Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia.

Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the Csf1r locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.

Photo-switchable Collectors for the Flotation of Lithium Aluminate for the Recycling of the Critical Raw Material Lithium.

Flotation of the mineral lithium aluminate by application of the natural product punicine from Punica granatum and some derivatives as collectors is examined. Punicines, 1-(2',5'-dihydroxyphenyl)-pyridinium compounds, are switchable molecules whose properties can be changed reversibly. They exist as cations, neutral mesomeric betaines, anions, and dianions depending on the pH. In light, they form radicals. Five punicine derivatives were prepared which possess ß-methyl, ß-chlorine, γ-tert.-butyl, and γ-acetyl groups attached to the pyridinium ring, and a pyrogallol derivative. On the other hand, LiAlO2 reacts with water to give species such as LiAl2(OH)7 on its surface. Flotations were performed applying the punicines in daylight (3000 lux), in darkness (<40 lux) and under UV-irradiation (4500 lux, 390-400 nm). The pH of the suspension, the collector's concentration, the conditioning time as well as the flotation time were varied. The recovery rates strongly depend on these parameters. For example, the recovery rate of lithium aluminate was increased by 116 % on changing the lighting condition from daylight to darkness, when the pyrogallol derivative of punicine was applied. UV, FTIR, TGA and zeta potential measurements as well as DFT calculations were performed in order to gain insight into the chemistry of punicines on the surface of LiAlO2 and LiAl2(OH)7 in water which influence the flotation's results.

Reconstruction of Paprosky IIIB acetabular defects with porous tantalum shells and augments using the footing technique.

Aims: The use of a porous metal shell supported by two augments with the 'footing' technique is one solution to manage Paprosky IIIB acetabular defects in revision total hip arthroplasty. The aim of this study was to assess the medium-term implant survival and radiological and clinical outcomes of this technique. Methods: We undertook a retrospective, two-centre series of 39 hips in 39 patients (15 male, 24 female) treated with the 'footing' technique for Paprosky IIIB acetabular defects between 2007 and 2020. The median age at the time of surgery was 64.4 years (interquartile range (IQR) 54.4 to 71.0). The median follow-up was 3.9 years (IQR 3.1 to 7.0). Results: The cumulative medium-term survival of the acetabular construct was 89%. Two hips (5.1%) required further revision due to shell loosening, one hip (2.6%) due to shell dislocation, and one hip (2.6%) due to infection. The median Harris Hip Score improved significantly from 47 points (IQR 41.5 to 54.9) preoperatively to 80 points (IQR 73.5 to 88.6) at the latest follow-up (p < 0.001). Conclusion: The reconstruction of Paprosky IIIB acetabular defects with porous tantalum shells and two augments using the 'footing' technique showed excellent medium-term results. It is a viable option for treating these challenging defects.

Lithium aluminate flotation by pH- and light-switchable collectors based on the natural product punicine.

Derivatives of the natural product punicine [1-(2',5'-dihydroxyphenyl)pyridinium chloride] were developed as switchable collectors for the flotation of lithium-containing engineered artifical minerals (EnAMs). These EnAMs are e.g. formed by pyrometallurgical processing of end-of-life lithium-ion batteries. Depending on the pH value and the lighting conditions, punicines exist in water as cations, two different electrostatically neutral mesomeric betaines, anionic tripoles, radical cations or radical anions. The radical species form by photochemically induced disproportionation reactions. We prepared punicine derivatives introducing alkyl chains in the pyridinium moiety (4-methyl, 4-ethyl, 4-octyl and 4-undecanyl) to install hydrophobic groups and examined the recovery rates of the flotation of lithium aluminate (LiAlO2). We varied the lighting conditions (darkness, daylight, LED irradiation at λ = 390-400 nm) and the pH value, the collector's and frother's concentration, and the flotation time. With our collectors, recovery rates of lithium aluminate up to 90% were accomplished when the flotation was conducted in Hallimond tubes exposed to daylight at pH 11 in water.

Case Report: Hip arthroplasty after fracture-related joint infection caused by extensively drug-resistant Klebsiella pneumoniae.

