[Unexpected emergencies and emergency findings in outpatient radiology practice]. / Unerwartete Notfälle und Notfallbefunde in der radiologischen Praxis.

CLINICAL/METHODICAL ISSUE: Radiological emergencies or incidental findings that require rapid treatment are part of the daily routine of radiological units in clinics-but also in outpatient radiology. What is special about the care of these patients in the outpatient radiological area? STANDARD RADIOLOGICAL METHODS: An acute or incidental diagnosis of an emergency situation generally occurs with CT or MRI. Outpatient radiology serves as a gatekeeper by preselecting critical cases and then, in close cooperation with all those involved, providing optimal therapy. METHODOLOGICAL INNOVATIONS: Use of CT and MRI to assess the emergency situation allows optimal therapy for the patient to be initiated. In outpatient radiology, close cooperation in the team with the patient and the referring physicians means achieving an optimal result, which can be a great opportunity. ACHIEVEMENTS: Close personal collaboration in the team with the referring physician and the patient is a decisive strength of outpatient radiology and can guarantee optimum care for the patient, especially in the case of acute emergencies or incidental findings which turn out to be clinical-radiological emergencies. The largest challenge in outpatient radiology is to select the critical cases of the many noncritical cases in the face of growing time and cost pressure in a time-economic manner. PRACTICAL RECOMMENDATIONS: Outpatient radiology should be aware of the chance for close cooperation and communication with referring physician and patient, especially in emergency situations-for the well-being of the patient, but also to increase the acceptance and significance of the field of radiology.

[Molecular ultrasound imaging: Clinical applications]. / Molekulare Ultraschallbildgebung: Chancen für die Klinik.

BACKGROUND: Contrast-enhanced ultrasound imaging is increasingly being used in clinical applications, particularly for cardiovascular and liver diagnostics. In this context the availability of new molecular contrast agents and the initiation of clinical translation promises new options for pathomechanistic diagnostics. MATERIAL AND METHODS: Analysis of the current literature on the development of molecular ultrasound contrast agents, the detection methods as well as the applications in preclinical and clinical studies. RESULTS: Molecular contrast agents have become established in preclinical research for the detection of inflammation and angiogenesis and have been continuously refined over recent years. They consist of gas filled microbubbles with a diameter of 1-5 µm and the gas core is stabilized by a shell made of lipids, proteins or polymers to which biomolecules are conjugated that determine the target specificity. The agent BR55 is the first clinically evaluated molecular ultrasound contrast agent. It binds to the angiogenesis marker vascular endothelial growth factor receptor 2 (VEGFR2) and has been studied in several preclinical and clinical phase I and II studies on tumor diagnostics and characterization. CONCLUSION: Molecular ultrasound imaging is rapidly evolving in preclinical research for a broad field of applications. Translation to clinical practice is conceivable for many indications and is already ongoing for BR55.

Functional and molecular ultrasound imaging: concepts and contrast agents.

Contrast-enhanced ultrasound has shown convincing results for monitoring vessel morphology, surrogate markers of vascularization and changes in molecular marker expression in oncological and cardiovascular diseases. Ultrasound contrast agents have the ability to increase the backscattering signal intensity of an ultrasound pulse. An interesting class of ultrasound contrast agents are gas filled microbubbles, which can be synthesized by external bubble encapsulation using sugar matrices or microspheres consisting of lipids or polymers with or without surfactant and by selecting gases with low blood solubility and diffusion coefficient such as perfluorocarbons or sulphur hexafluoride. Ultrasound contrast agents can be classified according to the rigidity of their shell. Soft-shell microbubbles are coated with a thin monolayer of surfactant molecules such as palmitic acid or phospholipids and are very sensitive to pressure changes. Hard-shell microbubbles have a rigid shell made of polymers such as polycyanoacrylate, which dramatically increases their stability. Depending on the acoustic properties of the microbubbles and on the purpose of the examination either destructive or non destructive methods are preferred for their detection. Microbubbles can be detected by destructive and non-destructive methods. Both soft- and hard-shell microbubbles coated with target-specific molecules can also be used for molecular imaging. Using target-specific approaches, the expression of several angiogenic markers such as VEGFR2, alphavbeta3 Integrins, ICAM, and E-selectin has been investigated in neoplastic and vascular diseases. This article summarizes the synthesis and properties of contrast agents as well as the indications, limitations and future potential of contrast-enhanced functional and molecular ultrasound.

