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.

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.

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.

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).

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.

Parinaroyl and pyrenyl phospholipids as probes for the lipid surface layer of human low density lipoproteins.

A simple protocol employing lipid transfer proteins was developed to label human low density lipoprotein (LDL) in a controlled manner with parinaroyl and pyrenyl phosphatidylcholines. In order to study the lipid fluidity in the surface lipid layer of LDL, the temperature-dependence of both polarization (parinaroyl probes) and excimer to monomer (E/M) intensity ratio (pyrenyl probes) were analyzed. A series of pyrenyl phosphatidylcholines containing a pyrenyl fatty acid varying from 6 to 14 carbons in length at the sn-2 position were inserted into LDL to investigate the lateral distribution of different phosphatidylcholines in the lipoprotein surface at 37 degrees C. Both polarization and E/M vs. temperature plots displayed discontinuities in the region of 22-32 degrees C, which coincides with the melting of the neutral lipid core, indicating that the latter induces an ordered to more disordered phase transition in the surface lipid layer. Determination of the E/M intensity ratio as a function of pyrene lipid concentration in LDL showed a linear relationship for the pyrenyl hexanoate and octanoate species, whereas a slope discontinuity was observed for the lipids containing a longer pyrenyl chain. These data suggest that two lipid domains with distinct properties exist in the surface layer and secondly, pyrenyl lipids partition between these domains in a chainlength-dependent manner. This is consistent with measurement of the tryptophan to pyrene energy transfer efficiency vs. pyrenyl lipid concentration, which showed a biphasic relationship for the long-chain pyrenyl lipids. These measurements further indicate that two surface lipid domains correspond to the protein-lipid boundary and the bulk lipid phase, respectively. The fact that relatively small changes in chainlength have a marked influence on the partitioning of pyrenyl lipids between the boundary and the bulk phase suggests also that native phospholipid species may not be randomly distributed in the surface lipid layer of LDL.

Distribution of estrogen receptors in hen oviduct chromatin fractions in the course of DNAase II digestion.

Hen oviduct chromatin was digested with DNAase II and two fractions were isolated: MgCl2-insoluble chromatin and MgCl2-soluble chromatin. The former contained 14 and 50% of the total DNA after a digestion time of 3 and 30 min, respectively. The fraction was characterized in sucrose gradients by a peak sedimenting at 11S. In the course of DNAase digestion this fraction lost most of its estrogen receptors as assayed by [3H]estradiol exchange reaction. The specific radioactivity of chromatin was particularly low in the 11S region. The MgCl2-soluble chromatin contained at most 5.1% of the total DNA. In sucrose gradients the fraction displayed peaks at 4S and 14S. After a 30 min DNAase digestion the specific radioactivity of chromatin in this fraction exceeded that of the MgCl2-insoluble fraction 7.7 fold. Material sedimenting at 14 S and at larger S values was enriched in estrogen receptors. The results suggest that estrogen receptors are unevenly distributed on hen oviduct chromain.

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.

Serum and tissue distribution of benzol[a]pyrene from intravenously injected chylomicrons in rat in vivo.

Rats were injected intravenously with chylomicrons (CM) containing benzo[a]pyrene (B[a]P), a carcinogenic aromatic hydrocarbon. The disappearance of B[a]P paralleled the removal of CM, both having a rapid initial decay and a secondary slow decay. After 5 min, at the end of the rapid phase, blood contained 19% of the total injected B[a]P, with 6% in blood cells and 13% in serum. At 60 min, serum contained 5% and blood cells 6% of the total B[a]P. During the slow phase, further distribution of B[a]P within serum albumin and various lipoproteins occurred, most of the label being in low density and very low density lipoproteins. Highest tissue specific activities of [3H]B[a]P were in the lung, liver and kidney tissues. These results suggest that in the rat, distribution of ingested polycyclic aromatic hydrocarbons in vivo tends to be primarily determined by the catabolism of chylomicrons.

Recovery of piecewise constant coefficients in optical diffusion tomography.

In optical diffusion tomography the reconstruction of the absorbtion and scattering coefficients is conventionally carried out in a pixel basis. The resulting number of unknowns makes the associated inverse problem severely ill-posed. We have recently proposed a new approach in which the goal is to reconstruct boundaries of piecewise constant tissue regions as well as the diffusion and absorption coefficients within these regions. This method assumes that there is a feasible initial guess on the domain boundaries. In this paper we propose an extension to this approach in which the initial estimate for the boundary and coefficient estimation is extracted from a conventional pixel based reconstruction using standard image processing operations. In the computation of the pixel based reconstruction the output least squares problem is augmented with an approximated total variation prior. The performance of the proposed approach is evaluated using simulated frequency domain data. It is shown that since the total variation type approach favors domains with constant coefficients it is well suited for the fixing of the starting point for the actual boundary and coefficient reconstruction method.

The surface lipid layer of human low density lipoprotein probed by dipyrenyl phospholipids.

Properties of the surface lipid-protein layer of human low density lipoprotein (LDL) have been studied with fluorescent phosphatidylcholine analogues containing a pyrenyl fatty acid of variable length at both sn-1 and sn-2 position of the glycerol moiety. Only intramolecular excimer formation takes place at low concentrations, as indicated by the independence of the ratio of excimer to monomer fluorescence intensities (E/M) on the amount of the incorporated dipyrenyl phospholipid. The E/M parameter which depends on the fluidity of the probe's environment were measured for a series of dipyrenyl phospholipids in three systems, i.e. in LDL, LDL-like lipid particles (LDp) and small unilamellar phosphatidylcholine/sphingomyelin/cholesterol vesicles (SUV). The data indicate that the fluidity of the phospholipid acyl chain region decreases in the order: SUV greater than LDp greater than LDL. This suggests that interactions with both the core lipids and the protein moiety (apoB-100) contribute to the rigidity of the surface lipid layer of LDL. Dipyrenyl phospholipids also detect the thermotropic transition of the core lipids of both LDL and LDp, suggesting that this transition influences the fluidity of the surface lipid layer.

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.

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.

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.

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.

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.

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.

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.

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.