Whole-Body MR Angiography in Patients with Peripheral Arterial Disease
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PHD THESIS DANISH MEDICAL BULLETIN Whole-body MR angiography in patients with peripheral arterial disease Yousef Jesper Wirenfeldt Nielsen IV. Nielsen YW, Eiberg JP, Løgager VB, Just S, Schroeder TV, Thomsen HS. Patient acceptance of whole-body MRA – a This review has been accepted as a thesis together with four previously published papers by the University of Copenhagen on the 4 th of June 2010 and defended on the prospective questionnaire study. Acta Radiol 2010; 18 th of October 2010. 51:277-83. Tutors: Henrik S. Thomsen, Torben V. Schroeder & Jonas P. Eiberg Official opponents: Håkan Ahlstrøm , Tim Leiner & Ulf Helgstrand 1.1 STUDY AIMS Correspondence: Department of Diagnostic Radiology, Copenhagen University The principal aim of the study was to investigate whole-body Hospital Herlev. Herlev Ringvej 75 – DK 2730. Denmark. magnetic resonance angiography (WB-MRA) as diagnostic tool in E-mail: ywnielsen@gmail.com patients with peripheral arterial disease (PAD). Focus has been on feasibility of WB-MRA with body coil acquisition, means of im- proving the technique, and patient acceptance of the method. Dan Med Bull 2010;57(12)B4231 Both an extracellular and a blood-pool MRI contrast agent have been used in the study. However, it has not been a study aim to perform a large scale comparison of WB-MRA using different contrast agents. 1. GENERAL PART Specific aims of individual studies This thesis is divided into 3 main sections: A general part, a special Study I part, and a conclusion. The general part describes the background The aim of this study was to investigate the feasibility of perform- for the study, and outlines the study aims. The special part sum- ing WB-MRA in a 3 Tesla (T) MRI system with use of body coil marises the results of the research, with reference to the original acquisition and a blood-pool contrast agent. papers. Overall results of the study are discussed in the conclu- sion. Study II The aim of this study was to determine the impact of a hybrid The thesis is based on 4 original studies: scan technique on the diagnostic performance of 3T WB-MRA using an extracellular contrast agent. I. Nielsen YW, Eiberg JP, Løgager VB, Hansen MA, Schroeder TV, Thomsen HS. Whole-body MR angiography with body Study III coil acquisition at 3T in patients with peripheral arterial The aim of this study was to investigate if addition of infra- disease using the contrast agent gadofosveset trisodium. genicular steady-state MRA (SS-MRA) to first-pass imaging im- Acad Radiol 2009; 16:654-61. proves diagnostic performance compared to first-pass imaging alone, in WB-MRA of patients with PAD. II. Nielsen YW, Eiberg JP, Løgager VB, Schroeder TV, Just S, Thomsen HS. Whole-body magnetic resonance angiogra- Study IV phy at 3 Tesla using a hybrid protocol in patients with pe- This study assessed patient acceptance of WB-MRA compared to ripheral arterial disease. Cardiovasc Intervent Radiol 2009; conventional x-ray angiography. 32:877-86. III. Nielsen YW, Eiberg JP, Løgager VB, Just S, Schroeder TV, 1.2 BACKGROUND Thomsen HS. Whole-body MRA with additional steady- state acquisition of the infra-genicular arteries in patients 1.2.1 Atherosclerosis with peripheral arterial disease. Cardiovasc Intervent Ra- Atherosclerotic cardiovascular disease (CVD) is the leading cause diol 2009; Epub Dec 3. of death in the Western world [1]. This chapter gives a brief over- view of the pathogenesis, risk factors and pharmacological treat- DANISH MEDICAL BULLETIN 1 ment of atherosclerosis. Finally, the systemic nature of athero- Intermittent claudication, defined as exercise-induced pain in the sclerosis will be discussed. muscles of the leg, is the earliest and most frequent symptom of Atherosclerosis is characterized by plaque formation in the walls PAD. Claudication begins after a reproducible length of walk, and of the large and medium size arteries. The first event in plaque resolves within few minutes after the patient stops walking. With formation is migration of monocytes into the arterial intima, disease progression (critical limb ischemia), PAD patients have where they differentiate into macrophages. These absorb lipids rest pain, and clinical findings might include ischemic ulceration and become foam cells. Arterial fatty streaks consist of intimal and gangrene. The Fontaine classification is the classic scheme collections of foam cells, and are considered the primary athero- used to describe the severity of PAD (Table 1) [12]. Patients in sclerotic lesion. More advanced stages of atherosclerosis occur Fontaine class III and IV suffer critical limb ischemia. when the lipid-loaded foam cells become apoptotic and release PAD is a frequent disease. In a population-based