Refine
Has Fulltext
- yes (16)
Is part of the Bibliography
- yes (16)
Document Type
- Journal article (16) (remove)
Language
- English (16) (remove)
Keywords
- imaging (16) (remove)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (4)
- Klinik und Poliklinik für Nuklearmedizin (3)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (2)
- Lehrstuhl für Orthopädie (2)
- Neurochirurgische Klinik und Poliklinik (2)
- Pathologisches Institut (2)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Hygiene und Mikrobiologie (1)
- Institut für Organische Chemie (1)
- Institut für Pharmazie und Lebensmittelchemie (1)
EU-Project number / Contract (GA) number
- 725229 (1)
Fibrosis is a pivotal player in heart failure development and progression. Measurements of (markers of) fibrosis in tissue and blood may help to diagnose and risk stratify patients with heart failure, and its treatment may be effective in preventing heart failure and its progression. A lack of pathophysiological insights and uniform definitions has hampered the research in fibrosis and heart failure. The Translational Research Committee of the Heart Failure Association discussed several aspects of fibrosis in their workshop. Early insidious perturbations such as subclinical hypertension or inflammation may trigger first fibrotic events, while more dramatic triggers such as myocardial infarction
and myocarditis give rise to full blown scar formation and ongoing fibrosis in diseased hearts. Aging itself is also associated with a cardiac phenotype that includes fibrosis. Fibrosis is an extremely heterogeneous phenomenon, as several stages of the fibrotic process exist, each with different fibrosis subtypes and a different composition of various cells and proteins — resulting in a very complex pathophysiology. As a result, detection of fibrosis, e.g. using current cardiac imaging modalities or plasma biomarkers, will detect only specific subforms of fibrosis, but cannot capture all aspects of the complex fibrotic process. Furthermore, several anti-fibrotic therapies are under investigation, but such therapies generally target aspecific aspects of the fibrotic process and suffer from a lack of precision. This review discusses the mechanisms and the caveats and proposes a roadmap for future research.
Immunotherapy with chimeric antigen receptor-engineered T-cells (CAR-T) is under investigation in multiple myeloma. There are reports of myeloma remission after CD19 CAR-T therapy, although CD19 is hardly detectable on myeloma cells by flow cytometry (FC). We apply single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM), and demonstrate CD19 expression on a fraction of myeloma cells (10.3–80%) in 10 out of 14 patients (density: 13–5,000 molecules per cell). In contrast, FC detects CD19 in only 2 of these 10 patients, on a smaller fraction of cells. Treatment with CD19 CAR-T in vitro results in elimination of CD19-positive myeloma cells, including those with <100 CD19 molecules per cell. Similar data are obtained by dSTORM analyses of CD20 expression on myeloma cells and CD20 CAR-T. These data establish a sensitivity threshold for CAR-T and illustrate how super-resolution microscopy can guide patient selection in immunotherapy to exploit ultra-low density antigens.
Introduction
Diagnosis and treatment of insertional tendinopathy of the Achilles tendon (IAT) remains a challenge. The aim of this study was to assess the influence of pre-operative radiological pathologies on the patient-reported outcomes following open debridement of all pathologies for IAT.
Materials and methods
In this IRB-approved retrospective correlation and comparative study, patients with pre-operative imaging were identified from the authors’ retrospective IAT database comprising of 118 patients. All were treated by a standardized surgical treatment strategy utilizing a midline, transachillary approach and debridement of all pathologies. A total of fifteen radiologic parameters were measured on radiographs (RX) and MRI. The patient-reported outcomes were assessed using the Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A-G) and the general health questionnaire SF-12 at a minimum follow-up of 12 months. The data are presented as mean ± SD (95% CI).
Results
88 patients (74.6%) with an average age of 50 ± 12 (47–52) years were included. Radiographs were available in 68 patients and MRI in 53. The mean follow-up was 3.8 ± 1.9 (3.4–4.3) years. The overall VISA-A-G was 81 ± 22 (77–86), the SF-12 PCS 54 ± 7 (52–55), and the SF-12 MCS 52 ± 9 (50–54) points. None of the assessed radiological parameters had a significant influence on the patient-reported outcome following surgical treatment for IAT.
