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Biomedical subjects

D Högemann

Publications and source records attributed to D Högemann.

9 recordsLinked to original sources

[Molecular imaging in magnetic resonance tomography and nuclear medicine].

The identification of genetic and biochemical changes allows a more conclusive characterization and classification of disease. Up to now this information is mostly obtained through in vitro analysis after resection or biopsy by immunohistopathology and molecular biology. There is a definite need for non-invasive detection and repeated monitoring of such changes in experimental research as well as in clinical trials. Therefore, it is necessary to develop radiological imaging techniques that not only visualize morphologic and physiologic alterations, but track genetic and biochemical processes. This short review reports some of the various ongoing research projects that address this problem and provide some very promising approaches.

Animals↗

Correlation of MRI and CT findings with histopathology in hepatic angiomyolipoma.

Hepatic angiomyolipomas are rare and often mimic other liver tumors. The aim of our study was to describe the CT and MRI findings and to correlate imaging features with histopathology. The CT and/or MR images were available for retrospective analysis in seven patients. Patients had non-enhanced as well as enhanced CT (n = 6) or MRI (n = 4) before and after administration of Gd-DTPA (n = 2) or MnDPDP, a liver specific contrast agent, (n = 3). In three patients CT and MRI did not detect fat, and in two patients the angiomyolipomas were also histopathologically devoid of fat. Vascularity ranged from hypervascular (n = 4) with arteriovenous shunts (n = 1) to equal (n = 1) or less (n = 2) postcontrast enhancement compared with the normal liver parenchyma. No uptake of the liver specific contrast agent, MnDPDP, was observed (n = 3). Predominantly, CT and MRI did not include angiomyolipoma in the differential diagnosis, and the initial histopathological evaluation was inconclusive in more than half the cases. Hepatic angiomyolipomas frequently manifest as solitary well-circumscribed heterogeneous masses in patients with no underlying liver disease or elevation of serum tumor markers. If present, the demonstration of intratumoral fat is helpful in the diagnosis of angiomyolipoma. The final diagnosis can be obtained by immunohistochemistry.

Adult↗

[Individual planning of liver surgery interventions with a virtual model of the liver and its associated structures].

BACKGROUND: In an interdisciplinary approach, HepaVision (MEVIS, Bremen), a software tool specifically developed for 3D visualization of the liver, was employed for individual planning of extensive liver resections and evaluation of living-relative donations. So far there is experience with more than 50 biphasic spiral CT examinations. RESULTS: The spatial relationship of large tumors to crucial hepatic structures, the demonstration and evaluation of anatomic variants regarding vascular supply and the risk stratification of liver failure by volumetric analysis on the basis of portal venous drainage supported precise indication for surgery. Surgical safety is increased by preoperative planning and simulation of necessary vessel reconstructions. By hiding selective areas of portal venous drainage or applying freely selectable clip planes, segmental as well as non-anatomical resections can be simulated and their effects analyzed. The virtual preoperative situs was confirmed intraoperatively in all 17 patients of our study population who underwent segmental liver resection for either a tumor or living-relative donation.

Adenoma, Liver Cell↗

[Basic principles of data acquisition and data processing for construction of high quality virtual models].

Creating models for virtual reality subdivides into several steps. The aim of the data acquisition is the extraction of nearly isotropic (same solution in all three axes) data sets with low noise content. An approximate isotropy can be achieved by suitable choice of scan parameters. For raw data reconstruction, the application of high-resolution reconstruction algorithms is prohibited due to increased noise. A missing isotropy can computationally be approximated by interpolation. Further noise suppression is achieved by applying filters. Additionally, the contrast of the object for segmentation can be increased by image processing operators. The correct choice of the segmentation method and the editing tools is essential for a precise segmentation with minimal user interaction. Prior to visualization, smoothing the shape of the segmented model (shape-based or morphological interpolation, polygon reduction of wire frame model) further improves the visual appearance of the 3D model.

Algorithms↗

In vitro model of the human liver parenchyma to study hepatotoxic side effects by Dy-EOB-DTPA.

RATIONALE AND OBJECTIVES: In vivo studies have shown species-specific toxicity after application of the liver-specific contrast agent Dy-ethoxybenzyl (EOB)-DTPA. To predict species differences in the laboratory, an in vitro model of the liver was used to examine the divergent results. METHODS: Rat, canine, porcine, and human hepatocytes were isolated and embedded between layers of collagen. During and after 48 hours of incubation with different concentrations of Dy-EOB-DTPA (maximum concentration 50 mmol/L), morphological changes and enzyme leakage were determined. RESULTS: The response to the contrast agent varied for hepatocytes from different species. For canine cells, morphological changes and cell death were evident with as little as 5 mmol/L Dy-EOB-DTPA. Rat hepatocytes tolerated up to 50 mmol/L Dy-EOB-DTPA, and enzyme leakage was transient. Only after incubation with 50 mmol/L Dy-EOB-DTPA was the formation of intracellular vacuoles evident. In contrast, even the highest concentration of Dy-EOB-DTPA did not cause an enzyme leakage of porcine or human hepatocytes, although similar vacuoles were seen. CONCLUSIONS: These data demonstrate a species-dependent toxicity for Dy-EOB-DTPA in vitro, with similar responses in porcine and human hepatocytes.

