Diffusion Tensor Imaging as a Diagnostic and Research Tool: A Study on Preterm Infants

Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) technique. DTI is based on free thermal motion (diffusion) of water molecules. The properties of diffusion can be represented using parameters such as fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity, which are calculated from DTI data. These parameters can be used to study the microstructure in fibrous structure such as brain white matter. The aim of this study was to investigate the reproducibility of region-of-interest (ROI) analysis and determine associations between white matter integrity and antenatal and early postnatal growth at term age using DTI. Antenatal growth was studied using both the ROI and tract-based spatial statistics (TBSS) method and postnatal growth using only the TBSS method. The infants included to this study were born below 32 gestational weeks or birth weight less than 1,501 g and imaged with a 1.5 T MRI system at term age. Total number of 132 infants met the inclusion criteria between June 2004 and December 2006. Due to exclusion criteria, a total of 76 preterm infants (ROI) and 36 preterm infants (TBSS) were accepted to this study. The ROI analysis was quite reproducible at term age. Reproducibility varied between white matter structures and diffusion parameters. Normal antenatal growth was positively associated with white matter maturation at term age. The ROI analysis showed associations only in the corpus callosum. Whereas, TBSS revealed associations in several brain white matter areas. Infants with normal antenatal growth showed more mature white matter compared to small for gestational age infants. The gestational age at birth had no significant association with white matter maturation at term age. It was observed that good early postnatal growth associated negatively with white matter maturation at term age. Growth-restricted infants seemed to have delayed brain maturation that was not fully compensated at term, despite catchup growth.

Neurobiology of pathological gambling. Brain imaging and epidemiological studies

Pathological gambling, a form of behavioral addiction, refers to maladaptive, compulsive gambling behavior severely interfering with an individual’s normal life. The prevalence of pathological gambling has been estimated to be 1–2% in western societies. The reward deficiency hypothesis of addiction assumes that individuals that have, or are prone, to addictions have blunted mesolimbic dopamine reward signaling, which leads to compulsive reward seeking in an attempt to compensate for the malfunctioning brain reward network. In this research project, the effects of gambling were measured using brain [11C] raclopride PET during slot machine gambling and possible brain structural changes associated with pathological gambling using MRI. The subjects included pathological gamblers and healthy volunteers. In addition, impulse control disorders associated with Parkinson’s disease were investigated by using brain [18F]fluorodopa PET and conducting an epidemiological survey. The results demonstrate mesolimbic dopamine release during gambling in both pathological gamblers and healthy volunteers. Striatal dopamine was released irrespective of the gambling outcome, whether the subjects won or not. There was no difference in gambling induced dopamine release between pathological gamblers and control subjects, although the magnitude of the dopamine release correlated with gambling related symptom severity in pathological gamblers. The results also show that pathological gambling is associated with extensive abnormality of brain white matter integrity, as measured with diffusion tensor imaging, similar to substance-addictions. In Parkinson’s disease patients with impulse control disorders, enhanced brain [18F] fluorodopa uptake in the medial orbitofrontal cortex was observed, indicating increased presynaptic monoamine function in this region, which is known to influence signaling in the mesolimbic system and reward processing. Finally, a large epidemiological survey in Finnish Parkinson’s disease patients showed that compulsive behaviors are very common in Parkinson disease and they are strongly associated with depression. These findings demonstrate the role of dopamine in pathological gambling, without support for the concept of reward deficiency syndrome.

Detection of Pathologic Changes Following Traumatic Brain Injury Using Magnetic Resonance Imaging

