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Wolfhard Semmler

Publications and source records attributed to Wolfhard Semmler.

27 records · Page 2Linked to original sources

Semiquantitative fast flow velocity measurements using catheter coils with a limited sensitivity profile.

Flow measurements can be used to quantify blood flow during MR-guided intravascular interventional procedures. In this study, a fast flow measurement technique is proposed that quantifies flow velocities in the vicinity of a small RF coil attached to an intravascular catheter. Since the small RF coil receives signal from only a limited volume around the catheter, a spatially nonselective signal reception is employed. To enhance signal from flowing blood, and suppress unwanted signal contributions from static material, a slice-selective RF excitation is used. At a velocity sensitivity of 150 cm/s, a temporal resolution of 2 x TR = 10.2 ms can be achieved. The flow measurement is combined with an automatic slice positioning to facilitate measurements during interventional procedures. The influence of the catheter position in the blood vessel on the velocity measurement was analyzed in simulations. For blood vessels with laminar flow, the simulation showed a systematic deviation between catheter measurement and true flow between -15% and 80%. In four animal experiments, the catheter velocity measurement was compared with results from a conventional ECG-triggered 2D phase-contrast (PC) technique. The shapes of the velocity time curves in the abdominal aorta were nearly identical to the conventional measurements. A relative scaling factor of 0.69-1.19 was found between the catheter velocity measurement and the reference measurement, which could be partly explained by the simulation results.

Animals↗

[Automatic slice tracking in interventional magnetic resonance imaging].

Magnetic resonance imaging (MRI) is ideally suited to monitor minimally invasive operations with catheters or needles, since it offers both a superior soft-tissue contrast and the possibility to perform functional tests. In the present study, small radio-frequency coils were attached to the instruments in order to localize the MR-invisible instruments. The implementation of active instrument tracking is described on the basis of the example of active catheter tracking. In this case, the current position information of the instrument is used to automatically position the MRI slice at the catheter location. In combination with a user interface, the interventional radiologist is offered the possibility to perform vascular interventions from within the MR scanner room. At image update rates of approximately 3 Hz, tracking and placement of catheters in vascular structures are possible with interactive switching of slice orientation and image contrast. In an animal model, the technique was successfully used to selectively visualize the abdominal vessels and their branches under MRI guidance.

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Targeting of endothelin receptors for molecular imaging of atherosclerosis in rabbits.

UNLABELLED: We wanted to determine whether a previously described in vivo accumulation of a (99m)Tc-labeled endothelin derivative in atherosclerotic lesions is mediated by binding to endothelin receptors. Furthermore, the expression of endothelin receptors in atherosclerotic lesions of 2 different rabbit animal models for atherosclerosis was to be evaluated to determine whether endothelin receptors generally are a suitable target for atherosclerosis imaging. METHODS: Normal vessels from untreated New Zealand White rabbits (NZW), balloon-denuded aortas from cholesterol-fed NZW, and atherosclerotic aortas from Watanabe Heritable Hyperlipidemic rabbits (WHHL) were used either as cross sections (cryosections) for receptor binding studies or for superfusion with a medium containing (125)I-labeled endothelin-1 or the (99m)Tc-labeled endothelin derivative. RESULTS: Cross sections of aortas from untreated NZW contained 45 +/- 11.10(6) endothelin A receptors per square millimeter and 55 +/-11.10(6).endothelin B receptors per square millimeter, cross sections of balloon-denuded aortas from cholesterol-fed NZW contained 106 +/- 16.10(6) endothelin A receptors per square millimeter and 27 +/- 16.10(6) endothelin B receptors per square millimeter, and cross sections of atherosclerotic aortas from WHHL contained 40 +/- 13.10(6) endothelin A receptors per square millimeter and 5 +/- 13.10(6) endothelin B receptors per square millimeter. Balloon-denuded aortas from cholesterol-fed NZW (366 +/- 132 amol.mm(-2), P < 0.001) and atherosclerotic aortas from WHHL (338 +/- 175 amol.mm(-2), P < 0.002) accumulated significantly more of the (99m)Tc-labeled endothelin derivative than did vessels from control animals (137 +/- 26 amol.mm(-2)). On the contrary, (125)I-labeled endothelin-1--bound receptor mediated to superfused aortas from untreated NZW (12 +/- 9 amol.mm(-2)) and to balloon-denuded aortas from cholesterol-fed NZW (19 +/- 5 amol.mm(-2)) but not to aortas from WHHL. This lack of receptor-specific accumulation of (125)I-endothelin-1 in atherosclerotic areas of WHHL aortas, and this receptor-specific accumulation in atherosclerotic balloon-denuded NZW aortas that does not significantly increase in comparison with normal aortas of untreated NZW, cause failure of endothelins to detect atherosclerotic lesions. CONCLUSION: Although the density and the ratio of endothelin receptor subtypes change because of the development of atherosclerotic lesions in rabbit aortas, endothelin receptor targeting for imaging of atherosclerosis is not suitable.

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Synthesis and characterization of HE-24.8: a polymeric contrast agent for magnetic resonance angiography.

