Investigation of ventricular cerebrospinal fluid flow phase differences between the foramina of Monro and the aqueduct of Sylvius

In this paper, phase contrast magnetic resonance flow measurements of the foramina of Monro and the aqueduct of Sylvius of seven healthy volunteers are presented. Peak volume flow rates are of the order of 150 mm3/s for the aqueduct of Sylvius and for the foramina of Monro. The temporal shift between these volume flows is analyzed with a high-resolution cross-correlation scheme which reveals high subject-specific phase differences. Repeated measurements show the invariability of the phase differences over time for each volunteer. The phase differences as a fraction of one period range from -0.0537 to 0.0820. A mathematical model of the pressure dynamics is presented. The model features one lumped compartment per ventricle. The driving force of the cerebrospinal fluid is modeled through pulsating choroid plexus. The model includes variations of the distribution of the choroid plexus between the ventricles. The proposed model is able to reproduce the measured phase differences with a very small (5%) variation of the distribution of the choroid plexus between the ventricles and, therefore, supports the theory that the choroid plexus drives the cerebrospinal fluid motio

Radiofrequency catheter ablation for supraventricular tachycardia in a paediatric population: characteristics of tachycardia mechanisms in a subpopulation with early onset

BACKGROUND In children, the first episode of supraventricular tachycardia occurs at various ages. The aim of this study is to describe age-specific tachycardia mechanisms, clinical findings, and outcome in a contemporary cohort of paediatric patients with supraventricular tachycardia. METHODS Retrospective analysis of 531 consecutive patients with structurally normal hearts under the age of 18 years who underwent invasive electrophysiological study for supraventricular tachycardia. The study population was divided into two groups, early-onset group (n = 57) and late-onset group (n = 474), according to the age of the occurrence of the first tachycardia before or after the age of 12 months. RESULTS Accessory pathway-mediated tachycardia was more common (82.5 versus 50.1%, p < 0.001) and the proportion of left-sided accessory pathways was more pronounced (74.5 versus 53.7%, p = 0.01) in the early-onset group than in the late-onset group. The antegrade and retrograde refractory periods of the accessory pathways were similar in both groups, but pre-excitation was more common in the early-onset group (50.9 versus 31.9%, p = 0.007). Typical atrioventricular nodal re-entrant tachycardia was more common (36.7 versus 7.0%, p < 0.001) in the late-onset group. There was no difference among the two groups regarding overall outcome. CONCLUSION Accessory pathway-mediated re-entrant tachycardia is the most common mechanism of recurrent supraventricular tachycardia in infants with structurally normal hearts who are later referred to an electrophysiological study. These pathways often cause pre-excitation and tend to be located on the left side whereas their refractory period is not different from that of patients with late-onset tachycardia

Dust-resistant microthermal mass-flow pitot-tube for fixed-wing drones (UAV)

Drones, commonly referred to as Unmanned Aerial Vehicles (UAVs), have become increasingly important for different applications. For the necessary velocity control, fixed-wing drones typically need a classical Pitot-tube, which consists of several components, including a large sensor which usually has to be calibrated before each flight. The microthermal mass-flow measurement principle enables a smaller sensor design, with less components and no pre-flight calibration. However, the drawback of such sensors is their increased sensitivity to particulate matter contamination. The aim of this paper is to present and test a new additively manufactured Pitot-tube design, which prevents a contamination of the microthermal flow sensor. The results of the particulate matter contamination experiment with the microthermal flow sensor show that the average induced error of 38.3% of the state of the art Pitot-tube design is reduced to 4% for the new additively manufactured Pitot-tube. The results of the flight test show a clear correlation of the differential pressure between the new additively manufactured (AM) Pitot-tube with microthermal flow sensing compared to the standard Pitot-tube design with a membrane sensor. Thus, the new AM Pitot-tube design enables accurate airspeed measurement even in environments with high concentration of particulate matter.ISSN:2212-827

18F-AzaFol for Detection of Folate Receptor-β Positive Macrophages in Experimental Interstitial Lung Disease-A Proof-of-Concept Study

