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- Casas Garcia, Belén, 1985-
(författare)
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Towards Personalized Models of the Cardiovascular System Using 4D Flow MRI
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Current diagnostic tools for assessing cardiovascular disease mostly focus on measuring a given biomarker at a specific spatial location where an abnormality is suspected. However, as a result of the dynamic and complex nature of the cardiovascular system, the analysis of isolated biomarkers is generally not sufficient to characterize the pathological mechanisms behind a disease. Model-based approaches that integrate the mechanisms through which different components interact, and present possibilities for system-level analyses, give us a better picture of a patient’s overall health status.One of the main goals of cardiovascular modelling is the development of personalized models based on clinical measurements. Recent years have seen remarkable advances in medical imaging and the use of personalized models is slowly becoming a reality. Modern imaging techniques can provide an unprecedented amount of anatomical and functional information about the heart and vessels. In this context, three-dimensional, three-directional, cine phase-contrast (PC) magnetic resonance imaging (MRI), commonly referred to as 4D Flow MRI, arises as a powerful tool for creating personalized models. 4D Flow MRI enables the measurement of time-resolved velocity information with volumetric coverage. Besides providing a rich dataset within a single acquisition, the technique permits retrospective analysis of the data at any location within the acquired volume.This thesis focuses on improving subject-specific assessment of cardiovascular function through model-based analysis of 4D Flow MRI data. By using computational models, we aimed to provide mechanistic explanations of the underlying physiological processes, derive novel or improved hemodynamic markers, and estimate quantities that typically require invasive measurements. Paper I presents an evaluation of current markers of stenosis severity using advanced models to simulate flow through a stenosis. Paper II presents a framework to personalize a reduced-order, mechanistic model of the cardiovascular system using exclusively non-invasive measurements, including 4D Flow MRI data. The modelling approach can unravel a number of clinically relevant parameters from the input data, including those representing the contraction and relaxation patterns of the left ventricle, and provide estimations of the pressure-volume loop. In Paper III, this framework is applied to study cardiovascular function at rest and during stress conditions, and the capability of the model to infer load-independent measures of heart function based on the imaging data is demonstrated. Paper IV focuses on evaluating the reliability of the model parameters as a step towards translation of the model to the clinic.
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| 2. |
- Dyverfeldt, Petter, 1980-
(författare)
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Extending MRI to the Quantification of Turbulence Intensity
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In cardiovascular medicine, the assessment of blood flow is fundamental to the understanding and detection of disease. Many pharmaceutical, interventional, and surgical treatments impact the flow. The primary purpose of the cardiovascular system is to drive, control and maintain blood flow to all parts of the body. In the normal cardiovascular system, fluid transport is maintained at high efficiency and the blood flow is essentially laminar. Disturbed and turbulent blood flow, on the other hand, appears to be present in many cardiovascular diseases and may contribute to their initiation and progression. Despite strong indications of an important interrelationship between flow and cardiovascular disease, medical imaging has lacked a non-invasive tool for the in vivo assessment of disturbed and turbulent flow. As a result, the extent and role of turbulence in the blood flow of humans have not yet been fully investigated.Magnetic resonance imaging (MRI) is a versatile tool for the non-invasive assessment of flow and has several important clinical and research applications, but might not yet have reached its full potential. Conventional MRI techniques for the assessment of flow are based on measurements of the mean velocity within an image voxel. The mean velocity corresponds to the first raw moment of the distribution of velocities within a voxel. An MRI framework for the quantification of any moment (mean, standard deviation, skew, etc.) of arbitrary velocity distributions is presented in this thesis.Disturbed and turbulent flows are characterized by velocity fluctuations that are superimposed on the mean velocity. The intensity of these velocity fluctuations can be quantified by their standard deviation, which is a commonly used measure of turbulence intensity. This thesis focuses on the development of a novel MRI method for the quantification of turbulence intensity. This method is mathematically derived and experimentally validated. Limitations and