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Background Multiple sclerosis (MS) is the most common cause of non-traumatic neurological disability affecting young adults during their best working years. Previous studies have shown that approximately two-thirds of patients with MS (PwMS) are unable to retain employment in the long term, and many retire soon after the diagnosis. However, it is not known, how the rate of retirement has changed over the decades, especially after the introduction of disease modifying therapies (DMTs). The year 1995 was selected as a division point because DMTs have been increasingly available ever since. Objective To evaluate the change in retirement rate due to MS and to present risk factors for early retirement. Methods A retrospective survey of all PwMS treated at the Department of Neurology, Kanta-Hame Central Hospital, Finland between 1978 and 2015, was conducted. The population was divided into two groups: those diagnosed before year 1995 and those diagnosed thereafter. A Kaplan-Meier analysis was performed to evaluate the time from diagnosis to beginning of a pension in both groups. Crude incidence rates, incidence rate differences as well as age and multivariable adjusted Cox proportional hazard regression analysis were calculated for all pension predictors collected. Results A total of 484 PwMS were identified, 140 of whom were diagnosed before the year 1995 and 344 after. Actual retirement rates were 88 (63%) before the year the year 1995 and 111 (32%) after, respectively. The hazard for disability pension diminished in PwMS diagnosed after the year 1995 compared to those diagnosed before, HR 0.41 (95% confidence interval 0.31-0.55). The median time from diagnosis to retirement was 8.3 years in the group diagnosed before year 1995 and 11.1 years in the group diagnosed later. Male sex and age were statistically significant risk factors in relapsing-remitting MS, HR for male sex 1.8 (95% confidence interval 1.18-2.75) and for age 1.1 (95% confidence interval 1.07-1.12). Only age was a risk factor in progressive MS with HR 1.09 (95% confidence interval 1.07-1.11). In subgroup of relapsing-remitting MS, not using disease modifying therapies was a statistically significant risk factor, HR 1.89 (95% confidence interval 1.19-3.01). Conclusion The rate of retirement due to MS in Finland has decreased significantly since 1995 and the median time from diagnosis to retirement has become longer. Not using disease modifying therapies for relapsing remitting MS was identified as one risk factor for losing ability to work prematurely.

Purpose Cardiomyocytes progenitor cells (CMPCs) are a candidate cell source for cardiac regenerative therapy. To assess their full potential for cardiac regeneration, it is essential to know if and how CMPCs sense and respond to the three-dimensional (3D) environment and the mechanical stimuli provided by the beating heart. Therefore, we study the response to cyclic strain of undifferentiated and predifferentiated human CMPCs in a 2D environment, as well as CMPC responses to unidirectionally constrained versus stress-free (unconstrained) 3D environments. The latter responses were studied using a hydrogel system that allows for interaction of the cells with a simulated ‘host’ tissue. Methods To test mechanosensitivity of CMPCs in 2D and 3D environments, the response of L9TB CMPCs to uniaxial (cyclic) strain (10% with 0.5 Hz) was investigated. To represent the 3D environment, CMPCs were cultured in unidirectionally constrained and stress-free collagen/Matrigel hydrogels, where the constrainment provides a static strain to the cells. The cellular mechanoresponse to the applied (cyclic) strain was quantified by cellular re-orientation away from the strain direction (strain avoidance). Next to cellular re-orientation, the effect of strain on cell differentiation was analyzed. Results Our results indicate that while undifferentiated cells maintain their original orientation, upon early cardiomyogenic differentiation (predifferentiated) CMPCs exhibit a distinct strain avoidance response during 48hrs of cyclic straining in a 2D environment. In 3D unidirectionally constrained hydrogels, undifferentiated CMPCs retain their cardiomyogenic profile. CMPCs cultured in 3D collagen/Matrigel hydrogels respond to static mechanical strains as expected by cell alignment. Conclusions Our results suggest that CMPCs respond to the presence of mechanical stimuli, in this research mimicked by the application of uniaxial (cyclic) strain in 2D and 3D environments, suggesting that CMPCs are indeed mechanosensitive. Although in 2D environments, mechanosensitivity of the CMPCs is dependent on their differentiation status. Our findings provide the first understanding of the ability of human CMPCs to sense mechanical stimuli, which is the first initial step in mechanotransduction. Mechanotransduction is essential for optimal recruitment, migration, and mechanical integration of progenitor cells into the injured myocardium. Therefore, the presented results can contribute to enhance efficacy of current treatments of cardiac disease, as well as to develop novel endogenous regeneration strategies.

Although GTPase of the immunity-associated protein (GIMAP) family are known to be most highly expressed in the cells of the immune system, their function and role remain still poorly characterized. Small GTPases in general are known to be involved in many cellular processes in a cell type-specific manner and to contribute to specific differentiation processes. Among GIMAP family, GIMAP4 is the only member reported to have true GTPase activity, and its transcription is found to be differentially regulated during early human CD4(+) T helper (Th) lymphocyte differentiation. GIMAP4 has been previously connected mainly with T- and B-cell development and survival and T-cell apoptosis. Here we show GIMAP4 to be localized into cytoskeletal elements and with the component of the trans golgi network, which suggests it to have a function in cellular transport processes. We demonstrate that depletion of GIMAP4 with RNAi results in downregulation of endoplasmic reticulum localizing chaperone VMA21. Most importantly, we discovered that GIMAP4 regulates secretion of cytokines in early differentiating human CD4(+) Th lymphocytes and in particular the secretion of interferon-γ also affecting its downstream targets.