Conclusion
In this retrospective correlation study, no significant association was found between preoperative radiographic and MRI radiologic parameters for IAT and postoperative patient-reported outcomes (VISA-A-G and SF-12).
Minimally invasive endovascular interventions have become an important tool for the treatment of cardiovascular diseases such as ischemic heart disease, peripheral artery disease, and stroke. X-ray fluoroscopy and digital subtraction angiography are used to precisely guide these procedures, but they are associated with radiation exposure for patients and clinical staff. Magnetic Particle Imaging (MPI) is an emerging imaging technology using time-varying magnetic fields combined with magnetic nanoparticle tracers for fast and highly sensitive imaging. In recent years, basic experiments have shown that MPI has great potential for cardiovascular applications. However, commercially available MPI scanners were too large and expensive and had a small field of view (FOV) designed for rodents, which limited further translational research. The first human-sized MPI scanner designed specifically for brain imaging showed promising results but had limitations in gradient strength, acquisition time and portability. Here, we present a portable interventional MPI (iMPI) system dedicated for real-time endovascular interventions free of ionizing radiation. It uses a novel field generator approach with a very large FOV and an application-oriented open design enabling hybrid approaches with conventional X-ray-based angiography. The feasibility of a real-time iMPI-guided percutaneous transluminal angioplasty (PTA) is shown in a realistic dynamic human-sized leg model.
The next-generation Event Horizon Telescope (ngEHT) will be a significant enhancement of the Event Horizon Telescope (EHT) array, with ∼10 new antennas and instrumental upgrades of existing antennas. The increased uv-coverage, sensitivity, and frequency coverage allow a wide range of new science opportunities to be explored. The ngEHT Analysis Challenges have been launched to inform the development of the ngEHT array design, science objectives, and analysis pathways. For each challenge, synthetic EHT and ngEHT datasets are generated from theoretical source models and released to the challenge participants, who analyze the datasets using image reconstruction and other methods. The submitted analysis results are evaluated with quantitative metrics. In this work, we report on the first two ngEHT Analysis Challenges. These have focused on static and dynamical models of M87* and Sgr A* and shown that high-quality movies of the extended jet structure of M87* and near-horizon hourly timescale variability of Sgr A* can be reconstructed by the reference ngEHT array in realistic observing conditions using current analysis algorithms. We identify areas where there is still room for improvement of these algorithms and analysis strategies. Other science cases and arrays will be explored in future challenges.
Thymic hyperplasia (TH) with lymphoepithelial sialadenitis (LESA)-like features (LESA-like TH) has been described as a tumor-like, benign proliferation of thymic epithelial cells and lymphoid follicles. We aimed to determine the frequency of lymphoma and autoimmunity in LESA-like TH and performed retrospective analysis of cases with LESA-like TH and/or thymic MALT-lymphoma. Among 36 patients (21 males) with LESA-like TH (age 52 years, 32–80; lesion diameter 7.0 cm, 1–14.5; median, range), five (14%) showed associated lymphomas, including four (11%) thymic MALT lymphomas and one (3%) diffuse large B-cell lymphoma. One additional case showed a clonal B-cell-receptor rearrangement without evidence of lymphoma. Twelve (33%) patients (7 women) suffered from partially overlapping autoimmune diseases: systemic lupus erythematosus (n = 4, 11%), rheumatoid arthritis (n = 3, 8%), myasthenia gravis (n = 2, 6%), asthma (n = 2, 6%), scleroderma, Sjögren syndrome, pure red cell aplasia, Grave’s disease and anti-IgLON5 syndrome (each n = 1, 3%). Among 11 primary thymic MALT lymphomas, remnants of LESA-like TH were found in two cases (18%). In summary, LESA-like TH shows a striking association with autoimmunity and predisposes to lymphomas. Thus, a hematologic and rheumatologic workup should become standard in patients diagnosed with LESA-like TH. Radiologists and clinicians should be aware of LESA-like TH as a differential diagnosis for mediastinal mass lesions in patients with autoimmune diseases.
