Biomedical subjects

Bernhard Schmidt

Publications and source records attributed to Bernhard Schmidt.

33 records · Page 2Linked to original sources

PubMed2004

Techniques and applications of automatic tube current modulation for CT.

Introduction of slip-ring technology with subsequent development of single- and multi-detector row helical computed tomographic (CT) scanners have expanded the applications of CT, leading to a substantial increase in the number of CT examinations being performed. Owing to concerns about the resultant increase in associated radiation dose, many technical innovations have been introduced. One such innovation is automatic tube current modulation. The purpose of automatic tube current modulation is to maintain constant image quality regardless of patient attenuation characteristics, thus allowing radiation dose to patients to be reduced. This review discusses the principles, clinical use, and limitations of different automatic tube current modulation techniques.

Equipment Design↗

PubMed2004

Radiation dose and image quality in pediatric CT: effect of technical factors and phantom size and shape.

PURPOSE: To evaluate effects of varying tube current and voltage on radiation dose, image noise, and image contrast with different phantom sizes and shapes. MATERIALS AND METHODS: Four round lucite phantoms with 8-32-cm diameters were scanned with multi-detector row computed tomography (CT) and 80-120 kVp. Radiation dose was based on CT dose index, image noise, and iodine contrast and measured with constant and variable tube currents that were age appropriate for each tube voltage. Radiation dose and image noise and contrast were compared in round and oval 24-cm phantoms. For various combinations of technical factors and phantom sizes and shapes, percentage differences were calculated for radiation dose and image noise and contrast. Associations between tube voltage and radiation dose, image noise, and image contrast in round and oval phantoms were determined by fitting second-degree polynomials to data. Differences in radiation dose and image noise and contrast, which were attributable to differences in tube voltage, were tested with paired t tests. RESULTS: With 165-mAs tube current, radiation doses with 140- and 80-kVp tube voltages were 103% ([41.9 mGy - 20.6 mGy]/20.6 mGy) and 58% ([10.2 mGy - 4.2 mGy]/10.1 mGy) higher in the 8-cm phantom than in the 32-cm phantom. When tube current was adapted for phantom size, radiation dose at 80 kVp in the 8-cm phantom was reduced by 82% ([10.1 mGy - 1.8 mGy]/10.1 mGy). In the 8-cm phantom, tube voltage was decreased from 120 to 80 kVp and tube current remained at 165 mAs, resulting in a 68% noise increase ([3.1 HU - 1.8 HU]/1.8 HU). With variable tube current, 80-kVp tube voltage in the 8-cm phantom led to a 138% noise increase ([7.3 HU - 3.1 HU]/3.1 HU). With reduced tube voltage, image contrast increased. In the 8-cm phantom, with a constant 165-mAs tube current and a decrease in tube voltage from 120 to 80 kVp, there was a 35% ([333 HU - 217 HU]/333 HU) increase in contrast. No difference was noted in radiation dose or noise between round and oval phantoms (P = .604 and P = .06, respectively), but a small statistically significant difference (1%) in contrast attenuation was demonstrated (P = .025). CONCLUSION: Reduced tube voltage for pediatric contrast material-enhanced CT reduces radiation dose and maintains image contrast. Image noise increases, but the effect is minimal in smaller phantoms. An additional reduction in tube current further reduces radiation dose.

Phantoms, Imaging↗

PubMed2004

Group II rhabdomyosarcoma and rhabdomyosarcomalike tumors: is radiotherapy necessary?

PURPOSE: In the prospective Cooperative Soft Tissue Sarcoma Study Group (CWS) 81, 86, 91, and 96 trials, radiotherapy was omitted in some patients with rhabdomyosarcoma and rhabdomyosarcoma-like tumors within Intergroup Rhabdomyosarcoma Study (IRS) group II. This analysis evaluates whether subgroups can be defined for which radiotherapy is not necessary. PATIENTS AND METHODS: Two hundred three patients who were registered between January 1981 and December 1998 were eligible for evaluation. Radiotherapy was given depending on tumor location, histology, and whether a secondary complete resection could be performed. The recommended radiation doses ranged from 32 to 54 Gy. RESULTS: One hundred ten patients did receive and 93 patients did not receive radiotherapy. The calculated local control after 5 years was 83% with and 65% without radiotherapy (P <.004). Event-free survival (EFS) at 5 years was 76% and 58%, respectively (P <.005). Overall survival (OS) at 5 years was 84% and 77% (P = not significant). The differences in local control were significant for the subgroups of irradiated patients with favorable histology, favorable site, and initial tumor size of less than 5 cm. A trend for improved local control with irradiation was observed for patients with unfavorable site, unfavorable histology, and large primary tumors. EFS was significantly improved for irradiated patients who had unfavorable histology, both favorable and unfavorable tumor sites, and small initial tumors. OS was significantly improved for patients with unfavorable histology through radiation. CONCLUSION: Local control and EFS in group II patients are improved with radiotherapy. No subgroup could be defined for which the omission of radiotherapy produced outcome equivalent to that of patients who were irradiated.

