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Biomedical subjects

M Vauhkonen

Publications and source records attributed to M Vauhkonen.

At least 19 recordsLinked to original sources

A biopsy-based quick test in the diagnosis of duodenal hypolactasia in upper gastrointestinal endoscopy.

BACKGROUND AND STUDY AIMS: The usefulness of a new quick test for endoscopic diagnosis of adult-type hypolactasia was tested in duodenal biopsies. In this test, an endoscopic biopsy from the postbulbar duodenum is incubated with lactose on a test plate, and a color reaction develops within 20 min as a result of hydrolyzed lactose (a positive result) in patients with normolactasia, whereas no reaction (a negative result) develops in patients with severe hypolactasia. PATIENTS AND METHODS: Two postbulbar duodenal biopsies were taken from 80 prospectively enrolled adult outpatients with dyspepsia. The biopsies were used for the Quick Lactase Test (Biohit PLC, Helsinki, Finland) and in biochemical disaccharidase (lactase, sucrase, and maltase) assays. In addition, the C/T (-13,910) genotype was determined from DNA extracted from gastric antral biopsies using polymerase chain reaction sequencing in genomic analysis of adult-type hypolactasia. RESULTS: Twenty-one of 22 patients (95 %; 95 % CI, 87 - 100 %) with biochemical lactase activity < 10 U/g protein, but none of the 58 patients with lactase activity of 10 U/g protein or more had a negative result in the Quick Lactase Test. Seven of the 80 patients (9 %; 95 % CI, 3 - 15 %) had a Quick Lactase Test result that indicated mild hypolactasia (a mild color reaction). All patients with celiac disease (n = 6) had a negative Quick Lactase Test result. Nine of 74 patients (six patients with celiac disease were excluded) had a CC (-13,910) genotype in genomic testing, indicating adult-type hypolactasia. All of them had negative test results with the Quick Lactase Test. Twenty-six patients had a TT genotype, indicating normolactasia, and none of these patients had a negative test result in the Quick Lactase Test. Six of 39 patients (15 %; 95 % CI, 4 - 27 %) with a CT genotype had a negative result in the Quick Lactase Test. CONCLUSIONS: The Quick Lactase Test effectively identifies patients with severe duodenal hypolactasia. In comparison with CC (adult-type hypolactasia) and TT individuals (normolactasia), the sensitivity and specificity of the Quick Lactase Test result was 100 %. In comparison with biochemical lactase assays, the sensitivity and specificity of a negative Quick Lactase Test for indicating hypolactasia (lactase activity < 10 U/g protein) were 95 % (95 % CI, 87 - 100 %) and 100 %, respectively.

Biopsy↗

Modelling the transport of ionizing radiation using the finite element method.

Radiation therapy treatment planning is based on the calculation of the absorbed dose in the patient domain. For exact dose calculations, the solution of three coupled Boltzmann transport equations (BTEs) is needed to cover the transport of photons, electrons and positrons. In many situations, however, two coupled systems for photons and electrons are enough. The use of numerical methods in finding the exact solution of the unknown particle fluxes is necessary. In the stationary case, the BTE has six variables, three spatial, two directional and one energy variable. In this paper, we describe an approach in which the finite element method (FEM) is used to solve the six-dimensional problem. For the coupled photon-electron system, the variational formulation and the existence and uniqueness of the solution are derived. We simulate the solution of two coupled BTEs describing the travelling of photons and electrons in two spatial dimensions. The results are compared to Monte Carlo calculations with good agreement.

Animals↗

Evaluation of gastrointestinal cancer tissues as a source of genetic information for forensic investigations by using STRs.

