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Biomedical subjects

W Semmler

Publications and source records attributed to W Semmler.

At least 19 recordsLinked to original sources

Interventional magnetic resonance imaging: an alternative to image guidance with ionising radiation.

At present, interventional procedures, such as stent placement, are performed under X-ray image guidance. Unfortunately with X-ray imaging, both patient and interventionalist are exposed to ionising radiation. Furthermore, X-ray imaging is lacking soft tissue contrast and is not capable of true 3-D displays of either interventional device or tissue morphology. Magnetic resonance imaging (MRI) offers excellent soft tissue contrast, 3-D acquisition techniques, as well as rapid image acquisition and reconstruction. Despite these advantages, MR-guided interventions are challenging owing to the limited access to the patient, strong magnetic and radio-frequency fields that require special interventional devices, inferior image frame rates and spatial resolution, and high MRI scanner noise. For MR-guided intravascular interventions, where access to the target organ is achieved through catheters, dedicated hardware and automated image slice positioning techniques have been developed. We illustrate that MR-guided renal embolisations can be performed in closed-bore high-field MR scanners.

Animals↗

A Faraday effect position sensor for interventional magnetic resonance imaging.

An optical sensor is presented which determines the position and one degree of orientation within a magnetic resonance tomograph. The sensor utilizes the Faraday effect to measure the local magnetic field, which is modulated by switching additional linear magnetic fields, the gradients. Existing methods for instrument localization during an interventional MR procedure often use electrically conducting structures at the instruments that can heat up excessively during MRI and are thus a significant danger for the patient. The proposed optical Faraday effect position sensor consists of non-magnetic and electrically non-conducting components only so that heating is avoided and the sensor could be applied safely even within the human body. With a non-magnetic prototype set-up, experiments were performed to demonstrate the possibility of measuring both the localization and the orientation in a magnetic resonance tomograph. In a 30 mT m(-1) gradient field, a localization uncertainty of 1.5 cm could be achieved.

Equipment Design↗

Targeted-HASTE imaging with automated device tracking for MR-guided needle interventions in closed-bore MR systems.

Percutaneous MR-guided interventions with needles require fast pulse sequences to image the needle trajectory with minimal susceptibility artifacts. Spin-echo pulse sequences are well suited for reducing artifact size; however, even with single-shot turbo spin-echo techniques, such as rapid acquisition with relaxation enhancement (RARE) or half-Fourier acquisition single-shot turbo spin-echo (HASTE), fast imaging remains challenging. In this work we present a HASTE pulse sequence that is combined with inner-volume excitation to reduce the scan time and limit the imaging field of view (FOV) to a small strip close to the needle trajectory (targeted-HASTE). To compensate for signal saturation from fast repeated acquisitions, a magnetization restore pulse (driven equilibrium Fourier transform (DEFT)) is used. The sequence is combined with dedicated active marker coils to measure the position and orientation of the needle so that the targeted-HASTE image slice is automatically repositioned. In an animal experiment the coils were attached to an MR-compatible robotic assistance system for MR-guided interventions. Needle insertion and infusion via the needle could be visualized with a temporal resolution of 1 s, and the needle tip could be localized even in the presence of a stainless steel mandrel.

Animals↗

[MRI of pulmonary perfusion].

Lung perfusion is a crucial prerequisite for effective gas exchange. Quantification of pulmonary perfusion is important for diagnostic considerations and treatment planning in various diseases of the lungs. Besides disorders of pulmonary vessels such as acute pulmonary embolism and pulmonary hypertension, these also include diseases of the respiratory tract and lung tissue as well as pulmonary tumors. This contribution presents the possibilities and technical requirements of MRI for diagnostic work-up of pulmonary perfusion.

Humans↗

[MRI safety aspects and artifacts of atrial septal defect and patent foramen ovale occluders at 1.5 tesla: a phantom study].

PURPOSE: To investigate the magnetic resonance safety and magnetic resonance artifact intensities of patent foramen ovale and atrial septal occluders in a phantom study. MATERIALS AND METHODS: Seven different commercial occluder models (Amplatzer ASD, Angel Wing ASD, Helex Septal Occluder, Cardia PFO-Star Generation I & III, Sideris Buttoned Device, Starflex ASD) were tested in a 1.5 Tesla whole-body MR scanner. Following a deflection test, the non-magnetic devices were imaged using different MRI pulse sequences including conventional spin echo, spoiled gradient echo as well as fast refocused steady-state pulse sequences (trueFISP) commonly used for cardiac MRI. Additionally, device temperatures were measured in the MR scanner during two imaging protocols (trueFISP, HASTE) with an MR-compatible fiber-optical thermometer. RESULTS: One ferromagnetic device (Sideris Buttoned Device) did not pass the deflection test and was excluded from further experiments. For typical cardiac imaging protocols, the remaining non-ferromagnetic devices showed only minor image artifacts with artifact sizes not exceeding 2 mm next to a strut. Heating was not observed in the devices. CONCLUSION: Non-ferromagnetic occluder models used in this study can safely be imaged with typical cardiac MRI protocols at 1.5 Tesla. The device artifact sizes are small enough to allow anatomical and functional MRI even in the immediate vicinity of the occluders.

