Activation of Humoral Immunity during the Pathogenesis of Experimental Chronic Lung Allograft Dysfunction.

Alloreactive and autoreactive antibodies have been associated with the development of chronic lung allograft dysfunction (CLAD), but their pathogenic role is disputed. Orthotopic left lung transplantation was performed in the Fischer-344 to Lewis rat strain combination followed by the application of ciclosporine for 10 days. Four weeks after transplantation, lipopolysaccharide (LPS) was instilled into the trachea. Lungs were harvested before (postoperative day 28) and after LPS application (postoperative days 29, 33, 40, and 90) for histopathological, immunohistochemical, and Western blot analyses. Recipient serum was collected to investigate circulating antibodies. Lung allografts were more strongly infiltrated by B cells and deposits of immunoglobulin G and M were more prominent in allografts compared to right native lungs or isografts and increased in response to LPS instillation. LPS induced the secretion of autoreactive antibodies into the circulation of allograft and isograft recipients, while alloreactive antibodies were only rarely detected. Infiltration of B cells and accumulation of immunoglobulin, which is observed in allografts treated with LPS but not isografts or native lungs, might contribute to the pathogenesis of experimental CLAD. However, the LPS-induced appearance of circulating autoreactive antibodies does not seem to be related to CLAD, because it is observed in both, isograft and allograft recipients.

Modification of chest radiography exposure parameters using a neonatal chest phantom.

BACKGROUND: The acquisition of chest radiographs in neonates is of critical importance in diagnostics because of the risk of respiratory distress syndrome and pneumothorax in preterm infants. OBJECTIVE: To achieve a dose reduction while preserving a diagnostic image quality for chest radiographs of neonates. MATERIALS AND METHODS: All radiographs, generated on a fully digital X-ray unit by using a neonatal chest phantom, were evaluated under variation of the tube voltage (40-70 kV) and mAs levels (1-10.2 mAs) with and without an additional 0.1-mm copper (Cu) filtration. Noise, contrast and contrast-to-noise ratio for bronchus, heart, lungs and vessels were determined. Visual assessment of the image quality was carried out by three radiologists using a Likert scale. To evaluate a maximally possible dose reduction, the dose of the radiographs with still acceptable image quality at a minimal dose was compared to the dose of the radiographs with the standard settings used in clinical routine. RESULTS: The noise showed decreasing values with increasing dose, while the contrast values were increased. For the contrast-to-noise ratio, a digressive course of the values as a function of the tube voltage was found. The visual evaluation of image quality showed the best evaluation of the structures at the lowest possible dose in the settings (44 kV, 3.36 mAs) with copper filtration and in the settings (44 kV, 1.56 mAs) without copper filtration. A maximum dose reduction from 8.29 µSv to 2.21 µSv (about 73%) was obtained. CONCLUSION: A dose reduction while preserving diagnostic image quality in a digital X-ray system is generally possible by reducing the tube voltage and simultaneous adaptation of the mAs settings.

[The new radiation protection legislation-part 2 : Modifications in radiology regarding approval procedure and special fields including teleradiology]. / Die neue Strahlenschutzgesetzgebung ­ Teil 2 : Änderungen in der Radiologie bezüglich Vorabkontrolle und Sonderbereiche, einschließlich Teleradiologie.

BACKGROUND: The entry of the new Radiation Protection Act and new Radiation Protection Regulation into force in Germany created many changes for radiology with regard to the old Radiation Protection Regulation and X­ray Regulation. OBJECTIVES: The substantial modifications in radiology regarding the areas of approval and notification procedures, teleradiology, screening, research and radon in the workplace are summarized. METHOD: Changes in the new Radiation Protection Act and Regulation compared to the old Radiation Protection Regulation and X­ray Regulation were evaluated. Thereby, the focus was on areas beyond the workflow in clinical routine. RESULTS AND CONCLUSION: The requirements for the approval and notification procedure have increased. For example, proof must be provided that a medical physics expert can be consulted. The establishment of deadlines for the process by the responsible authorities may accelerate the procedure and create planning certainty.

[The new radiation protection legislation-part 1 : Modifications in radiology for the workflow in clinical routine]. / Die neue Strahlenschutzgesetzgebung ­ Teil 1 : Änderungen für die arbeitstägliche Routine in der Radiologie.