Background: Interstitial lung disease (ILD) is a common and severe complication in rheumatic diseases. Folate receptor-β is expressed on activated, but not resting macrophages which play a key role in dysregulated tissue repair including ILD. We therefore aimed to pre-clinically evaluate the potential of $^{18}$F-AzaFol-based PET/CT (positron emission computed tomography/computed tomography) for the specific detection of macrophage-driven pathophysiologic processes in experimental ILD. Methods: The pulmonary expression of folate receptor-β was analyzed in patients with different subtypes of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. PET/CT was performed at days 3, 7, and 14 after BLM instillation using the $^{18}$F-based folate radiotracer $^{18}$F-AzaFol. The specific pulmonary accumulation of the radiotracer was assessed by ex vivo PET/CT scans and quantified by ex vivo biodistribution studies. Results: Folate receptor-β expression was 3- to 4-fold increased in patients with fibrotic ILD, including idiopathic pulmonary fibrosis and connective tissue disease-related ILD, and significantly correlated with the degree of lung remodeling. A similar increase in the expression of folate receptor-β was observed in experimental lung fibrosis, where it also correlated with disease extent. In the mouse model of BLM-induced ILD, pulmonary accumulation of $^{18}$F-AzaFol reflected macrophage-related disease development with good correlation of folate receptor-β positivity with radiotracer uptake. In the ex vivo imaging and biodistribution studies, the maximum lung accumulation was observed at day 7 with a mean accumulation of 1.01 ± 0.30% injected activity/lung in BLM-treated vs. control animals (0.31 ± 0.06% % injected activity/lung; p < 0.01). Conclusion: Our preclinical proof-of-concept study demonstrated the potential of $^{18}$F-AzaFol as a novel imaging tool for the visualization of macrophage-driven fibrotic lung diseases

Quantification of brain glucose metabolism by 18F-FDG PET with real-time arterial and image-derived input function in mice

Kinetic modeling of PET data derived from mouse models remains hampered by the technical inaccessibility of an accurate input function (IF). In this work, we tested the feasibility of IF measurement with an arteriovenous shunt and a coincidence counter in mice and compared the method with an image-derived IF (IDIF) obtained by ensemble-learning independent component analysis of the heart region. METHODS: (18)F-FDG brain kinetics were quantified in 2 mouse strains, CD1 and C57BL/6, using the standard 2-tissue-compartment model. Fits obtained with the 2 IFs were compared regarding their goodness of fit as assessed by the residuals, fit parameter SD, and Bland-Altman analysis. RESULTS: On average, cerebral glucose metabolic rate was 10% higher for IDIF-based quantification. The precision of model parameter fitting was significantly higher using the shunt-based IF, rendering the quantification of single process rate constants feasible. CONCLUSION: We demonstrated that the arterial IF can be measured in mice with a femoral arteriovenous shunt. This technique resulted in higher precision for kinetic modeling parameters than did use of the IDIF. However, for longitudinal or high-throughput studies, the use of a minimally invasive IDIF based on ensemble-learning independent component analysis represents a suitable alternative

Evaluation of 99mTc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early stages of interstitial lung disease associated with systemic sclerosis

