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Biomedical subjects

W Semmler

Publications and source records attributed to W Semmler.

At least 37 records · Page 2Linked to original sources
PubMed1999

Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent.

BACKGROUND: Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS: Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS: In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.

Animals↗
PubMed1999

Mechanism of gadophrin-2 accumulation in tumor necrosis.

The molecular mechanism by which gadophrin-2 targets necrotic tumor tissue was investigated. Biodistribution studies and magnetic resonance imaging (MRI) and histologic/autoradiographic correlation were performed in xenograft mouse models bearing human tumors (HT 29, WiDr, LX 1). Binding of gadophrin-2 to DNA, lipids, or proteins was determined by fluorescence spectrophotometry. Protein binding was determined by dialysis and gel electrophoresis. Accumulation of gadophrin-2 was low (<0.7% injected dose/g tissue at 24 hours after injection) in viable tumor but higher in necrotic tumor regions and was readily detectable by MRI. Within a given tumor, the agent preferentially localized in the periphery of necrotic areas. Within these regions gadophrin-2 was bound to interstitial albumin and not other proteins, lipids, or DNA. Tumoral accumulation of gadophrin-2 most likely occurs through its binding to plasma albumin and subsequent slow extravasation into the tumor interstitium.

Animals↗
PubMed1999

[Phosphorus-31-MR spectroscopy imaging in preoperative embolization treatment of meningioma].

PURPOSE: 31P MR spectroscopic imaging (31P SI) was evaluated in a clinical study as a method for monitoring presurgical devascularization of meningiomas. The aim was to assess noninvasively metabolic alterations in tumor and in healthy brain tissue before and after embolization. METHODS: Localized 31P MR spectra of the brain were obtained by means of 2D-SI (voxel size: 36 cm3) using a 1,5-T whole-body MR tomograph. RESULTS: Eleven of 19 patients with intracranial meningiomas examined in this study underwent preoperative embolization therapy; eight patients were examined before and after treatment. After embolization, alterations of pH and of the concentrations of high-energy phosphates (nucleoside-5' triphosphate = NTP, phosphocreatine = PCr), inorganic phosphate (Pi), and membrane constituents were observed in the tumors. A tendency of [Pi] increase and decrease of [NTP], [PCr], and pH predominated, which is explained by ischemic processes after tumor devascularization. CONCLUSION: 31P SI is applicable in clinical studies and detects alterations of phosphate metabolism in a meningioma after embolization.

Adult↗
PubMed1999

Gadolinium neutron capture therapy (GdNCT) of melanoma cells and solid tumors with the magnetic resonance imaging contrast agent Gadobutrol.

RATIONALE AND OBJECTIVES: The therapeutic gain of neutron capture therapy with a neutral macrocyclic gadolinium (Gd) complex (Gadobutrol) was evaluated through in vitro and in vivo studies in a beam of low-energy neutrons. METHODS: Neutron irradiation for both the in vitro and in vivo studies was performed in a beam of low-energy neutrons produced by the research reactor of the Hahn-Meitner-Institut, Berlin. Malignant melanoma cells of human origin were irradiated in the presence or absence of Gadobutrol. In vivo irradiation was performed on tumor-bearing nude mice. The tumor site was irradiated subsequent to intratumoral injection of Gadobutrol and compared with irradiation in the absence of the Gd complex. RESULTS: In vitro studies showed a Gd-dependent delay of cell proliferation as a consequence of neutron irradiation. In animals, intratumoral administration of the Gd complex at a dose of 1.2 mmol Gd/kg before neutron irradiation results in a significant delay in tumor growth with respect to the control groups. CONCLUSIONS: In vitro and in vivo studies showed a therapeutic benefit with the neutral Gd complex and suggest Gd-containing magnetic resonance contrast media are potential candidates for neutron capture therapy. The Gd dose used in the irradiation experiments was four times the presently accepted high dose in clinical magnetic resonance imaging.

Animals↗
PubMed1999

[Effective use of time in community psychiatry--utopia and the reality of network management].