Background: Approximately two percent of Finns have sequels after traumatic brain injury (TBI), and many TBI patients are young or middle-aged. The high rate of unemployment after TBI has major economic consequences for society, and traumatic brain injury often has remarkable personal consequences, as well. Structural imaging is often needed to support the clinical TBI diagnosis. Accurate early diagnosis is essential for successful rehabilition and, thus, may also influence the patient’s outcome. Traumatic axonal injury and cortical contusions constitute the majority of traumatic brain lesions. Several studies have shown magnetic resonance imaging (MRI) to be superior to computed tomography (CT) in the detection of these lesions. However, traumatic brain injury often leads to persistent symptoms even in cases with few or no findings in conventional MRI. Aims and methods: The aim of this prospective study was to clarify the role of conventional MRI in the imaging of traumatic brain injury, and to investigate how to improve the radiologic diagnostics of TBI by using more modern diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) techniques. We estimated, in a longitudinal study, the visibility of the contusions and other intraparenchymal lesions in conventional MRI at one week and one year after TBI. We used DWI-based measurements to look for changes in the diffusivity of the normal-appearing brain in a case-control study. DTI-based tractography was used in a case-control study to evaluate changes in the volume, diffusivity, and anisotropy of the long association tracts in symptomatic TBI patients with no visible signs of intracranial or intraparenchymal abnormalities on routine MRI. We further studied the reproducibility of different tools to identify and measure white-matter tracts by using a DTI sequence suitable for clinical protocols. Results: Both the number and extent of visible traumatic lesions on conventional MRI diminished significantly with time. Slightly increased diffusion in the normal-appearing brain was a common finding at one week after TBI, but it was not significantly associated with the injury severity. Fractional anisotropy values, that represent the integrity of the white-matter tracts, were significantly diminished in several tracts in TBI patients compared to the control subjects. Compared to the cross-sectional ROI method, the tract-based analyses had better reproducibility to identify and measure white-matter tracts of interest by means of DTI tractography. Conclusions: As conventional MRI is still applied in clinical practice, it should be carried out soon after the injury, at least in symptomatic patients with negative CT scan. DWI-related brain diffusivity measurements may be used to improve the documenting of TBI. DTI tractography can be used to improve radiologic diagnostics in a symptomatic TBI sub-population with no findings on conventional MRI. Reproducibility of different tools to quantify fibre tracts vary considerably, which should be taken into consideration in the clinical DTI applications.

Magnetic Resocance Imaging Methods in the Follow-up of Multiple Sclerosis and in Farby Disease

Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disorder of the central nervous system. MS is the most common disabling central nervous system (CNS) disease of young adults in the Western world. In Finland, the prevalence of MS ranges between 1/1000 and 2/1000 in different areas. Fabry disease (FD) is a rare hereditary metabolic disease due to mutation in a single gene coding α-galactosidase A (alpha-gal A) enzyme. It leads to multi-organ pathology, including cerebrovascular disease. Currently there are 44 patients with diagnosed FD in Finland. Magnetic resonance imaging (MRI) is commonly used in the diagnostics and follow-up of these diseases. The disease activity can be demonstrated by occurrence of new or Gadolinium (Gd)-enhancing lesions in routine studies. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are advanced MR sequences which can reveal pathologies in brain regions which appear normal on conventional MR images in several CNS diseases. The main focus in this study was to reveal whether whole brain apparent diffusion coefficient (ADC) analysis can be used to demonstrate MS disease activity. MS patients were investigated before and after delivery and before and after initiation of diseasemodifying treatment (DMT). In FD, DTI was used to reveal possible microstructural alterations at early timepoints when excessive signs of cerebrovascular disease are not yet visible in conventional MR sequences. Our clinical and MRI findings at 1.5T indicated that post-partum activation of the disease is an early and common phenomenon amongst mothers with MS. MRI seems to be a more sensitive method for assessing MS disease activity than the recording of relapses. However, whole brain ADC histogram analysis is of limited value in the follow-up of inflammatory conditions in a pregnancy-related setting because the pregnancy-related physiological effects on ADC overwhelm the alterations in ADC associated with MS pathology in brain tissue areas which appear normal on conventional MRI sequences. DTI reveals signs of microstructural damage in brain white matter of FD patients before excessive white matter lesion load can be observed on conventional MR scans. DTI could offer a valuable tool for monitoring the possible effects of enzyme replacement therapy in FD.