Artifacts↗

[High resolution reconstruction of PET images using the iterative OSEM algorithm].

AIM: Improvement of the spatial resolution in positron emission tomography (PET) by incorporation of the image-forming characteristics of the scanner into the process of iterative image reconstruction. METHODS: All measurements were performed at the whole-body PET system ECAT EXACT HR(+) in 3D mode. The acquired 3D sinograms were sorted into 2D sinograms by means of the Fourier rebinning (FORE) algorithm, which allows the usage of 2D algorithms for image reconstruction. The scanner characteristics were described by a spatially variant line-spread function (LSF), which was determined from activated copper-64 line sources. This information was used to model the physical degradation processes in PET measurements during the course of 2D image reconstruction with the iterative OSEM algorithm. To assess the performance of the high-resolution OSEM algorithm, phantom measurements performed at a cylinder phantom, the hotspot Jaszczack phantom, and the 3D Hoffmann brain phantom as well as different patient examinations were analyzed. RESULTS: Scanner characteristics could be described by a Gaussian-shaped LSF with a full-width at half-maximum increasing from 4.8 mm at the center to 5.5 mm at a radial distance of 10.5 cm. Incorporation of the LSF into the iteration formula resulted in a markedly improved resolution of 3.0 and 3.5 mm, respectively. The evaluation of phantom and patient studies showed that the high-resolution OSEM algorithm not only lead to a better contrast resolution in the reconstructed activity distributions but also to an improved accuracy in the quantification of activity concentrations in small structures without leading to an amplification of image noise or even the occurrence of image artifacts. CONCLUSION: The spatial and contrast resolution of PET scans can markedly be improved by the presented image restauration algorithm, which is of special interest for the examination of both patients with brain disorders and small animals.

Algorithms↗

The adhesive properties of recombinant soluble L-selectin are modulated by its glycosylation.

The leukocyte adhesion molecule L-selectin, which mediates the initial steps of leukocyte attachment to vascular endothelium, is intensely glycosylated. Different glycoforms of L-selectin are expressed on different leukocyte subsets and differences in L-selectin glycosylation appear to be correlated with the leukocyte's ability to attach to different endothelial targets. In the present study we addressed the question whether glycosylation of L-selectin influences L-selectin-ligand interactions. To obtain different glycoforms of L-selectin, recombinant proteins were expressed both in the baby hamster kidney (BHK) cell line and in the human myelogenous cell line K562, resulting in sL-sel[BHK] or sL-sel[K562], respectively. The glycosylation characteristics of the purified proteins were determined. The most striking differences in glycosylation were seen in the terminal sialylation. Each of the two proteins carried sialic acids in the alpha 2-3 position, while alpha 2-6-bound sialic acids were found exclusively on sL-sel[K562]. To investigate their adhesive properties, both recombinant sL-selectins were used in cell adhesion assays and interactions with the ligands present on various hematopoietic cell lines or activated human cardiac microvascular endothelial cells were examined. The binding capacity of sL-sel[K562] was about 1.6 fold higher compared to sL-sel[BHK] under static as well as under flow conditions. These findings indicate that the terminal sialylation pattern of L-selectin modulates its binding characteristics.

Adhesives↗

Intracoronary delivery of Gd-DTPA and Gadophrin-2 for determination of myocardial viability with MR imaging.