OBJECTIVE: The development of community psychiatry needs an increasing network management between inpatient and outpatient care. As a whole the question of management structure is open for discussion. Instruments such as psychosocial workshops and community psychiatric team conferences are in need of a critical survey. METHODS: Our paper offers data in basic network management referring to false connections in interinstitutional cooperation by phone. RESULTS: The number of false connections is on a highly significant level, up to six times higher when contacting ambulant complementary staffs or administrative levels than within medical systems. CONCLUSION: These results demonstrate a large gap between utopia and reality of network management. Community psychiatric systems must take care for longitudinal medical staff orientation in structural management.

Case Management↗
PubMed1999

Magnetic marker monitoring of esophageal, gastric and duodenal transit of non-disintegrating capsules.

The purpose of the study was to investigate in detail the esophageal, gastric and duodenal passage of non-disintegrating capsules in a fasted, healthy volunteer using Magnetic Marker Monitoring (MMM). Five independent experiments were performed. In each case the same healthy male volunteer ingested one magnetically marked capsule after fasting for at least 8 h. The magnetic dipole fields of the capsules were recorded by biomagnetic multichannel measuring equipment. The positions of the capsules were calculated from the recorded data by methods established in magnetic source imaging. The esophageal, gastric and duodenal passages of the capsules were successfully reconstructed from all recorded data sets. The spatial resolution of the capsules' three-dimensional positions in the organs of the gastrointestinal tract was within a range of several millimeters, with a chosen temporal resolution of up to four milliseconds. The esophageal transit times were between 3-13 s, the gastric residence times were between 14-133 min and the duodenal transit times were between 7-245 s. The data demonstrate that Magnetic Marker Monitoring permits the detailed investigation of the gastrointestinal transit of solids.

Adult↗
PubMed1998

Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in vivo by using transferrin receptor pathways.

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the transferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R1 = 23.6 and R2 = 52.1 liter/mmol.s (0.47 T). Bound transferrin was 280 micrograms/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25-55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5-15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-mediated endocytosis allows in vivo detection of tumors by MR imaging.

Animals↗
PubMed1998

Molecular imaging of atherosclerosis using a technetium-99m-labeled endothelin derivative.

UNLABELLED: Endothelins have been implicated in the pathogenesis of atherosclerosis and restenosis. The aim of this study was to characterize the potential of an endothelin derivative labeled with 99mTc for imaging experimental atherosclerosis in vivo. METHODS: Atherosclerosis was induced by balloon denudation of the infrarenal aorta in eight New Zealand white rabbits followed by a 6-wk period of a standard or 0.5% cholesterol diet in four animals, respectively. Another four rabbits served as controls, without balloon denudation and cholesterol feeding. Digital subtraction angiograms and planar whole-body scintigrams were obtained after intravenous injection of 74 MBq of the 99mTc-labeled endothelin derivative. The aorta was dissected for autoradiography, sudan-III staining, morphometry and immunohistology (anti-alpha-actin, RAM 11) 5 hr after injection. RESULTS: The lesions induced in the infrarenal aorta could be detected in vivo (whole-body scintigrams) in all treated animals only 15 min after injection of 99mTc-endothelin derivative. Autoradiography of the excised aorta revealed good correlation of tracer accumulation and sudan-III-stained lesions. The ratio of accumulation between the induced lesions and untreated vessel wall was 6.8 +/- 1.4 in the cholesterol-fed animals and 6.3 +/- 1.8 in the animals without cholesterol feeding. Accumulation of the endothelin derivative correlated with the number of smooth muscle cells (r = 0.924) but not with the amount of macrophages, the area or the maximum thickness of the plaques. CONCLUSION: Scintigraphic visualization of experimentally induced atherosclerosis in vivo is feasible using an endothelin derivative labeled with 99mTc.

Angiography, Digital Subtraction↗
PubMed1997

[Contrast media for optical mammography].