This case-report focuses on a 23-year-old soldier suffering from a fracture-related hip joint infection (FRI) due to extensively drug-resistant Klebsiella pneumoniae and S. epidermidis. The patient underwent multiple septic revision surgeries including the removal of remaining shrapnel accompanied by last-resort antimicrobial therapy with cefiderocol and colistin. Additionally, the surgeries included repeated tissue sampling for microbiological and histopathological analysis. An antibiotic-loaded cemented filler containing cefiderocol was used to improve local antimicrobial therapy. The biopsies prior to and during hip replacement surgery confirmed successful microbe eradication. Hip arthroplasty restored hip joint function and significantly improved patient's quality of life. The utilization of a trabecular metal shell and a meta-diaphyseally anchored cementless hip stem ensured secure implant fixation and early patient mobilisation. An adjusted biofilm active oral antimicrobial therapy after arthroplasty intervention was continued to prevent early periprosthetic joint infection. This case emphasizes the difficulties of managing FRI and multidrug-resistant pathogens. It contributes valuable insight into navigating complex orthopedic cases while ensuring successful hip arthroplasty outcomes. In conclusion, early interdisciplinary collaboration, appropriate antimicrobial therapy along with tailored surgical interventions are crucial for managing such complex cases successfully.

Deep learning aided preoperative diagnosis of primary central nervous system lymphoma.

The preoperative distinction between glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) can be difficult, even for experts, but is highly relevant. We aimed to develop an easy-to-use algorithm, based on a convolutional neural network (CNN) to preoperatively discern PCNSL from GBM and systematically compare its performance to experienced neurosurgeons and radiologists. To this end, a CNN-based on DenseNet169 was trained with the magnetic resonance (MR)-imaging data of 68 PCNSL and 69 GBM patients and its performance compared to six trained experts on an external test set of 10 PCNSL and 10 GBM. Our neural network predicted PCNSL with an accuracy of 80% and a negative predictive value (NPV) of 0.8, exceeding the accuracy achieved by clinicians (73%, NPV 0.77). Combining expert rating with automated diagnosis in those cases where experts dissented yielded an accuracy of 95%. Our approach has the potential to significantly augment the preoperative radiological diagnosis of PCNSL.

Nonradiology Health-Care Professionals Significantly Benefit From AI Assistance in Emergency-Related Chest Radiography Interpretation.

BACKGROUND: Chest radiographs (CXRs) are still of crucial importance in primary diagnostics, but their interpretation poses difficulties at times. RESEARCH QUESTION: Can a convolutional neural network-based artificial intelligence (AI) system that interprets CXRs add value in an emergency unit setting? STUDY DESIGN AND METHODS: A total of 563 CXRs acquired in the emergency unit of a major university hospital were retrospectively assessed twice by three board-certified radiologists, three radiology residents, and three emergency unit-experienced nonradiology residents (NRRs). They used a two-step reading process: (1) without AI support (woAI); and (2) with AI support (wAI) providing additional images with AI overlays. Suspicion of four suspected pathologies (pleural effusion, pneumothorax, consolidations suspicious for pneumonia, and nodules) was reported on a five-point confidence scale. Confidence scores of the board-certified radiologists were converted into four binary reference standards (RFS I-IV) of different sensitivities. Performance by radiology residents and NRRs woAI/wAI were statistically compared by using receiver-operating characteristics (ROCs), Youden statistics, and operating point metrics derived from fitted ROC curves. RESULTS: NRRs could significantly improve performance, sensitivity, and accuracy wAI in all four pathologies tested. In the most sensitive RFS IV, NRR consensus improved the area under the ROC curve (mean, 95% CI) in the detection of the time-critical pathology pneumothorax from 0.846 (0.785-0.907) woAI to 0.974 (0.947-1.000) wAI (P < .001), which represented a gain of 30% in sensitivity and 2% in accuracy (while maintaining an optimized specificity). The most pronounced effect was observed in nodule detection, with NRR wAI improving sensitivity by 53% and accuracy by 7% (area under the ROC curve woAI, 0.723 [0.661-0.785]; wAI, 0.890 [0.848-0.931]; P < .001). The RR consensus wAI showed smaller, mostly nonsignificant gains in performance, sensitivity, and accuracy. INTERPRETATION: In an emergency unit setting without 24/7 radiology coverage, the presented AI solution features an excellent clinical support tool to nonradiologists, similar to a second reader, and allows for a more accurate primary diagnosis and thus earlier therapy initiation.

Cold physical plasma treatment optimization for improved bone allograft processing.

