Biomedical subjects

T Flohr

Publications and source records attributed to T Flohr.

At least 55 records · Page 3Linked to original sources

PubMed2000

Spiral interpolation algorithm for multislice spiral CT--part I: theory.

This paper presents the adaptive axial interpolator (AAI), a novel spiral interpolation approach for multislice spiral computed tomography (CT) implemented in a clinical multislice CT scanner, the SOMATOM Volume Zoom (Siemens Medical Systems, Forchheim, Germany). The method works on parallel-beam data generated from the acquired fan-beam data by azimuthal rebinning. Spiral interpolation is performed by distance-dependent weighting; i.e., for each ray, its distance to the image plane is evaluated and serves as an argument to a freely selectable weighting function, resulting in a weight factor. A normalization step is applied to the weight factors to ensure that the sum of all corresponding weights (i.e., the weights applied to rays that contribute to the same ray in the interpolated sinogram) is 1. By selection of appropriate weighting functions and suitable adjustment of the tube current, it is possible to keep the slice sensitivity profiles (SSP) as well as the pixel noise constant for all pitch values in the relevant range. Also, a large range of slice-thickness can be reconstructed from a given collimation. The method is, thus, very versatile. Further advantages are that it uses the entire applied dose for imaging and allows for efficient implementation using a table lookup approach.

Algorithms↗

PubMed2000

Spiral interpolation algorithms for multislice spiral CT--part II: measurement and evaluation of slice sensitivity profiles and noise at a clinical multislice system.

The recently introduced multislice data acquisition for computed tomography (CT) is based on multirow detector design, increased rotation speed, and advanced z-interpolation and z-filtering algorithms. We evaluated slice sensitivity profiles (SSPs) and noise of a clinical multislice spiral CT (MSCT) scanner with M = 4 simultaneously acquired slices and adaptive axial interpolator (AAI) reconstruction software. SSPs were measured with a small gold disk of 50 microm thickness and 2-mm diameter located at the center of rotation (COR) and 100 mm off center. The standard deviation of CT values within a 20-cm water phantom was used as a measure of image noise. With a detector slice collimation of S = 1.0 mm, we varied spiral pitch p from 0.25 to 2.0 in steps of 0.025. Nominal reconstructed slice thicknesses were 1.25, 1.5, and 2.0 mm. For all possible pitch values, we found the full-width at half maximum (FWHM) of the respective sensitivity profile at the COR equivalent to the selected nominal slice thickness. The profiles at 100 mm off center are broadened less than 7 % on the average compared with the FWHM at the COR. In addition, variation of the full-width at tenth maximum (FWTM) at the COR was below 10% for p < or = 1.75. Within this range, image noise varied less than 10% with respect to the mean noise level. The slight increase in measured slice-width above p = 1.75 for nominal slice-widths of 1.25 and 1.50 mm is accompanied by a decrease of noise according to the inverse square root relationship. The MSCT system that we scrutinized provides reconstructed slice-widths and image noise, which can be regarded as constant within a wide range of table speeds. With respect to this, MSCT is superior to single-slice spiral CT. These facts can be made use of when defining and optimizing clinical protocols: the spiral pitch can be selected almost freely, and scan protocols can follow the diagnostic requirements without technical restrictions. In summary, MSCT offers constant image quality while scan times are reduced drastically. Volume scans with three-dimensional (3-D) isotropic resolution are routinely feasible for complete anatomical regions.

Algorithms↗

PubMed2000

Single-slice rebinning reconstruction in spiral cone-beam computed tomography.