Near infrared imaging is a non-invasive imaging modality which uses light of a spectral range between 650 and 1000 nm for tissue transillumination. Near infrared photons can penetrate by diffusion into tissue up to several centimeters due to low absorption by intrinsic chromophors (e.g. hemoglobine). During the last years optical mammography has become field of growing interest. Several prototypes of near infrared scanners have been developed for clinical studies in order to obtain transillumination images of the breast. The results indicated, that discrimination of tumors located up to several centimeters below the tissue surface (e.g. breast tumors) from surrounding healthy tissue did not succeed with sufficient specificity. The diagnostic potential of near infrared imaging can be enhanced using dyes as contrast agents. Specially designed cyanine dye derivatives are potential contrast agents because of their suitable optical properties and pharmacokinetic behaviour leading to an increased tumor fluorescence in animals after intravenous injection.

Animals↗
PubMed1997

Determination of plasma protein adsorption on magnetic iron oxides: sample preparation.

PURPOSE: The purpose of this study was to investigate the influence of the sample preparation on the plasma protein adsorption pattern of polysaccharide-stabilized iron oxide particles by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). METHODS: The iron oxide particles were incubated in vitro in human plasma for five minutes. Thereafter, four different methods for particle recovery, including adsorbed proteins from surplus plasma, were investigated: centrifugation, magnetic separation, gel filtration and membrane-based static microfiltration. Adsorbed proteins were desorbed from the particle surfaces by surfactants and analyzed by 2-D PAGE, as described elsewhere (1,2). RESULTS: All the techniques investigated were able to separate small-size iron oxides (approx. 110 nm) and adsorbed proteins from excess plasma. The gels obtained by the different separation procedures displayed almost identical adsorption patterns. Major proteins identified were: fibrinogen, IgG, albumin and an unclassified protein of about 70 kDa with a pI value of 6.5-7.5. CONCLUSIONS: Centrifugation was regarded as the most suitable separation method due to its speed and ease of use. In contrast to gel filtration, any washing media can be used. The magnetic separation process is restricted to particles with high inducible magnetic saturation, in particular, to iron oxides with overall sizes > 50 nm.

Adsorption↗
PubMed1997

Magnetic resonance imaging-histomorphologic correlation studies on paramagnetic metalloporphyrins in rat models of necrosis.

RATIONALE AND OBJECTIVES: The authors intended to confirm previous findings that paramagnetic porphyrins are avid only for intratumoral nonviable tissues, but not for viable tumor cells, and to test the hypothesis that necrosis, regardless of location and origin, can be visualized by metalloporphyrin enhanced magnetic resonance imaging (MRI). METHODS: Intravenous administrations of gadolinium mesoporphyrin (Gd-MP), manganese tetraphenylporphyrin (Mn-TPP), manganese methylpyrroporphyrin-gadopentetate dimeglumine complex (Mn-MPP-Gd) and manganese tetra(4-sulfonatophenyl)porphyrin (MnTPPS4) at 0.05 mmol/kg were compared with those of gadopentetate dimeglumine (Gd-DTPA) at 0.1 mmol/kg in 38 rats with cholestatic liver necrosis, alcohol- and laser-induced coagulation necrosis in liver, and skeletal muscle, reperfused hepatic infarction, and segmental renal infarction. T1-weighted spin echo MRI (TR/TE = 300/15 mseconds) was acquired before and as long as 48 hours after injection, matched with histologic findings, and correlated with Gd/ Mn tissue content measurements. RESULTS: Both Gd-DTPA and the four metalloporphyrins initially caused a similar nonspecific negative contrast enhancement in the necrosis. However, a strong and persisting positive enhancement (necrosis-to-normal contrast ratio ranging from 1.5 to 2.0) developed only with metalloporphyrins in all types of necrosis. In liver and kidney, Gd and Mn concentrations at 24 hours were comparable in necrotic and normal tissues. In muscle, the concentrations were more than eight times higher in necrotic than in normal tissue. CONCLUSIONS: The implied affinity of metalloporphyrins for necrosis with presumably increased relaxivity suggests a possible mode of targetability for MRI contrast media that may elicit novel applications.