sources of error are investigated and guidelines for adequate application of MRI measurements of turbulence intensity are outlined. Furthermore, the method is adapted to the quantification of turbulence intensity in the pulsatile blood flow of humans and applied to a wide range of cardiovascular diseases. In these applications, elevated turbulence intensity was consistently detected in regions where highly disturbed flow was anticipated, and the effects of potential sources of errors were small.Diseased heart valves are often replaced with prosthetic heart valves, which, in spite of improved benefits and durability, continue to fall short of matching native flow patterns. In an in vitro setting, MRI was used to visualize and quantify turbulence intensity in the flow downstream from four common designs of prosthetic heart valves. Marked differences in the extent and degree of turbulence intensity were detected between the different valves.Mitral valve regurgitation is a common valve lesion associated with progressive left atrial and left ventricular remodelling, which may often require surgical correction to avoid irreversible ventricular dysfunction. The spatiotemporal dynamics of flow disturbances in mitral regurgitation were assessed based on measurements of flow patterns and turbulence intensity in a group of patients with significant regurgitation arising from similar valve lesions. Peak turbulence intensity occurred at the same time in all patients and the total turbulence intensity in the left atrium appeared closely related to the severity of regurgitation.MRI quantification of turbulence intensity has the potential to become a valuable tool in investigating the extent, timing and role of disturbed blood flow in the human cardiovascular system, as well as in the assessment of the effects of different therapeutic options in patients with vascular or valvular disorders.
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| 3. |
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| 4. |
- Dyverfeldt, Petter, et al.
(författare)
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MRI Turbulence Quantification
- 2009
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Ingår i: Proc. Intl. Soc. Mag. Reson. Med.. ; , s. 1858-
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Konferensbidrag (refereegranskat)
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| 6. |
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| 7. |
- Ebbers, Tino, et al.
(författare)
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Higher order weighted least-squares phase offset correction for improved accuracy in phase-contrast MRI
- 2008
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Konferensbidrag (refereegranskat)abstract
- Phase-contrast magnetic resonance imaging has the ability to accurately measure blood flow and myocardial velocities in the human body. Unwanted spatially varying phase offsets are, however, always present and may deteriorate the measurements significantly. Some of these phase offsets can be estimated based on the pulse sequence (1), but effects caused by eddy currents are more difficult to predict. A linear fit of the phase values is often estimated from either a number of manually defined areas containing stationary tissue or by semi-automatic detection of stationary tissue using the
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| 9. |
- Zajac, Jakub
(författare)
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Assessment of Ventricular Function in Normal and Failing Hearts Using 4D Flow CMR
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Heart failure is a common disorder and a major cause of illness and death in the population, creating an enormous health-care burden. It is a complex condition, representing the end-point of many cardiovascular diseases. In general heart failure progresses slowly over time and once it is diagnosed it has a poor prognosis which is comparable with that of many types of cancer.The heart has an ability to adapt in response to long lasting increases in hemodynamic demand; the heart conforms its shape and size in order to maintain adequate cardiac output. This process is called remodeling and can be triggered by pathologies such as hypertension or valvular disease. When the myocardial remodeling is maintained chronically it becomes maladaptive and is associated with an increased risk of heart failure.In many cases, heart failure is associated with left bundle branch block (LBBB). This electrical disturbance leads to dyssynchronous left ventricular (LV) contraction and relaxation which may contribute to cardiac dysfunction and ultimately heart failure. Mechanical dyssynchrony can be treated with cardiac resynchronization therapy (CRT). However, many heart failure patients do not demonstrate clinical improvement despite CRT.Blood flow plays an important role in the normal development of the fetal heart. However, flow-induced forces may also induce changes in the heart cells that could lead to pathological remodeling in the adult heart. Until recently, measurement tools have been inadequate in describing the complex three-dimensional and time-varying characteristics of blood flow within the beating heart.4D (3D + time) flow