Anatomy-guided multi-resolution image reconstruction in PET.

Objective. In this paper, we propose positron emission tomography image reconstruction using a multi-resolution triangular mesh. The mesh can be adapted based on patient specific anatomical information that can be in the form of a computed tomography or magnetic resonance imaging image in the hybrid imaging systems. The triangular mesh can be adapted to high resolution in localized anatomical regions of interest (ROI) and made coarser in other regions, leading to an imaging model with high resolution in the ROI with clearly reduced number of degrees of freedom compared to a conventional uniformly dense imaging model.Approach.We compare maximum likelihood expectation maximization reconstructions with the multi-resolution model to reconstructions using a uniformly dense mesh, a sparse mesh and regular rectangular pixel mesh. Two simulated cases are used in the comparison, with the first one using the NEMA image quality phantom and the second the XCAT human phantom.Main results.When compared to the results with the uniform imaging models, the locally refined multi-resolution mesh retains the accuracy of the dense mesh reconstruction in the ROI while being faster to compute than the reconstructions with the uniformly dense mesh. The locally dense multi-resolution model leads also to more accurate reconstruction than the pixel-based mesh or the sparse triangular mesh.Significance.The findings suggest that triangular multi-resolution mesh, which can be made patient and application specific, is a potential alternative for pixel-based reconstruction.

Costs of multidrug-resistant TB treatment in Finland and Estonia affected by the 2019 WHO guidelines.

BACKGROUND: Multidrug-resistant TB (MDR-TB) is a growing problem in the effort to end the global TB epidemic. In 2019, the WHO adopted a new standardised regiment for MDR-TB, consisting of only oral medications.METHODS: We estimated the impact of the new guidelines on the costs of TB treatment in Estonia and Finland. For both countries, the costs of the two most common new drug regimens were calculated, including drug costs, as well as care- and monitoring-related costs.RESULTS: In Turku, Finland, treatment costs with the old regimen were €178,714; this could either increase by 10% or decrease by 18%, depending on the duration of bedaquiline use (6 months vs. 20 months). In Estonia, treatment costs with the old regimen were €33,664, whereas the new regimens were associated with a 40% increase in overall costs.CONCLUSIONS: The 2019 WHO guidelines have led to significant changes in the costs of MDR-TB treatment in Finland and Estonia. These changes depend mostly on the drug regimen administered and on care-related practices, with important differences between countries and even within the same country due to local practices.

OMEGA-open-source emission tomography software.

In this paper we present OMEGA, an open-source software, for efficient and fast image reconstruction in positron emission tomography (PET). OMEGA uses the scripting language of MATLAB and GNU Octave allowing reconstruction of PET data with a MATLAB or GNU Octave interface. The goal of OMEGA is to allow easy and fast reconstruction of any PET data, and to provide a computationally efficient, easy-access platform for development of new PET algorithms with built-in forward and backward projection operations available to the user as a MATLAB/Octave class. OMEGA also includes direct support for GATE simulated data, facilitating easy evaluation of the new algorithms using Monte Carlo simulated PET data. OMEGA supports parallel computing by utilizing OpenMP for CPU implementations and OpenCL for GPU allowing any hardware to be used. OMEGA includes built-in function for the computation of normalization correction and allows several other corrections to be applied such as attenuation, randoms or scatter. OMEGA includes several different maximum-likelihood and maximum a posteriori (MAP) algorithms with several different priors. The user can also input their own priors to the built-in MAP functions. The image reconstruction in OMEGA can be computed either by using an explicitly computed system matrix or with a matrix-free formalism, where the latter can be accelerated with OpenCL. We provide an overview on the software and present some examples utilizing the different features of the software.

Contrast enhancement in EIT imaging of the brain.

We consider electrical impedance tomography (EIT) imaging of the brain. The brain is surrounded by the poorly conducting skull which has low conductivity compared to the brain. The skull layer causes a partial shielding effect which leads to weak sensitivity for the imaging of the brain tissue. In this paper we propose an approach based on the Bayesian approximation error approach, to enhance the contrast in brain imaging. With this approach, both the (uninteresting) geometry and the conductivity of the skull are embedded in the approximation error statistics, which leads to a computationally efficient algorithm that is able to detect features such as internal haemorrhage with significantly increased sensitivity and specificity. We evaluate the approach with simulations and phantom data.