Abstract Background Given the need for early detection of organ involvement in systemic sclerosis, we evaluated 99mTc-rhAnnexin V-128 for the detection of early stages of interstitial lung disease (ILD) in respective animal models using single photon emission computed tomography (SPECT/CT). Methods In bleomycin (BLM)-challenged mice, fos-related antigen 2 (Fra-2) transgenic (tg) mice and respective controls, lung injury was evaluated by analysis of hematoxylin and eosin (HE) and Sirius red staining, with semi-quantification of fibrosis by the Ashcroft score. Apoptotic cells were identified by TUNEL assay, cleaved caspase 3 staining and double staining with specific cell markers. To detect early stages of lung remodeling by visualization of apoptosis, mice were injected intravenously with 99mTc-rhAnnexin V-128 and imaged by small animal SPECT/CT. For confirmation, biodistribution and ex vivo autoradiography studies were performed. Results In BLM-induced lung fibrosis, inflammatory infiltrates occurred as early as day 3 with peak at day 7, whereas pulmonary fibrosis developed from day 7 and was most pronounced at day 21. In accordance, the number of apoptotic cells was highest at day 3 compared with saline controls and then decreased over time. Epithelial cells (E-cadherin+) and inflammatory cells (CD45+) were the primary cells undergoing apoptosis in the earliest remodeling stages of experimental ILD. This was also true in the pathophysiologically different Fra-2 tg mice, where apoptosis of CD45+ cells occurred in the inflammatory stage. In accordance with the findings on tissue level, at day 3 in the BLM and at week 16 in the Fra-2 tg model, biodistribution and/or ex vivo autoradiography showed increased pulmonary uptake of 99mTc-rhAnnexin V-128 compared with controls. However, accumulation of the radiotracer and thus the signal intensity in lungs was too low to allow the differentiation of healthy and injured lungs in vivo. Conclusion At the tissue level, 99mTc-rhAnnexin V-128 successfully demonstrated early stages of ILD in two animal models by detection of apoptotic epithelial and/or inflammatory cells. In vivo, however, we did not detect early lung injury. It remains to be investigated whether the same applies to human ILD

Chemoselective 18F-incorporation into pyridyl acyltrifluoroborates for rapid radiolabelling of peptides and proteins at room temperature

A new prosthetic group is reported for 18F-labelling of peptides and proteins based on the chemoselective ligation of potassium acyltrifluoroborates (KATs) and hydroxylamines without any detectable 18F/19F isotope exchange at the acyltrifluoroborate moiety. The new building block is appended via a common amide bond at room temperature with no need for protecting groups which enables an effective orthogonal 18F-radiolabelling.ISSN:1359-7345ISSN:1364-548

Visualisation of interstitial lung disease by molecular imaging of integrin αvβ3 and somatostatin receptor 2

OBJECTIVE To evaluate integrin αvβ3 (alpha-v-beta-3)-targeted and somatostatin receptor 2 (SSTR2)-targeted nuclear imaging for the visualisation of interstitial lung disease (ILD). METHODS The pulmonary expression of integrin αvβ3 and SSTR2 was analysed in patients with different forms of ILD as well as in bleomycin (BLM)-treated mice and respective controls using immunohistochemistry. Single photon emission CT/CT (SPECT/CT) was performed on days 3, 7 and 14 after BLM instillation using the integrin αvβ3-targeting Lu-DOTA-RGD and the SSTR2-targeting Lu-DOTA-NOC radiotracer. The specific pulmonary accumulation of the radiotracers over time was assessed by in vivo and ex vivo SPECT/CT scans and by biodistribution studies. RESULTS Expression of integrin αvβ3 and SSTR2 was substantially increased in human ILD regardless of the subtype. Similarly, in lungs of BLM-challenged mice, but not of controls, both imaging targets were stage-specifically overexpressed. While integrin αvβ3 was most abundantly upregulated on day 7, the inflammatory stage of BLM-induced lung fibrosis, SSTR2 expression peaked on day 14, the established fibrotic stage. In agreement with the findings on tissue level, targeted nuclear imaging using SPECT/CT specifically detected both imaging targets ex vivo and in vivo, and thus visualised different stages of experimental ILD. CONCLUSION Our preclinical proof-of-concept study suggests that specific visualisation of molecular processes in ILD by targeted nuclear imaging is feasible. If transferred into clinics, where imaging is considered an integral part of patients' management, the additional information derived from specific imaging tools could represent a first step towards precision medicine in ILD

Radiopharmaceuticals for Targeted Tumor Diagnosis and Therapy

Radiopharmaceutical research and development is carried out by the Center for Radiopharmaceutical Science as part of the PSI Life Science Department, the Department of Applied BioSciences at the Swiss Federal Institute of Technology Zürich and the University Hospital Zürich. The common theme is the search for radioactive-labeled tracer molecules, which bind to specific targets in the body. Such radiopharmaceuticals are applied either systemically into the blood stream or locally to patients. Due to their specific molecular binding properties combined with the emitted radiation, they can be used for non-invasive imaging of tumors and the destruction of tumor cells. In this first of two articles, we will present exemplified topics from the research activities of the groups involved with tumor targeting