Adolescent↗

PubMed2003

The human SUMF1 gene, required for posttranslational sulfatase modification, defines a new gene family which is conserved from pro- to eukaryotes.

Recently, the human C(alpha)-formylglycine (FGly)-generating enzyme (FGE), whose deficiency causes the autosomal-recessively transmitted lysosomal storage disease multiple sulfatase deficiency (MSD), has been identified. In sulfatases, FGE posttranslationally converts a cysteine residue to FGly, which is part of the catalytic site and is essential for sulfatase activity. FGE is encoded by the sulfatase modifying factor 1 (SUMF1) gene, which defines a new gene family comprising orthologs from prokaryotes to higher eukaryotes. The genomes of E. coli, S. cerevisiae and C. elegans lack SUMF1, indicating a phylogenetic gap and the existence of an alternative FGly-generating system. The genomes of vertebrates including mouse, man and pufferfish contain a sulfatase modifying factor 2 (SUMF2) gene encoding an FGE paralog of unknown function. SUMF2 evolved from a single exon SUMF1 gene as found in diptera prior to divergent intron acquisition. In several prokaryotic genomes, the SUMF1 gene is cotranscribed with genes encoding sulfatases which require FGly modification. The FGE protein contains a single domain that is made up of three highly conserved subdomains spaced by nonconserved sequences of variable lengths. The similarity among the eukaryotic FGE orthologs varies between 72% and 100% for the three subdomains and is highest for the C-terminal subdomain, which is a hotspot for mutations in MSD patients.

Alanine↗

PubMed2003

Targeting myeloperoxidase to azurophilic granules in HL-60 cells.

Myeloperoxidase (MPO) is a cationic protein and one of the major constituents of azurophilic granules in neutrophils. Here, we examined whether intracellular transport of MPO and serglycin, a chondroitin sulfate (CS)-bearing proteoglycan, is correlated. First, we examined binding of MPO to CS-Sepharose and measured an ionic interaction, which was disrupted by 200-400 mM NaCl. Next, HL-60 promyelocytes were activated with a phorbol ester, which induced an almost complete rerouting of serglycin from the granular to the secretory pathway, concomitant with a similar effect on MPO transport and secretion. We then used the membrane-permeable cross-linker dithiobis(succininmidylpropionate; DSP) after labeling HL-60 cells with [35S]methionine and [35S]cysteine for 19 h. Immunoprecipitation of MPO revealed its cross-linking to high molecular material having the appearance of a proteoglycan in sodium dodecyl sulfate-polyacrylamide gels. This assumption was confirmed by labeling HL-60 cells with [35S]sulfate for 10 min followed by DSP cross-linking and immunoprecipitation. From three granular enzymes immunoprecipitated, only the cationic MPO was cross-linked to [35S]sulfate-labeled serglycin in appreciable quantities, whereas cathepsin D or beta-N-acetylhexosaminidase was not. Thus, intracellular transport of MPO appears to be linked to that of serglycin. Extracts from high buoyant density organelles from human placenta containing MPO activity were subjected to CS-affinity chromatography. Proteins binding to CS were identified by mass spectrometry as MPO, lactoferrin, cathepsin G, and azurocidin/cationic antimicrobial protein of molecular weight 37 kDa, suggesting that serglycin may be a general transport vehicle for the cationic granular proteins of neutrophils.

Chondroitin Sulfates↗

PubMed2003

Multiple sulfatase deficiency is caused by mutations in the gene encoding the human C(alpha)-formylglycine generating enzyme.