Adverse Outcome Pathway for Embryonic Vascular Disruption: ToxCast HTS predictive model qualified by a validated human angiogenesis assay

Baltika, the world’s first oblique icebreaker designed to break ice sideways, left Murmansk on 20 March 2015 and headed to the Russian Arctic. The purpose of the three-week voyage to Kara Sea and the Gulf of Ob was to evaluate the vessel’s icebreaking performance and operational capability through extensive full-scale trials in challenging Arctic ice conditions. In the ice-free Barents Sea, the seakeeping characteristics of the asymmetric icebreaker hull were also evaluated in moderate seas. Performance trials were carried out in three different ice thicknesses, ranging from 40 cm thick saline sea ice in the Kara Sea to up to 1.22 m thick hard low-saline ice outside the Sabetta LNG terminal in the Gulf of Ob. During these trials, Baltika exceeded her design icebreaking capability of 3 knots in 1 m thick ice in both ahead and astern directions. In addition, the oblique icebreaking mode was demonstrated for the first time, and the vessel performed beyond expectations. While the main goal of the trial voyage was to confirm Baltika’s icebreaking capability, both the vessel’s crew and the designers gained considerable operational experience during the daily operations in the challenging ice conditions. After the best way to tackle obstacles such as ridged ice fields was discovered, Baltika was found out to be equivalent - sometimes even superior - to conventional icebreakers despite her lower propulsion power. There have always been those who have doubted the feasibility of the oblique icebreaker concept. The extensive full-scale ice trials in the Russian Arctic have shown that Baltika, the first icebreaker with an asymmetric hull, could not only break ice sideways, but also sometimes out-perform conventional icebreakers in other operational situations as well. The concept is thus seen to hold potential for a number of missions such as escort and port icebreaking and in offshore projects.

Cytotoxic T lymphocyte–associated protein 4 (CTLA-4) and inducible T-cell co-stimulator (ICOS) genes are important mediators of T-cell activation in autoimmune diseases. The aim of the current study was to assess the impact of CTLA-4 and ICOS genes on the susceptibility to type 1 diabetes among two populations with different disease incidence rates. Three single nucleotide polymorphisms (SNPs) within the CTLA-4 region (+49A/G, CT60A/G, CTBC217_1C/T) and two SNPs within the ICOS region (CTIC154_1 C/T, CTIC159 C/G) were genotyped in 955 control subjects and 574 diabetic patients of Estonian and Finnish descent. The current study confirms the involvement of the CTLA-4 but not the ICOS gene in susceptibility to type 1 diabetes. However, the risk alleles and the defined main risk haplotype were more common in the Finnish controls compared with the Estonians, indicating that this gene locus might also be one of the contributing factors to the higher disease incidence in Finland.

Objectives: To evaluate the prognostic significance of tumor volume in computed tomographic (CT) images of non-Hodgkin lymphoma patients. To compare CT volumes with those measured by magnetic resonance imaging (MRI). Methods: Twenty-five patients with B cell-type non-Hodgkin lymphoma (16 men, 9 women, age range, 48-77 years) were imaged with CT at 5 time points. The volumes and volume reductions were associated with clinical characteristics and treatment outcome. The CT-derived tumor volumes were correlated with MRI volumes derived earlier for the same patients. Results: Good agreement was found between 1-dimensional (1D), 2D, and 3D analyses. The CT-derived median tumor volumes were 306 cm 3 , 174 cm 3 , 75 cm 3 , 28 cm 3 , and 15 cm 3 at the 5 time points. These volumes were found to associate, for example, with mortality and tumor malignancy. The CT-based tumor volumes showed good correlation with MRI. Conclusions: Tumor volume quantification is a powerful tool that associates with clinical characteristics and treatment outcome.

The increasing incidence of type 1 diabetes observed in the past 60 years has spawned massive efforts in multiple research fields to elucidate the aetiology of this disease. While GWAS studies provide a good genetic basis for the current knowledge, it is clear that environmental triggers and their influence in disease prevalence and origin are highly important. The realization of disease heterogeneity has created a requirement for better biomarkers to complement the known autoantibody markers and to more successfully predict the severity and onset time of the disease. Such biomarkers would be needed both for prevention as well as for monitoring disease activity and response to preventive and therapeutic measures. Systematic holistic approaches concentrating on the triggering molecular mechanisms, pancreatic beta cells, immune response, as well as the influence of diet and environment, are necessary to understand the disease pathogenesis and find a cure. The current genomic knowledge is being broadened with accompanying studies in epigenetics and transcriptomic regulation, metabolomics, proteomics and lipidomics, covering the whole system from beta cells, the profile and cellular balance of the infiltrating lymphocytes, to gut microbiota and viral infections. Here we highlight interesting recent findings in type 1 diabetes research.