Imaging Neuroinflammation in Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system CNS), where inflammation and neurodegeneration lead to irreversible neuronal damage. In MS, a dysfunctional immune system causes auto‐reactive lymphocytes to migrate into CNS where they initiate an inflammatory cascade leading to focal demyelination, axonal degeneration and neuronal loss. One of the hallmarks of neuronal injury and neuroinflammation is the activation of microglia. Activated microglia are found not only in the focal inflammatory lesions, but also diffusely in the normal‐appearing white matter (NAWM), especially in progressive MS. The purine base, adenosine is a ubiquitous neuromodulator in the CNS and also participates in the regulation of inflammation. The effect of adenosine mediated via adenosine A2A receptors has been linked to microglial activation, whereas modulating A2A receptors may exert neuroprotective effects. In the majority of patients, MS presents with a relapsing disease course, later advancing to a progressive phase characterised by a worsening, irreversible disability. Disease modifying treatments can reduce the severity and progression in relapsing MS, but no efficient treatment exists for progressive MS. The aim of this research was to investigate the prevalence of adenosine A2A receptors and activated microglia in progressive MS by using in vivo positron emission tomography (PET) imaging and [11C]TMSX and [11C](R)‐PK11195 radioligands. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed to evaluate structural brain damage. Non‐invasive input function methods were also developed for the analyses of [11C]TMSX PET data. Finally, histopathological correlates of [11C](R)‐PK11195 radioligand binding related to chronic MS lesions were investigated in post‐mortem samples of progressive MS brain using autoradiography and immunohistochemistry. [11C]TMSX binding to A2A receptors was increased in NAWM of secondary progressive MS (SPMS) patients when compared to healthy controls, and this correlated to more severe atrophy in MRI and white matter disintegration (reduced fractional anisotropy, FA) in DTI. The non‐invasive input function methods appeared as feasible options for brain [11C]TMSX images obviating arterial blood sampling. [11C](R)‐PK11195 uptake was increased in the NAWM of SPMS patients when compared to patients with relapsing MS and healthy controls. Higher [11C](R)‐PK11195 binding in NAWM and total perilesional area of T1 hypointense lesions was associated with more severe clinical disability, increased brain atrophy, higher lesion load and reduced FA in NAWM in the MS patients. In autoradiography, increased perilesional [11C](R)‐PK11195 uptake was associated with increased microglial activation identified using immunohistochemistry. In conclusion, brain [11C]TMSX PET imaging holds promise in the evaluation of diffuse neuroinflammation in progressive MS. Being a marker of microglial activation, [11C](R)‐ PK11195 PET imaging could possibly be used as a surrogate biomarker in the evaluation of the neuroinflammatory burden and clinical disease severity in progressive MS.

Antenatal inflammation and brain pathology in preterm infants

Chorioamnionitis is known to be an important risk factor underlying preterm delivery, and it has also been suggested to associate with brain lesions and deviant neurological development in both preterm and term infants. Cytokines are believed to be the link causing the deleterious effects of inflammation to the nervous system. Their genetic regulation has also been suggested to play a role, as interleukin (IL)-6 -174 and -572 genotypes, which partly regulate IL-6 synthesis responses, have been connected with deviant neurological development in preterm infants. We evaluated the association of histological chorioamnionitis with brain lesions, regional brain volumes, and the functioning of the auditory pathway in very low birth weight/very low gestational age (VLBW/VLGA) infants. In addition, we investigated the association between IL-6 -174 and -572 genotypes and histological chorioamnionitis, neonatal infections, and brain lesions and regional brain volumes in VLBW/VLGA infants. This study is a part of a larger multidisciplinary project PIPARI (Development and Functioning of Very Low Birth Weight Infants from Infancy to School Age), in which the survivors of a 6-year cohort of VLBW/VLGA infants (n=274) are being followed until school age in Turku University Central Hospital, Finland. Placental samples were collected in the delivery room, and were analyzed for histological inflammatory findings. Blood samples from the infants were collected and DNA was genotyped for IL-6-174 and -572 polymorphisms (GG/GC/CC). Brain ultrasound examinations were performed repeatedly in the neonatal intensive care unit and at term age, and were analysed for structural brain lesions. Brain magnetic resonance imaging was performed at term age, and was analysed for regional brain volumes. In addition, diffusion tensor imaging was performed at term, and was used to analyse fractional anisotrophy and the apparent diffusion coefficient of inferior colliculus. The brainstem auditory evoked potential recordings were carried out according to the routine clinical procedure at median age of 30 days after term age. In our study, we found that histological chorioamnionitis was not an independent risk factor for brain lesions, reduced regional brain volumes or abnormal functioning of the auditory pathway in VLBW/VLGA infants. In addition, we found that IL-6 -174 GG and -572 GC genotypes were associated with a higher incidence of histological chorioamnionitis, and that -174 CC genotype associated with higher incidence of septicaemia. The analysed IL-6 genotypes were not associated with other brain lesions, but a reduced volume of basal ganglia and thalami was associated with IL-6 -174 CC and -572 GG genotypes. In conclusion, our findings suggest that histological chorioamnionitis is not an independent risk factor for the brain development of VLBW/VLGA infants, or that the risk caused by inflammation does not exceed the risks attributed to other underlying pathologies behind preterm deliveries. In addition, our findings give reason to propose that IL-6 promoter genotypes have a role in the defence against serious infections and in the brain development of VLBW/VLGA infants.

