asymptomatic congenital heart disease and in prospective, controlled studies of long-COVID. I also developed mathematical tools to model 129Xe MR signals during acquisition and reconstruction. The insights gained from my work underscore the potential for 129Xe gas-exchange MRI biomarkers towards a better understanding of cardiopulmonary disease. My work also provides a way to generate a deeper imaging and physiologic understanding of gas-exchange in vivo in healthy participants and patients with chronic lung and heart disease

    Cerebrovascular dysfunction in cerebral small vessel disease

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    INTRODUCTION: Cerebral small vessel disease (SVD) is the cause of a quarter of all ischaemic strokes and is postulated to have a role in up to half of all dementias. SVD pathophysiology remains unclear but cerebrovascular dysfunction may be important. If confirmed many licensed medications have mechanisms of action targeting vascular function, potentially enabling new treatments via drug repurposing. Knowledge is limited however, as most studies assessing cerebrovascular dysfunction are small, single centre, single imaging modality studies due to the complexities in measuring cerebrovascular dysfunctions in humans. This thesis describes the development and application of imaging techniques measuring several cerebrovascular dysfunctions to investigate SVD pathophysiology and trial medications that may improve small blood vessel function in SVD. METHODS: Participants with minor ischaemic strokes were recruited to a series of studies utilising advanced MRI techniques to measure cerebrovascular dysfunction. Specifically MRI scans measured the ability of different tissues in the brain to change blood flow in response to breathing carbon dioxide (cerebrovascular reactivity; CVR) and the flow and pulsatility through the cerebral arteries, venous sinuses and CSF spaces. A single centre observational study optimised and established feasibility of the techniques and tested associations of cerebrovascular dysfunctions with clinical and imaging phenotypes. Then a randomised pilot clinical trial tested two medications’ (cilostazol and isosorbide mononitrate) ability to improve CVR and pulsatility over a period of eight weeks. The techniques were then expanded to include imaging of blood brain barrier permeability and utilised in multi-centre studies investigating cerebrovascular dysfunction in both sporadic and monogenetic SVDs. RESULTS: Imaging protocols were feasible, consistently being completed with usable data in over 85% of participants. After correcting for the effects of age, sex and systolic blood pressure, lower CVR was associated with higher white matter hyperintensity volume, Fazekas score and perivascular space counts. Lower CVR was associated with higher pulsatility of blood flow in the superior sagittal sinus and lower CSF flow stroke volume at the foramen magnum. Cilostazol and isosorbide mononitrate increased CVR in white matter. The CVR, intra-cranial flow and pulsatility techniques, alongside blood brain barrier permeability and microstructural integrity imaging were successfully employed in a multi-centre observational study. A clinical trial assessing the effects of drugs targeting blood pressure variability is nearing completion. DISCUSSION: Cerebrovascular dysfunction in SVD has been confirmed and may play a more direct role in disease pathogenesis than previously established risk factors. Advanced imaging measures assessing cerebrovascular dysfunction are feasible in multi-centre studies and trials. Identifying drugs that improve cerebrovascular dysfunction using these techniques may be useful in selecting candidates for definitive clinical trials which require large sample sizes and long follow up periods to show improvement against outcomes of stroke and dementia incidence and cognitive function

    Modern meat: the next generation of meat from cells

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    Modern Meat is the first textbook on cultivated meat, with contributions from over 100 experts within the cultivated meat community. The Sections of Modern Meat comprise 5 broad categories of cultivated meat: Context, Impact, Science, Society, and World. The 19 chapters of Modern Meat, spread across these 5 sections, provide detailed entries on cultivated meat. They extensively tour a range of topics including the impact of cultivated meat on humans and animals, the bioprocess of cultivated meat production, how cultivated meat may become a food option in Space and on Mars, and how cultivated meat may impact the economy, culture, and tradition of Asia

    Myotonic dystrophy type 1:clinical genetics and multisystem involvement

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    Myotonic dystrophy type 1 (DM1) is a multisystem disorder affecting patients of all ages. The two main symptoms of DM1 consist of myotonia (inability to relax muscles) and muscle weakness, but DM1 can potentially affect almost every organ system in the human body. DM1 is caused by an inherited CTG-repeat expansion in the DMPK gene. At this time, curative or disease-modifying treatment options are not yet available. Consequently, management of DM1 affected individuals focuses on monitoring disease progression and early detection of possible complications. Moreover, it is of great importance to provide adequate information to patients and their caregivers. The current thesis aimed to improve DM1 patient management by adding to the current knowledge of the genetic inheritance of DM1 and multisystem involvement. Specifically, the thesis pays attention to the inheritance of small-sized DM1 repeat expansions, to the cardiac follow-up of DM1 patients, and describes energy expenditure and body composition of affected individuals

    New perspectives in surgical treatment of aortic diseases

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