[Advances in the staging of renal cell carcinoma with high-resolution imaging]. / Fortschritte im Staging des Nierenzellkarzinoms mittels hochauflösender Bildgebung.

Modern imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) allow high-resolution imaging of the abdomen. Modern scanners made high temporal as well as high spatial resolution available. Therapeutic approaches to the treatment of renal cell carcinoma have been improved over the recent years. Besides conventional and open laparoscopic tumor nephrectomy and nephron sparing, surgical approaches such as local tumor cryotherapy and radiofrequency ablation (RF) are ablative modalities and are used increasingly. Improved anesthesiological methods and new surgical approaches also allow curative treatment in extended tumors. Prerequisites for preoperative imaging modalities include visualization of the kidney tumor as well as its staging. Tumor-related infiltration of the renal pelvis or invasion of the perinephric fat and the renal hilus has to be excluded prior to nephron sparing surgery. In cases with extended tumors with infiltration of the inferior vena cava, it is necessary to visualize the exact extension of the tumor growth towards the right atrium in the vena cava. The radiologist should be informed about the diagnostic possibilities and limitations of the imaging modalities of CT and MRI in order to support the urologist in the planning and performance of surgical therapeutical approaches.

[Experimental testing of a new coil design for endoluminal MRI applied to the pig stomach]. / Experimentelle Erprobung eines neuen Spulendesigns zur endoluminalen MRT am Beispiel des Schweinemagens.

PURPOSE: Experimental feasibility study of a new MR-Coil concept for enhanced visualization of the gastric wall. MATERIAL AND METHODS: The newly developed single-loop receiver coil for endoluminal imaging (Fraunhofer Institute, St. Ingbert, Germany) was evaluated in 4 explanted pig stomachs in a 1.5T MR unit (Siemens Symphony, Erlangen, Germany) with T1 w and T2 w MR sequences in three planes. The new coil consists of a foldable and self-expanding single loop coil (receiver coil) of a shape memory metal (nitinol). It was covered with a biocompatible material (silicone) to prevent direct contact of the wire with stomach tissue. The coil assumes a circular configuration with a diameter of 8 cm because of its memory metal properties. The flexible characteristics of the material used allow the passage through the instrument channel (13 mm diameter) of a specially designed MR-compatible endoscope. The purpose of our study was to assess feasibility of the coil design as a first step in developing a new endoluminal MRI-concept. Additionally the number and signal intensity of visible gastric wall layers were evaluated and findings were correlated with histopathological results of a pig stomach. RESULTS: The new coil concept was a feasible system in all 4 cases and showed good image quality for analysis. On T1 w images, 3 layers were visible in all cases, and on T2 w images 4 different gastric wall layers were seen in 2 cases. Due to histopathological correlation, the different gastric wall layers were identified as follows: mucosa, submucosa and muscularis propria if three layers were depicted; in cases of 4 visible wall layers, serosa and subserosa could be detected additionally. For each gastric wall layer, a distinct signal intensity was found. CONCLUSION: The new MR coil concept for endoluminal imaging proved to be a feasible technique. Good differentiation of gastric wall layers in the pig stomach could be demonstrated. We have shown that endoscopic MR-imaging with our new coil concept is a valuable technique for the visualization of gastric wall layers. Due to this fact, follow-up studies including assessing safety aspects are necessary to finally conduct an experimental-clinical study on in-vivo human gastric specimens to detect tumor growth and morphology within the gastric wall. Endoscopic MRI may have the potential in the future to overcome today's limitations of diagnostic imaging in gastric cancer.

The use of chimeric A2K(b) tetramers to monitor HLA A2 immune responses in HLA A2 transgenic mice.

HLA A2 (A2) transgenic mice are currently being used to compare different vaccination protocols. However, the monitoring of A2 restricted CTL in A2 transgenic mice have been hampered by poor staining efficiency of mouse CTL by A2 tetramers. We demonstrate here that chimeric A2 tetramers containing mouse H-2K(b) (K(b)) alpha3 domain (A2K(b) tetramers) can be used as staining reagents to monitor A2 restricted CTL responses in A2 transgenic mice. The increased ability of A2K(b) tetramers to stain mouse A2 restricted CTL, as compared with A2 tetramers, correlated with their higher binding affinity for mouse A2 restricted CTL. The use of these novel staining reagents will allow efficient comparison of vaccination strategies and rapid identification of novel CTL epitopes in A2 transgenic mice.