At the advent of multislice computed tomography ICT) a variety of approximate cone-beam algorithms have been proposed suited for reconstruction of small cone-angle CT data in a spiral mode of operation. The goal of this study is to identify a practical and efficient approximate cone-beam method, extend its potential for medical use, and demonstrate its performance at medium cone-angles required for area detector CT. We will investigate two different approximate single-slice rebinning algorithms for cone-beam CT: the multirow Fourier reconstruction (MFR) and an extension of the advanced single-slice rebinning method (ASSR), which combines the idea of ASSR with a z-filtering approach. Thus, both algorithms, MFR and ASSR, are formulated in the framework of z-filtering using optimized spiral interpolation algorithms. In each view, X-ray samples to be used for reconstruction are identified, which describe an approximation to a virtual reconstruction plane. The performance of approximate reconstruction should improve as the virtual reconstruction plane better fits the spiral focus path. The image quality of the respective reconstruction will be assessed with respect to image artifacts, spatial resolution, contrast resolution, and image noise. It turns out that the ASSR method using tilted reconstruction planes is a practical and efficient algorithm, providing image quality comparable to that of a single-row scanning system even with a 46-row detector at a table feed of 64 mm. Both algorithms tolerate any table feed below the maximum value associated to the detector height. Due to the z-filter approach, all detector data sampled can be used for image reconstruction.

Algorithms↗

PubMed2000

Efficient correction for CT image artifacts caused by objects extending outside the scan field of view.

The purpose of this paper is to develop a method of eliminating CT image artifacts generated by objects extending outside the scan field of view, such as obese or inadequately positioned patients. CT projection data are measured only within the scan field of view and thus are abruptly discontinuous at the projection boundaries if the scanned object extends outside the scan field of view. This data discontinuity causes an artifact that consists of a bright peripheral band that obscures objects near the boundary of the scan field of view. An adaptive mathematical extrapolation scheme with low computational expense was applied to reduce the data discontinuity prior to convolution in a filtered backprojection reconstruction. Despite extended projection length, the convolution length was not increased and thus the reconstruction time was not affected. Raw projection data from ten patients whose bodies extended beyond the scan field of view were reconstructed using a conventional method and our extended reconstruction method. Limitations of the algorithm are investigated and extensions for further improvement are discussed. The images reconstructed by conventional filtered backprojection demonstrated peripheral bright-band artifacts near the boundary of the scan field of view. Images reconstructed with our technique were free of such artifacts and clearly showed the anatomy at the periphery of the scan field of view with correct attenuation values. We conclude that bright-band artifacts generated by obese patients whose bodies extend beyond the scan field of view were eliminated with our reconstruction method, which reduces boundary data discontinuity. The algorithm can be generalized to objects with inhomogeneous peripheral density and to true "Region of Interest Reconstruction" from truncated projections.

Algorithms↗

PubMed2000

Cardiac imaging by means of electrocardiographically gated multisection spiral CT: initial experience.

The authors introduce a method for cardiac investigations by using electrocardiographically gated spiral scanning with a four-section computed tomographic system. Three-dimensional images were reconstructed by means of a 250-msec temporal resolution and continuous volume coverage by using a dedicated multisection cardiac volume reconstruction algorithm. Motion-free thin-section volume images were acquired with thin sections and overlapping image increments within a single breath hold. Data segment shifts in time allowed for multiphase imaging.

Calcinosis↗

PubMed1999

Detection of mutations in the DNA polymerase delta gene of human sporadic colorectal cancers and colon cancer cell lines.

To test the hypothesis whether DNA polymerases acquire mutator properties during tumor development (mutator hypothesis), we examined DNA polymerase delta mRNA in 6 colon cancer cell lines (DLD-1, HCT116, SW48, HT29, SW480 and SW620) and 7 sporadic human colorectal cancers. For analysis we used amplification of cDNA by polymerase chain reaction, single-strand conformation polymorphism and sequencing techniques. In 5 of the cell lines, 9 mutations leading to changes of the amino acid sequence of DNA polymerase delta were detected. Most mutations were found in the cell lines DLD-1, HCT116 and SW48 for which defects in mismatch repair genes had been identified previously. In the majority of cases, wild type and mutated sequences were present. In 2 cell lines (HCT116 and SW48), a single-nucleotide deletion occurred at the same position. This resulted in a premature termination codon by which the DNA interaction domain of the enzyme was eliminated. Furthermore, sequence deviations were found in the tumor tissues of 4 colon cancer patients. Wild-type and altered sequences were present simultaneously. The deviations included missense mutations (2 cases) and silent mutations (2 cases). The missense mutations and one of the silent mutations were found in normal mucosa as well. In addition, the mutation clustered region of a tumor suppressor gene, often found to be defective in colon cancer, the adenomatous polyposis coli (APC) gene, was investigated in surgical specimens and cell lines. One carcinoma and 2 cell lines exhibited amino acid changes in both the DNA polymerase delta gene and in the mutation clustered region of the APC gene. Since most of the mutations detected in the DNA polymerase delta mRNA are likely to alter the structure of the protein, the enzyme is expected to be functionally impaired. In particular, copying fidelity might be decreased, thus contributing to the high mutation rate observed in colorectal cancer.