The aim of this study was to compare intracoronary (i.c.) administration of Gadophrin-2, a necrosis-avid contrast agent (NACA), and nonspecific agent Gd-DTPA for determination of myocardial viability (MV) in acute myocardial infarction (AMI) with MRI. Reperfused AMI was induced in 12 dogs by transcatheter balloon occlusion of coronary artery. In 6 dogs each, Gd-DTPA at 0.1 mmol/kg or Gadophrin-2 at 0.005 mmol/kg was administered into coronary artery by fast bolus (n = 3) or slow infusion (n = 3). Serial ECG-triggered cardiac MRI of T1-weighted segmented turbo fast low-angle shot (FLASH) sequence was conducted and compared with triphenyltetrazolium chloride (TTC) histochemical staining. The contrast ratio and infarct size were quantified and analysed statistically. No cardiovascular side effects were found with local delivery of both agents. After i.c. administration, Gadophrin-2 induced a strong (CR > or = 1.78) and persistent (> or = 10 h) contrast enhancement of infarcted region. The infarct size defined with Gadophrin-2 was almost identical to that with TTC staining throughout the postcontrast period. With a dose 20 times higher, Gd-DTPA also strongly enhanced infarct-to-normal contrast; however, the enhancement diminished with time, i.e. from early strong to later faint enhancement and eventual loss of contrast. The delineated infarct size was also unstable, i.e. from early overestimation to later underestimation and eventual disappearance of the enhanced infarct. In combination with PTCA procedure, i.c. administration of MRI contrast agents may prove useful for post-procedure verification of diagnosis. The NACA-enhanced MRI may serve as an in vivo surrogate of postmortem histochemical staining for determination of MV. Although applicable in clinical setting, cardiac MRI with nonspecific Gd-DTPA is less reliable and should be performed within less than 1 h after contrast.

Animals↗

Magnetic marker monitoring of disintegrating capsules.

Magnetic marker monitoring was studied for its applicability to investigate the in vivo fate and behavior of disintegrating magnetically marked dosage forms. As a model, hard gelatin capsules were filled with an effervescent mixture of lactose, ascorbic acid and sodium hydrogen carbonate containing 1.3 mg black iron oxide as a magnetic label. The accuracy of the localization procedure whilst calculating all parameters of the dipole in one fitting procedure was checked in phantom experiments where the capsules were moved in well-defined paths with respect to the measurement device. The calculated position coordinates of the capsules deviated between less than 2 mm up to 8 mm from the expected position values depending on the distance between the sensor area and the capsule's path. Further experiments on the in vitro disintegration of the capsules showed that the value of the magnetic moment of the capsules can serve as a measure for their disintegration behavior. In vivo monitoring of the capsules was performed in eight experiments where a healthy volunteer swallowed each time one of the capsules. It was found that the in vivo disintegration behavior of the capsules corresponds well to their disintegration observed in water of about 37 degrees C.

Adult↗

Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands.

We report here the in vivo diagnostic use of a peptide-dye conjugate consisting of a cyanine dye and the somatostatin analog octreotate as a contrast agent for optical tumor imaging. When used in whole-body in vivo imaging of mouse xenografts, indotricarbocyanine-octreotate accumulated in tumor tissue. Tumor fluorescence rapidly increased and was more than threefold higher than that of normal tissue from 3 to 24 h after application. The targeting conjugate was also specifically internalized by primary human neuroendocrine tumor cells. This imaging approach, combining the specificity of ligand/receptor interaction with near-infrared fluorescence detection, may be applied in various other fields of cancer diagnosis.

Animals↗

Near-infrared fluorescent dyes for enhanced contrast in optical mammography: phantom experiments.

Optical mammography with near-infrared (NIR) light using time-domain, frequency-domain, or continuous-wave techniques is a novel imaging modality to locate human breast tumors. By investigating excised specimens of normal and diseased mamma tissue we were able to demonstrate that differences in their scattering properties are a poor predictive parameter for normal and diseased mamma tissue. This paper describes the application of a NIR dye to improve the differentiation between breast tumors and normal tissue in a rat model. The NIR dye furnished a high tumor-to-tissue contrast ratio (6:1) in fluorescence images. Furthermore, this dye was used to develop liquid scattering phantoms with absorbing and fluorescent inhomogeneities. Using frequency-domain and time-domain instrumentation these inhomogeneities were localized at sufficient contrast by their increased absorption and fluorescence. Contrast between inhomogeneities and surrounding medium could be improved by combining fluorescence and transmittance images.

Breast Neoplasms↗

USPIO-enhanced direct MR imaging of thrombus: preclinical evaluation in rabbits.