cardiovascular magnetic resonance (CMR) enables acquisition of three-dimensional, three-directional, time-resolved velocity data from which visualization and quantification of the blood flow patterns over a complete cardiac cycle can be performed. In this thesis, novel 4D Flow CMR based methods are used to study the intraventricular blood flow in healthy subjects and heart failure patients with and without ventricular dyssynchrony in order to gain new knowledge of the ventricular function.Different flow components were assessed in normal heart ventricles. It was found that inflowing blood that passes directly to outflow during the same heartbeat (the Direct Flow component) was larger and possessed more kinetic energy (KE) than other flow components. Diastolic flow through the normal heart appears to create favorable conditions for effective systolic ejection. This organized blood flow pattern within the normal LV is altered in heart failure patients and is associated with decreased preservation of KE which might be unfavorable for efficient LV ejection. Inefficient flow of blood through the heart may influence diastolic wall stress, and thus contribute to pathological myocardial remodeling.In dyssynchronous LVs of heart failure patients with LBBB, Direct Flow showed even more reduced preservation of KE compared to similarly remodeled LVs without LBBB. Furthermore, in LBBB patients, LV filling hemodynamic forces, acting on the myocardium, were more orthogonal to the main flow direction compared to patients without LBBB. Deviation of LV flow forces and reduction of KE preservation and may reflect impairment of LV diastolic function and less efficient ensuing ejection related to dyssynchrony in these failing ventricles.Blood flow patterns were also studied with respect to fluctuations of the velocity of the flow (turbulent flow) in normal and failing LVs. In failing hearts, turbulent kinetic energy (TKE) was higher during diastole than in healthy subjects. TKE is a cause of energy loss and can thus be seen as a measure of flow inefficiency.Elucidating the transit of multidimensional blood flow through the heart chambers is fundamental in understanding the physiology of the heart and to detect abnormalities in cardiac function. The 4D Flow CMR parameters presented in this thesis can be utilized to detect altered intracardiac blood flow and may be used as markers of deteriorating cardiac function, pathological remodeling and mechanical dyssynchrony in heart failure.
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| 10. |
- Ziegler, Magnus, 1990-
(författare)
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Improving Assessments of Hemodynamics and Vascular Disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Blood vessels are more than simple pipes, passively enabling blood to pass through them. Their form and function are dynamic, changing with both aging and disease. This process involves a feedback loop wherein changes to the shape of a blood vessel affect the hemodynamics, causing yet more structural adaptation. This feedback loop is driven in part by the hemodynamic forces generated by the blood flow, and the distribution and strength of these forces appear to play a role in the initiation, progression, severity, and the outcome of vascular diseases.Magnetic Resonance Imaging (MRI) offers a unique platform for investigating both the form and function of the vascular system. The form of the vascular system can be examined using MR-based angiography, to generate detailed geometric analyses, or through quantitative techniques for measuring the composition of the vessel wall and atherosclerotic plaques. To complement these analyses, 4D Flow MRI can be used to quantify the functional aspect of the vascular system, by generating a full time-resolved three-dimensional velocity field that represents the blood flow.This thesis aims to develop and evaluate new methods for assessing vascular disease using novel hemodynamic markers generated from 4D Flow MRI and quantitative MRI data towards the larger goal of a more comprehensive non-invasive examination oriented towards vascular disease. In Paper I, we developed and evaluated techniques to quantify flow stasis in abdominal aortic aneurysms to measure this under-explored aspect of aneurysmal hemodynamics. In Paper II, the distribution and intensity of turbulence in the aorta was quantified in both younger and older men to understand how aging changes this aspect of hemodynamics. A method to quantify the stresses generated by turbulence that act on the vessel wall was developed and evaluated using simulated flow data in Paper III, and in Paper V this method was utilized to examine the wall stresses of the carotid artery. The hemodynamics of vascular disease cannot be uncoupled from the anatomical changes the vessel wall undergoes, and therefore Paper IV developed and evaluated a semi-automatic method for quantifying several aspects of vessel wall composition. These developments, taken together, help generate more valuable information from imaging data, and can be pooled together with other methods to form a more comprehensive non-invasive examination for vascular disease.
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