In musculoskeletal surgery, the treatment of large bone defects is challenging and can require the use of bone graft substitutes to restore mechanical stability and promote host-mediated regeneration. The use of bone allografts is well-established in many bone regenerative procedures, but is associated with low rates of ingrowth due to pre-therapeutic graft processing. Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen (O2) and nitrogen (N2) species, is suggested to be advantageous in biomedical implant processing. CPP is a promising tool in allograft processing for improving surface characteristics of bone allografts towards enhanced cellularization and osteoconduction. However, a preclinical assessment regarding the feasibility of pre-therapeutic processing of allogeneic bone grafts with CPP has not yet been performed. Thus, this pilot study aimed to analyze the bone morphology of CPP processed allografts using synchrotron radiation-based microcomputed tomography (SR-µCT) and to analyze the effects of CPP processing on human bone cell viability and function. The analyzes, including co-registration of pre- and post-treatment SR-µCT scans, revealed that the main bone morphological properties (total volume, mineralized volume, surface area, and porosity) remained unaffected by CPP treatment if compared to allografts not treated with CPP. Varying effects on cellular metabolic activity and alkaline phosphatase activity were found in response to different gas mixtures and treatment durations employed for CPP application. It was found that 3 min CPP treatment using a He + 0.1% N2 gas mixture led to the most favourable outcome regarding a significant increase in bone cell viability and alkaline phosphatase activity. This study highlights the promising potential of pre-therapeuthic bone allograft processing by CPP prior to intraoperative application and emphasizes the need for gas source and treatment time optimization for specific applications.

Database of segmentations and surface models of bones of the entire lower body created from cadaver CT scans.

The range of applications of digital surface models of the bones in science and industry is wide. Three-dimensional reconstructions of bones are used in biomechanics, biomedical engineering, medical image processing, orthopedics, traumatology, radiology, patient education, anatomy, anthropometry, forensic anthropology, ergonomics, usability and human factors engineering, or accident and injury analysis and prevention. No open access database or repository of skeletal surface models of the full lower extremities exists. Therefore, the objective of this publication was to provide access to consistent complete bone models of the pelvis and lower limbs of multiple subjects, including biometric data. Segmentations and surface models of the bones of the lower extremities of more than twenty subjects were created from open access postmortem whole-body computed tomography scans. The database provides a broad range of applications by giving access to the data of the complete process chain, from the raw medical imaging data through the segmentations to the surface models.

The assessment of left ventricular volume and function in gated small animal 18F-FDG PET/CT imaging: a comparative study of three commercially available software tools.

BACKGROUND: Several software tools have been developed for gated PET imaging that use distinct algorithms to analyze tracer uptake, myocardial perfusion, and left ventricle volumes and function. Studies suggest that different software tools cannot be used interchangeably in humans. In this study, we sought to compare the left ventricular parameters in gated 18F-FDG PET/CT imaging in mice by three commercially available software tools: PMOD, MIM, and QGS. METHODS AND RESULTS: Healthy mice underwent ECG-gated 18F-FDG imaging using a small-animal nanoPET/CT (Mediso) under isoflurane narcosis. Reconstructed gates PET images were subsequently analyzed in three different software tools, and cardiac volume and function (end-diastolic (EDV), end-systolic volumes (ESV), stroke volume (SV), and ejection fraction (EF)) were evaluated. While cardiac volumes correlated well between PMOD, MIM, and QGS, the left ventricular parameters and cardiac function differed in agreement using Bland-Altman analysis. EDV in PMOD vs. QGS: r = 0.85; p < 0.001, MIM vs. QGS: r = 0.92; p < 0.001, and MIM vs. PMOD: r = 0.88; p < 0.001, showed good correlations. Correlation was also found in ESV: PMOD vs. QGS: r = 0.48; p = 0.07, MIM vs QGS: r = 0.79; p < 0.001, and MIM vs. PMOD: r = 0.69; p < 0.01. SV showed good correlations in: PMOD vs. QGS: r = 0.73; p < 0.01, MIM vs. QGS: r = 0.86; p < 0.001, and MIM vs. PMOD: r = 0.92; p < 0.001. However, EF among correlated poorly: PMOD vs. QGS: r = -0.31; p = 0.26, MIM vs. QGS: r = 0.48; p = 0.07, and MIM vs. PMOD: r = 0.23; p = 0.41. Inter-class and intra-class correlation coefficient were > 0.9 underlining repeatability in using PMOD, MIM, and QGS for cardiac volume and function assessment. CONCLUSIONS: All three commercially available software tools are feasible in small animal cardiac volume assessment in gated 18F-FDG PET/CT imaging. However, due to software-related differences in agreement analysis for cardiac volumes and function, PMOD, MIM, and QGS cannot be used interchangeably in murine research.