Animals↗
PubMed1997

The influence of the sample preparation on plasma protein adsorption patterns on polysaccharide-stabilized iron oxide particles and N-terminal microsequencing of unknown proteins.

The in vivo organ distribution of i.v. injected drug carriers is strongly influenced by the adsorption of plasma proteins after i.v. injection, e.g. uptake by the mononuclear phagocytic system (MPS). 2-D PAGE could be established to analyze plasma protein adsorption patterns on polysaccharide-stabilized aqueous iron oxide dispersions used as contrast agents in Magnetic Resonance Imaging (MRI). After incubation in human plasma, centrifugation, a washing procedure and a solubilization step were carried out to obtain the proteins adsorbed onto these ultrasmall particles (65 nm in diameter). Patterns of adsorbed proteins were analyzed in dependence on the washing medium used, i.e. highly purified water, phosphate buffered saline and Krebs buffer pH 7.4. Conductivity and composition of the washing medium influenced the adsorption of IgG onto the particles, but had little effect on the other proteins present. IgG was strongly reduced when using the relatively high conductive buffers. The more stabilizing polysaccharide was desorbed the larger was the total amount of adsorbed proteins. Appearance of two unknown chains of spots in the range of appr. 92 kDa, accounting for appr. 10% and 2% of the overall detected protein amount, was observed only when using Krebs buffer during the washing process. Performing N-terminal microsequencing one unknown chain of spots could be identified as a dimer of fibrinogen gamma chains.

Adsorption↗
PubMed1996

Paramagnetic metalloporphyrins: infarct avid contrast agents for diagnosis of acute myocardial infarction by MRI.

In previous experiments in tumors we demonstrated that metalloporphyrins are particularly avid for nonviable tumor components. This study was performed to find out whether these agents can be used as MRI contrast agents for the visualization of acute myocardial infarction (MI). A total of 44 rats, 6 normal controls and 38 with occlusive MI (2-24 h old), were used. Gadolinium mesoporphyrin (Gd-MP) or manganese tetraphenylporphyrin (Mn-TPP) was intravenously injected at doses of 0.1, 0.05, and 0.01 mmol/kg. Three to 24 h after injection, axial and coronal T1-weighted (TR/TE 300/15 ms) spin-echo MR images were obtained before and after killing the animals and correlated with triphenyl tetrazolium chloride (TTC) histochemical preparations. The Gd-MP content in infarcted and noninfarcted myocardium was measured using inductively coupled plasma atomic emission spectroscopy (ICP-AES). MRI without contrast media could not discern the MI. However, 3-24 h after injection of either Gd-MP or Mn-TPP, the infarcted area was positively stained on MR images. This area matched well with the negatively TTC-stained area on the heart slices (r = 0.97). The contrast ratios between the infarcted necrotic myocardium and the noninfarcted regions varied from 150 to 300% depending on the type of agents and doses used. Neither false-positive nor false-negative findings were encountered. The metalloporphyrin concentration was more than 10 times higher in the infarcted than in the noninfarcted heart. Metalloporphyrins appear to be promising MRI contrast agents for detection and quantification of necrosis in MI. These preclinical results may open new perspectives in cardiac imaging.

Animals↗
PubMed1996

Magnetic resonance lymphography in rats: effects of muscular activity and hyperthermia on the lymph node uptake of intravenously injected superparamagnetic iron oxide particles.