Aged↗

PubMed1999

[The technical bases and uses of multi-slice CT].

In this review the technical principles and applications of multi-slice CT are discussed. Multi-slice CT systems allow simultaneous acquisition of up to 4 slices by using multi-row detector systems. Intuitive geometrical arguments are used to establish the limitation to a maximum of 4 slices which is kept by all currently existing multi-slice CT systems. Two different construction principles of the detector are discussed, the "Fixed Array" detector and the "Adaptive Array" detector. The extension of conventional 360 LI and 180 LI spiral interpolation techniques to multi-slice spiral CT is explained as well as a new generalized multi-slice spiral weighting concept, the so-called "Adaptive Axial Interpolation". Several techniques to improve multi-slice spiral image quality are discussed. Finally, some examples for clinical applications are given, and the principle of ECG triggered and ECG gated cardiac examinations with optimized temporal resolution is presented. Multi-slice CT systems are a milestone with respect to increased volume coverage, shorter scan times, improved axial (longitudinal) resolution and better use of the X-ray tube output. Additionally, new clinical applications are possible such as Cardiac CT.

Electrocardiography↗

PubMed1999

Efficient object scatter correction algorithm for third and fourth generation CT scanners.

X-ray photons which are scattered inside the object slice and reach the detector array increase the detected signal and produce image artifacts as "cupping" effects in large objects and dark bands between regions of high attenuation. The artifact amplitudes increase with scanned volume or slice width. Object scatter can be reduced in third generation computed tomography (CT) geometry by collimating the detector elements. However, a correction can still improve image quality. For fourth generation CT geometry, only poor anti-scatter collimation is possible and a numeric correction is necessary. This paper presents a correction algorithm which can be parameterized for third and fourth generation CT geometry. The method requires low computational effort and allows flexible application to different body regions by simple parameter adjustments. The object scatter intensity which is subtracted from the measured signal is calculated with convolution of the weighted and windowed projection data with a spatially invariant "scatter convolution function". The scatter convolution function is approximated for the desired scanner geometry from pencil beam simulations and measurements using coherent and incoherent differential scatter cross section data. Several examples of phantom and medical objects scanned with third and fourth generation CT systems are discussed. In third generation scanners, scatter artifacts are effectively corrected. For fourth generation geometry with poor anti-scatter collimation, object scatter artifacts are strongly reduced.

Algorithms↗

PubMed1999

A mutation detected in DNA polymerase delta cDNA from Novikoff hepatoma cells correlates with abnormal catalytic properties of the enzyme.

