Pulsatile Blood Flow Simulations in Computed Tomography(CT) Scan-Based and Idealized Geometries of Human Aorta

Blood flow in human aorta is an unsteady and complex phenomenon. The complex patterns are related to the geometrical features like curvature, bends, and branching and pulsatile nature of flow from left ventricle of heart. The aim of this work was to understand the effect of aorta geometry on the flow dynamics. To achieve this, 3D realistic and idealized models of descending aorta were reconstructed from Computed Tomography (CT) images of a female patient. The geometries were reconstructed using medical image processing code. The blood flow in aorta was assumed to be laminar and incompressible and the blood was assumed to be Newtonian fluid. A time dependent pulsatile and parabolic boundary condition was deployed at inlet. Steady and unsteady blood flow simulations were performed in real and idealized geometries of descending aorta using a Finite Volume Method (FVM) code. Analysis of Wall Shear Stress (WSS) distribution, pressure distribution, and axial velocity profiles were carried out in both geometries at steady and unsteady state conditions. The results obtained in thesis work reveal that the idealization of geometry underestimates the values of WSS especially near the region with sudden change of diameter. However, the resultant pressure and velocity in idealized geometry are close to those in real geometry

Toiminnan laadun kehittäminen liiketoimintaprosessien avulla/Case CT Laastit Oy

Tutkimuksen tavoitteena oli selvittää case-yrityksen kahden liiketoimintaprosessin toimintojen laatu. Tutkimuskohteena oli nykyisen laadunhallintajärjestelmän toimivuus sekä prosessiajattelun kypsyys yritysjohdon ja henkilöstön näkökulmasta. Liiketoimintaprosessit valittiin tarkastelukohteeksi, koska ne muodostavat toiminnan luonnollisen etenemisen kaikissa organisaatiomuodoissa, ja prosessiajattelu on myös pohjana ISO 9000 -standardissa. Tutkimuksen teoriaosassa määriteltiin laadun käsitteet, toiminnan kehittämisen perusteet ja laadun hallintajärjestelmät. Tämän lisäksi tarkasteltiin kahta tutkimusta laatuyrityksistä ja laadun kehittämisestä. Tutkimuksen empiirinen osa toteutettiin kvalitatiivisena tapaustutkimuksena. Liiketoimintaprosesseihin perustuvaa toiminnan laatua tarkasteltiin yritysjohdon ja henkilöstön näkökulmasta. Lisäksi myynti- ja tuotantoprosessien osalta selvitettiin erot halutun toiminnan ja toteutuneen toiminnan välillä. Tutkimuksen mukaan myynti- ja tuotantoprosessit olivat toteutuneen toiminnan mukaisia pienin muutoksin ja tarkennuksin. Tutkimukset toteutettiin kyselynä ja haastatteluina.

GPS-signal Source Based on Direct Digital Synthesis

This thesis presents the design and implementation of a GPS-signal source suitable for receiver measurements. The developed signal source is based on direct digital synthesis which generates the intermediate frequency. The intermediate frequency is transfered to the final frequency with the aid of an Inphase/Quadrature modulator. The modulating GPS-data was generated with MATLAB. The signal source was duplicated to form a multi channel source. It was shown that, GPS-signals ment for civil navigation are easy to generate in the laboratory. The hardware does not need to be technically advanced if navigation with high level of accuracy is not needed. It was also shown that, the Inphase/Quadrature modulator can function as a single side band upconverter even with a high intermediate frequency. This concept reduces the demands required for output filtering.

Innovation process management of complex consumer products and services in new innovation paradigm – case location based business

Innovation is the word of this decade. According to innovation definitions, without positive sales impact and meaningful market share the company’s product or service has not been an innovation. Research problem of this master thesis is to find out what is the innovation process of complex new consumer products and services in new innovation paradigm. The objective is to get answers to two research questions: 1) What are the critical success factors what company should do when it is implementing the paradigm change in mass markets consumer business with complex products and services? 2) What is the process or framework one firm could follow? The research problem is looked from one company’s innovation creation process, networking and organization change management challenges point of views. Special focus is to look the research problem from an existing company perspective which is entering new business area. Innovation process management framework of complex new consumer products and services in new innovation paradigm has been created with support of several existing innovation theories. The new process framework includes the critical innovation process elements companies should take into consideration in their daily activities when they are in their new business innovation implementing process. Case company location based business implementation activities are studied via the new innovation process framework. This case study showed how important it is to manage the process, look how the target market and the competition in it is developing during company’s own innovation process, make decisions at right time and from beginning plan and implement the organization change management as one activity in the innovation process. In the end this master thesis showed that all companies need to create their own innovation process master plan with milestones and activities. One plan does not fit all, but all companies can start their planning from the new innovation process what was introduced in this master thesis.