BACKGROUND: On 31 December 2018, the new Radiation Protection Regulation came into effect in Germany and made the new Radiation Protection Act more concrete. The old Radiation Protection Regulation and X­ray Regulation have thereby been replaced. OBJECTIVES: The substantial modifications regarding the practical daily routine in radiology are summarized. METHODS: Modifications and innovations of the New Radiation Protection Act and Regulation compared to the old Radiation Protection Regulation and X­ray Regulation and accordances were evaluated. Thereby the main focus was in the relevance for workflow in clinical routine. RESULTS AND CONCLUSION: The new legislation contains a number of regulations that provide crucial tools for implementation of radiation protection, quality assurance, and dose optimization. However, this also requires additional time and personnel.

Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience.

Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention.BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%.BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk-benefit assessments.

Native T1 mapping and extracellular volume fraction measurement for assessment of right ventricular insertion point and septal fibrosis in chronic thromboembolic pulmonary hypertension.

OBJECTIVES: The aim of this study was to assess septal and right ventricular insertion point (RVIP) fibrosis in patients with chronic thromboembolic pulmonary hypertension (CTEPH) via native T1 mapping and extracellular volume fraction (ECV) determination and to analyze correlations with functional parameters. METHODS: Imaging was performed at 1.5 Tesla in 24 patients diagnosed with CTEPH and 24 controls. T1 values were measured within the septal myocardium, the upper and lower RVIP, and the lateral wall at basal short axis section. RESULTS: The mean septal native T1 values were 1012.8 ms ± 50.5 in the CTEPH group and 956.9 ms ± 24.4 in controls (p < 0.001), upper RIVP 1050.8 ms ± 64.2 vs. 965.3 ms ± 37.1 (p < 0.001), and lower RVIP 1084.4 ms ± 93.1 vs. 959.8 ms ± 40.4 (p < 0.001). The corresponding mean ECV values were also significantly increased in the CTEPH group (p < 0.001). Native septal T1 showed a strong negative correlation with right ventricular ejection fraction (k = -0.92; p = 0.01). CONCLUSIONS: We conclude that native T1 mapping and ECV assessment enable visualization and quantification of septal fibrosis in CTEPH patients. The results also correlate well with right ventricular ejection fraction. Therefore, these parameters might be useful for prognosis and as therapy-monitoring tool in the future. KEY POINTS: • Septal native T1 and ECV values are significantly higher in CTEPH patients. • Native T1 and ECV values are elevated even in absence of LGE. • These techniques therefore enable an improved quantification of septal fibrosis in CTEPH. • Native T1 values also correlate well with right ventricular EF and PA-pressure. • Prognosis and therapy-monitoring might be assessable in the future with these parameters.

Neovascularization of osteoporotic metaphyseal bone defects: A morphometric micro-CT study.

PURPOSE: Neovascularization is essential for bone regeneration in fractures. This study aimed to investigate the microvascular morphology and distribution in the non-injured femur and the neovascularization of the metaphyseal critical size defect in a small animal model of osteoporosis. MATERIALS AND METHODS: Female rats (n=7) were ovariectomized (OVX) and received a multideficiency diet. Three months after OVX, a 5mm wedge shaped critical size defect was cut at the distal femoral metaphysis and stabilized with a T-shaped mini-plate. After six weeks, the animals were euthanized, and femora were removed and decalcified for micro-CT measurement of fracture neovascularization. RESULTS: No fracture healing was observed along the critical size defects. In the non-injured bone, micro-vessel distribution showed a specific pattern, thereby enabling a differentiation between epi-, meta- and diaphysis. Micro-CT based morphometry revealed a significant reduction of the vascular volume fraction as well as the vascular thickness (p<0.001) in the critical size defect compared to the intact contralateral femur. Blood volume related vascular surface (vascular surface/volume) increased significantly (p<0.001). Connectivity density and tissue volume related vascular surface (vascular surface density) did not change significantly. CONCLUSIONS: Micro-CT based vascular morphometry demonstrated differences between epi-, meta- and diaphysis in the non-injured bone as well as differences between the critical size defect and the non-injured metaphysis. As angiogenesis is a crucial prerequisite that precedes osteogenesis, our results may influence further evaluation of osteoconductive or osteogenic biomaterials in this small animal model of osteoporosis.

Systemic atherosclerosis causes detrusor overactivity: functional and morphological changes in hyperlipoproteinemic apoE-/-LDLR-/- mice.