Effects of Obesity and Weight Loss Following Bariatric Surgery on Brain Function, Structural Integrity and Metabolism

Obesity is one of the key challenges to health care system worldwide and its prevalence is estimated to rise to pandemic proportions. Numerous adverse health effects follow with increasing body weight, including increased risk of hypertension, diabetes, hypercholesterolemia, musculoskeletal pain and cancer. Current evidence suggests that obesity is associated with altered cerebral reward circuit functioning and decreased inhibitory control over appetitive food cues. Furthermore, obesity causes adverse shifts in metabolism and loss of structural integrity within the brain. Prior cross-sectional studies do not allow delineating which of these cerebral changes are recoverable after weight loss. We compared morbidly obese subjects with healthy controls to unravel brain changes associated with obesity. Bariatric surgery was used as an intervention to study which cerebral changes are recoverable after weight loss. In Study I we employed functional magnetic resonance imaging (fMRI) to detect the brain basis of volitional appetite control and its alterations in obesity. In Studies II-III we used diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to quantify the effects of obesity and the effects of weight loss on structural integrity of the brain. In study IV we used positron emission tomography (PET) with [18F]-FDG in fasting state and during euglycemic hyperinsulinemia to quantify effects of obesity and weight loss on brain glucose uptake. The fMRI experiment revealed that a fronto-parietal network is involved in volitional appetite control. Obese subjects had lower medial frontal and dorsal striatal brain activity during cognitive appetite control and increased functional connectivity within the appetite control circuit. Obese subjects had initially lower grey matter and white matter densities than healthy controls in VBM analysis and loss of integrity in white matter tracts as measured by DTI. They also had initially elevated glucose metabolism under insulin stimulation but not in fasting state. After the weight loss following bariatric surgery, obese individuals’ brain volumes recovered and the insulin-induced increase in glucose metabolism was attenuated. In conclusion, obesity is associated with altered brain function, coupled with loss of structural integrity and elevated glucose metabolism, which are likely signs of adverse health effects to the brain. These changes are reversed by weight loss after bariatric surgery, implicating that weight loss has a causal role on these adverse cerebral changes. Altogether these findings suggest that weight loss also promotes brain health.Key words: brain, obesity, bariatric surgery, appetite control, structural magnetic resonance