Purpose
Repeat surgery in patients with primary hyperparathyroidism (pHPT) is associated with an increased risk of complications and failure. This stresses the need for optimized strategies to accurately localize a parathyroid adenoma before repeat surgery is performed. However, evidence on the extent of required diagnostics for a structured approach is sparse.
Methods
A retrospective single-center evaluation of 28 patients with an indication for surgery due to pHPT and previous thyroid or parathyroid surgery was performed. Diagnostic workup, surgical approach, and outcome in terms of complications and successful removement of parathyroid adenoma with biochemical cure were evaluated.
Results
Neck ultrasound, sestamibi scintigraphy, C11-methionine PET-CT, and selective parathyroid hormone venous sampling, but not MRI imaging, effectively detected the presence of a parathyroid adenoma with high positive predictive values. Biochemical cure was revealed by normalization of calcium and parathormone levels 24-48h after surgery and was achieved in 26/28 patients (92.9%) with an overall low rate of complications. Concordant localization by at least two diagnostic modalities enabled focused surgery with success rates of 100%, whereas inconclusive localization significantly increased the rate of bilateral explorations and significantly reduced the rate of biochemical cure to 80%.
Conclusion
These findings suggest that two concordant diagnostic modalities are sufficient to accurately localize parathyroid adenoma before repeat surgery for pHPT. In cases of poor localization, extended diagnostic procedures are warranted to enhance surgical success rates. We suggest an algorithm for better orientation when repeat surgery is intended in patients with pHPT.
Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity.
Although chest radiograph (CXR) is commonly used in diagnosing pediatric community acquired pneumonia (pCAP), limited data on interobserver agreement among radiologists exist. PedCAPNETZ is a prospective, observational, and multicenter study on pCAP. N = 233 CXR from patients with clinical diagnosis of pCAP were retrieved and n = 12 CXR without pathological findings were added. All CXR were interpreted by a radiologist at the site of recruitment and by two external, blinded pediatric radiologists. To evaluate interobserver agreement, the reporting of presence or absence of pCAP in CXR was analyzed, and prevalence and bias‐adjusted kappa (PABAK) statistical testing was applied. Overall, n = 190 (82%) of CXR were confirmed as pCAP by two external pediatric radiologists. Compared with patients with pCAP negative CXR, patients with CXR‐confirmed pCAP displayed higher C‐reactive protein levels and a longer duration of symptoms before enrollment (p < .007). Further parameters, that is, age, respiratory rate, and oxygen saturation showed no significant difference. The interobserver agreement between the onsite radiologists and each of the two independent pediatric radiologists for the presence of pCAP was poor to fair (69%; PABAK = 0.39% and 76%; PABAK = 0.53, respectively). The concordance between the external radiologists was fair (81%; PABAK = 0.62). With regard to typical CXR findings for pCAP, chance corrected interrater agreement was highest for pleural effusions, infiltrates, and consolidations and lowest for interstitial patterns and peribronchial thickening. Our data show a poor interobserver agreement in the CXR‐based diagnosis of pCAP and emphasized the need for harmonized interpretation standards.
Whereas the role of calcium ions (Ca\(^{2+}\)) in plant signaling is well studied, the physiological significance of pH‐changes remains largely undefined.
Here we developed CapHensor, an optimized dual‐reporter for simultaneous Ca\(^{2+}\) and pH ratio‐imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio‐temporal relationships between membrane voltage, Ca\(^{2+}\)‐ and pH‐dynamics revealed interconnections previously not described.
In tobacco PTs, we demonstrated Ca\(^{2+}\)‐dynamics lag behind pH‐dynamics during oscillatory growth, and pH correlates more with growth than Ca\(^{2+}\). In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA‐responses and even opened stomata in the presence of ABA, disclosing an important pH‐dependent GC signaling node. In MCs, a flg22‐induced membrane depolarization preceded Ca2+‐increases and cytosolic acidification by c. 2 min, suggesting a Ca\(^{2+}\)/pH‐independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage‐, Ca\(^{2+}\)‐ and pH‐responses.