PURPOSE: The prevalence of systemic atherosclerosis and overactive bladder/detrusor overactivity increases almost simultaneously with age but an association between these diseases has not yet been proved. We evaluated changes in bladder function and morphology, including vascularization, in apoE(-/-)LDLR(-/-) double knockout mice with systemic atherosclerosis but without central nervous system involvement. MATERIALS AND METHODS: Cystometry was performed in awake, freely moving 60-week-old apoE(-/-)LDLR(-/-) mice and C57BL/6N controls. The mice were sacrificed and perfused with Microfil® contrast medium. The bladder was excised, dissected and scanned by nano-computerized tomography, including 3-dimensional reconstruction. Samples then underwent histomorphological analysis. RESULTS: In apoE(-/-)LDLR(-/-) mice cystometry revealed a significant decrease in the peak-peak interval, micturition interval, functional bladder capacity and micturition volume. However, maximum bladder pressure increased. Nano-computerized tomography revealed a significant reduction in bladder wall thickness, segment volume, vascular volume and the vascular volume fraction. Histomorphologically bladder specimens showed a thickened media of intramural vessels, activated endothelial cells and intramural inflammatory cells. CONCLUSIONS: To our knowledge this study presents a new in vivo mouse model of nonneurogenic detrusor overactivity caused by systemic atherosclerosis. Decreased bladder wall vascularization seems to be a major factor for detrusor overactivity onset. Capillaries are rarified with reduced lumina due to thickened media. Activated endothelial cells and the infiltration of inflammatory cells in apoE(-/-)LDLR(-/-) mice underlines once more that atherosclerosis is an inflammatory process that may also be relevant to the onset of detrusor overactivity.

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis.

Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis. Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-κB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.

Right ventricular adaptation to pulmonary pressure load in patients with chronic thromboembolic pulmonary hypertension before and after successful pulmonary endarterectomy--a cardiovascular magnetic resonance study.

BACKGROUND: The aim of the study was to characterize RV adaptation to varying loading conditions in patients with chronic thromboembolic hypertension (CTEPH) before and after pulmonary endarterectomy (PEA). Nearly 4% of patients with pulmonary embolism develop CTEPH. PEA offers a cure with excellent outcome. By use of cardiovascular magnetic resonance (CMR) combined with hemodynamic measurements pulmonary arterial elastance (Ea-pulm_i), end-systolic right ventricular elastance (Ees-RV_i) and ventriculo-arterial coupling (Ea-pulm_i/Ees-RV_i) can be studied before and after PEA. METHODS: Sixty-five patients (mean age 41±12 years, 28 female) underwent CMR pre- and post-PEA. Ejection fraction (EF), end-diastolic (EDVi), end-systolic (ESVi), and stroke (SVi) volumes were indexed for body surface area. Ea-pulm_i was calculated as pulmonary artery mean pressure (mPAP)/SVi, and Ees-RV_i as mPAP/ESVi. RESULTS: mPAP decreased from 47±12 to 25±9 mmHg, p=0.0001. Ea-pulm_i was increased before PEA and normalized afterwards (2.8±2.1 vs. 0.85±0.4 mmHg/ml/m2, p=0.0001). Ees-RV_i was depressed before and after PEA (0.72±0.27 vs. 0.66±0.3 mmHg/ml/m2, p=0.13). EF improved from 25±12% to 46±10%, p=0.0001, because ventriculo-arterial coupling was restored (4.2±3 vs. 1.4±0.6, p=0.0001). EDVi and ESVi mproved significantly (EDVi 92±32 to 72±23 ml, p=0.0001; ESVi 69±31 to 41±18 ml, p=0.0001). CONCLUSION: RV function is largely determined by afterload and returns to normal once afterload is normalized. This is paralleled by a significant improvement of CMR indices of right ventricular remodelling.

C1-esterase inhibitor deficiency in pediatric heart transplant recipients: incidence and findings on ultrasound.

BACKGROUND: Acquired angioedema of the bowel caused by a deficiency of C1-esterase inhibitor can lead to severe abdominal pain with sudden onset, mimicking an acute surgical abdomen. In contrast to hereditary angioedema, which usually manifests in childhood, acquired angioedema is broadly recognized to affect people older than 40 years. OBJECTIVE: To determine the incidence of acquired angioedema in a cohort of pediatric heart transplant recipients and assess imaging findings on ultrasonography. MATERIALS AND METHODS: A cohort of 207 children and adolescents who had undergone heart transplantation were assessed at regular follow-up examinations for incidence of acquired angioedema. All patients received ACE inhibitors and immune inhibitors. Control examinations carried out in 3-month intervals included history, assessment of clinical symptoms, physical examination, US of the abdomen and laboratory blood analysis. In addition, if clinical symptoms were newly encountered, children were admitted between regularly scheduled intervals. We analyzed results of abdominal US for pathological findings of the bowel, and we assessed imaging findings in children diagnosed with acquired angioedema. RESULTS: Acquired angioedema was diagnosed in 3/207 patients (2 girls ages 16 and 17 years and 1 boy age 9 months). These children presented with sudden onset of severe abdominal pain. The bowel wall was thickened in the presence of ascites. After a mean of 72 h, abdominal pains resolved. Thickening of bowel loops dissolved and ascites disappeared. CONCLUSION: Single episodes of acquired angioedema were encountered in 1.4% of our series of pediatric heart transplant recipients. Radiologists should be familiar with this disease so they can diagnose it on US imaging.