Malignant tissue samples may sometimes be the only source of biological material for forensic investigations, including identification of individuals or paternity testing. However, in use of such samples, uncertainties due to microsatellite instability (MSI) and loss of heterozygosity (LOH) often associated with neoplasias may be encountered. In this study, we have analysed the applicability of autosomal tetranucleotide short tandem repeat (STR) markers, which are routinely used in forensic analysis, to gain genetic information. MSI and LOH were analysed in 41 surgically removed gastrointestinal cancer specimens and the adjascent non-cancerous tissue marginals. The cancer specimens showed great variability in their genetic phenotypes due to MSI or LOH, with only 32% being microsatellite-stable. Of the 15 autosomal STR loci analysed, only TH01 had no MSI-type alteration in these samples. The loci most frequently affected by MSI were D8S1179, D21S11, D18S51 and D19S433 (MSI in 15-17% of cases). LOH-type alterations were observed at all of the loci, including the amelogenin locus used for sex determination. The highest LOH frequency was found at locus D18S51 (27%). The genetic alterations at the marker loci may indicate false homozygosity or heterozygosity, and false gender may result from erroneous deduction of DNA profiles. Therefore, typing of autosomal STRs from malignant tissues in forensic settings warrants careful interpretation of MSI and LOH results together with microscopic analysis of a tissue specimen. Results by two commercially available and widely used forensic DNA profiling kits used here were comparable.

Aged↗

Correlation between the allelic distribution of STRs in a Finnish population and phenotypically different gastrointestinal tumours: a study using four X-chromosomal markers (DXS7423, DXS8377, ARA, DXS101).

Microsatellite instability in tumours has been suggested as a model to study the process of short tandem repeat (STR) mutations. In the present study we have determined the allelic variation of four X-STRs (DXS7423, DXS8377, DXS101 and ARA) in a Finnish population of 103 individuals, and assessed whether a comparable allelic distribution could be found in a series of gastrointestinal cancers differing by the level of microsatellite instability. Fifty-seven gastric and colorectal cancers were stratified by autosomal STRs, and the mononucleotide marker BAT-26 into stable, low-level unstable and high-level unstable microsatellite (MSI-H) cancers, of which the last produced the majority of X-STR alleles. For the four markers analysed, a significant correlation of allele distribution between our Finnish population sample and MSI-H tumours was noted. Together, the eight MSI-H tumours found represented 80%, 66-80% and 100% of the DXS101 alleles in the Finnish, and in previously described Caucasian and Korean population samples, respectively. Of the ARA, DXS7423 and DXS8377 alleles in the Finnish population, 42%, 75% and 79% were found in the MSI-H cancers, respectively. The results suggest that analysis of STR variation in a relatively small number of MSI-H cancers may aid in pre-evaluation of their allelic distribution in a population.

Alleles↗

Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study.

BACKGROUND AND AIMS: Serum levels of gastrin-17 (S-G-17) and pepsinogen I (S-PGI) are biomarkers of gastric antral and corpus mucosa, respectively. In a prospective multicentre investigation, we determined whether these tests, together with the assay of Helicobacter pylori antibodies, are a non-endoscopic tool for the diagnosis of atrophic gastritis. MATERIALS AND METHODS: The series comprised 404 consecutive adult outpatients undergoing diagnostic upper-gastrointestinal endoscopy for various dyspeptic symptoms in five outpatient clinics. Gastric biopsies from the antrum and corpus (at least two biopsies from both sites) were available from all patients, and they were evaluated according to the guidelines of the updated Sydney system. S-PGI and S-G-17 were assayed with ELISA methods using monoclonal antibodies to pepsinogen I and amidated gastrin-17. In addition to the fasting level (S-G-17(fast)), a postprandial S-G-17 (S-G-17(prand)) level was measured 20 min after ingestion of a protein-rich drink. H. pylori antibodies were determined using a polyclonal EIA method. RESULTS: S-G-17(prand) (and S-G-17(fast)) and S-PGI levels decreased with increasing grade of atrophy of the antrum or corpus, respectively. S-G-17(prand) levels were significantly lower in patients with advanced (moderate or severe) atrophic antral H. pylori gastritis than in those with non-atrophic H. pylori gastritis. All patients with a resected antrum demonstrated S-G-17(prand) levels that were almost undetectable. Of the nine patients with an H. pylori-positive moderate or severe atrophic antral gastritis, six had S-G-17(prand) levels below 5 pmol/l. Similarly, S-PGI levels were significantly lower in patients with advanced corpus atrophy than in those without. Of the 45 patients with moderate or severe corpus atrophy in endoscopic biopsies, 35 patients had S-PGI levels < 25 microg/l. By using the cut-off levels for S-G-17(prand) and S-PGI with the best discrimination, the sensitivity and specificity of the blood test panel in delineation of patients with advanced atrophic gastritis (either in the antrum or the corpus, or both) were 83% and 95%, respectively. The predictive values of the positive and negative test results were 75% and 97%, respectively. In the diagnosis of atrophic gastritis, the application of S-G-17(fast) showed a slightly lower sensitivity and specificity than the application of S-G-17(prand) as a biomarker for antral atrophy. CONCLUSIONS: The diagnosis of atrophic gastritis obtained with the blood test panel of S-G-17, S-PGI and H. pylori antibodies is in good agreement with the endoscopic and biopsy findings. The panel is a tool for non-endoscopic diagnosis and screening of atrophic gastritis.

