Detection of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of Novel PET Imaging Probes With Experimental Models

Atherosclerosis is a life-long vascular inflammatory disease and the leading cause of death in Finland and in other western societies. The development of atherosclerotic plaques is progressive and they form when lipids begin to accumulate in the vessel wall. This accumulation triggers the migration of inflammatory cells that is a hallmark of vascular inflammation. Often, this plaque will become unstable and form vulnerable plaque which may rupture causing thrombosis and in the worst case, causing myocardial infarction or stroke. Identification of these vulnerable plaques before they rupture could save lives. At present, in the clinic, there exists no appropriated, non-invasive method for their identification. The aim of this thesis was to evaluate novel positron emission tomography (PET) probes for the detection of vulnerable atherosclerotic plaques and to characterize, two mouse models of atherosclerosis. These studies were performed by using ex vivo and in vivo imaging modalities. The vulnerability of atherosclerotic plaques was evaluated as expression of active inflammatory cells, namely macrophages. Age and the duration of high-fat diet had a drastic impact on the development of atherosclerotic plaques in mice. In imaging of atherosclerosis, 6-month-old mice, kept on high-fat diet for 4 months, showed matured, metabolically active, atherosclerotic plaques. [18F]FDG and 68Ga were accumulated in the areas representative of vulnerable plaques. However, the slow clearance of 68Ga limits its use for the plaque imaging. The novel synthesized [68Ga]DOTA-RGD and [18F]EF5 tracers demonstrated efficient uptake in plaques as compared to the healthy vessel wall, but the pharmacokinetic properties of these tracers were not optimal in used models. In conclusion, these studies resulted in the identification of new strategies for the assessment of plaque stability and mouse models of atherosclerosis which could be used for plaque imaging. In the used probe panel, [18F]FDG was the best tracer for plaque imaging. However, further studies are warranted to clarify the applicability of [18F]EF5 and [68Ga]DOTA-RGD for imaging of atherosclerosis with other experimental models.

Surface transformation hardening of carbon steel with high power fiber laser

This study investigated the surface hardening of steels via experimental tests using a multi-kilowatt fiber laser as the laser source. The influence of laser power and laser power density on the hardening effect was investigated. The microhardness analysis of various laser hardened steels was done. A thermodynamic model was developed to evaluate the thermal process of the surface treatment of a wide thin steel plate with a Gaussian laser beam. The effect of laser linear oscillation hardening (LLOS) of steel was examined. An as-rolled ferritic-pearlitic steel and a tempered martensitic steel with 0.37 wt% C content were hardened under various laser power levels and laser power densities. The optimum power density that produced the maximum hardness was found to be dependent on the laser power. The effect of laser power density on the produced hardness was revealed. The surface hardness, hardened depth and required laser power density were compared between the samples. Fiber laser was briefly compared with high power diode laser in hardening medium-carbon steel. Microhardness (HV0.01) test was done on seven different laser hardened steels, including rolled steel, quenched and tempered steel, soft annealed alloyed steel and conventionally through-hardened steel consisting of different carbon and alloy contents. The surface hardness and hardened depth were compared among the samples. The effect of grain size on surface hardness of ferritic-pearlitic steel and pearlitic-cementite steel was evaluated. In-grain indentation was done to measure the hardness of pearlitic and cementite structures. The macrohardness of the base material was found to be related to the microhardness of the softer phase structure. The measured microhardness values were compared with the conventional macrohardness (HV5) results. A thermodynamic model was developed to calculate the temperature cycle, Ac1 and Ac3 boundaries, homogenization time and cooling rate. The equations were numerically solved with an error of less than 10-8. The temperature distributions for various thicknesses were compared under different laser traverse speed. The lag of the was verified by experiments done on six different steels. The calculated thermal cycle and hardened depth were compared with measured data. Correction coefficients were applied to the model for AISI 4340 steel. AISI 4340 steel was hardened by laser linear oscillation hardening (LLOS). Equations were derived to calculate the overlapped width of adjacent tracks and the number of overlapped scans in the center of the scanned track. The effect of oscillation frequency on the hardened depth was investigated by microscopic evaluation and hardness measurement. The homogeneity of hardness and hardened depth with different processing parameters were investigated. The hardness profiles were compared with the results obtained with conventional single-track hardening. LLOS was proved to be well suitable for surface hardening in a relatively large rectangular area with considerable depth of hardening. Compared with conventional single-track scanning, LLOS produced notably smaller hardened depths while at 40 and 100 Hz LLOS resulted in higher hardness within a depth of about 0.6 mm.

Family-based dietary intervention in the STRIP study – influences on diet and diet-related attitudes

The focus of this dissertation was to investigate the effects of family-based dietary intervention during childhood and adolescence. The participants comprised of children and parents who participated in a longitudinal, randomised atherosclerosis prevention trial (STRIP study). The intervention families (n=540) took part in a dietary intervention since the child’s age of 8- months. The control group (n=522) did not receive any tailored dietary intervention. The main focus of the intervention was to improve the quality of dietary fat. The diet of children and parents was evaluated by daily food records and dietrelated attitudes by a questionnaire. The dietary intervention influenced, favourably, the dietary fat quality in children and parents. Fat quality improved mainly by the decrease of saturated fat intake. Some minor effects of the intervention were also observed in children’s fruit and vegetable (F&V) consumption although the F&V consumption was very low. The intervention increased parental interest in healthy eating, but there was no difference in interest in natural products or in attitudes towards hedonic eating attitudes between the intervention and control parents. Parents’ interest in healthy eating associated with parents’ and children’s high fruit and vegetable consumption but not with their fat quality ratio. On the other hand, dietary fat quality improved at every level of interest in healthy eating. It seems that the main target of the intervention, the dietary fat quality of the children, was promoted effectively. In the future, more emphasis should be given on increasing unsaturated fat intake and on elevating F&V consumption in children. Children’s diet, especially F&V consumption, associated with diet-related attitudes of the parents. Therefore, co-operation with parents and family-based premises for working should be capitalized upon when promoting healthy eating in children and adolescents.