GTPase of the immunity-associated protein (GIMAP) family members are differentially regulated during human Th cell differentiation and have been previously connected to immune-mediated disorders in animal studies. GIMAP4 is believed to contribute to the Th cell subtype–driven immunological balance via its role in T cell survival. GIMAP5 has a key role in BB-DR rat and NOD mouse lymphopenia. To elucidate GIMAP4 and GIMAP5 function and role in human immunity, we conducted a study combining genetic association in different immunological diseases and complementing functional analyses. Single nucleotide polymorphisms tagging the GIMAP haplotype variation were genotyped in Finnish type 1 diabetes (T1D) families and in a prospective Swedish asthma and allergic sensitization birth cohort. Initially, GIMAP5 rs6965571 was associated with risk for asthma and allergic sensitization (odds ratio [OR] 3.74, p = 0.00072, and OR 2.70, p = 0.0063, respectively) and protection from T1D (OR 0.64, p = 0.0058); GIMAP4 rs13222905 was associated with asthma (OR 1.28, p = 0.035) and allergic sensitization (OR 1.27, p = 0.0068). However, after false discovery rate correction for multiple testing, only the associations of GIMAP4 with allergic sensitization and GIMAP5 with asthma remained significant. In addition, transcription factor binding sites surrounding the associated loci were predicted. A gene–gene interaction in the T1D data were observed between the IL2RA rs2104286 and GIMAP4 rs9640279 (OR 1.52, p = 0.0064) and indicated between INS rs689 and GIMAP5 rs2286899. The follow-up functional analyses revealed lower IL-2RA expression upon GIMAP4 knockdown and an effect of GIMAP5 rs2286899 genotype on protein expression. Thus, the potential role of GIMAP4 and GIMAP5 as modifiers of immune-mediated diseases cannot be discarded.

Purpose Physical activity is a key to independent functional ability among older adults but few interventions have been conducted in assisted‑living residences. A pedometer has been stated to be ‘a good-enough’ measuring device for the assessment of walking activity in older populations. Research has, however, focused more on community dwelling older adults than on those residing in assisted-living facilities. The aim of this pilot study was to assess the feasibility of a pedometer‑based walking program in an assisted-living facility, and to explore the challenges and obstacles for the implementation of such a program. Materials and methods A pilot intervention study was done with 8 residents between 68 and 89 years of age residing in one assisted‑living facility in Finland. The participants were given pedometers and were asked to walk as usual for a period of one week in order to measure the baseline number of steps. Then, personal goals were assessed based on these baseline figures. Motivational materials and meetings with the participants and attendant nurses were also provided. Participants were encouraged to increase their daily number of steps from their baseline levels by 5% weekly for a period of 6 weeks. Post intervention, seven of the participants and their nurses (n=13) filled in questionnaires concerning the use and usability of the pedometer. Results At baseline, the median number of steps taken by the participants was 800 per day, the daily average being 1369. Post intervention the median was 884 and daily average 1458 steps, demonstrating an increase but no statistically significant changes in the number of steps. Most of the nurses (9/13) believed the pedometer actually encouraged the residents to walk more, but because of technical difficulties, fewer nurses (5/13) found the pedometer to be useful in practice in terms of encouragement for more activity. The participants and nurses found the pedometer easy to use but reported problems with it falling off, underestimating step counts, and inaccuracy. Conclusion Motivating sedentary older adults living in an assisted‑living facility to walk more by employing a pedometer-based walking program is possible but challenging. Integrating the program into daily routines and systematic communication between the research team and the staff of the participating site are needed in order to support the adoption and sustained usage of the new technology. The accuracy and reliability of the pedometer need improvement in terms of use by people with shuffling and low-impact gaits. Better clips to prevent dislodging as well as easier to read numbers are also recommended. Overall, the findings from this study suggest that there is a need for improved pedometer technology to be used with older adults residing in assisted-living residences.

In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.

In recent years increasing evidence has been provided on frequent simultaneous coexistence of inflammatory diseases and allergies in upper and lower airways. To achieve a good standard of measurement of upper airways, an objective method should be used. A total of 48 nasal cavities with nasal stuffiness associated with chronic sinusitis were measured with acoustic rhinometry (AR) and High-resolution computer tomography volumetry (HRCTV). Comparison of volumes and minimum cross-sectional areas measured with these methods was performed. The volumes measured from the nostril with both methods were the anterior (0–10 mm), middle (11–40 mm) and posterior (41–70 mm) volumes. The AR cross-sectional area curve was analysed based on two minimal notches corresponding to local minimal areas. A series of 1-mm coronal CT images without intervening gaps were made and analysed based on two minimal voxel values, which were later converted to cross-sectional areas corresponding to local, minimum cross-sectional areas (MCA). Furthermore, the distances of these 2 MCAs from the nostril were also measured. Strong statistically significant (P

Objective. To estimate fetal volume and weight in diabetic and normal pregnancy using high-resolution magnetic resonance imaging. Methods. T1-weighted magnetic resonance imaging was combined with semiautomatic segmentation technique. The accuracy of fetal volume estimations thus obtained was compared with conventional ultrasound-based weight estimations in ten pregnant women with insulin-dependent diabetes mellitus and ten women with normal pregnancy. Examinations were made within 48 hours before delivery. Results. Ultrasound-based estimations of fetal weight showed a correlation rate of r =0.77 with the actual birth weights in the whole material, while volume determinations based on magnetic resonance imaging showed a significantly better correlation rate of r =0.95. Diabetic women did not differ from the normal pregnancy group with regard to birth weight or the accuracy of weight estimations. Conclusions. High-resolution magnetic resonance imaging combined with semiautomatic segmentation software was fo...