Adult↗

A MATLAB package for the EIDORS project to reconstruct two-dimensional EIT images.

The EIDORS (electrical impedance and diffuse optical reconstruction software) project aims to produce a software system for reconstructing images from electrical or diffuse optical data. MATLAB is a software that is used in the EIDORS project for rapid prototyping, graphical user interface construction and image display. We have written a MATLAB package (http://venda.uku.fi/ vauhkon/) which can be used for two-dimensional mesh generation, solving the forward problem and reconstructing and displaying the reconstructed images (resistivity or admittivity). In this paper we briefly describe the mathematical theory on which the codes are based on and also give some examples of the capabilities of the package.

Algorithms↗

A new computational approach for cortical imaging.

Estimation of current or potential distribution on the cortex is used to obtain information about neural sources from the scalp recorded electroencephalogram. If the active sources in the brain are superficial, the estimated field distribution on the cortex also yields information about the active source configuration. In these cases, these methods can be used as source localization methods. In this study, we concentrate on finite-element-based cortex potential estimation. Usually these methods require surface interpolation of the recorded voltages at the electrodes onto the entire scalp surface. We propose a new computational approach which does not require the use of surface interpolation but does it implicitly and uses only the recorded data at the electrodes. We refer to this method as the systematic approach (SA). We compare the SA with the surface interpolation approach (IA) and show that the SA is able to produce somewhat better accuracy than the IA. However, the main asset is that the sensitivity of the cortical potential maps to the regularization parameter is significantly lower than with the IA.

Brain Mapping↗

Effects of electrode properties on EEG measurements and a related inverse problem.

A trend in EEG measurements is to increase the number of measurement electrodes in order to improve the spatial resolution of the recorded voltage distribution at the scalp. It is assumed that this would implicate better accuracy in the EEG inverse estimates. However, this does not necessarily hold. The reason for this is that the electrodes create a well conducting shunting "layer" on the scalp which affects the voltage distribution. This may decrease the information obtained and may therefore worsen the inverse estimates. Electrodes in EEG inverse problems are commonly modeled as point electrodes. This model cannot take into account the possible shunting effect of the electrodes. In this study the measurement electrodes are modeled using the so-called complete electrode model which takes into account the actual size of the electrode, the contact impedance between the skin and the electrode and also the shunting effect of the electrodes. In this paper the effects of the electrode size and the contact impedance on the voltage distribution are studied by simulations. It is shown that, depending on the size and the contact impedance of the electrodes, increasing the number of electrodes does not necessarily improve the accuracy of the inverse estimates. We also conclude that the use of the point electrode model is quite adequate in normal EEG studies. The use of a complete electrode model is necessary if electrodes cover more than 50% of the surface area.