Bioimpedance-based measurement method for simultaneous acquisition of respiratory and cardiac gating signals.

Respiratory and cardiac motion artefacts impair the quality and reliability of medical imaging, particularly in nuclear medicine. At worst, the interpretation of distorted images may lead to inadequate or unnecessary treatment. Image artefacts can be minimized by gating the image acquisition according to respiratory phase and cardiac contractions. However, currently there are no clinically established dual-gating methods in nuclear medicine imaging. The aim of this study is to validate a previously determined optimized bioimpedance measurement configuration against traditional respiratory and cardiac measurement systems in 12 volunteers. High agreement and excellent correlations (r = 0.944-0.999) were found between respiratory peak-to-peak amplitudes as well as temporal respiratory and cardiac intervals. Above all, good quality respiratory and cardiac gating signals were obtained from all test subjects with a fairly regular sinus rhythm. Importantly, both signals were acquired simultaneously with a single device. Due to the simplicity of this inexpensive method, the technique has high potential to be adopted for dual-gating in clinical practice in the future.

A measurement system and image reconstruction in magnetic induction tomography.

Magnetic induction tomography (MIT) is a technique for imaging the internal conductivity distribution of an object. In MIT current-carrying coils are used to induce eddy currents in the object and the induced voltages are sensed with other coils. From these measurements, the internal conductivity distribution of the object can be reconstructed. In this paper, we introduce a 16-channel MIT measurement system that is capable of parallel readout of 16 receiver channels. The parallel measurements are carried out using high-quality audio sampling devices. Furthermore, approaches for reconstructing MIT images developed for the 16-channel MIT system are introduced. We consider low conductivity applications, conductivity less than 5 S m(-1), and we use a frequency of 10 MHz. In the image reconstruction, we use time-harmonic Maxwell's equation for the electric field. This equation is solved with the finite element method using edge elements and the images are reconstructed using a generalized Tikhonov regularization approach. Both difference and static image reconstruction approaches are considered. Results from simulations and real measurements collected with the Philips 16-channel MIT system are shown.

Oligonucleotide array comparative genomic hybridization refines the structure of 8p23.1, 17q12 and 20q13.2 amplifications in gastric carcinomas.

Oligonucleotide array comparative genomic hybridization (aCGH) was applied on fifteen gastric cancer (GCA) samples to reveal information of DNA copy number changes at an exon-level resolution. Twelve of the samples represented the intestinal (IGCA) and three the diffuse (DGCA) type of GCA. The samples had previously been assessed for genetic stability by microsatellite analysis and categorized into microsatellite phenotypes according to the type of alterations. As compared to our previous results obtained using cDNA platforms, the oligonucleotide platforms revealed more aberrations per sample (0-45 vs. 0-22). A total of 22 amplifications were detected by the oligonucleotide arrays. Ten of the amplicons had also been detected on the cDNA platform, but five of them spanned only one or a few cDNA clones, thus resembling apparent outliers. Two tumors showed five or more amplifications by oligonucleotide aCGH, suggesting the presence of an amplifier phenotype. The amplifications occurred irrespective of the microsatellite phenotypes. None of the DGCA tumors showed more than one aberration, whereas the IGCA tumors showed several aberrations. The increased resolution of the oligonucleotide arrays enabled the detection of amplicon boundaries at gene level, allowing, e.g., the determination of the 17q12 core amplicon and interstitial losses within the 8p23.1-->p22 and 20q13.2-->q13.1 amplifications. Previously no losses have been reported within amplified regions in GCA. In addition to novel amplified regions, the oligonucleotide array results describe novel targets for amplicons at 8p11 (SFRP1), 11p12 (LRRC4C), and 19q13.2 (CEACAM6).

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.

Approximation errors and model reduction in optical tomography.

Model reduction is often required in optical diffusion tomography (ODT), typically due to limited available computation time or computer memory. In practice, this often means that we are bound to use sparse meshes in the model for the forward problem. Conversely, if we are given more and more accurate measurements, we have to employ increasingly accurate forward problem solvers in order to exploit the information in the measurements. In this paper we apply the approximation error theory to ODT. We show that if the approximation errors are estimated and employed, it is possible to use mesh densities that would be unacceptable with a conventional measurement model.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.