Tissue oxygenation of the skeletal muscle and of the heart during hemodynamic alterations in rats.

In the anaesthetized, open-chest rat, electrical stimulation of the sympathetic or parasympathetic nerves in the cervical area produced significant changes in the heart rate. The subsequent alterations in cardiac output and in total peripheral resistance did not alter the oxygenation of resting skeletal muscle. This means that the skeletal muscle of intact rats provided sufficient O2 to withstand shortlasting changes in hemodynamics. The increase in mean tissue PO2 on the heart after the bilateral vagotomy was the consequence of an increased perfusion due to the increased heart rate. The absence of vasoconstrictor nerve impulses after the bilateral dissection of the sympathetic cord induced a dilation of the vascular bed and therefore an increase in the tissue PO2 of the heart.

Influence of normovolemic hemodilution with 10% HES 200 on tissue PO2 in the M. tibialis ant. of 7 male volunteers.

The aim of the present study was to investigate the effect of normovolemic hemodilution with a middle molecular HES solution on oxygen supply and PO2 pressure distribution in the extremity muscles of healthy male subjects. In addition to a significant reduction of the hematocrit (Hct) by hemodilution from about 44% to about 37% and unchanged arterial blood gas values, an increase of the mean muscle PO2 from about 16 mmHg (before hemodilution) to about 27 mmHg (30 minutes after having reached normovolemia) was observed. The increase of the mean tissue PO2 is demonstrable already 30 minutes after the start of infusion (t = 30) (see Table 2). The markedly raised level of the tissue PO2 in the M. tibialis anterior as compared with the initial value is demonstrable both during and after normovolemic hemodilution. In addition to this dilution-related increase of the mean tissue PO2, a marked change of configuration of the PO2 histograms is found. There is an increase filling of the PO2 classes in the pressure ranges above 40 mmHg. The conspicuous increase of the intra-individual dispersion of PO2 mean values during and after infusion of HES 200 cannot be interpreted for the moment. Similar observations were, for example, reported by Landgraf and Ehrly in 1985 when measuring the muscular tissue oxygen pressure in patients with intermittent claudication before, after and during infusion of 0.9% saline solution. This could be interpreted as an increased perfusion of certain areas of the muscular capillary system.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle PO2 in the initial phase of increased local oxygen demand (rhythmical muscle contraction) in rats with portacaval shunt (PCA).

The influence of a hyperdynamic syndrome caused by PCA on PO2 distribution in skeletal muscle of rats during the initial phase of muscle activity was examined. Rhythmical muscle contraction of the m. biceps femoris was induced by direct electrical stimulation. Tissue PO2 of the contracting muscle was recorded continuously from the start of the 210 s-long activity period up to 140 s after the last contraction using a multiwire surface electrode. In comparison with controls no different behaviour of mean muscle PO2 in the initial phase of contraction was found. After muscle activity mean PO2 decreased to a lower level in rats with PCA than in controls. This might be a further indication of the disturbing influence of a hyperdynamic syndrome on the regulating mechanisms of the microcirculation.

Circadian course of PO2-oscillations in skeletal muscle of intact and portacaval shunted (PCA) rats.

In rats several circadian rhythms such as heart rate, body temperature, and locomotor activity are known. Several authors found a loss of day-night-rhythm (locomotor activity, EEG) after portacaval shunting (PCA). The aim of this study was to evaluate whether muscle PO2 oscillations are circadian and whether they are altered after time-limited hypercirculation caused by PCA. 126 days after operation tissue PO2 of m. rectus abdominis of 9 rats with PCA and 10 controls was measured with a multi-wire surface electrode. All animals were kept under constant conditions and each animal was measured 6 times at intervals of 4 hours in order to get a circadian PO2 course. In controls the circadian course of mean muscle PO2 resembled a sine oscillation with high values at night and low values in the afternoon. In PCA-rats the time course of mean muscle PO2 showed 3 oscillations with different amplitudes, each with a period length of 24 hours. Our results indicate that oscillations of muscle PO2 are determined principal by circadian locomotor activity and that time-limited hypercirculation influences the circadian course of mean muscle PO2.

Imaging in the age of molecular medicine: monitoring of anti-angiogenic treatments.