CT and PET/CT Hybrid Imaging of Coronary Artery Disease

Coronary artery disease (CAD) is a chronic process that evolves over decades and may culminate in myocardial infarction (MI). While invasive coronary angiography (ICA) is still considered the gold standard of imaging CAD, non-invasive assessment of both the vascular anatomy and myocardial perfusion has become an intriguing alternative. In particular, computed tomography (CT) and positron emission tomography (PET) form an attractive combination for such studies. Increased radiation dose is, however, a concern. Our aim in the current thesis was to test novel CT and PET techniques alone and in hybrid setting in the detection and assessment of CAD in clinical patients. Along with diagnostic accuracy, methods for the reduction of the radiation dose was an important target. The study investigating the coronary arteries of patients with atrial fibrillation (AF) showed that CAD may be an important etiology of AF because a high prevalence of CAD was demonstrated within AF patients. In patients with suspected CAD, we demonstrated that a sequential, prospectively ECG-triggered CT technique was applicable to nearly 9/10 clinical patients and the radiation dose was over 60% lower than with spiral CT. To detect the functional significance of obstructive CAD, a novel software for perfusion quantification, CarimasTM, showed high reproducibility with 15O-labelled water in PET, supporting feasibility and good clinical accuracy. In a larger cohort of 107 patients with moderate 30-70% pre-test probability of CAD, hybrid PET/CT was shown to be a powerful diagnostic method in the assessment of CAD with diagnostic accuracy comparable to that of invasive angiography and fractional flow reserve (FFR) measurements. A hybrid study may be performed with a reasonable radiation dose in a vast majority of the cases, improving the performance of stand-alone PET and CT angiography, particularly when the absolute quantification of the perfusion is employed. These results can be applied into clinical practice and will be useful for daily clinical diagnosis of CAD.

Lipotoxicity in Obesity and Coronary Artery Disease. Studies by PET, CT and MR

Lipotoxicity is a condition in which fatty acids (FAs) are not efficiently stored in adipose tissue and overflow to non-adipose tissue, causing organ damages. A defect of adipose tissue FA storage capability can be the primary culprit in the insulin resistance condition that characterizes many of the severe metabolic diseases that affect people nowadays. Obesity, in this regard, constitutes the gateway and risk factor of the major killers of modern society, such as cardiovascular disease and cancer. A deep understanding of the pathogenetic mechanisms that underlie obesity and the insulin resistance syndrome is a challenge for modern medicine. In the last twenty years of scientific research, FA metabolism and dysregulations have been the object of numerous studies. Development of more targeted and quantitative methodologies is required on one hand, to investigate and dissect organ metabolism, on the other hand to test the efficacy and mechanisms of action of novel drugs. The combination of functional and anatomical imaging is an answer to this need, since it provides more understanding and more information than we have ever had. The first purpose of this study was to investigate abnormalities of substrate organ metabolism, with special reference to the FA metabolism in obese drug-naïve subjects at an early stage of disease. Secondly, trimetazidine (TMZ), a metabolic drug supposed to inhibit FA oxidation (FAO), has been for the first time evaluated in obese subjects to test a whole body and organ metabolism improvement based on the hypothesis that FAO is increased at an early stage of the disease. A third objective was to investigate the relationship between ectopic fat accumulation surrounding heart and coronaries, and impaired myocardial perfusion in patients with risk of coronary artery disease (CAD). In the current study a new methodology has been developed with PET imaging with 11C-palmitate and compartmental modelling for the non-invasive in vivo study of liver FA metabolism, and a similar approach has been used to study FA metabolism in the skeletal muscle, the adipose tissue and the heart. The results of the different substudies point in the same direction. Obesity, at the an early stage, is associated with an impairment in the esterification of FAs in adipose tissue and skeletal muscle, which is accompanied by the upregulation in skeletal muscle, liver and heart FAO. The inability to store fat may initiate a cascade of events leading to FA oversupply to lean tissue, overload of the oxidative pathway, and accumulation of toxic lipid species and triglycerides, and it was paralleled by a proportional growth in insulin resistance. In subjects with CAD, the accumulation of ectopic fat inside the pericardium is associated with impaired myocardial perfusion, presumably via a paracrine/vasocrine effect. At the beginning of the disease, TMZ is not detrimental to health; on the contrary at the single organ level (heart, skeletal muscle and liver) it seems beneficial, while no relevant effects were found on adipose tissue function. Taken altogether these findings suggest that adipose tissue storage capability should be preserved, if it is not possible to prevent excessive fat intake in the first place.