Tumor development is characterized by accumulation of mutations. Such mutations, if induced by carcinogens in DNA polymerase genes, would confer mutator properties on the DNA replication machinery, even at later stages of development. To investigate whether DNA polymerase delta can be mutated, we compared these enzymes from highly malignant Novikoff hepatoma cells and from regenerating normal rat liver. We sequenced the DNA polymerase delta cDNA from both sources and investigated the physico-chemical properties, inhibition characteristics, and copying fidelity of the purified enzymes. The cDNA sequences examined included the entire reading frame encoding the catalytic subunit (subunit I) of DNA polymerase delta. First-strand cDNAs were prepared from total RNA of both normal rat liver and Novikoff cells by reverse transcription, and the polymerase delta sequences were amplified by the polymerase chain reaction. cDNA (3325 bp) were sequenced. A single heterozygous mutation (CGG --> CAG) has been detected in nucleotide position 1948 (codon 648) of the polymerase delta gene from Novikoff cells, resulting in an Arg to Gln change. Position 648 lies just proximal to the conserved region VI, which is part of the "fingers" subdomain of alpha-like polymerases. This subdomain is involved in dNTP binding. Upon comparison of biochemical characteristics of partially purified DNA polymerase delta from both Novikoff cells and rat liver, the following properties of the enzyme from Novikoff cells were found to be altered: (i) K(50) values for nucleotide analogs (e.g. butylphenyl-dGTP) were lower, (ii) sensitivity to various antineoplastic drugs (e.g. doxorubicin, topotecan and distamycin) was enhanced, (iii) copying fidelity was decreased when primer templates containing O(6)-methylguanine were used, and (iv) the activity of DNA polymerase delta from Novikoff tumor cells was less stimulated by lactate dehydrogenase than the enzyme from normal cells. The altered biochemical characteristics of DNA polymerase delta from Novikoff cells suggest mutator properties. We conclude that the point mutation detected in the cDNA might be causally related to the observed changes in inhibition characteristics and copying fidelity.

Amino Acid Sequence↗

PubMed1999

Subsecond multi-slice computed tomography: basics and applications.

The recent advent of multislice-scanning is the first real quantum leap in computed tomography since the introduction of spiral CT in the early 90s. We discuss basic theoretical considerations important for the design of multislice scanners. Then, specific issues, like the design of the detector and spiral interpolation schemes are addressed briefly for the SOMATOM PLUS 4 Volume Zoom. The theoretical concepts are validated with phantom measurements. We finally show the large potential of the new technology for clinical applications. The concurrent acquisition of multiple slices results in a dramatic reduction of scan time for a given scan technique. This allows scanning volumes previously inaccessible. Similarly, given volumes can be scanned at narrower collimation, i.e. higher axial resolution in a given time. From data acquired at narrow collimation, both high-resolution studies and standard images can be reconstructed in the so-called Combi-Mode. This on the one hand reduces dose exposure to the patient because repeated scanning of a patient is no longer required. On the other hand, standard reconstructions benefit from narrow collimation as Partial Volume Artifacts are drastically suppressed. The rotational speed of 0.5 s of the SOMATOM PLUS 4 Volume Zoom furthermore opens up a whole range of new applications in cardiac CT. For the first time, virtually motion-free images can be acquired even for large volumes in a single breathhold by the combination of fast rotation and ECG triggering, respectively gating. We explain the underlying concepts and present initial results. The paper concludes with a brief discussion of the impact of the new technique on image display and postprocessing.

Artifacts↗

PubMed1999

Binding of monocytes from normolipidemic hyperglycemic patients with type 1 diabetes to endothelial cells is increased in vitro.

Increased endothelial binding and emigration of monocytes play a dominant role in the pathogenesis of atherosclerosis in diabetes mellitus. Previous studies revealed that hyperlipidemia correlates with monocyte binding in vitro. The aim of this study was to characterize the monocyte-endothelial interaction of leucocytes of hyperglycemic patients with type 1 diabetes but lacking hyperlipidemia. We isolated monocytes from healthy controls and normolipidemic type 1 diabetes patients with elevated levels of HbA1c and quantified monocyte binding by an immunoilluminometric cell adhesion assay. Purity of isolated monocytes was at least 98%. Endothelial binding of monocytes from patients with type 1 diabetes was found to be significantly increased compared to controls (19.2 +/- 3.9% vs. 14.9 +/- 3.5%). This difference of monocyte binding remained unchanged if the endothelial cells were stimulated with 27.7 mmol/l glucose for seven days prior to adhesion studies (31.5 +/- 4.9% in diabetes patients vs. 25.8 +/- 4.1% in controls) whereby monocyte binding markedly increased under these hyperglycemic conditions. Furthermore, an increased CD11b expression could be demonstrated on monocytes of normolipidemic hyperglycemic type 1 diabetes patients. Thus, we suggest that hyperglycemia per se may contribute to increased monocyte binding to endothelial cells by promoting leucocyte integrin expression. Recently performed studies of our group strengthen the hypothesis that this monocyte activation is mediated by stimulation of the beta-isoform of proteinkinase C.