Electric Impedance↗

Simultaneous reconstruction of internal tissue region boundaries and coefficients in optical diffusion tomography.

In this paper we propose a new numerical method to the inverse problem in optical diffusion tomography. We consider the reconstruction of the diffusion and absorption coefficients (kappa, mu(a)) within a domain omega which is known to consist of a set of disjoint regions of distinct tissue types. The assumption is that the regions of different tissues are bounded by smooth boundary curves and have constant absorption and diffusion coefficients. The goal in the proposed method is to reconstruct simultaneously the boundaries of the tissue regions together with the absorption and diffusion coefficients within these regions. The solution of the problem is based on the finite element method and subdivision of the elements. The performance of the proposed method is evaluated by simulations in which the optical parameters (kappa, mu(a)) are relevant in medical applications of optical tomography. It is shown that the proposed method is able to recover both the boundaries and the coefficients with good accuracy.

Image Processing, Computer-Assisted↗

Sensitivity matrix and reconstruction algorithm for EIT assuming axial uniformity.

In electrical impedance tomography (EIT) two-dimensional models continue to be applied despite their known inability to provide correct reconstruction. In this paper, a reconstruction algorithm that assumes a translationally invariant conductivity distribution is described. A more precise forward solver is obtained by taking off-slice currents into consideration. An appropriate sensitivity matrix is derived. Numerical evidence for the improvement in precision compared to two-dimensional reconstruction is given.

Algorithms↗

Errors due to the truncation of the computational domain in static three-dimensional electrical impedance tomography.

In electrical impedance tomography (EIT), an approximation for the internal resistivity distribution is computed based on the knowledge of the injected currents and measured voltages on the surface of the body. The currents spread out in three dimensions and therefore off-plane structures have a significant effect on the reconstructed images. A question arises: how far from the current carrying electrodes should the discretized model of the object be extended? If the model is truncated too near the electrodes, errors are produced in the reconstructed images. On the other hand if the model is extended very far from the electrodes the computational time may become too long in practice. In this paper the model truncation problem is studied with the extended finite element method. Forward solutions obtained using so-called infinite elements, long finite elements and separable long finite elements are compared to the correct solution. The effects of the truncation of the computational domain on the reconstructed images are also discussed and results from the three-dimensional (3D) sensitivity analysis are given. We show that if the finite element method with ordinary elements is used in static 3D EIT, the dimension of the problem can become fairly large if the errors associated with the domain truncation are to be avoided.

Biometry↗

Effects of local skull inhomogeneities on EEG source estimation.

The accuracy of the head model affects the solutions of the EEG inverse problems. If a simple three-sphere model and standard conductivity values for brain, skull and scalp regions are used, significant errors may occur in the dipole localisation. One of the most sensitive head model parameters is the conductivity of the skull. A realistic three-dimensional finite-element model provides a method to study the effect of inhomogeneities of the skull on the solutions of EEG inverse problems. In this paper the effect of a local skull conductivity inhomogeneity on source estimation accuracy is analyzed by computer simulations for different numbers of electrodes. It is shown that if the inhomogeneity of the skull conductivity is not taken into account, localisation errors of approximately 1 cm can be encountered in the equivalent current dipole estimation. This modelling error introduces a bias to the solution which cannot be compensated by increasing the number of electrodes.

Biophysical Phenomena↗

Subspace regularization method for the single-trial estimation of evoked potentials.

A method for the single-trial estimation of the evoked potentials is proposed. The method is based on the so-called subspace regularization approach in which the second-order statistics of the set of the measurements is used to form a prior information model for the evoked potentials. The method is closely related to the Bayesian estimation. The performance of the proposed method is evaluated using realistic simulations. As a specific application the method is applied to the estimation of the target responses in the P300 test.