Bioactive Glass in Lumbar Spondylodesis. A Pre-Clinical and Clinical Study

Bioactive glasses (BGs) form a group of synthetic, surface-active, composition-dependent, silica-based biomaterials with osteoconductive, osteopromotive, and even angiogenic, as well as antibacterial, properties. A national interdisciplinary research group, within the Combio Technology Program (2003–2007), developed a porous load-bearing composite for surgical applications made of BG 1–98 and polymer fibers. The pre-clinical part of this thesis focused on the in vitro and in vivo testing of the composite materials in a rabbit femur and spinal posterolateral fusion model. The femur model failed to demonstrate the previously seen positive effect of BG 1–98 on osteogenesis, probably due to the changed resorption properties of BG in the form of fibers. The spine study was terminated early due to adverse events. In vitro cultures showed the growth inhibition of human mesenchymal stems next to BG 1–98 fibers and radical pH changes. A prospective, long-term, follow-up study was conducted on BG–S53P4 and autogenous bone used as bone graft substitutes for instrumented posterolateral spondylodesis in the treatment of degenerative spondylolisthesis (n=17) and unstable burst fractures (n=10) during 1996–1998. The operative outcome was evaluated from X-rays and CT scans, and a clinical examination was also performed. On the BG side, a solid fusion was observed in the CT scans of 12 patients, and a partial fusion was found in 5 patients, the result being a total fusion rate in all fusion sites (n=41) 88% for levels L4/5 and L5/S1 in the spondylolisthesis group. In the spine fracture group, solid fusion was observed in five patients, and partial fusion was found in five resulting in a total fusion rate of 71% of all fusion sites (n=21). The pre-clinical results suggest that under certain conditions the physical form of BG can be more critical than its chemical composition when a clinical application is designed. The first long-term clinical results concerning the use of BG S53P4 as bone graft material in instrumented posterolateral spondylodesis seems to be a safe procedure, associated with a very low complication rate. BG S53P4 used as a stand-alone bone substitute cannot be regarded as being as efficient as AB in promoting solid fusion.

Advanced epithelial ovarian cancer – studies on preoperative [18F] FDG PET/CT and HE4 profile during primary chemotherapy

Epithelial ovarian cancer (EOC) is usually diagnosed in an advanced stage. The prognosis depends highly on the amount of the residual tumor in surgery. In patients with extensive disease, neoadjuvant chemotherapy (NACT) is used to diminish the tumor load before debulking surgery. New non-invasive methods are needed to preoperatively evaluate the disease dissemination and operability. [18F] FDG PET/CT (Positron emission tomography/computed tomography) is a promising method for cancer diagnostics and staging. The biomarker profiles during treatment can predict patient’s outcome. This prospective study included 41 EOC patients, 21 treated with primary surgery and 20 with NACT and interval surgery. The performances of preoperative contrast enhanced PET/CT (PET/ceCT) and diagnostic CT (ceCT) were compared. Perioperative visual estimation of tumor spread was studied in primary and interval surgery. The profile of the serum marker HE4 (Human epididymis 4) during primary chemotherapy was evaluated. In primary surgery, surgical findings were found to form an adequate reference standard for imaging studies. After NACT, the sensitivity for visual estimation of cancer dissemination was significantly worse. Preoperative PET/ceCT was more effective than ceCT alone in detecting extra-abdominal disease spread. The high number of supradiaphragmatic lymph node metastases detected by PET/ceCT at the time of diagnosis brings new insight in EOC spread patterns. The sensitivity of both PET/CT and ceCT remained modest in intra-abdominal areas important to operability. The HE4 profile was in concordance with the CA125 profile during primary chemotherapy. Its role in the evaluation of EOC chemotherapy response will be clarified in further studies.