Adult↗

PubMed1998

An efficient Fourier method for 3-D radon inversion in exact cone-beam CT reconstruction.

The radial derivative of the three-dimensional (3-D) radon transform of an object is an important intermediate result in many analytically exact cone-beam reconstruction algorithms. We briefly review Grangeat's approach for calculating radon derivative data from cone-beam projections and then present a new, efficient method for 3-D radon inversion, i.e., reconstruction of the image from the radial derivative of the 3-D radon transform, called direct Fourier inversion (DFI). The method is based directly on the 3-D Fourier slice theorem. From the 3-D radon derivative data, which is assumed to be sampled on a spherical grid, the 3-D Fourier transform of the object is calculated by performing fast Fourier transforms (FFT's) along radial lines in the radon space. Then, an interpolation is performed from the spherical to a Cartesian grid using a 3-D gridding step in the frequency domain. Finally, this 3-D Fourier transform is transformed back to the spatial domain via 3-D inverse FFT. The algorithm is computationally efficient with complexity in the order of N3 logN. We have done reconstructions of simulated 3-D radon derivative data assuming sampling conditions and image quality requirements similar to those in medical computed tomography (CT).

Algorithms↗

PubMed1997

A mouse cytomegalovirus glycoprotein retains MHC class I complexes in the ERGIC/cis-Golgi compartments.

The principle by which mouse cytomegalovirus blocks antigen presentation in the MHC class I pathway was investigated. The responsible gene m152, encoding a type I transmembrane glycoprotein of 40 kDa, is a member of a gene family located in the right-hand terminal region of the 230 kb virus genome. Expression of m152 in murine and human cells arrested the export of mouse class I complexes from the ER-Golgi intermediate compartment/cis-Golgi compartment and inhibited lysis by cytotoxic T cells. The plasma membrane transport of human MHC class I molecules was not affected. The deletion of the cytoplasmic tail of gp40 did not lift its effect on class I molecule export, indicating that this protein differs in its functions from known immunosubversive viral gene products and represents a novel principle by which a herpesvirus shuts off MHC class I function.

3T3 Cells↗

PubMed1997

A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter.

Human cytomegalovirus inhibits peptide import into the endoplasmic reticulum (ER) by the MHC-encoded TAP peptide transporter. We identified the open reading frame US6 to mediate this effect. Expression of the 21 kDa US6 glycoprotein in human cytomegalovirus-infected cells correlates with the inhibition of peptide transport during infection. The subcellular localization of US6 is ER restricted and is identical with TAP. US6 protein is found in complexes with TAP1/2, MHC class I heavy chain, beta2-microglobulin, calnexin, calreticulin, and tapasin. TAP inhibition, however, is independent of the presence of class I heavy chain and tapasin. The results establish a new mechanism for viral immune escape and a novel role for ER-resident proteins to regulate TAP via its luminal face.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Human cytomegalovirus inhibits peptide translocation into the endoplasmic reticulum for MHC class I assembly.

Human cytomegalovirus (HCMV) genes expressed in the early phase of infection mediate the destabilization of nascent major histocompatibility complex (MHC) class I molecules in infected cells and thus prevent antigen presentation to CD8+ T lymphocytes. We report that HCMV genes interfere with the MHC class I pathway of antigen presentation by at least two mechanisms. Firstly, permissive infection of fibroblasts is characterized by a continuous decline in the capacity to translocate peptides from the cytosol into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). Inactivation of peptide transport is operative despite augmented TAP expression during HCMV infection. Secondly, TAP molecules fail to associate with MHC class I heavy chains indicating that HCMV early gene expression also interferes with MHC class I maturation. A temperature-sensitive mutant of HCMV, ts9, which lacks 15 kb of DNA encoding the genes US1-US15 of HCMV, had lost the capacity to interfere with MHC class I assembly and to inhibit the peptide translocation function of TAP. One of the genes deleted in ts9, US11, which was reported to downregulate the expression of MHC class I molecules, does not affect peptide transport by TAP. Therefore, we conclude that HCMV encodes at least two early gene functions that interfere with the MHC class I antigen presentation pathway.