C(alpha)-formylglycine (FGly) is the catalytic residue in the active site of eukaryotic sulfatases. It is posttranslationally generated from a cysteine in the endoplasmic reticulum. The genetic defect of FGly formation causes multiple sulfatase deficiency (MSD), a lysosomal storage disorder. We purified the FGly generating enzyme (FGE) and identified its gene and nine mutations in seven MSD patients. In patient fibroblasts, the activity of sulfatases is partially restored by transduction of FGE encoding cDNA, but not by cDNA carrying an MSD mutation. The gene encoding FGE is highly conserved among pro- and eukaryotes and has a paralog of unknown function in vertebrates. FGE is localized in the endoplasmic reticulum and is predicted to have a tripartite domain structure.

Alanine↗

PubMed2003

Identification of formylglycine in sulfatases by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

C(alpha)-Formylglycine, the catalytic amino acid residue in the active site of sulfatases, is generated by post-translational modification of a cysteine or serine residue. We describe a highly sensitive procedure for the detection of C(alpha)-formylglycine-containing peptides in tryptic digests of sulfatase proteins. The protocol is based on the formation of hydrazone derivatives of C(alpha)-formylglycine-containing peptides when using dinitrophenylhydrazine as a matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). The hydrazone derivatives desorb and ionize with high efficiency and can be detected in the sub-femtomole range. The presence of C(alpha)-formylglycine is indicated by a mass increment of 180.13 u, corresponding to the hydrazone moiety, and also by a unique C-terminal fragment ion, characteristic of sulfatases, that becomes prominent in MALDI post-source decay mass spectra of the hydrazone derivatives.

Alanine↗

PubMed2003

Advances in cardiac imaging with 16-section CT systems.

RATIONALE AND OBJECTIVES: The authors present advances in electrocardiographically (ECG) gated cardiac spiral scanning with recently introduced 16-section computed tomographic (CT) equipment. MATERIALS AND METHODS: The authors discuss the technical principles of ECG-gated cardiac scanning. They give an overview on system properties and on the detector design. They describe ECG-gated scan- and image-reconstruction techniques and ECG-controlled dose modulation ("ECG pulsing") for a reduction of the patient dose. They discuss key parameters for image quality and present simulation and phantom studies and they give preliminary values for the patient dose. RESULTS: An extension of the adaptive cardiac volume reconstruction for ECG-gated spiral CT provides adequate image quality for up to 16 sections. With the smallest reconstructed section width (about 0.83 mm) and overlapping image reconstruction, cylindrical holes 0.6-0.7 mm in diameter can be resolved in a transverse resolution phantom independent of the heart rate. For coronary CT angiography, the influence of transverse resolution is most pronounced for coronary segments that are only slightly tilted relative to the scan plane. In this case, visualization of stents and plaques is considerably improved with 1.0-mm or smaller section width. For 0.42-second gantry rotation time, temporal resolution reaches its optimum (105 msec) at a heart rate of 81 beats per minute. Effective patient dose for the standard protocols recommended by the manufacturer ranges from 0.45 mSv (male) for ECG-triggered calcium scoring to 7.1 mSv (male) for high-resolution ECG-gated coronary CT angiography. With ECG pulsing, the dose is reduced by 30%-50% depending on the patient's heart rate. CONCLUSION: Clinical experience will be needed to evaluate fully the potential of 16-section technology for cardiac imaging.

Artifacts↗

PubMed2003

[Advanced method for calculating the scatter signal contribution in CT detectors by the Monte Carlo method].

Multislice spiral CT scanners allow to acquire multiple slices simultaneously. With increasing numbers of slices, not only the total extent of slice collimation increases, but also the contribution of scatter radiation to the detector signal. A fast method for calculating the scatter signal would offer the possibility to correct the measured detector signal. Monte Carlo methods allow to simulate the paths of photons through a 3D volume, both in a patient- and scanner-specific fashion. If a scatter photon leaves the volume, its path can be followed and its interaction with an element of the detector be checked. This conventional way of calculating the scatter signal is time-consuming. In order to reduce the calculation time, a more efficient method was developed (Method of Weights). Every time an interaction occurs inside of the 3D volume, the probability of a detector hit due to photon scattering is calculated for each detector channel. The respective value is added to the scatter signal per detector with the corresponding weight. Simulated values of scatter-to-primary-signal ratios were confirmed by data available in the literature. Both the conventional and fast methods for the calculation of scatter signals yielded identical values within the range of statistical accuracy. Assuming the same computing time, the standard deviation for the conventional method was 5 times higher than for the fast one. The presented method allows to significantly reduce the computation time. It may therefore provide a basis for "real time" methods to correct for the scatter signal, especially in case of increasing numbers of slices.