Late-onset spinal motor neuronopathy- a new neuromuscular disease

The aim of this study was to clarify the clinical phenotype of late-onset spinal motor neuronopathy (LOSMoN), an adult-onset autosomal dominant lower motor neuron disorder identified first in two families in Eastern Finland, in order to clarify its genetic background. Motor neuron disorders (MNDs) are characterized by dysfunction and premature death of motor neurons in the brain and spinal cord. MNDs can manifest at any age of the human lifespan, ranging from pre- or neonatal forms such as spinal muscular atrophy type I (SMA I) to those preferentially affecting the older age groups exemplified by sporadic amyotrophic lateral sclerosis (ALS). With a combination of genetic linkage analysis and genome sequencing using DNA from a total of 55 affected members of 17 families and a whole genome scan, we were able to show that LOSMoN is caused by the c.197G>T p.G66V mutation in the gene CHCHD10. This study showed that LOSMoN has very characteristic features that help to differentiate it from other more malignant forms of motor neuron disease, such as ALS, which was erroneously diagnosed in many patients in our cohort. Lack of fibrillations in the first dorsal interosseus muscle on EMG and extensive grouping of non-atrophic type IIA/2A fibers on muscle biopsy were shown to be common findings in LOSMoN, but rare or absent in ALS patients. The results of this study will help clinicians recognize the characteristic phenotype of LOSMoN disease and thus improve their diagnostic accuracy, and will also allow physicians to provide adequate genetic counseling for patients.

Activity-based life cycle costing model for cost estimation and monitoring – Case: manned and autonomous dry bulk carrier

Recent developments in automation, robotics and artificial intelligence have given a push to a wider usage of these technologies in recent years, and nowadays, driverless transport systems are already state-of-the-art on certain legs of transportation. This has given a push for the maritime industry to join the advancement. The case organisation, AAWA initiative, is a joint industry-academia research consortium with the objective of developing readiness for the first commercial autonomous solutions, exploiting state-of-the-art autonomous and remote technology. The initiative develops both autonomous and remote operation technology for navigation, machinery, and all on-board operating systems. The aim of this study is to develop a model with which to estimate and forecast the operational costs, and thus enable comparisons between manned and autonomous cargo vessels. The building process of the model is also described and discussed. Furthermore, the model’s aim is to track and identify the critical success factors of the chosen ship design, and to enable monitoring and tracking of the incurred operational costs as the life cycle of the vessel progresses. The study adopts the constructive research approach, as the aim is to develop a construct to meet the needs of a case organisation. Data has been collected through discussions and meeting with consortium members and researchers, as well as through written and internal communications material. The model itself is built using activity-based life cycle costing, which enables both realistic cost estimation and forecasting, as well as the identification of critical success factors due to the process-orientation adopted from activity-based costing and the statistical nature of Monte Carlo simulation techniques. As the model was able to meet the multiple aims set for it, and the case organisation was satisfied with it, it could be argued that activity-based life cycle costing is the method with which to conduct cost estimation and forecasting in the case of autonomous cargo vessels. The model was able to perform the cost analysis and forecasting, as well as to trace the critical success factors. Later on, it also enabled, albeit hypothetically, monitoring and tracking of the incurred costs. By collecting costs this way, it was argued that the activity-based LCC model is able facilitate learning from and continuous improvement of the autonomous vessel. As with the building process of the model, an individual approach was chosen, while still using the implementation and model building steps presented in existing literature. This was due to two factors: the nature of the model and – perhaps even more importantly – the nature of the case organisation. Furthermore, the loosely organised network structure means that knowing the case organisation and its aims is of great importance when conducting a constructive research.