Neuroreceptor availability and cerebral morphology in human obesity

Obesity is a major challenge to human health worldwide. Little is known about the brain mechanisms that are associated with overeating and obesity in humans. In this project, multimodal neuroimaging techniques were utilized to study brain neurotransmission and anatomy in obesity. Bariatric surgery was used as an experimental method for assessing whether the possible differences between obese and non-obese individuals change following the weight loss. This could indicate whether obesity-related altered neurotransmission and cerebral atrophy are recoverable or whether they represent stable individual characteristics. Morbidly obese subjects (BMI ≥ 35 kg/m2) and non-obese control subjects (mean BMI 23 kg/m2) were studied with positron emission tomography (PET) and magnetic resonance imaging (MRI). In the PET studies, focus was put on dopaminergic and opioidergic systems, both of which are crucial in the reward processing. Brain dopamine D2 receptor (D2R) availability was measured using [11C]raclopride and µ-opioid receptor (MOR) availability using [11C]carfentanil. In the MRI studies, voxel-based morphometry (VBM) of T1-weighted MRI images was used, coupled with diffusion tensor imaging (DTI). Obese subjects underwent bariatric surgery as their standard clinical treatment during the study. Preoperatively, morbidly obese subjects had significantly lower MOR availability but unaltered D2R availability in several brain regions involved in reward processing, including striatum, insula, and thalamus. Moreover, obesity disrupted the interaction between the MOR and D2R systems in ventral striatum. Bariatric surgery and concomitant weight loss normalized MOR availability in the obese, but did not influence D2R availability in any brain region. Morbidly obese subjects had also significantly lower grey and white matter densities globally in the brain, but more focal changes were located in the areas associated with inhibitory control, reward processing, and appetite. DTI revealed also signs of axonal damage in the obese in corticospinal tracts and occipito-frontal fascicles. Surgery-induced weight loss resulted in global recovery of white matter density as well as more focal recovery of grey matter density among obese subjects. Altogether these results show that the endogenous opioid system is fundamentally linked to obesity. Lowered MOR availability is likely a consequence of obesity and may mediate maintenance of excessive energy uptake. In addition, obesity has adverse effects on brain structure. Bariatric surgery however reverses MOR dysfunction and recovers cerebral atrophy. Understanding the opioidergic contribution to overeating and obesity is critical for developing new psychological or pharmacological treatments for obesity. The actual molecular mechanisms behind the positive change in structure and neurotransmitter function still remain unclear and should be addressed in the future research.

European Association of Veterinary Diagnostic Imaging : 4th European conferece : matkakertomus

Mirja Ruohoniemi

Real-time Imaging and Mosaicking of Planar Surfaces

Laajojen pintojen kuvaaminen rajoitetussa työskentelytilassa riittävällä kuvatarkkuudella voi olla vaikeaa. Kuvaaminen on suoritettava osissa ja osat koottava saumattomaksi kokonaisnäkymäksi eli mosaiikkikuvaksi. Kuvauslaitetta käsin siirtelevän käyttäjän on saatava välitöntä palautetta, jotta mosaiikkiin ei jäisi aukkoja ja työ olisi nopeaa. Työn tarkoituksena oli rakentaa pieni, kannettava ja tarkka kuvauslaite paperi- ja painoteollisuuden tarpeisiin sekä kehittää palautteen antamiseen menetelmä, joka koostaaja esittää karkeaa mosaiikkikuvaa tosiajassa. Työssä rakennettiin kaksi kuvauslaitetta: ensimmäinen kuluttajille ja toinen teollisuuteen tarkoitetuista osista. Kuvamateriaali käsiteltiin tavallisella pöytätietokoneella. Videokuvien välinen liike laskettiin yksinkertaisella seurantamenetelmällä ja mosaiikkikuvaa koottiin kameroiden kuvanopeudella. Laskennallista valaistuksenkorjausta tutkittiin ja kehitetty menetelmä otettiin käyttöön. Ensimmäisessä kuvauslaitteessa on ongelmia valaistuksen ja linssivääristymien kanssa tuottaen huonolaatuisia mosaiikkikuvia. Toisessa kuvauslaitteessa nämä ongelmat on korjattu. Seurantamenetelmä toimii hyvin ottaen huomioon sen yksinkertaisuuden ja siihen ehdotetaan monia parannuksia. Työn tulokset osoittavat, että tosiaikainen mosaiikkikuvan koostaminen megapikselin kuvamateriaalista on mahdollista kuluttajille tarkoitetulla tietokonelaitteistolla.

Performance Evaluation of Imaging Systems

Imaging systems have developed latest years and developing is still continuing following years. Manufacturers of imaging systems give promises for the quality of the performance of imaging systems to advertise their products. Promises for the quality of the performance are often so good that they will not be tested in normal usage. The main target in this research is to evaluate the quality of the performance of two imaging systems: Scanner and CCD color camera. Optical measurement procedures were planned to evaluate the quality of imaging performances. Other target in this research is to evaluate calibration programs for the camera and the scanner. Measuring targets had to choose to evaluate the quality of imaging performances. Manufacturers have given definitions for targets. The third task in this research is to evaluate and consider how good measuring targets are.