An enteric ultrastructural surface atlas of the model insect Manducasexta.

The tobacco hornworm is a laboratory model that is particularly suitable for analyzing gut inflammation, but a physiological reference standard is currently unavailable. Here, we present a surface atlas of the healthy hornworm gut generated by scanning electron microscopy and nano-computed tomography. This comprehensive overview of the gut surface reveals morphological differences between the anterior, middle, and posterior midgut, allowing the screening of aberrant gut phenotypes while accommodating normal physiological variations. We estimated a total resorptive midgut surface of 0.42 m2 for L5d6 larvae, revealing its remarkable size. Our data will support allometric scaling and dose conversion from Manduca sexta to mammals in preclinical research, embracing the 3R principles. We also observed non-uniform gut colonization by enterococci, characterized by dense biofilms in the pyloric cone and downstream of the pylorus associated with pore and spine structures in the hindgut intima, indicating a putative immunosurveillance function in the lepidopteran hindgut.

Pilot study of non-contrast-enhanced MRI vs. ultrasound in renal transplant recipients with acquired cystic kidney disease: a prospective intra-individual comparison.

The incidence of renal cell carcinoma (RCC) after kidney transplantation is 15-fold increased. Acquired cystic kidney disease (ACKD) is one of the known risk factors. We performed a small pilot study to assess the role of non-enhanced magnetic resonance imaging (MRI) as a tool for intensified screening in renal transplant recipients with ACKD. Renal ultrasound was used to assess the native kidneys of 215 renal transplant recipients. Thirty patients with 54 kidneys, fulfilling the criteria of ACKD, underwent non-enhanced MRI at 1.5T using T2- and T1-weighed as well as diffusion-weighted sequences with a high spatial resolution. Among the 54 kidneys assessed by both methods, three RCCs were identified (6%). Of those, one RCC was detected by both imaging methods (33%), while two RCCs were diagnosed by MRI alone (67%). MRI identified an additional four proteinaceous or hemorrhagic cysts that did not fulfill the criteria for RCC but were classified as suspicious. All of these lesions were stable in size and appearance in follow-up studies. In conclusion, non-enhanced MRI was more sensitive than ultrasound in identifying RCCs and lesions suspicious for RCC and thus appears to be a useful secondary screening tool in patients with ACKD after renal transplantation.

A pilot study of the characterization of hepatic tissue strain in children with cystic-fibrosis-associated liver disease (CFLD) by acoustic radiation force impulse imaging.

BACKGROUND: Progressive fibrotic alterations of liver tissue represent a major complication in children with cystic fibrosis. Correct assessment of cystic-fibrosis-associated liver disease (CFLD) in clinical routine is a challenging issue. Sonographic elastography based on acoustic radiation force impulse imaging (ARFI) is a new noninvasive approach for quantitatively assessing in vivo elasticity of biological tissues in many organs. OBJECTIVE: To characterize ARFI elastography as a diagnostic tool to assess alteration of liver tissue elasticity related to cystic fibrosis in children. MATERIALS AND METHODS: ARFI elastography and B-mode US imaging were performed in 36 children with cystic fibrosis. The children's clinical history and laboratory parameters were documented. According to the findings on conventional US, children were assigned to distinct groups indicating severity of hepatic tissue alterations. The relationship between US findings and respective elastography values was assessed. Additionally, differences between ARFI elastography values of each US group were statistically tested. RESULTS: Children with sonomorphologic characteristics of fibrotic tissue remodeling presented significantly increased values for tissue elasticity. Children with normal B-mode US or discrete signs of hepatic tissue alterations showed a tendency toward increased tissue stiffness indicating early tissue remodeling. CONCLUSION: Assessment of children with CFLD by means of ARFI elastography yields adequate results when compared to conventional US. For detection of early stages of liver disease with mild fibrotic reactions of hepatic tissue, ARFI elastography might offer diagnostic advantages over conventional US. Thus, liver stiffness measured by means of elastography might represent a valuable biological parameter for evaluation and follow-up of CFLD.