The applications of a new segmentation software, Anatomatic, in the evaluation of volumetric measurements of brain infarctions and the new Medimag 3D software in the evaluation of 3D image representation of infarctions are described. These programs are applied to magnetic resonance imaging. The aim of this study is to evaluate the use of these software packages in making accurate volumetric measurements in 40 patients with right cerebral infarctions, in determining the correlations between the quantitated lesions and neurological/neuropsychological dysfunctions and in creating realistic 3D views of the infarctions. Using Anatomatic, reproducible infarction volumes were achieved with ease and within a reasonably fast time. Medimag helped achieve realistic 3D representations of the infarctions. When compared, the semiautomatic segmentation proved to be much faster and yielded higher infarction volumes than the manual segmentation technique. Significantly positive correlations between the infarction volumes and neurological dysfunctions and neuropsychological deficit (neglect) helped to explain the effect of volumes on the clinical status of the patients.

The objectives of the present study was to correlate the segmented magnetic resonance imaging (MRI) volumes of intracranial cerebrospinal fluid (CSF) spaces (expressing the extent of brain atrophy) and cerebral plaques with the neurological disability in secondary progressive multiple sclerosis (MS). Earlier studies have mainly correlated MS plaques and neurological disability measured by expanded disability status scale (EDSS). The data on the association between brain atrophy and EDSS or regional functional scoring scale (RFSS) are very limited. We measured the volumes of intracranial CSF spaces in 28 patients with secondary progressive MS using MRI, and semiautomatic segmentation software. The volumes of T1-weighted hypointense and T2-weighted hyperintense MS plaques were also measured. In multiple regression analysis, increasing volumes of total (P=0.006) and relative (P=0.005) intracranial CSF spaces were significantly associated with worsening neurological disability as expressed by EDSS. No associations were found between these intracranial CSF space volumes and total RFSS scores. The mean volume of T2-weighted plaques showed a tendency to associate with total RFSS score (r=0.40, P=0.03), but no correlations were detected between T1- or T2-weighted plaque volumes and EDSS. The application of a new segmentation technique in quantifying intracranial cerebrospinal fluid spaces allowed an exact and sensitive way of assessing brain atrophy. The associations between brain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.

The electroencephalogram (EEG) visualization software was developed containing two-dimensional (2D) and three-dimensional (3D) brain mapping modules. The input to the program is standard clinical individual patient data recorded using digital EEG and magnetic resonance imaging (MRI). The software utilizes several techniques, such as heuristic triangulation, ray casting, Gouraud shading, and image fusion to form multimodal 3D images. The program has been applied to the 3D visualization of various EEG signals, "cortical" EEG signals, and potential fields generated by a computer model. The developed program appears to operate efficiently and intuitively in PC/Windows environment.

Semiautomatic segmentation methods using High Resolution Computed Tomography (HRCT) or Magnetic Resonance Imaging give accurate and reproducible volumetric measurements in various intracranial diseases. In this prospective study, for the first time in literature, with the help of a new semiautomatic segmentation technique and coronal HRCT, we correlated the volumes and cross-sectional areas of the nasal cavity with those obtained by clinical acoustic rhinometry in 14 patients with chronic sinusitis. The measurements obtained by both techniques showed statistically significant correlations between volumes in the anterior and middle parts, but statistically poor correlations between the volumes in the posterior part of the nasal cavity. Coronal HRCT and our new microcomputer applicable semiautomatic segmentation software proved compatible with daily clinical practice. Based on the promising results of our study, we recommend the use of this technique in the validation studies of acoustic rhinometry and in complicated cases as a complementary examination in the evaluation of nasal cavity.

This study focuses on three-dimensional (3D) presentations of medical images such as magnetic resonance (MR) images and computed tomography (CT) images. Also multimodal presentations of medical images and signals, including different visualization techniques are considered. A C++ class library together with graphical user interfaces was developed for presenting the results. The implemented software operates in PC/Windows environment. It was tested with various medical images including raw MR and CT data and segmented images, and was applied in a hospital environment. The software operates relatively fast and the quality of resulting pictures is adequate for all tested medical applications. Further applications of 3D presentations in clinical medicine are considered.