Imaging techniques applied for detection of secretion, transgene delivery and G proteincoupled receptors in reproductive and endocrine cells in vivo and in vitro

Post-testicular sperm maturation occurs in the epididymis. The ion concentration and proteins secreted into the epididymal lumen, together with testicular factors, are believed to be responsible for the maturation of spermatozoa. Disruption of the maturation of spermatozoa in the epididymis provides a promising strategy for generating a male contraceptive. However, little is known about the proteins involved. For drug development, it is also essential to have tools to study the function of these proteins in vitro. One approach for screening novel targets is to study the secretory products of the epididymis or the G protein-coupled receptors (GPCRs) that are involved in the maturation process of the spermatozoa. The modified Ca2+ imaging technique to monitor release from PC12 pheochromocytoma cells can also be applied to monitor secretory products involved in the maturational processes of spermatozoa. PC12 pheochromocytoma cells were chosen for evaluation of this technique as they release catecholamines from their cell body, thus behaving like endocrine secretory cells. The results of the study demonstrate that depolarisation of nerve growth factor -differentiated PC12 cells releases factors which activate nearby randomly distributed HEL erythroleukemia cells. Thus, during the release process, the ligands reach concentrations high enough to activate receptors even in cells some distance from the release site. This suggests that communication between randomly dispersed cells is possible even if the actual quantities of transmitter released are extremely small. The development of a novel method to analyse GPCR-dependent Ca2+ signalling in living slices of mouse caput epididymis is an additional tool for screening for drug targets. By this technique it was possible to analyse functional GPCRs in the epithelial cells of the ductus epididymis. The results revealed that, both P2X- and P2Y-type purinergic receptors are responsible for the rapid and transient Ca2+ signal detected in the epithelial cells of caput epididymides. Immunohistochemical and reverse transcriptase-polymerase chain reaction (RTPCR) analyses showed the expression of at least P2X1, P2X2, P2X4 and P2X7, and P2Y1 and P2Y2 receptors in the epididymis. Searching for epididymis-specific promoters for transgene delivery into the epididymis is of key importance for the development of specific models for drug development. We used EGFP as the reporter gene to identify proper promoters to deliver transgenes into the epithelial cells of the mouse epididymis in vivo. Our results revealed that the 5.0 kb murine Glutathione peroxidase 5 (GPX5) promoter can be used to target transgene expression into the epididymis while the 3.8 kb Cysteine-rich secretory protein-1 (CRISP-1) promoter can be used to target transgene expression into the testis. Although the visualisation of EGFP in living cells in culture usually poses few problems, the detection of EGFP in tissue sections can be more difficult because soluble EGFP molecules can be lost if the cell membrane is damaged by freezing, sectioning, or permeabilisation. Furthermore, the fluorescence of EGFP is dependent on its conformation. Therefore, fixation protocols that immobilise EGFP may also destroy its usefulness as a fluorescent reporter. We therefore developed a novel tissue preparation and preservation techniques for EGFP. In addition, fluorescence spectrophotometry with epididymal epithelial cells in suspension revealed the expression of functional purinergic, adrenergic, cholinergic and bradykinin receptors in these cell lines (mE-Cap27 and mE-Cap28). In conclusion, we developed new tools for studying the role of the epididymis in sperm maturation. We developed a new technique to analyse GPCR dependent Ca2+ signalling in living slices of mouse caput epididymis. In addition, we improved the method of detecting reporter gene expression. Furthermore, we characterised two epididymis-specific gene promoters, analysed the expression of GPCRs in epididymal epithelial cells and developed a novel technique for measurement of secretion from cells.