The physical and biological properties of a water-soluble polymeric contrast agent based on a complex of N-(2-hydroxypropyl)methacrylamide copolymer with gadolinium (HE-24.8) were investigated, and its potential for experimental magnetic resonance (MR) angiography was assessed. Relaxivities of Gd-DTPA-BMA, Gd-DTPA-HSA (human serum albumin), and HE-24.8 were determined at 1.5 T. Thermic stability and biocompatibility of HE-24.8 were assessed in vitro and by analyzing kinetics and organ distribution in rats for up to 2 weeks. For comparison, HE-24.8- and Gd-DTPA-HSA-enhanced micro-MR angiographies of brain, chest, and subcutaneous tumors in rats were performed. T1 relaxivity of HE-24.8 (21.3 +/- 1.1 mM(-1) s(-1)) was 5-fold higher than that of Gd-DTPA-BMA (4.1 +/- 0.1 mM(-1) s(-1)) and twice as high as that of Gd-DTPA-HSA (12.4 +/- 0.2 mM(-1) s(-1)). Varying the molecular weight of the polymer (15-46 kDa) did not significantly change the T1 relaxivity. In rats, 20 and 10% of the injected dose of HE-24.8 was detected at 24 and 168 h postinjection, respectively. Upon a relatively rapid initial renal clearance, no specific retention in any organ was noted, with some exception for the reticulo-endothelial system. No measurable release of gadolinium from the polymer-Gd complex or cell toxicity was observed during its incubation in aqueous environment. Excellent display of rat and tumor vascularization was achieved with Gd-DTPA-HSA and HE-24.8; however, contrast of vessels was higher in HE-24.8-enhanced scans. HE-24.8 is considered a macromolecular contrast agent highly suited for experimental MR studies.

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Optical molecular imaging of lymph nodes using a targeted vascular contrast agent.

We develop a highly specific antibody-dye conjugate for optical imaging of peripheral lymph nodes. The contrast agent consists of the monoclonal antibody recognizing endothelial ligands for the lymphocyte homing receptor L-selectin, MECA-79, and a near-infrared (near-IR) fluorescent indotricarbocyanine dye. The targeting and biodistribution behavior of MECA-79 is studied after radio-iodination and intravenous injection into mice demonstrating specific uptake in lymph nodes and accumulation in high endothelial venules (HEV). After conjugation of MECA-79 with indotricarbocyanine dye, the fluorescence imaging properties of the MECA-79 dye conjugate are examined by intravenous injection in nude mice and laser-induced fluorescence whole-body imaging in vivo. The MECA-79 antibody-dye conjugate accumulates in peripheral lymph nodes, whereas an isotype antibody-dye conjugate does not. Specific lymph node near-IR fluorescent signals become detectable within minutes after injection, and stable imaging persists for more than 24 h. The results demonstrate that vascular targeting of endothelial expression of glyocproteins is feasible to visualize the accumulation of near-IR fluorescent MECA-79 in lymph nodes, making this technology potentially useful to characterize processes of inflammation.

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Dynamic contrast-enhanced magnetic resonance imaging rapidly indicates vessel regression in human squamous cell carcinomas grown in nude mice caused by VEGF receptor 2 blockade with DC101.

The purpose of our study was the investigation of early changes in tumor vascularization during antiangiogenic therapy with the vascular endothelial growth factor (VEGF) receptor 2 antibody (DC101) using dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). Subcutaneous heterotransplants of human skin squamous cell carcinomas in nude mice were treated with DC101. Animals were examined before and repeatedly during 2 weeks of antiangiogenic treatment using Gd-DTPA-enhanced dynamic T1-weighted MRI. With a two-compartment model, dynamic data were parameterized in "amplitude" (increase of signal intensity relative to precontrast value) and k(ep) (exchange rate constant). Data obtained by MRI were validated by parallel examinations of histological sections immunostained for blood vessels (CD31). Already 2 days after the first DC101 application, a decrease of tumor vascularization was observed, which preceded a reduction of tumor volume. The difference between treated tumors and controls became prominent after 4 days, when amplitudes of treated tumors were decreased by 61% (P =.02). In line with change of microvessel density, the decrease in amplitudes was most pronounced in tumor centers. On day 7, the mean tumor volumes of treated (153 +/- 843 mm(3)) and control animals (596 +/- 384 mm(3)) were significantly different (P =.03). After 14 days, treated tumors showed further growth reduction (83 +/- 93 mm(3)), whereas untreated tumors (1208 +/- 822 mm(3)) continued to increase (P =.02). Our data underline the efficacy of DC101 as antiangiogenic treatment in human squamous cell carcinoma xenografts in nude mice and indicate DCE MRI as a valuable tool for early detection of treatment effects before changes in tumor volume become apparent.

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Experimental study of the rat for the assessment of barium coating on the gastric mucosa: efficacy of ranitidine and acetylcysteine administration.

PURPOSE: In order to improve the preparation method for barium examination of the stomach by ranitidine and acetylcysteine use, the effect on the rat gastric mucosa caused by the administration of ranitidine and acetylcysteine was studied. MATERIALS AND METHODS: Rat stomach that had been treated with ranitidine or acetylcysteine at different intervals and examined in vivo was excised and coated with a barium suspension. A radiograph was subsequently taken and evaluated in regard to the removal of gastric mucus and imaging of the areae gastricae (AG). The removal of mucus was assessed by six blind observers. The imaging of AG was estimated as a percentage of the imaged AG area per total gastric corpus. RESULTS: No change was seen on the radiograph with ranitidine preparation, while the mucus was distinctly removed and AG well-imaged in the group studied 15 minutes after the peroral administration of acetylcysteine. CONCLUSION: Proper preparation for barium study of the stomach should involve treatment with a mucolytic agent about 15 minutes before the examination. H2-blockers must be used supplementally in the short term.

Acetylcysteine↗