Humans↗

PubMed2003

Adaptive noninvasive assessment of intracranial pressure and cerebral autoregulation.

BACKGROUND AND PURPOSE: A mathematical model has previously been introduced to estimate noninvasively intracranial pressure (nICP). In the present multicenter study, we investigated the ability of model to adapt to the state of cerebral autoregulation (SCA). This modification was intended to improve the quality of nICP estimation and noninvasive assessment of pressure reactivity of the cerebrovascular system. METHODS: We studied 145 patients after severe head injuries or stroke. All patients had direct ICP, arterial blood pressure (ABP), and transcranial Doppler middle cerebral artery blood flow velocity (FV) monitored. The SCA was assessed by moving correlation (Mx index) of cerebral perfusion pressure (CPP=ABP-ICP) and cerebral blood flow velocity and correlation of ABP and ICP (PRx index). nICP was calculated from ABP and FV waveforms. When nICP was used instead of ICP, the SCA was continuously estimated, and the model was dynamically adapted to the SCA. RESULTS: High and moderate correlations between invasively (Mx, PRx) and noninvasively (nMx, nPRx) estimated autoregulation indexes were observed (Mx: R=0.90, P<0.001; PRx: R=0.62, P<0.001). Values of Mx and nMx indicated contradictory SCA in 4 of 167 evaluated recordings; values of PRx and nPRx were contradictory in 27 recordings. When the model was adapted to the SCA, the mean error of ICP estimation decreased significantly (P<0.005). CONCLUSIONS: Continuous adaptation of the model to SCA improves the accuracy of noninvasive estimation of ICP and ICP dynamics. The same model provides a noninvasive and continuous assessment of SCA.

Adolescent↗

PubMed2002

Locating the anomalous scatterer substructures in halide and sulfur phasing.

Improved data quality now makes it feasible to exploit the weak anomalous signal derived only from the sulfurs inherent to the protein or in particular from halide ions incorporated by soaking. The latter technique requires the location of a high number of partially occupied halide sites. This number appears to be roughly proportional to the exposed protein surface. This paper explores the application of dual-space ab initio methods as implemented in the program SHELXD to the location of substructures of sulfur in SAD experiments, bromide in SAD and MAD experiments and iodide using SAD and SIRAS to determine the anomalous-atom substructure. Sets of atoms consistent with the Patterson function were generated as a starting point for the dual-space recycling procedure in SHELXD. The substructure is then expanded to the full structure by maximum-likelihood phasing with SHARP and density modification with the program DM. Success in the location of the substructures and subsequent phasing depends critically on the quality of the data and on the extent of the anomalous signal. This varies with each crystal and soak, but for the same crystal the significance of the anomalous signal was found to be highly sensitive to the redundancy of the intensity measurements, which in some cases made all the difference. This is illustrated by the determination of the previously unknown structure of repeat 11 of the human mannose-6-phosphate/insulin-like growth factor II receptor (Man6P/IGFII-receptor), with 310 amino acids in the asymmetric unit, which was phased by soaking the crystals in a cryoprotectant solution containing halide anions.

Amino Acid Sequence↗

PubMed2002

Defective oligomerization of arylsulfatase a as a cause of its instability in lysosomes and metachromatic leukodystrophy.

In one of the most common mutations causing metachromatic leukodystrophy, the P426L-allele of arylsulfatase A (ASA), the deficiency of ASA results from its instability in lysosomes. Inhibition of lysosomal cysteine proteinases protects the P426L-ASA and restores the sulfatide catabolism in fibroblasts of the patients. P426L-ASA, but not wild type ASA, was cleaved by purified cathepsin L at threonine 421 yielding 54- and 9-kDa fragments. X-ray crystallography at 2.5-A resolution showed that cleavage is not due to a difference in the protein fold that would expose the peptide bond following threonine 421 to proteases. Octamerization, which depends on protonation of Glu-424, was impaired for P426L-ASA. The mutation lowers the pH for the octamer/dimer equilibrium by 0.6 pH units from pH 5.8 to 5.2. A second oligomerization mutant (ASA-A464R) was generated that failed to octamerize even at pH 4.8. A464R-ASA was degraded in lysosomes to catalytically active 54-kDa intermediate. In cathepsin L-deficient fibroblasts, degradation of P426L-ASA and A464R-ASA to the 54-kDa fragment was reduced, while further degradation was blocked. This indicates that defective oligomerization of ASA allows degradation of ASA to a catalytically active 54-kDa intermediate by lysosomal cysteine proteinases, including cathepsin L. Further degradation of the 54-kDa intermediate critically depends on cathepsin L and is modified by the structure of the 9-kDa cleavage product.

