A Two-pronged Binding Mechanism of IgG to the Neonatal Fc Receptor Controls Complex Stability and IgG Serum Half-life

The success of recombinant monoclonal immunoglobulins (IgG) is rooted in their ability to target distinct antigens with high affinity combined with an extraordinarily long serum half-life, typically around 3 weeks. The pharmacokinetics of IgGs is intimately linked to the recycling mechanism of the neonatal Fc receptor (FcRn). For long serum half-life of therapeutic IgGs, the highly pH-dependent interaction with FcRn needs to be balanced to allow efficient FcRn binding and release at slightly acidic pH and physiological pH, respectively. Some IgGs, like the antibody briakinumab has an unusually short half-life of ∼8 days. Here we dissect the molecular origins of excessive FcRn binding in therapeutic IgGs using a combination of hydrogen/deuterium exchange mass spectrometry and FcRn affinity chromatography. We provide experimental evidence for a two-pronged IgG-FcRn binding mechanism involving direct FcRn interactions with both the Fc region and the Fab regions of briakinumab, and correlate the occurrence of excessive FcRn binding to an unusually strong Fab-FcRn interaction

Cardiac imaging procedures and the COVID-19 pandemic:recommendations of the European Society of Cardiovascular Radiology (ESCR)

The severe acute respiratory syndrome coronavirus 2019 (SARS-CoV-2) pandemic currently constitutes a significant burden on worldwide health care systems, with important implications on many levels, including radiology departments. Given the established fundamental role of cardiovascular imaging in modern healthcare, and the specific value of cardiopulmonary radiology in COVID-19 patients, departmental organisation and imaging programs need to be restructured during the pandemic in order to provide access to modern cardiovascular services to both infected and non-infected patients while ensuring safety for healthcare professionals. The uninterrupted availability of cardiovascular radiology services remains, particularly during the current pandemic outbreak, crucial for the initial evaluation and further follow-up of patients with suspected or known cardiovascular diseases in order to avoid unnecessary complications. Suspected or established COVID-19 patients may also have concomitant cardiovascular symptoms and require further imaging investigations. This statement by the European Society of Cardiovascular Radiology (ESCR) provides information on measures for safety of healthcare professionals and recommendations for cardiovascular imaging during the pandemic in both non-infected and COVID-19 patients

CMR for myocardial characterization in ischemic heart disease: state-of-the-art and future developments

Ischemic heart disease and its sequelae are one of the major contributors to morbidity and mortality worldwide. Over the last decades, technological developments have strengthened the role of noninvasive imaging for detection, risk stratification, and management of patients with ischemic heart disease. Cardiac magnetic resonance (CMR) imaging incorporates both functional and morphological characterization of the heart to determine presence, acuteness, and severity of ischemic heart disease by evaluating myocardial wall motion and function, the presence and extent of myocardial edema, ischemia, and scarring. Currently established clinical protocols have already demonstrated their diagnostic and prognostic value. Nevertheless, there are emerging imaging technologies that provide additional information based on advanced quantification of imaging biomarkers and improved diagnostic accuracy, therefore potentially allowing reduction or avoidance of contrast and/or stressor agents. The aim of this review is to summarize the current state of the art of CMR imaging for ischemic heart disease and to provide insights into promising future developments

Comparison of medical-grade and calibrated consumer-grade displays for diagnosis of subtle bone fissures

To compare the diagnostic accuracy of medical-grade and calibrated consumer-grade digital displays for the detection of subtle bone fissures. Three experienced radiologists assessed 96 digital radiographs, 40 without and 56 with subtle bone fissures, for the presence or absence of fissures in various bones using one consumer-grade and two medical-grade displays calibrated according to the DICOM-Grayscale Standard Display Function. The reference standard was consensus reading. Subjective image quality was also assessed by the three readers. Statistical analysis was performed using receiver operating characteristic analysis and by calculating the sensitivity, specificity, and Youden's J for each combination of reader and display. Cohen's unweighted kappa was calculated to assess inter-rater agreement. Subjective image quality was compared using the Wilcoxon signed-rank test. No significant differences were found for the assessment of subjective image quality. Diagnostic performance was similar across all readers and displays, with Youden's J ranging from 0.443 to 0.661. The differences were influenced more by the reader than by the display used for the assessment. No significant differences were found between medical-grade and calibrated consumer-grade displays with regard to their diagnostic performance in assessing subtle bone fissures. Calibrated consumer-grade displays may be sufficient for most radiological examinations. aEuro cent Diagnostic performance of calibrated consumer-grade displays is comparable to medical-grade displays. aEuro cent There is no significant difference with regard to subjective image quality. aEuro cent Use of calibrated consumer-grade displays could cut display costs by 60-80%

Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging:From Basic Concepts to Emerging Methods