RATIONALE AND OBJECTIVES: We investigated the influence of muscular activity and regional body temperature changes on the accumulation of intravenously (i.v.) administered, dextran-coated superparamagnetic iron oxide (SPIO) particles in the lymph nodes of rats. METHODS: Four groups of rats (N = 21) were used. Five rats were allowed to move freely after i.v. contrast administration (group 1). In another five rats, muscular inactivity (group 2) was induced during i.v. injection of SPIO particles and for up to 2 hr thereafter by anesthesia. In seven rats (likewise anesthetized), the contrast agent was administered while the extremities of one side of the body were warmed in a water bath for 2 hr (group 3). The rats in groups 1-3 received 100 mumol Fe/kg of the contrast agent. Four rats not given SPIO particles served as the control group (group 4). The lymph nodes of all animals were removed 24 hr after SPIO administration and were embedded in an agar matrix for magnetic resonance imaging at 1.5 T using a proton-density-weighted spin-echo (PD-SE) sequence and a T2*-weighted gradient-recalled echo (T2* GRE) sequence. RESULTS: Signal loss varied widely among the different lymph nodes in group 1. A pronounced signal reduction was observed in the mesenteric (PD-SE = 20 +/- 6%, T2* GRE = 55 +/- 19%), iliac (PD-SE = 13 +/- 13%, T2* GRE = 44 +/- 24%), and popliteal (PD-SE = 24 +/- 7%, T2* GRE = 70 +/- 11%) lymph nodes and only a moderate reduction in the mandibular (PD-SE = 4 +/- 7%, T2* GRE = 42 +/- 15%), axillary (PD-SE = 0 +/- 4%, T2* GRE = 8 +/- 7%), and inguinal (PD-SE = 5 +/- 5%, T2* GRE = 34 +/- 18%) lymph nodes. The least pronounced signal loss occurred in the peripheral lymph nodes of group 2, ranging from 0 +/- 3% for PD-SE sequences and 10 +/- 11% for T2* GRE sequences to 13 +/- 15% for PD-SE sequences and 41 +/- 19% for T2* GRE sequences. In group 3, the uptake of contrast material in the peripheral lymph nodes of the hyperthermal side was significantly more pronounced than on the contralateral side (p < .01), and the contrast agent was distributed more evenly to the different lymph node groups than in group 1. CONCLUSION: Muscular activity and regional hyperthermia markedly influence the accumulation of SPIO particles in different lymph node groups in rats. These findings must be considered in preclinical studies and in the clinical administration of MR lymphography.

Anesthesia↗
PubMed1996

[An interstitial miniature antenna for localized in vivo P-31 MR spectroscopy].

BACKGROUND: Phosphorus spectroscopy can be used to assess response in tumor therapy and to monitor response. An additional response parameter would be useful for individualization in oncological therapy. Methodical problems of localisation and contamination make it more difficult to interpret and reproduce the spectra. Interstitial and endoluminal spectroscopy antennas placed directly within or close to the tumor could provide help in this problem. MATERIAL AND METHOD: We developed an interstitial 31P MRS antenna together with a tuning network which can be used in thermometry catheters for hyperthermia within an internal lumen of 1.1 mm in diameter. A prototype of this type of miniature antenna suitable for use in Siemens MRI scanners at 1.5 T was described spectroscopically with regard to excitation profile, range and SNR. RESULTS: In terms of quality, the excitation profiles of the interstitial antennas in relation to orientation correspond to those of comparable but considerably larger endocavitary antennas and catheter coils for MR imaging and spectroscopy. Maximum sensitivity was achieved by aligning the coil normal perpendicular to the B0 field. Signal losses of up to 50% have to be reckoned with when using other orientations. The maximum range of the interstitial antenna was determined using spectroscopy and was found to be 5 mm, i.e. 9 times coil radius. The sensitivity (SNR, detection sensitivity) of the studied type of interstitial antenna allows in vivo 31P spectroscopy to be performed despite the unusually low axial dimension (coil radius r = 0.55 mm). The prototype of the described interstitial antenna was used to measure an in vivo spectrum from the back muscle of a rabbit in 10 min. Nevertheless, the detection volume of at least some ml necessary for 31P spectroscopy results mainly from the large antenna length. CONCLUSION: The sensitivity (SNR, detection sensitivity) of the interstitial antenna needs to be further improved in order to assess treatment response in patients. However, the construction principle is suitable for intracavitary 31P spectroscopy antenna with larger diameters, which can be used for advanced rectal, cervical and prostate carcinomas.

Animals↗