PURPOSE: To test the hypothesis that ultrasmall superparamagnetic iron oxide (USPIO) particles may diffuse into nonendothelialized fresh thrombi and thus allow for direct magnetic resonance (MR) imaging of a thrombus. MATERIALS AND METHODS: Stagnation thrombi of different thrombus ages (1, 3, 5, 7, and 9 days) were induced in the external jugular veins of 25 rabbits. Direct MR imaging of thrombi was performed by using a fat-saturated T1-weighted gradient-echo sequence (three-dimensional [3D] magnetization prepared rapid acquisition gradient echo) before and 24 hours after intravenous administration of USPIO (particle size, 25 nm; 200 micromol per kilogram of body weight). Thrombus length on 3D reconstruction images was compared with that depicted on a radiographic venogram and with histologic findings (joint reference standard). In addition, T2*-weighted gradient-echo images were acquired and scored semiquantitatively. RESULTS: The hyperintensity of the thrombus segment depicted on T1-weighted images (thrombus length determined with 3D reconstruction images divided by true thrombus length) increased significantly after administration of contrast medium at a thrombus age of 3 days (0.6 +/- 0.4 [SD] to 0.8 +/- 0.4; P =.02), 5 days (0.1 +/- 0.1 to 1.0 +/- 0.1; P <.001), and 7 days (0 to 0.6 +/- 0.4; P =.02), but not at an age of 1 and 9 days. No significant change in the thrombus signal intensity was observed on T2*-weighted images. CONCLUSION: The animal model showed that direct MR imaging of the thrombus improved 24 hours after USPIO administration with a T1-weighted sequence. No improvement was seen with the T2*-weighted sequence.

Animals↗

Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits.

RATIONALE AND OBJECTIVES: Inflammatory atherosclerotic plaques are characterized by increased endothelial permeability and multiple macrophages. Blood-pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammatory plaques. The objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by MRI and histology. METHODS: Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T. Four groups of five animals each were studied: (1) without ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or 200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron stains. RESULTS: Animals receiving 200 micromol Fe/kg demonstrated areas of focal signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P = 0.009). The number of images with this finding in groups 2 and 3 was not significantly different compared with controls. By microscopy, SPIO-iron was seen in the endothelial cells and subendothelial intimal macrophages of atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating iron uptake also showed a high macrophage content. CONCLUSIONS: SPIO accumulates in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques with increased endothelial permeability and a high macrophage content, two established features of plaque inflammation, it may have a potential for noninvasive assessment of inflammatory atherosclerotic plaques.

Animals↗

Macromolecular contrast agents for optical imaging of tumors: comparison of indotricarbocyanine-labeled human serum albumin and transferrin.

Macromolecules accumulate in solid tumors and can thus be used as carriers for the delivery of attached contrast agents to tumors. We report the synthesis and use of serum protein-dye conjugates consisting of transferrin (Tf) or human serum albumin (HSA) and an indotricarbocyanine (ITCC) derivative as contrast agents for the optical imaging of tumors. The compounds were characterized with respect to their photophysical properties and tested in vitro for their ability to bind to tumor cells and in vivo for their potential to delineate experimental tumors. In contrast to HAS-ITTC, Tf-ITCC showed receptor-mediated uptake by HT29 human colon cancer cells in vitro. After intravenous injection into HT29 tumor-bearing nude mice both compounds induced increased fluorescence contrast of tumors in vivo. After 24 h the contrast between tumor and normal tissue was significantly higher for Tf-ITCC than for HAS-ITCC. Dye-induced fluorescence was found to be predominantly located in perinecrotic areas of the tumor. Furthermore, Tf-ITCC produced fluorescence of viable tumor cells, whereas HAS-ITCC fluorescence was recorded along connective tissue. We conclude that ITCC-labeled Tf and HSA can serve as macromolecular contrast agents for the optical imaging of tumors, with Tf-ITCC showing higher efficiency.

Animals↗

Hydrophilic cyanine dyes as contrast agents for near-infrared tumor imaging: synthesis, photophysical properties and spectroscopic in vivo characterization.

We have synthesized a group of glucamine and gluosamine-substituted cyanine dyes structurally related to indocyanine green (ICG) and have characterized these compounds with regard to their potential as contrast agents for biomedical optical imaging. The compounds reported herein exhibit increased hydrophilicity and less plasma protein binding (< 50%), and are thus expected to have different pharmacokinetic properties compared with ICG. Furthermore, we measured enhanced fluorescence quantum yields (7-15%) in a physiological environment with respect to ICG. For the derivative with the highest hydrophilicity (5a) the efflux from tumor and normal tissue was monitored by intensity-modulated diffuse optical spectroscopy after intravenous injection into tumor-bearing rats. In comparison with ICG, 5a exhibited a considerably enhanced tissue-efflux half-life (73 min versus less than 10 min for ICG in tumor tissue), a two-fold higher initial tissue absorption coefficient compared to ICG, and finally, it generated an elevated tumor-to-tissue concentration gradient up to 1 h after injection. In conclusion, compounds such as 5a are promising contrast agents for optical imaging, and could facilitate highly sensitive and specific detection of breast cancer or other malignancies by utilizing mechanisms similar to contrast-enhanced magnetic resonance imaging or computerized tomography.

Animals↗