Animals↗

[3-dimensional (3-D) visualization of the liver for planning extensive liver resections].

Preoperative planning of liver resections in patients with liver tumors is based on sonography, computed tomography and magnetic resonance imaging. A new three-dimensional (3D) visualization program was developed based on CT data. This visualization program was used for preoperative planning in 6 patients with liver tumors in problematic intrahepatic localizations. In 5 out of 6 patients the liver resection could be performed as preoperatively planned. The intraoperative findings agreed with the 3D visualization in all these patients. 3D Visualization of the liver allowed clear and interactive planning of liver resections and improved the preparation of complex liver resections.

Adenoma, Liver Cell↗

[Performance of different CT angiography imaging modalities in detecting renal artery stenoses].

PURPOSE: Purpose of the study was to compare the sensitivity and specificity of various display modalities in the detection of renal artery stenosis. In particular, the difference between hard-copy reading and interactive analysis at the workstation was assessed. MATERIALS AND METHODS: Selected patients (n = 31) with expected suboptimal conditions for CT angiography due to long-standing hypertension and compromised renal function were included. Six radiologists evaluated independently a total of 77 renal arteries with 49 renal artery stenoses proven by angiography. Image analysis included: mode A: interactive display, analysis of multiplanar reformats and axial sections at the workstation, mode B: visualization of MIPs in the coronal and axial planes as hard copies only, mode C: visualization of MIPs and axial sections as hard copies only. RESULTS: The following sensitivities and specificities were found for internal readers and (readers from outside institutions): mode A: 94.8%, 87.9%, mode B: 97.7% (95.1%), 80.3% (75.4%); mode C: 97.0% (95.3%), 78.8% (76.6%). The differences were statistically not significant (p > 0.05). CONCLUSIONS: Standardized hard copies of MIPs plus axial CT provide sufficient accuracy to detect renal artery stenosis compared to interactive imaging even in this highly selected group of patients.

Adult↗

16-BAC/SDS-PAGE: a two-dimensional gel electrophoresis system suitable for the separation of integral membrane proteins.

Integral membrane proteins, particularly those with more than one transmembrane domain, have traditionally been difficult to separate by two-dimensional electrophoretic methods. Here we report the adaptation of a previously published procedure [D. E. Macfarlane (1989) Anal. Biochem. 176, 457-463] for the analytical and semipreparative separation of membrane proteins. The first dimension involves discontinuous gel electrophoresis in an acidic buffer system using the cationic detergent benzyldimethyl-n-hexadecylammonium chloride (16-BAC). The second dimension consists of discontinuous SDS-PAGE. Using carbonate-washed membranes of synaptic vesicles and clathrin-coated vesicles as examples, we demonstrate that complex membrane protein mixtures can be resolved with a resolution at least fivefold higher than that of one-dimensional SDS-PAGE. Protein patterns are highly reproducible and proteins with single or multiple transmembrane domains are resolved as clearly distinct spots. Smearing of bands or losses of protein are minimal. Several spots were identified by immunoblotting and internal sequencing. Thus, this method is suitable for the analytical and semipreparative characterization of membrane proteins derived from complex biological samples.

Animals↗

Improvement of MRI probes to allow efficient detection of gene expression.

Recently, it has been demonstrated that magnetic resonance imaging (MRI) utilizing monocrystalline iron oxide nanoparticles (MIONs) targeted to an engineered transferrin receptor enables imaging of gene expression. However, the relatively high doses of iron oxides used indicated the need for improved MR imaging probes to monitor changes in gene expression in vivo. Using alternative conjugation chemistries to link targeting ligands and iron oxide nanoparticles, we present the development and characterization as well as improved receptor binding and MRI detection of a novel imaging probe. Iron oxide nanoparticles with a cross-linked dextran coat were conjugated to transferrin (Tf) through the linker molecule N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) to yield Tf-S-S-CLIO. The characteristics of this conjugate were evaluated in comparison to Tf-MION and Tf-CLIO generated by oxidative activation of the dextran-coat with subsequent reduction of Schiff's base. SPDP conjugation allowed approximately a 4-fold increase in the number of Tf molecules attached per iron oxide nanoparticle and resulted in a more than 10-fold improvement of binding and uptake by cells. This translated into an imaging probe that was 16 times better for imaging gene expression in a cellular MRI assay. This novel probe for MRI may substantially increase the sensitivity for the detection of endogenous or genetically induced transferrin receptor expression in small numbers of cells and may significantly reduce the imaging dose from over 100 mg/kg to doses of iron oxides that are currently used in clinical imaging.

Animals↗