Brain imaging studies in severe somatization

Somatization was described 4000 years ago but the pathophysiology of the, phenomenon is unknown. The aim of this investigation was to explore whether central nervous system (CNS) pathology is associated with severe somatization which was operationalized as somatization disorder (SD) and undifferentiated somatoform disorder. The study sample consisted of severely somatizing people who were included into the study after a multi-phase screening procedure in order to exclude psychiatric comorbidities and physical illnesses. Diagnosis of somatization disorder or undifferentiated sofatoform disorder were set according to Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV). The first study explored the regional cerebral metabolic rate of glucose (rCMRGlc) in severely somatizing females and found it to be reduced in several regions of the brain compared to healthy controls. The second study observed brain morphology with magnetic resonance imaging (MRI) based on the findings from the first study and showed enlarged caudate nuclei in somatizing women compared to healthy volunteers. The third study investigated temperament factors and brain metabolism, and their association with severe somatization. Low caudate and putamen metabolism, low novelty seeking as well as high harm avoidance were found to be associated with severe somatization in women, reduced caudate metabolism having the strongest association. The last study is a report of man with left-side gradient of multiple symptoms of unknown origin in the body. The examination revealed a hypermetabolic nucleus putamen on the contralateral side. All the main results reported in these four articles are original findings. The results suggest that CNS pathology is involved in the pathophysiology of severe somatization.

Imaging of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of PET Tracers for Vascular Inflammation

Atherosclerosis is a vascular inflammatory disease causing coronary artery disease, myocardial infarct and stroke, the leading causes of death in Finland and in many other countries. The development of atherosclerotic plaques starts already in childhood and is an ongoing process throughout life. Rupture of a plaque and the following occlusion of the vessel is the main reason for myocardial infarct and stroke, but despite extensive research, the prediction of rupture remains a major clinical problem. Inflammation is considered a key factor in the vulnerability of plaques to rupture. Measuring the inflammation in plaques non-invasively is one potential approach for identification of vulnerable plaques. The aim of this study was to evaluate tracers for positron emission tomography (PET) imaging of vascular inflammation. The studies were performed with a mouse model of atherosclerosis by using ex vivo biodistribution, autoradiography and in vivo PET and computed tomography (CT). Several tracers for inflammation activity were tested and compared with the morphology of the plaques. Inflammation in the atherosclerotic plaques was evaluated as expression of active macrophages. Systematic analysis revealed that the uptake of 18F-FDG and 11C-choline, tracers for metabolic activity in inflammatory cells, was more prominent in the atherosclerotic plaques than in the surrounding healthy vessel wall. The tracer for αvβ3 integrin, 18Fgalacto- RGD, was also found to have high potential for imaging inflammation in the plaques. While 11C-PK11195, a tracer targeted to receptors in active macrophages, was shown to accumulate in active plaques, the target-to-background ratio was not found to be ideal for in vivo imaging purposes. In conclusion, tracers for the imaging of inflammation in atherosclerotic plaques can be tested in experimental pre-clinical settings to select potential imaging agents for further clinical testing. 18F-FDG, 18F-galacto-RGD and 11C-choline choline have good properties, and further studies to clarify their applicability for atherosclerosis imaging in humans are warranted.

Imaging and Characterisation of Dirt Particles in Pulp and Paper

Dirt counting and dirt particle characterisation of pulp samples is an important part of quality control in pulp and paper production. The need for an automatic image analysis system to consider dirt particle characterisation in various pulp samples is also very critical. However, existent image analysis systems utilise a single threshold to segment the dirt particles in different pulp samples. This limits their precision. Based on evidence, designing an automatic image analysis system that could overcome this deficiency is very useful. In this study, the developed Niblack thresholding method is proposed. The method defines the threshold based on the number of segmented particles. In addition, the Kittler thresholding is utilised. Both of these thresholding methods can determine the dirt count of the different pulp samples accurately as compared to visual inspection and the Digital Optical Measuring and Analysis System (DOMAS). In addition, the minimum resolution needed for acquiring a scanner image is defined. By considering the variation in dirt particle features, the curl shows acceptable difference to discriminate the bark and the fibre bundles in different pulp samples. Three classifiers, called k-Nearest Neighbour, Linear Discriminant Analysis and Multi-layer Perceptron are utilised to categorize the dirt particles. Linear Discriminant Analysis and Multi-layer Perceptron are the most accurate in classifying the segmented dirt particles by the Kittler thresholding with morphological processing. The result shows that the dirt particles are successfully categorized for bark and for fibre bundles.