Amino Acid Sequence↗

PubMed2002

Clinical applications of a non-invasive ICP monitoring method.

BACKGROUND AND PURPOSE: Until now the assessment of intracranial pressure (ICP) requires invasive methods. A previously introduced mathematical model allowed the non-invasive estimation of ICP (nICP) from arterial blood pressure (ABP) and blood flow velocity (FV). In various studies we have investigated the accuracy of this method and possible clinical applications. METHODS AND RESULTS: Selected hemodynamic parameters, calculated from the cerebral blood FV and the ABP curves, were used to express the relationship between ABP input and ICP output by linear transformation rules. In several clinical studies the accuracy and possible benefits of this method of non-invasive ICP (nICP) assessment were investigated. ASSESSMENT OF ICP PLATEAU WAVES: In 17 severely head injured patients we verified this model by comparison of nICP and measured ICP during generation of plateau waves, recorded in seven of these patients. In all simulations plateau elevations of ICP were well replicated. The correlation coefficient between increase of nICP and real ICP was R=0.98; P<0.001. LUMBAR INFUSION TESTS: Twenty one hydrocephalic patients were studied. Parallel increases in real ICP and nICP during lumbar infusion tests were evidently visible. Resistance of cerebrospinal fluid outflow (Rcsf) was computed using nICP and compared with Rcsf computed from real ICP. The mean error between real and non-invasive Rcsf was 4.1+/-2.2 mmHg min/ml. CEREBRAL AUTOREGULATION: One hundred and forty five patients were studied after severe head injuries. The state of autoregulation was assessed by moving correlation of cerebral perfusion pressure (CPP=ABP-ICP) and FV (Mx index). nICP instead of ICP was used to continuously estimate the state of autoregulation and to dynamically adapt the nICP procedure to this state. A median error between ICP and nICP of 6.0 mmHg was observed. Directly and non-invasively assessed Mx indices correlated highly significantly (R=0.9; P<0.001). CONCLUSIONS: The results demonstrate that the nICP assessment model constitutes a reliable method to monitor ICP and may therefore provide various useful clinical applications.

Blood Flow Velocity↗

PubMedDate not supplied

Inherently 3-dimensional method for measurement of computed tomographic resolution anisotropy.

OBJECTIVE: Current techniques to measure computed tomography (CT) spatial resolution use separate methods for in-plane and out-of-plane directions. The growing use of near-isotropic voxel size necessitates a new single method that inherently measures resolution in any direction. METHOD: We introduce a method using a set of numerous glass microspheres suspended in a small volume from which a mean sphere image is constructed. Projecting asymptotes after imaging different microsphere sets with decreasing diameters provides an inherently 3-dimensional measure of spatial resolution and anisotropy. We apply the method to both a flat-panel and multidetector CT scanner. RESULTS: The full-width at half-maximum from line profiles through mean sphere in transverse directions corresponds to known microsphere diameters. Increased longitudinal full-width at half-maximum corresponds to known anisotropy, which is larger for a multidetector CT scanner than for a flat-panel CT scanner. CONCLUSIONS: A new single method to measure CT resolution is inherently isotropic.

Anisotropy↗

PubMedDate not supplied

An extensible software-based platform for reconstruction and evaluation of CT images.

A collection of software applications dedicated to clinical x-ray computed tomography (CT) has been developed. These tools are designed for routine and scientific work and represent a complete platform, which is called syngo Explorer. The user can reconstruct, process, and view CT images in a personal computer environment independently of specialized hardware. To manage patient data and to allow full database access, the system uses the syngo platform (Siemens Medical Solutions, Erlangen, Germany), which serves as a framework for the management and visualization of Digital Imaging and Communications in Medicine (DICOM) images. Part of the philosophy behind syngo Explorer is to quickly provide specialized solutions and to be able to respond to user requests at once. Thus, syngo Explorer was built by choosing a modular setup that comprises standard and specific reconstruction algorithms as well as various artifact reduction techniques; it also helps one attain better insights into dose issues. Various raw data formats of commercial CT scanners are supported. Reconstruction algorithms equivalent to those on the manufacturer's scanner console are provided. A non-syngo Windows XP (Microsoft, Redmond, Wash) version of the application is available.

Algorithms↗