Analysis of fixation materials in micro-CT: It doesn't always have to be styrofoam.

Good fixation of filigree specimens for micro-CT examinations is often a challenge. Movement artefacts, over-radiation or even crushing of the specimen can easily occur. Since different specimens have different requirements, we scanned, analysed and compared 19 possible fixation materials under the same conditions in the micro-CT. We focused on radiodensity, porosity and reversibility of these fixation materials. Furthermore, we have made sure that all materials are cheap and easily available. The scans were performed with a SkyScan 1173 micro-CT. All dry fixation materials tested were punched into 5 mm diameter cylinders and clamped into 0.2 ml reaction vessels. A voxel size of 5.33 µm was achieved in a 180° scan in 0.3° steps. Ideally, fixation materials should not be visible in the reconstructed image, i.e., barely binarised. Besides common micro-CT fixation materials such as styrofoam (-935 Hounsfield Units) or Basotect foam (-943 Hounsfield Units), polyethylene air cushions (-944 Hounsfield Units), Micropor foam (-926 Hounsfield Units) and polyurethane foam, (-960 Hounsfield Units to -470 Hounsfield Units) have proved to be attractive alternatives. Furthermore, more radiopaque materials such as paraffin wax granulate (-640 Hounsfield Units) and epoxy resin (-190 Hounsfield Units) are also suitable as fixation materials. These materials often can be removed in the reconstructed image by segmentation. Sample fixations in the studies of recent years are almost all limited to fixation in Parafilm, Styrofoam, or Basotect foam if the fixation type is mentioned at all. However, these are not always useful, as styrofoam, for example, dissolves in some common media such as methylsalicylate. We show that micro-CT laboratories should be equipped with various fixation materials to achieve high-level image quality.

Feasibility of periprocedural decision on the administration of intravenous contrast media in MRI for endometriosis.

PURPOSE: To assess the feasibility of a periprocedural decision on the administration of intravenous contrast media in MRI for endometriosis and to evaluate the frequency and reasons of contrast administrations, the corresponding MRI diagnoses, and outcome. METHODS: In this retrospective, descriptive cross-sectional single-center study all patients were included, who received a pelvic MRI for evaluation of endometriosis between April 2021 and February 2023. Frequency and reasons of optional intravenous administration of contrast media, corresponding MRI diagnoses and clinical outcome data were noted after re-review of all images, review of radiology reports and review of patients' medical records. The decision on the administration of intravenous contrast media had been made by experienced radiologists, depending on the findings of the non-contrast sequences and the presence of ancillary questions. RESULTS: 303 consecutive patients (mean age, 33.4 years +/- 8.3 [standard deviation]) were evaluated. Periprocedural decision on the administration of intravenous contrast media had been made in all cases. For 219/303 (72.3%) patients, it was decided after review of the non-contrast sequences and exclusion of ancillary questions that contrast administration was not required. 84/303 (27.7%) patients received contrast media, and the most frequent reasons were indeterminate ovarian lesion (41/84 cases, 48.8%) or suspicion of pelvic venous congestion syndrome (26/84 cases, 31.0%). No relevant differences in patient outcomes could be noted (non-contrast/contrast MRI). CONCLUSIONS: A periprocedural decision on the administration of contrast media in MRI for endometriosis is feasible with little effort. It allows the administration of contrast media to be avoided in most cases. If the administration of contrast media is deemed necessary, repeat examinations can be avoided.

A quantitative micro-tomographic gut atlas of the lepidopteran model insect Manduca sexta.

The tobacco hornworm is used extensively as a model system for ecotoxicology, immunology and gut physiology. Here, we established a micro-computed tomography approach based on the oral application of the clinical contrast agent iodixanol, allowing for a high-resolution quantitative analysis of the Manduca sexta gut. This technique permitted the identification of previously unknown and understudied structures, such as the crop or gastric ceca, and revealed the underlying complexity of the hindgut folding pattern, which is involved in fecal pellet formation. The acquired data enabled the volume rendering of all gut parts, the reliable calculation of their volumes, and the virtual endoscopy of the entire alimentary tract. It can provide information for accurate orientation in histology uses, enable quantitative anatomical phenotyping in three dimensions, and allow the calculation of locally effective midgut concentrations of applied chemicals. This atlas will provide critical insights into the evolution of the alimentary tract in lepidopterans.