Bayes Theorem↗

Three-dimensional electrical impedance tomography based on the complete electrode model.

In electrical impedance tomography an approximation for the internal resistivity distribution is computed based on the knowledge of the injected currents and measured voltages on the surface of the body. It is often assumed that the injected currents are confined to the two-dimensional (2-D) electrode plane and the reconstruction is based on 2-D assumptions. However, the currents spread out in three dimensions and, therefore, off-plane structures have significant effect on the reconstructed images. In this paper we propose a finite element-based method for the reconstruction of three-dimensional resistivity distributions. The proposed method is based on the so-called complete electrode model that takes into account the presence of the electrodes and the contact impedances. Both the forward and the inverse problems are discussed and results from static and dynamic (difference) reconstructions with real measurement data are given. It is shown that in phantom experiments with accurate finite element computations it is possible to obtain static images that are comparable with difference images that are reconstructed from the same object with the empty (saline filled) tank as a reference.

Electric Conductivity↗

Iodine-123 labeled nor-beta-CIT as a potential tracer for serotonin transporter imaging in the human brain with single-photon emission tomography.

Iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) (nor-beta-CIT) is an analogue of beta-CIT, which has high affinity to the serotonin transporter. Initial single-photon emission tomography (SPET) studies with [123I]nor-beta-CIT were performed in five healthy volunteers. In addition, its metabolism in plasma was investigated with gradient high performance liquid chromatography. [123I]nor-beta-CIT was prepared by a method which gave a specific radioactivity of more than 180 GBq/micromol. Unchanged [123I]nor-beta-CIT in plasma accounted for 43% and 19% of total radioactivity after 30 and 180 min, respectively. The dynamic SPET studies demonstrated a high and rapid uptake of radioactivity in the brain (6%/ID at 30 min). Highest accumulation was observed in the striatum, the mid-brain and the thalamus. The specific binding in the mid-brain was 33% higher compared with that of [123I]beta-CIT. The high radioactivity in the mid-brain is assumed to represent the accumulation of [123I]nor-beta-CIT in the serotonin transporter-rich regions, which indicates that [123I]nor-beta-CIT might be a potential tracer for visualization of serotonin transporter sites in the human brain with SPET.

Adult↗

A Kalman filter approach to track fast impedance changes in electrical impedance tomography.

In electrical impedance tomography (EIT), an estimate for the cross-sectional impedance distribution is obtained from the body by using current and voltage measurements made from the boundary. All well-known reconstruction algorithms use a full set of independent current patterns for each reconstruction. In some applications, the impedance changes may be so fast that information on the time evolution of the impedance distribution is either lost or severely blurred. In this paper, we propose an algorithm for EIT reconstruction that is able to track fast changes in the impedance distribution. The method is based on the formulation of EIT as a state-estimation problem and the recursive estimation of the state with the aid of the Kalman filter. The performance of the proposed method is evaluated with a simulation of human thorax in a situation in which the impedances of the ventricles change rapidly. We show that with optimal current patterns and proper parameterization, the proposed approach yields significant enhancement of the temporal resolution over the conventional reconstruction strategy.

Algorithms↗

Tikhonov regularization and prior information in electrical impedance tomography.

The solution of impedance distribution in electrical impedance tomography is a nonlinear inverse problem that requires the use of a regularization method. The generalized Tikhonov regularization methods have been popular in the solution of many inverse problems. The regularization matrices that are usually used with the Tikhonov method are more or less ad hoc and the implicit prior assumptions are, thus, in many cases inappropriate. In this paper, we propose an approach to the construction of the regularization matrix that conforms to the prior assumptions on the impedance distribution. The approach is based on the construction of an approximating subspace for the expected impedance distributions. It is shown by simulations that the reconstructions obtained with the proposed method are better than with two other schemes of the same type when the prior is compatible with the true object. On the other hand, when the prior is incompatible with the true object, the method will still give reasonable estimates.

Algorithms↗