This project involves the development of a fast semi-automatic segmentation procedure to make an accurate volumetric estimation of brain lesions. This method has been applied in the segmentation of demyelination plaques in Multiple Sclerosis (MS) and right cerebral hemispheric infarctions in patients with neglect. The developed segmentation method includes several image processing techniques, such as image enhancement, amplitude segmentation, and region growing. The entire program operates on a PC-based computer and applies graphical user interfaces. Twenty three patients with MS and 43 patients with right cerebral hemisphere infarctions were studied on a 0.5 T MRI unit. The MS plaques and cerebral infarctions were thereafter segmented. The volumetric accuracy of the program was demonstrated by segmenting Magnetic Resonance (MR) images of fluid filled syringes. The relative error of the total volume measurement based on the MR images of syringes was 1.5%. Also the repeatability test was carried out as inter-and intra-observer study in which MS plaques of six randomly selected patients were segmented. These tests indicated 7% variability in the inter-observer study and 4% variability in the intra-observer study. Average time used to segment and calculate the total plaque volumes for one patient was 10 min. This simple segmentation method can be utilized in the quantitation of anatomical structures, such as air cells in the sinonasal and temporal bone area, as well as in different pathological conditions, such as brain tumours, intracerebral haematomas and bony destructions.

A large number of computerized conductivity models of the human thorax have been created to study bioelectric phenomena in human beings. Devised models have varied greatly in the level of anatomical detail incorporated thus restricting the accuracy and validity of conducted simulations. This paper introduces a highly detailed anatomically accurate three-dimensional computer model of the conductive anatomy of the human thorax for calculating electric fields generated by equivalent bioelectric sources and different externally applied sources. The anatomy of the devised model is based on high resolution colour cryosection images of the US National Library of Medicine's Visible Human Man data set and is comprised of more anatomical detail than prior computer models. The model is based on the finite difference method and is readily applicable for the analysis of a wide range of biomedical field problems, such as electrocardiography, impedance cardiography, tissue stimulations, and especially, in development of measurement systems.

This paper describes a segmentation method primarily developed for reconstructing resistive head models for electroencephalographic modelling purposes. The method was implemented by combining several image processing techniques, such as amplitude segmentation, region growing, and image fusion. Also a graphical user interface was developed to enable semiautomatic approach to the segmentation process. This method was developed especially for segmentation of the brain and skull from T1-weighted magnetic resonance images, but can also be applied in any segmentation procedure. The entire project was implemented successfully in a PC-based computer running the Unix/NeXTstep ™ operating system.

Characterizing constitutive activities and inducibility of various cytochrome P450 isozymes is important for elucidating species and individual differences in susceptibility to many toxicants. Although expression of certain P450s has been studied in homogenized tissues, the ability to assess functional enzyme activity without tissue disruption would further our understanding of interactive factors that modulate P450 activities. We used precision-cut, viable rat liver slices and confocal laser cytometry to determine the regional enzyme activities of P450 isozymes in situ. Livers from control and beta-naphthoflavone (beta NF)-treated rats were sectioned with a Krumdieck tissue slicer into 250-microns thick sections. A slice perfusion chamber that mounts on the cytometer stage was developed to allow for successive measurement of region-specific P450-dependent O-dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzyloxyresorufin (EROD, PROD, and BROD activity, respectively) in the same liver slice. Images of the accumulated fluorescent resorufin product within the tissue were acquired using a confocal laser cytometer in confocal mode. As expected, slices isolated from beta NF-treated rats showed high levels of centrilobular EROD activity compared to slices from control rats, whereas PROD and BROD activities remained at control levels. These techniques should allow for the accurate quantification of regional and cell-specific P450 enzyme activity and, with subsequent analysis of the same slice, the ability to correlate specific P450 mRNAs or other factors with enzymatic activity. Moreover, these techniques should be amenable to examination of similar phenomena in other tissues such as lung and kidney, where marked heterogeneity in cellular P450 expression patterns is also known to occur. Images Figure 1. Figure 2. Figure 3. Figure 3. Figure 4. Figure 4. Figure 5. Figure 6.

Background The accuracy of texture analysis in clinical evaluation of magnetic resonance images depends considerably on imaging arrangements and various image quality parameters. In this paper, we study the effect of slice thickness on brain tissue texture analysis using a statistical approach and classification of T1-weighted images of clinically confirmed multiple sclerosis patients. Methods We averaged the intensities of three consecutive 1-mm slices to simulate 3-mm slices. Two hundred sixty-four texture parameters were calculated for both the original and the averaged slices. Wilcoxon's signed ranks test was used to find differences between the regions of interest representing white matter and multiple sclerosis plaques. Linear and nonlinear discriminant analyses were applied with several separate training and test sets to determine the actual classification accuracy. Results Only moderate differences in distributions of the texture parameter value for 1-mm and simulated 3-mm-thick slices were found. Our study also showed that white matter areas are well separable from multiple sclerosis plaques even if the slice thickness differs between training and test sets. Conclusions Three-millimeter-thick magnetic resonance image slices acquired with a 1.5 T clinical magnetic resonance scanner seem to be sufficient for texture analysis of multiple sclerosis plaques and white matter tissue.

Objective: The aim of this study was to determine the volume of non―Hodgkin lymphomas (NHLs) using semiautomatic segmentation and to correlate these results with clinical findings, treatment, and prognosis in patients with B-cell―type NHL. Methods: For this study, 29 patients with NHL underwent magnetic resonance imaging at 5 time points after onset of disease. Volumetric analysis of the tumors was accomplished with semiautomatic segmentation by the Anatomatic software. Results: The median tumor volumes from the first to the fifth examination were 468, 256, 90, 38, and 33 cm 3 . Good correlation with 1-dimensional and 2-dimensional measures, used as standard methods in response categorization, was found. Surprisingly, volume reductions in excess of 239 cm 3 after only 1 week of chemotherapy decreased the survival probability. Conclusions: Volume measurements seem to be highly informative for prognosis in the very early stages of treatment for patients with NHL.