We propose close interrelation in Ca\(^{2+}\)‐ and pH‐signaling that is cell type‐ and stimulus‐specific and the pH having crucial roles in regulating PT growth and stomata movement.
Background: Pheochromocytomas and paragangliomas (PPGLs) are rare but potentially harmful tumors that can vary in their clinical presentation. Tumors may be found due to signs and symptoms, as part of a hereditary syndrome or following an imaging procedure. Objective: To investigate potential differences in clinical presentation between PPGLs discovered by imaging (iPPGLs), symptomatic cases (sPPGLs) and those diagnosed during follow-up because of earlier disease/known hereditary mutations (fPPGL). Design: Prospective study protocol, which has enrolled patients from six European centers with confirmed PPGLs. Data were analyzed from 235 patients (37 iPPGLs, 36 sPPGLs, 27% fPPGLs) and compared for tumor volume, biochemical profile, mutation status, presence of metastases and self-reported symptoms. iPPGL patients were diagnosed at a significantly higher age than fPPGLs (P<0.001), found to have larger tumors (P=0.003) and higher metanephrine and normetanephrine levels at diagnosis (P=0.021). Significantly lower than in sPPGL, there was a relevant number of self-reported symptoms in iPPGL (2.9 vs 4.3 symptoms, P< 0.001). In 16.2% of iPPGL, mutations in susceptibility genes were detected, although this proportion was lower than that in fPPGL (60.9%) and sPPGL (21.5%). Patients with PPGLs detected by imaging were older, have higher tumor volume and more excessive hormonal secretion in comparison to those found as part of a surveillance program. Presence of typical symptoms indicates that in a relevant proportion of those patients, the PPGL diagnosis had been delayed. Precis: Pheochromocytoma/paraganglioma discovered by imaging are often symptomatic and carry a significant proportion of germline mutations in susceptibility genes.
Opioid receptors (ORs) are classified among the oldest and best investigated drug targets due to their fundamental role in the treatment of pain and related disorders. ORs are divided in three conventional subtypes (μ, κ, δ) and the non‐classical nocicepetin receptor. All ORs are family A G protein‐coupled receptors (GPCRs), and are located on the cell surface. Modern biophysical methods use light to investigate physiological processes at organismal, cellular and subcellular level. Many of these methods rely on fluorescent ligands, thus highlighting their importance. This review addresses the advancements in the development of opioid fluorescent ligands and their use in biological, pharmacological and imaging applications.
Expansion microscopy (ExM) is a novel tool to improve the resolution of fluorescence-based microscopy that has not yet been used to visualize intracellular pathogens. Here we show the expansion of the intracellular pathogen Chlamydia trachomatis, enabling to differentiate its two distinct forms, catabolic active reticulate bodies (RB) and infectious elementary bodies (EB), on a conventional confocal microscope. We show that ExM enables the possibility to precisely locate chlamydial effector proteins, such as CPAF or Cdu1, within and outside of the chlamydial inclusion. Thus, we claim that ExM offers the possibility to address a broad range of questions and may be useful for further research on various intracellular pathogens.
Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor.
15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples.
\(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression.
In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.
Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon computed tomography (SPECT) with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) to assess striatal dopaminergic innervation. Unilateral movement execution led to event-related desynchronization (ERD) followed by a rebound after movement termination event-related synchronization (ERS) of oscillatory beta activity in the STN and primary sensorimotor cortex of both hemispheres. Dopamine deficiency directly influenced movement-related beta-modulation, with greater beta-suppression in the most dopamine-depleted hemisphere for both ipsi- and contralateral hand movements. Cortical-subcortical, but not interhemispheric subcortical coherencies were modulated by movement and influenced by striatal dopaminergic innervation, being stronger in the most dopamine-depleted hemisphere. The data are consistent with a role of dopamine in shielding subcortical structures from an excessive cortical entrapment and cross-hemispheric coupling, thus allowing fine-tuning of movement.