MRI evaluation of end-organ damage in diabetes and hypertension
Elderen, S.G.C. van
Citation
Elderen, S. G. C. van. (2010, December 21). MRI evaluation of end-organ damage in diabetes and hypertension. Retrieved from
https://hdl.handle.net/1887/16265
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Cha pter 1
General introduction and outline
11 General introduction and outline
INTRODUCTION
Diabetes mellitus and hypertension disease are important public health problems with a worldwide increasing prevalence. The global prevalence of diabetes rises from 2.8% in 2000 to 4.4% in 2010 (1). Diabetes and hypertensive patients have a signifi cantly increased risk of cardiovascular disease like myocardial infarction, stroke and of cardiovascular death due to not totally unraveled pathophysiological mechanisms. Recent advances in knowledge have contributed to the understanding of the increased cardiovascular disease risk in these high risk populations by assigning a role for changes in the wall of the aorta (2,3).
The aorta is a complex organ originating from the heart and passing blood to all end- organs. Importantly the aorta is an elastic tube with a capacity to distend and recoil in re- sponse to high pulsatile fl ow resulting from cardiac contraction. Herewith, the aorta has the capacity to reduce cardiac afterload and to facilitate continuous perfusion of the end-organs.
Intrinsic aortic wall abnormalities have been described in diabetes due to high glucose levels resulting in formation of advanced glycation end products which crosslink to collagen in the aortic vessel wall (4). In patients with hypertension, continuous hemodynamic stress at the aortic wall leads to structural and functional changes in the arterial wall (5). Possibly, arterial stiff ness and endothelial dysfunction precede the presence of clinical hypertension (6). Infl ammatory mechanisms and formation of atherosclerosis also play an important role in aortic wall changes in diabetes and hypertension (2). These complex heterogeneous mecha- nisms result in degeneration of the aortic vessel wall, leading to reduced aortic elasticity.
Stiff ening of the aorta may initiate a negative cascade aff ecting the heart and all other end-organs. As a consequence of aortic stiff ness, cardiac remodeling, compromised perfu- sion of the coronary arteries, and subsequently diastolic and systolic cardiac dysfunction may occur, which may ultimately lead to heart failure and cardiac death (7). Furthermore, stiff ness of the central large arteries results in a defi cient absorption of the pulse wave and an increase in central pulse pressure. This high pulsatile fl ow is transmitted from the aorta to all end-organs like the brain and kidneys causing damage to the endothelial and smooth muscle cells, disrupting the cerebral and renal arterioles. Also, aortic stiff ness may represent systemic endothelial dysfunction or wall thickening caused by shared underlying mecha- nisms. Numerous recent reports emphasize the importance of aortic stiff ness as a prognostic indicator for future cardiovascular disease and mortality in diabetes (8,9) and hypertensive patients (10).
Aortic stiff ness can be assessed by means of pulse wave velocity (PWV) measurements (11).
PWV is defi ned as the velocity of the systolic pulse wave front propagating through the aorta, refl ecting the elastic properties of the aortic vessel wall. During the last decades, Magnetic Resonance Imaging (MRI) has emerged as a reliable, accurate, ionizing radiation-free modal- ity for a general evaluation of anatomy and function of the heart, brain and vessels. MRI has
Chapter 1
12
also been established as a non-invasive accurate tool for assessment of aortic stiff ness by measuring aortic PWV (12).
In this thesis, subclinical end-organ damage of the heart, brain and kidneys and their relationship with aortic stiff ness will be assessed using a comprehensive MRI evaluation in diabetes mellitus and hypertensive patients.
Furthermore, new developments in high magnetic fi eld MRI, with the introduction of hu- man 7 Tesla MRI scanners, potentially contribute to imaging of end-organ damage at early stages of disease. In the fi nal two chapters of this thesis, development of coronary magnetic resonance angiography (MRA) at high fi eld 7 Tesla MRI is described, relevant for studying coronary artery disease with subsequent myocardial ischemic and functional end-organ damage. Coronary artery disease remains the leading cause of death for men and women in the Western world (13). The technique of coronary MRA, most commonly applied at 1.5 Tesla MRI, remains challenging due to the small diameter of the coronary arteries and cardiac and respiratory motion, and is not yet routinely applicable as a clinical diagnostic tool.
The current gold standard for the diagnosis of hemodynamically signifi cant coronary artery disease is x-ray coronary angiography. X-ray coronary angiography, however, has a few disadvantages. A small but signifi cant risk of complications has been reported and these are related to the invasive nature of the procedure, radiation exposure and the use of iodinated contrast agents (14). In addition, up to 40% of patients who undergo invasive x-ray coronary angiography are found to have no signifi cant coronary artery lumen stenosis (15). For these reasons, there is a strong need for an alternative technique that is noninvasive, more cost eff ective, and which can provide not only information about the vessel lumen but also about the vessel wall and myocardial condition, without the need for ionizing radiation and neph- rotoxic contrast agents.
MRI systems with higher fi eld strengths enable imaging with increased signal-to-noise ratio, allowing improved spatial resolution, improved temporal resolution and/or reduced scanning times (16-18). Individually or in combination, these improvements are likely to result in improved image quality, and ultimately better access to small diameter and branching ves- sels. High fi eld coronary MRA is therefore a promising tool for the non-invasive identifi cation of signifi cant proximal coronary artery disease without the use of ionizing radiation (19,20).
Because of the large resonance frequency increase going from low 1.5 and 3 Tesla to high 7 Tesla magnetic fi eld strength MR, considerable technical challenges are expected for cardio- vascular studies at 7 Tesla to account for the increased magnetic fi eld inhomogeneities. In the studies performed for this thesis, we show the implementation and the benefi ts of imaging coronary MRA at 7 Tesla.
13 General introduction and outline
OUTLINE OF THIS THESIS
This thesis evaluates MRI assessed end-organ damage, and the role of aortic pulse wave ve- locity in diabetes and hypertensive patients. In addition, the application and implementation of innovative MR techniques will be discussed.
Chapter 2 studies the independent and contributive eff ect of diabetes mellitus and hyper- tension on aortic pulse wave velocity. In chapter 3 the infl uence of aortic pulse wave velocity on cardiac and cerebral MR fi ndings is evaluated in hypertensive patients. In chapter 4 a similar evaluation regarding the eff ect of aortic pulse wave velocity on cardiac and cerebral MR fi ndings is assessed in type 1 diabetes mellitus patients. Chapter 5 describes a role of aortic pulse wave velocity in renal function of type 1 diabetes mellitus. Chapter 6 shows two separate vascular mechanisms; cerebral perfusion and aortic pulse wave velocity, being re- lated to white matter brain atrophy in type 1 diabetes mellitus. Chapter 7 reports accelerated progression of brain atrophy with cognitive consequences in elderly type 2 diabetes mellitus patients. Chapter 8 evaluates the metabolic eff ect of diabetes mellitus on the skeletal muscle in patients carrying a mitochondrial mutation, present in approximately 1% of all diabetes patients, using the MR Phosphorus-Spectroscopy technique. Chapter 9 shows feasibility of imaging techniques to perform coronary imaging at 7 Tesla MR fi eld strength. In chapter 10 a fi rst comparison study of coronary MR angiography at 7 Tesla in healthy volunteers is assessed showing the benefi ts of imaging at high magnetic fi eld strength.
Chapter 1
14
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15 General introduction and outline
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