Texture analysis accuracy of images acquired by magnetic resonance imaging depends on various image quality parameters, such as magnetic field strength, imaging sequence, noise, spatial resolution and slice thickness. In this paper, the effect of slice thickness on texture analysis of histologically confirmed multiple sclerosis subjects is studied by statistical means. Original consecutive 1 mm slices have been averaged by Matlab to simulate 3 mm slices at the same location. Both slice types are analyzed by MaZda, a texture analysis tool, to calculate 292 texture parameters. Wilcoxon’s signed rank test is applied to test differences in texture parameters between regions of interest. Our results indicate that tissue separability is nearly equal with the studied slice thicknesses, depending slightly on the imaging sequence. Most of the texture parameters are well separable with both slice thicknesses.

The need for quantitative image analysis, especially for MR images, is increasing because of the promising results in diagnosis and follow up of various clinical treatments. This document describes briefly a new software project targeted to computer aided diagnosis. The research focus has been in image segmentation, texture analysis, and volumetric analysis. The developed software enables boundary based segmentation algorithms, and provides interfaces for further analysis of the data. The software is based on two previously started software projects of our research group: Anatomatic+ and Segmentator. The new software has an intuitive user interface and is fast enough for use in medical scientific and practical work.

Transforming growth factors beta 1 and beta 2 (TGF-beta 1 and TGF-beta 2) are well-characterized strong inducers of collagen gene expression. A 100 pM concentration of TGF-beta 1 or TGF-beta 2 increases pro alpha 1(I) collagen mRNA levels in human skin fibroblasts 6.6-fold and 7.0-fold respectively, and also increases the accumulation of procollagens in the cell culture medium. Interleukin-1 beta (IL-1 beta) is an inflammatory mediator which also regulates connective tissue metabolism. A small concentration of IL-1 beta (0.01-1.0 unit/ml) slightly increases pro alpha 1(I) collagen mRNA levels (2.2-fold). Here we provide evidence that IL-1 beta prevents the stimulatory effect of TGFs-beta on collagen synthesis in human skin fibroblasts. An IL-1 beta concentration of 1 unit/ml is enough to keep pro alpha 1(I) collagen mRNA levels at control values in cells stimulated by 100 pM-TGF-beta 1. Thus the results indicate that IL-1 beta inhibits collagen synthesis in cells activated by TGFs-beta, whereas it does not significantly change or might even stimulate collagen gene expression in non-activated cells.

Signal strength based positioning technology offers both cost advantages and technical challenges compared with other positioning methods. This study analyzes measurements taken in a commercial retail environment to develop a set of practical expectations and guidelines in the use of signal strength based positioning systems. A commercially available positioning engine for wireless LANs was used as a readily reproducible basis for the experiments.

In primary progressive multiple sclerosis (PPMS) abnormalities in brain magnetic resonance imaging (MRI) differ from abnormalities in other subtypes of multiple sclerosis (MS). It was investigated whether the extent of brain and spinal cord MRI abnormalities is reflected in the neurological disability in PPMS. Focal and diffuse changes and atrophy in central nervous system (CNS) in patients with PPMS (n = 28) and healthy controls (n = 20) were assessed by semi-automatic MRI segmentation and volumetric analysis. The measurements were related to neurological disability as expressed by the expanded disability status scale (EDSS), the regional functional scoring system (RFSS), the arm index and the ambulation index. Plaques in T1- and/or T2-weighted images were seen in all brains, while spinal plaques were detected in 23 of 28 patients (82%). The total volumes of brain and spinal cord were significantly smaller in patients than in controls (P = 0.001 and 0.000, respectively). The volumes of T1 or T2 lesions in the brain correlated to the ambulation index (r = 0.51, P = 0.005 and r = 0.53, P = 0.004, respectively). No correlations were detected between MRI measurements and total EDSS score, but relative brain atrophy correlated inversely with the total RFSS scores, poor arm index and higher cerebral disturbances (r = -0.53, P = 0.004; r = -0.53, P = 0.004; and r = -0.52, P = 0.005, respectively). Although the number of spinal T2 lesions correlated with sensory disturbances (r = 0.60, P = 0.001), no correlations were found between EDSS subscores and spinal cord atrophy. These findings show that marked atrophy of brain and spinal cord detected by volumetric quantitation correlates with neurological disability. This observation indicates the importance of neurodegenerative events in PPMS.

The presence of inflammation in decidual and myometrial samples as defined by histopathologic examination and the association between the myometrial inflammation and different maternal infectious morbidity and labor-related clinical variables were evaluated in 648 consecutive women who underwent cesarean section at various gestational periods. Altogether, 1,205 histologic (559 decidual and 646 myometrial) samples were studied. In normal pregnancies, myometrial inflammatory lesions were detected rarely before parturition, indicating their abnormality in these cases. After ruptured fetal membranes with advanced cervical dilatation and in patients with clinical chorioamnionitis, myometrial samples commonly were infiltrated by leukocytes, up to moderate and marked densities. Moderate to marked myometrial inflammation showed no diagnostic value in high-risk term parturients for the prediction of postoperative endometritis. Our study is the first to show the frequency of myometrial inflammation in nonselected consecutive pregnant women and, thus, is important for better understanding the myometrial inflammatory response during human parturition.