Animals↗

PubMed1995

Role of accessory cells in cytokine production by T cells in chronic B-cell lymphocytic leukemia.

We investigated the production of cytokines by highly purified T helper cells from B-cell chronic lymphocytic leukemia (B-CLL) patients stimulated by different activation pathways, and we studied the influence of various accessory cell populations on the pattern of the secretion of cytokines, including interleukin (IL)-2, IL-4, interferon-gamma (IFN-gamma), and IL-10. Neither a qualitative nor a quantitative difference in cytokine production and proliferative capacity was observed in CLL-derived purified T cells compared with normal individuals, when T cells were stimulated by different pathways, including CD3, CD2, and costimulation with CD28. Addition of autologous accessory cells (aAC), however, dramatically influenced the cytokine pattern of normal versus B-CLL-derived T cells. CLL cells as aAC caused a marked increase of IL-2, whereas IFN-gamma was only slightly induced and IL-4 was not influenced. In contrast, in normal individuals addition of aAC, which predominantly consisted of monocytes, resulted in a significant increase of IFN-gamma and a reduction of IL-4 secretion. IL-2 production was inhibited by higher concentrations of aAC. The increased stimulation of IL-2 production by CLL cells was not specific to the leukemic cell population, as purified B cells from normal individuals had the same effect. On the other hand, purified monocytes from CLL patients and controls both induced IFN-gamma production and inhibited IL-4 secretion. After antigen-specific stimulation with tetanus toxoid, cytokine secretion was influenced by the type of aAC in a similar pattern. We conclude that T helper cells derived from patients with B-CLL are intrinsically normal and that the predominance of B cells as accessory cells in CLL significantly alters the immune function of T helper cells in vitro.

Antigen-Presenting Cells↗

PubMed1994

IFP 35 is an interferon-induced leucine zipper protein that undergoes interferon-regulated cellular redistribution.

We have isolated a new human cDNA, named IFP 35, whose expression is regulated by interferons (IFN). Induction of IFP 35 mRNA in HeLa cells by IFN is due, at least in part, to increased transcription. In response to IFN treatment, the expression of IFP 35 mRNA is seen in a wide range of different cell types, including fibroblasts, macrophages, and epithelial cells. The cDNA sequence encodes a 282-amino acid protein with a deduced molecular mass of 31,130 Da. In vitro translation of mRNA obtained by both in vitro transcription and hybrid selection resulted in the synthesis of a 35-kDa protein. Antisera raised against IFP 35 recognized a protein with an apparent molecular mass of 35 kDa in HeLa cells. Amino acid sequence analysis revealed a leucine zipper motif in an alpha-helical configuration at the extreme amino terminus of IFP 35. Notable IFP 35 is a unique novel leucine zipper protein in that it lacks a basic domain critical for DNA binding. IFP 35 can specifically form homodimers in vitro. Western blot analysis of fractionated cell extracts indicates increased nuclear localization following IFN treatment.

Amino Acid Sequence↗

PubMed1992

An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase.

Interferon gamma induces expression of a protein termed IFP 53 according to its molecular weight of 53 kDa. IFP 53 shows significant sequence homology to rabbit peptide chain release factor as well as to bovine tryptophanyl-tRNA synthetase. IFP 53 has been shown to possess release factor activity for the UGA stop codon. We demonstrate here, by using a recombinant IFP 53 fusion protein, that IFP 53 tryptophanylates tRNA. These data indicate that IFP 53 is a protein with two activities: peptide chain termination and aminoacylation.

Acylation↗