study, PAD (an- lipids to the extracellular space. This accelerates collagen produc- kle-brachial index <0.9) was present in 19% of subjects > 55 years tion and a true atherosclerotic plaque consisting of a lipid core old [13]. Traditional cardiovascular risks factors (advanced age, surrounded by a fibrous cap is the result [2]. Initially, the plaque male gender, diabetes, smoking, hypertension, hyperlipidaemia) does not narrow the arterial lumen by in-growth, instead remod- are related to PAD [14]. Due to con-comitant atherosclerotic elling occurs and the plaque expands through the outer layers of complications in the coronary and cerebrovascular beds, PAD the arterial wall. However, at some point compensatory enlarge- patients have increased risk of mortality compared to the general ment is no longer possible, and the plaque begins to expand population [15]. inwards leading to progressive reduction of the arterial lumen. An accurate medical history and thorough physical examination Artherosclerotic plaques usually do not cause ischemic symptoms are important factors in the diagnostic approach to the PAD pa- before luminal narrowing exceeds 50%. Hence, a large quantum tient. However, exact determination of the extent of atheroscle- of asymptomatic atherosclerosis may be present once symptoms rosis requires diagnostic imaging, which is the subject of the next occur. The majority of acute cardiovascular events are due to chapter. plaque complications that acutely occlude the arterial lumen [3]. Treatment options of PAD include preventive measures against Plaque rupture causes platelet aggregation and formation of an atherosclerosis, surgery, and endovascular interventions. Preven- occluding thrombus at the site of the plaque (atherothrombosis). tive measures with life-style modifications (smoking cessation and Additionally, particulate matter may also be shed from the rup- exercise) as well as pharmacological interventions (antihyperten- tured plaque leading to embolization. Together, these mecha- sives, antiplatelets, blood sugar control, antihyperlipidaemics) are nisms account for most of the acute ischemic manifestations of the most important part of PAD treatment [14]. Surgical proce- atherosclerosis (unstable angina, myocardial infarction, and dures are endarterectomy, bypass grafting, and amputation, ischemic stroke). whereas endovascular interventions are PTA (percutaneous trans- Established risk factors for atherosclerosis include hypertension, luminal angioplasty) and stent placement. diabetes, dyslipidaemia, smoking, obesity, and physical inactivity [4]. Lifestyle modifications such as reductions in the amount of Table 1. The Fontaine classification dietary fat, calorie control, exercise, and smoking cessation are Stage Symptoms / Findings important factors in prevention of atherosclerosis. Pharmacologi- I Asymptomatic cal treatment of hypertension, diabetes, and dyslipidaemia is also essential in management of patients with atherosclerosis. An- II a Intermittant claudication other important mechanism in atherosclerosis treatment is plate- Pain-free walking distance > 200 m let inhibition, since platelets are key components in the atherothrombotic process succeeding plaque rupture. II b Intermittant claudication Presence of atherosclerosis in one vascular bed often implies Pain-free walking distance < 200 m presence of the disease in other vascular territories. Hence, atherosclerosis is regarded a systemic disease. Predisposed sites III Rest pain for atherosclerosis exist in the vascular tree including the carot- IV Tissue loss and/or gangrene ids, coronaries, aorta, renal arteries, and lower extremity arteries from the level of the aortic bifurcation. Low shear stress acting on the endothelium in the outer areas of vessel bifurcations is be- lieved to play a role in the development of atherosclerosis in these predisposed areas [5]. 1.2.3 Diagnostic imaging of atherosclerosis Numerous studies have investigated the systemic nature of atherosclerosis. In patients with peripheral arterial disease (PAD) Numerous imaging methods are used clinically to depict athero- con-comitant carotid stenosis has been found in 25% [6;7], renal sclerotic lesions. This chapter gives an overview of these meth- artery stenosis in 14% [8], and coronary heart disease (CHD) in ods. 46% [9]. Similary, 14% of patients with primary CHD also suffer PAD [10]. A recent study showed that polyvascular disease (> 1 Conventional x-ray angiography region) is present in 71% of vascular surgery patients with athero- In conventional x-ray angiography a catheter is placed inside the sclerosis [11]. arterial system. Most commonly, the common femoral artery is used to gain arterial access, but other options include brachial 1.2.2 Peripheral arterial disease and trans-lumbar access. With the catheter tip advanced