The popularity of digital imaging devices and PACS installations has increased during the last years. Still, images are analyzed and diagnosed using conventional techniques. Our research group begun to study the requirements for digital image diagnostic methods to be applied together with PACS systems. The research was focused on various image analysis procedures (e.g., segmentation, volumetry, 3D visualization, image fusion, anatomic atlas, etc.) that could be useful in medical diagnosis. We have developed Image Analysis software (www.medimag.net) to enable several image-processing applications in medical diagnosis, such as volumetry, multimodal visualization, and 3D visualizations. We have also developed a commercial scalable image archive system (ActaServer, supports DICOM) based on component technology (www.acta.fi), and several telemedicine applications. All the software and systems operate in NT environment and are in clinical use in several hospitals. The analysis software have been applied in clinical work and utilized in numerous patient cases (500 patients). This method has been used in the diagnosis, therapy and follow-up in various diseases of the central nervous system (CNS), respiratory system (RS) and human reproductive system (HRS). In many of these diseases e.g. Systemic Lupus Erythematosus (CNS), nasal airways diseases (RS) and ovarian tumors (HRS), these methods have been used for the first time in clinical work. According to our results, digital diagnosis improves diagnostic capabilities, and together with PACS installations it will become standard tool during the next decade by enabling more accurate diagnosis and patient follow-up.© (2001) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The application of a new segmentation software, Anatomatic in the evaluation of volumetric measurements of ovarian tumours and the new Medimag three-dimensional (3D) software in the evaluation of 3D image representation of ovarian tumours with 1.5 T magnetic resonance imaging (MRI) is described. Our goal was to compare MRI based volumetry with operative findings at laparotomy for six consecutive patients with suspected ovarian tumours. Volumetric analysis and three dimensional image reconstructions of the tumours were obtained. At laparotomy, the tumour sizes were measured in situ, and the volumes were calculated. Using Anatomatic, reproducible tumour volumes were achieved with ease and within a reasonably fast time in patients with ovarian tumours without ascites. Medimag helped achieve realistic 3D representations of the tumours. For the four solitary tumours segmentation based volumetry and laparotomy findings agreed in three cases. In one patient with an oval shaped tumour, the segmented volume was double as compared to that estimated at laparotomy. Of the two patients with multiple tumours, both patients had significant ascites, and volumetry misinterpreted the fluid as tumour cyst fluid and markedly overestimated the tumour size. In conclusion, the MRI based segmentation volumetry and 3D image reconstructions are rapid, and reproducible methods of measuring ovarian tumours in patients without significant ascites.

To estimate fetal volume and weight in diabetic and normal pregnancy using high-resolution magnetic resonance imaging.T1-weighted magnetic resonance imaging was combined with semiautomatic segmentation technique. The accuracy of fetal volume estimations thus obtained was compared with conventional ultrasound-based weight estimations in ten pregnant women with insulin-dependent diabetes mellitus and ten women with normal pregnancy. Examinations were made within 48 hours before delivery.Ultrasound-based estimations of fetal weight showed a correlation rate of r=0.77 with the actual birth weights in the whole material, while volume determinations based on magnetic resonance imaging showed a significantly better correlation rate of r=0.95. Diabetic women did not differ from the normal pregnancy group with regard to birth weight or the accuracy of weight estimations.High-resolution magnetic resonance imaging combined with semiautomatic segmentation software was found to be accurate in determining fetal volume and, consequently, better than conventional ultrasound-based techniques in estimating fetal weight. The use of magnetic resonance imaging in fetal weight estimation may be recommended for clinical situations where an accurate weight estimate is considered essential.

The paper describes the application of new semi-automatic segmentation software to the task of detection of anatomical structures and lesion and their three-dimensional (3D) visualisation in 23 patients with secondary progressive multiple sclerosis (MS). The purpose is to study the correlation between magnetic resonance imaging (MRI) parameters (volumes of plaques and cerebrospinal fluid spaces) and clinical deficits (neurological deficits in the form of EDSS and RFSS scores, and neuropsychological deficits). The software operates in PC/Windows and PC/NeXTstep environments and utilises graphical user interfaces. Quantitative accuracy is measured by performing segmentation of fluid-filled syringes (relative error of 1.5%), and reproducibility is measured by intra- and inter-observer studies (3% and 7% variability, respectively). The mean volumes of MS plaques show significant correlations with the total RFSS scores (p = 0.04). Relative intracranial cerebrospinal fluid (CSF) space volumes show statistically significant correlation with EDSS scores (p = 0.01). The mean volume of MS plaques shows a significant correlation with the overall neuropsychological deficits (p = 0.03). 3D visualisation helps to understand the relationship of lesions to the surrounding brain structures. The use of semiautomatic segmentation techniques is recommended in the clinical diagnosis of MS patients.