Individual dietary counselling during and after pregnancy: Impact on diet and body weight

In Finland, maternity and child health clinics play a key role in promoting health in young families. Currently, obesity causes the greatest challenges to clinics. In obese pregnant women, an increased risk for metabolic diseases exist which can affect both the mother and child. The purpose of this thesis was to explore the role of dietary counselling: in Finnish health clinics; in the regulation of dietary intake; and in affecting the body weight of women. The main aim was to test the effect of dietary counselling and probiotic intervention on dietary intake and maternal body weight during and after pregnancy. In addition to dietary counselling, the effect of other factors, such as eating behaviour on dietary intake and body weight control after pregnancy was assessed. Another aim was also to evaluate dietary counselling practices by nurses (n = 327) in Finnish health clinics assessed by a questionnaire. At the beginning of the pregnancy, women (n = 256) enrolled in a dietary intervention study, were randomised into three groups. One group received dietary counselling with probiotics, one had counselling with placebo and the third group was the control group. The control group consisted of women whom did not receive counselling and took placebo. Probiotics and placebo supplements were used until the end of exclusive breastfeeding or six months after pregnancy. Women were followed from early pregnancy up to four years after pregnancy. Follow-up visits took place three times during pregnancy, at one and six months, and one, two and four years after pregnancy. Dietary counselling, provided by a nutritionist, aimed to influence the quality of dietary fat intake. Dietary counselling is important to provide in clinics, as determined by the nurses, and these nurses expressed a want to improve their own nutritional knowledge through education. The nurses had varying knowledge of current dietary recommendations. Dietary counselling for women during and after pregnancy resulted in beneficial changes in dietary intake up to one year after pregnancy and body weight and waist circumference up to four years after pregnancy. Probiotics had a beneficial effect together with dietary counselling on waist circumference until one year after pregnancy, but not throughout the long term, four years after pregnancy. Other factors, such as eating behaviour, associated with dietary intake and body weight control after pregnancy. Specifically, dietary recommendations are reached amongst women whom had high cognitive restraint in their eating behaviour and did not demonstrate uncontrolled eating. Overweight women more frequently emotionally ate compared to normal weight women and women with central adiposity related more frequently to having an uncontrolled eating behaviour than women with normal waist circumference. In addition, being overweight prior to pregnancy and excessive weight gain during pregnancy associated with increased body weight retention after pregnancy. This study showed that individual dietary counselling is useful in influencing dietary intake which adheres to dietary recommendations and this counselling influences, favourably, body weight after pregnancy. Especially, women with the risk for weight retention, such as women who have emotional and uncontrolled eating behaviours, who were overweight prior to pregnancy or those who had excessive weight gain during pregnancy, may benefit from individual dietary counselling. This study underscores the need to develop dietary counselling practices for pregnant women and their follow-up after pregnancy in Finnish health clinics. These practices include increasing the efficacy of the counselling such as collaboration with families, having knowledgable health professionals and having sufficient resources.

Weldability of high strength aluminium alloys

The need for reduced intrinsic weight of structures and vehicles in the transportation industry has made aluminium research of interest. Aluminium has properties that are favourable for structural engineering, including good strength-to-weight ratio, corrosion resistance and machinability. It can be easily recycled saving energy used in smelting as compared to steel. Its alloys can have ultimate tensile strength of up to 750 MPa, which is comparable to steel. Aluminium alloys are generally weldable, however welding of high strength alloys like the 7xxx series pose considerable challenges. This paper presents research on the weldability of high strength aluminium alloys, principally the 7xxx series. The weldability with various weld processes including MIG, TIG, and FSW, is discussed in addition to consideration of joint types, weld defects and recommendations for minimizing or preventing weld defects. Experimental research was carried out on 7025-T6 and AW-7020 alloys. Samples were welded, and weld cross sections utilized in weld metallurgy studies. Mechanical tests were carried out including hardness tests and tensile tests. In addition, testing was done for the presence of Al2O3 on exposed aluminium alloy. It was observed that at constant weld heat input using a pulsed MIG system, the welding speed had little or no effect on the weld hardness. However, the grain size increased as the filler wire feed rate, welding current and welding speed increased. High heat input resulted in lower hardness of the weld profile. Weld preheating was detrimental to AW- 7020 welds; however, artificial aging was beneficial. Acceptable welds were attained with pulsed MIG without the removal of the Al2O3 layer prior to welding. The Al2O3 oxide layer was found to have different compositions in different aluminium alloys. These findings contribute useful additional information to the knowledge base of aluminium welding. The application of the findings of this study in welding will help reduce weld cost and improve high strength aluminium structure productivity by removing the need for pre-weld cleaning. Better understanding of aluminium weld metallurgy equips weld engineers with information for better aluminium weld design.