Angiogenesis is a complex multistep process and a crucial pre-requisite for tumor growth, invasion and metastasis. A profound knowledge of the mechanisms including the elucidation of markers for angiogenic vessels is essential for the generation of new anti-angiogenic chemotherapeutic agents and the improvement of specific imaging techniques. During the last decades, numerous angiogenesis inhibitors have been developed and some of them have shown promising results in preclinical and clinical trials. However, the response to anti-angiogenic treatment is often delayed and shows high inter-individual variations. In order to improve anti-angiogenic therapy, new specific surrogate markers are necessary that allow the characterization of different angiogenic steps, especially at the early stage. In this respect, non-invasive imaging is a potent tool for characterizing the tumor vascularization and for sensitive and longitudinal treatment monitoring. In particular, new molecular imaging techniques might ultimately improve the characterization of the angiogenic tumor phenotype and stage. This review summarizes the current status of different imaging modalities e.g. MRI, CT, US, nuclear and optical imaging with respect to the imaging of tumor angiogenesis and of anti-angiogenic treatments. It also includes new approaches in molecular imaging, which give deep insight into the tumor stage and the response of tumor vessels to anti-angiogenic therapy. Thus, this may lead to a more personalized cancer therapy in future.

[Bilateral adrenal vein sampling in single catheter technique using a 4F cobra catheter in regular and inverse configuration]. / Bilaterale selektive Nebennierenvenen-Blutentnahme: Einzelkatheter-Technik mittels eines 4F-Kobra-Katheters in Standard- und Inversionstechnik.

In Conn's syndrome, adrenal vein sampling (AVS) is used to secure the site of hormonal overproduction. The left adrenal vein is usually easy to explore, the right is difficult. Examination requires several differently configured catheters. Here, we introduce a new technique for AVS using a single cobra catheter, which was tested in n = 13 patients. In an inverted configuration, the cobra catheter can be used to explore the left side, while the regular configuration can be used for the right side. The technical details are described in the manuscript. In all patients, left AVS could be performed successfully using the inverted catheter configuration. In n = 11 patients, right AVS was carried out successfully with a cobra catheter in regular configuration. In two cases, a Sidewinder-I catheter was required due to a steep angle of the adrenal vein.

Current role and future perspective of MRI for diagnosis and characterization of renal cell carcinoma.

During the past years, magnetic resonance imaging (MRI) has been established as a reliable method for examination of the kidneys. Modern MRI systems enable to visualize renal masses with a high spatial resolution. This enables not only to differentiate between benign lesions and renal cancer but also to define the tumor stage with high accuracy. The impact of a precise preoperative staging has increased significantly due to stage adapted therapy approaches such as nephron sparing surgery or local ablative techniques (e.g. radiofrequency ablation). Tumor-related infiltration of the renal pelvis, infiltration of the perinephric fat or a tumor thrombus within the inferior caval vein has to be diagnosed with high accuracy to enable these stage adapted treatment regimens. This article introduces into clinically established "morphologic" MRI techniques for diagnosis and staging of renal cell carcinoma (RCC). Besides detection and staging of kidney cancer, the recent development of molecularly targeted therapies in patients with metastatic or non-operable tumors has led to novel diagnostic demands. To evaluate treatment efficiency, more information than just tumor morphology should be provided. Functional imaging techniques including dynamic contrast enhanced (DCE) MRI, diffusion weighted imaging (DWI), arterial spin labeling (ASL) and MR-spectroscopy are being investigated in preclinical and clinical trials. While some new techniques have shown promising results for a broad clinical application, others seem to be suited for dedicated questions only.

[Molecular imaging in oncology using targeted ultrasound contrast agents]. / Molekulare Bildgebung in der Onkologie: Tumor-spezifische Ultraschallkontrastmittel.

Molecular imaging enables to assess disease-associated processes at the cellular and molecular level. Nuclear medicine techniques are already available in the clinical routine. Besides these techniques, intensive research has been performed in the field of ultrasound. The development of target-specific ultrasound contrast agents in combination with modern imaging systems transformed ultrasound to a capable molecular imaging technique. It has been shown that the expression of disease-associated endothelial receptors can be assessed using targeted microbubbles, demonstrating its high value in the diagnosis of several diseases. The broad availability of suitable ultrasound systems promises a wide utilisation in the clinical routine, once clinically approved contrast agents are available. This review summarizes the basics and the current status of molecular ultrasound imaging.