After the introduction of digital imagin devices in medicine computerized tissue recognition and classification have become important in research and clinical applications. Segmented data can be applied among numerous research fields including volumetric analysis of particular tissues and structures, construction of anatomical modes, 3D visualization, and multimodal visualization, hence making segmentation essential in modern image analysis. In this research project several PC based software were developed in order to segment medical images, to visualize raw and segmented images in 3D, and to produce EEG brain maps in which MR images and EEG signals were integrated. The software package was tested and validated in numerous clinical research projects in hospital environment.

The objective of this study was to determine nasal cavity volumes and cross-sectional profiles from segmented coronal high-resolution computed tomography (HRCT) images. Pathological mucosal changes and congenital sinonasal variants were quantitated and three-dimensional (3D) images for determining sinonasal airway diseases evaluated by using the new semiautomatic segmentation software, Anatomatic. Anterior to posterior cross-sectional profiles of the sinonasal airway were obtained from acoustic rhinometry and segmented coronal HRCT images and compared in five patients having complaints of nasal obstruction and chronic sinusitis. Results showed that accurate volumes of air spaces in the nasal cavity and paranasal sinuses were obtained. When compared, the cross-sectional profiles of the nasal cavities obtained from acoustic rhinometry and the segmentation technique were similar in the anterior portion, but differed in the posterior portion. The results obtained by coronal HRCT and segmentation were more reliable than those produced with acoustic rhinometry. 3D images acquired from segmented images were found to help make a good pre-operative assessment of the whole sinonasal compartment. Segmentation and volumetric analysis using the Anatomatic technique also proved to be well suited to the evaluation of the nasal cavity and paranasal sinus geometry in patients with sinonasal diseases.

Semiautomatic segmentation methods using High Resolution Computed Tomography (HRCT) or Magnetic Resonance Imaging give accurate and reproducible volumetric measurements in various intracranial diseases. In this prospective study, for the first time in literature, with the help of a new semiautomatic segmentation technique and coronal HRCT, we correlated the volumes and cross-sectional areas of the nasal cavity with those obtained by clinical acoustic rhinometry in 14 patients with chronic sinusitis. The measurements obtained by both techniques showed statistically significant correlations between volumes in the anterior and middle parts, but statistically poor correlations between the volumes in the posterior part of the nasal cavity. Coronal HRCT and our new microcomputer applicable semiautomatic segmentation software proved compatible with daily clinical practice. Based on the promising results of our study, we recommend the use of this technique in the validation studies of acoustic rhinometry and in complicated cases as a complementary examination in the evaluation of nasal cavity.

Quantitative magnetic resonance (MR) imaging of the brain is useful in multiple sclerosis (MS) in order to obtain reliable indices of disease progression. The goal of this project was to estimate the total volume of gliotic and non gliotic plaques in chronic progressive multiple sclerosis with the help of a semiautomatic segmentation method developed at the Ragnar Granit Institute. Youth developed program running on a PC based computer provides de displays of the segmented data, in addition to the volumetric analyses. The volumetric accuracy of the program was demonstrated by segmenting MR images of fluid filed syringes. An anatomical atlas is to be incorporated in the segmentation system to estimate the distribution of MS plaques in various neural pathways of the brain. A total package including MS plaque volume estimation, estimation of brain atrophy and ventricular enlargement, distribution of MS plaques in different neural segments of the brain has ben planned for the near future. Our study confirmed that total lesion volumes in chronic MS disease show a poor correlation to EDSS scores but show a positive correlation to neuropsychological scores. Therefore accurate total volume measurements of MS plaques using the developed semiautomatic segmentation technique helped us to evaluate the degree of neuropsychological impairment.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Although epidemiological studies suggest that aflatoxin B1 (AFB1) is a human carcinogen, at least in the presence of hepatitis B virus infection, animal studies have demonstrated large differences in species sensitivity to AFB1, and the sensitivity of humans relative to experimental animals remains unclear. The purpose of this study was to determine the profile of AFB1 metabolism and the extent of AFB1 binding to cell macromolecules in human liver slices under experimental conditions that would allow direct comparison to similar endpoints in the rat, a species sensitive to the carcinogenic actions of AFB1. Liver slices were prepared from three individual human liver samples with a Krumdieck tissue slicer and incubated with 0.5 microM [3H]AFB1 for 2 hr. Significant interindividual variations were observed in the rates of oxidative metabolite formation and in specific binding to cell macromolecules. The rates of oxidative metabolism of AFB1 to AFQ1, AFP1, and AFM1 in the three human liver samples were similar to those previously observed in rat liver slices. AFB1-GSH conjugate formation was not detected in any of the human liver samples, and yet specific binding of AFB1 to cell macromolecules was considerably lower in the human liver slices relative to that in rat liver slices. AFB1-DNA binding levels ranged from 3 to 26% of control rat and AFB1-RNA binding levels ranged from 25 to 49% of control rat. The AFB1-protein binding level in the one human sample measured was 20% of that observed for control rat. While these results suggest that humans do not form as much AFBO as the rat, they are also consistent with the hypothesis that humans do not possess GST isozyme(s) with high specific activity toward AFBO. Significant individual differences in AFB1 metabolism and binding between humans suggest the presence of genetic and/or environmental factors that may confer large variability in susceptibility to AFB1.