BACKGROUND:  Late gadolinium enhancement (LGE) is a widely used cardiac magnetic resonance imaging (MRI) technique to diagnose a broad range of ischemic and non-ischemic cardiomyopathies. Since its development and validation against histology already more than two decades ago, the clinical utility of LGE and its span of applications have increased considerably. METHODS:  In this review we will present the basic concepts of LGE imaging and its diagnostic and prognostic value, elaborate on recent developments and emerging methods, and finally discuss future prospects. RESULTS:  Continuous developments in 3 D imaging methods, motion correction techniques, water/fat-separated imaging, dark-blood methods, and scar quantification improved the performance and further expanded the clinical utility of LGE imaging. CONCLUSION:  LGE imaging is the current noninvasive reference standard for the assessment of myocardial viability. Improvements in spatial resolution, scar-to-blood contrast, and water/fat-separated imaging further strengthened its position. KEY POINTS:   · LGE MRI is the reference standard for the noninvasive assessment of myocardial viability. · LGE MRI is used to diagnose a broad range of non-ischemic cardiomyopathies in everyday clinical practice.. · Improvements in spatial resolution and scar-to-blood contrast further strengthened its position. · Continuous developments improve its performance and further expand its clinical utility. CITATION FORMAT: · Holtackers RJ, Emrich T, Botnar RM et al. Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging: From Basic Concepts to Emerging Methods. Fortschr Röntgenstr 2022; DOI: 10.1055/a-1718-4355

Optimization of the Reconstruction Settings for Low-Dose Ultra-High-Resolution Photon-Counting Detector CT of the Lungs

Photon-counting detector computed tomography (PCD-CT) yields improved spatial resolution. The combined use of PCD-CT and a modern iterative reconstruction method, known as quantum iterative reconstruction (QIR), has the potential to significantly improve the quality of lung CT images. In this study, we aimed to analyze the impacts of different slice thicknesses and QIR levels on low-dose ultra-high-resolution (UHR) PCD-CT imaging of the lungs. Our study included 51 patients with different lung diseases who underwent unenhanced UHR-PCD-CT scans. Images were reconstructed using three different slice thicknesses (0.2, 0.4, and 1.0 mm) and three QIR levels (2–4). Noise levels were determined in all reconstructions. Three raters evaluated the delineation of anatomical structures and conspicuity of various pulmonary pathologies in the images compared to the clinical reference reconstruction (1.0 mm, QIR-3). The highest QIR level (QIR-4) yielded the best image quality. Reducing the slice thickness to 0.4 mm improved the delineation and conspicuity of pathologies. The 0.2 mm reconstructions exhibited lower image quality due to high image noise. In conclusion, the optimal reconstruction protocol for low-dose UHR-PCD-CT of the lungs includes a slice thickness of 0.4 mm, with the highest QIR level. This optimized protocol might improve the diagnostic accuracy and confidence of lung imaging

Quantum iterative reconstruction on a photon-counting detector CT improves the quality of hepatocellular carcinoma imaging

Abstract Background Excellent image quality is crucial for workup of hepatocellular carcinoma (HCC) in patients with liver cirrhosis because a signature tumor signal allows for non-invasive diagnosis without histologic proof. Photon-counting detector computed tomography (PCD-CT) can enhance abdominal image quality, especially in combination with a novel iterative reconstruction algorithm, quantum iterative reconstruction (QIR). The purpose of this study was to analyze the impact of different QIR levels on PCD-CT imaging of HCC in both phantom and patient scans. Methods Virtual monoenergetic images at 50 keV were reconstructed using filtered back projection and all available QIR levels (QIR 1–4). Objective image quality properties were investigated in phantom experiments. The study also included 44 patients with triple-phase liver PCD-CT scans of viable HCC lesions. Quantitative image analysis involved assessing the noise, contrast, and contrast-to-noise ratio of the lesions. Qualitative image analysis was performed by three raters evaluating noise, artifacts, lesion conspicuity, and overall image quality using a 5-point Likert scale. Results Noise power spectra in the phantom experiments showed increasing noise suppression with higher QIR levels without affecting the modulation transfer function. This pattern was confirmed in the in vivo scans, in which the lowest noise levels were found in QIR-4 reconstructions, with around a 50% reduction in median noise level compared with the filtered back projection images. As contrast does not change with QIR, QIR-4 also yielded the highest contrast-to-noise ratios. With increasing QIR levels, rater scores were significantly better for all qualitative image criteria (all p < .05). Conclusions Without compromising image sharpness, the best image quality of iodine contrast optimized low-keV virtual monoenergetic images can be achieved using the highest QIR level to suppress noise. Using these settings as standard reconstruction for HCC in PCD-CT imaging might improve diagnostic accuracy and confidence