Orthopaedic applications of cold physical plasma.

Cold physical plasma (CPP) technology is of high promise for various medical applications. The interplay of specific components of physical plasma with living cells, tissues and organs on a structural and functional level is of paramount interest with the aim to induce therapeutic effects in a controlled and replicable fashion. In contrast to other medical disciplines such as dermatology and oromaxillofacial surgery, research reports on CPP application in orthopaedics are scarce. The present implementation of CPP in orthopaedics involves surface modifications of orthopaedic materials and biomaterials to optimize osseointegration. In addition, the influence of CPP on musculoskeletal cells and tissues is a focus of research, including possible adverse reactions and side effects. Its bactericidal aspects make CPP an attractive supplement to current treatment regimens in case of microbial inflammations such as periprosthetic joint infections. Attributed anticancerogenic and pro-apoptotic effects underline the clinical relevance of CPP as an additive in treating malignant bone lesions. The present review outlines ongoing research in orthopaedics involving CPP; it distinguishes considerations for safe application and the need for more evidence-based research to facilitate robust clinical implementation.

Psychological Factors as Risk Contributors for Poor Hip Function after Periacetabular Osteotomy.

Psychologic comorbidities have been identified as risk factors for poor outcomes in orthopedic procedures, but their influence on the outcome of hip-preserving periacetabular osteotomy (PAO) remains uncertain. This retrospective cohort study aimed to assess the impact of patients' psychological health on the outcome of PAO in patients with hip dysplasia (HD) and acetabular retroversion (AR). The study included 110 patients undergoing PAO for HD or AR between 2019 and 2021. Standardized questionnaires were administered to assess psychological factors, postoperative hip function, and activity level (mean follow-up: 25 months). Linear regression analyses were used to examine the associations between psychological factors and postoperative hip function and activity level. Both HD and AR patients showed improved postoperative hip function and activity levels. Linear regression analyses revealed that depression significantly impaired postoperative outcomes in both groups, whereas somatization negatively influenced the outcome in AR patients. General health perceptions significantly contributed to an improved postoperative outcome. These findings highlight the importance of concomitantly addressing psychologically relevant factors in order to improve patient outcomes after PAO procedures. Future prospective studies should continue to investigate the impact of various psychological factors and explore possibilities of incorporating psychological support into routine postoperative care for these patient cohorts.

Detection of apoptosis by [18F]ML-10 after cardiac ischemia-reperfusion injury in mice.

OBJECTIVE: Myocardial infarction leads to ischemic heart disease and cell death, which is still a major obstacle in western society. In vivo imaging of apoptosis, a defined cascade of cell death, could identify myocardial tissue at risk. METHODS: Using 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in a mouse model of transient ligation of the left anterior descending (LAD) artery. 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET imaging indicated the defect area. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) histology stain indicated cardiac apoptosis. RESULTS: [18F]ML-10 uptake was evident in the ischemic area after transient LAD ligation in ex vivo autoradiography and in vivo PET imaging. Detection of [18F]ML-10 is in line with the defect visualized by [18F]FDG and the histological approach of TUNEL staining. CONCLUSION: The tracer [18F]ML-10 is suitable for detecting apoptosis after transient LAD ligation in mice.

Assessment of left ventricular function with gated myocardial perfusion SPECT and gated myocardial FDG PET in patients with left ventricular mechanical dyssynchrony.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) and left ventricular function are intertwined. Gated myocardial perfusion SPECT (MPS) and gated fluorodeoxyglucose positron emission computed tomography (FDG PET) is an elegant way for repeated assessment of myocardial dyssynchrony and myocardial function. To the knowledge of the authors at the time this manuscript was prepared, there was no comprehensive evaluation of the interplay of LVMD and left ventricular function as measured by gated MPS and gated FDG PET; as well as no evaluation of the agreement between the two methods. METHODS: Patients were assigned to the reference cohort (RC) and the dyssynchrony cohort (DC) based on the phase analysis results of gated MPS datasets. Subsequently left ventricular function was analyzed. RESULTS: We demonstrated that LVMD as detected by gated MPS is associated with a significantly higher end-diastolic volume (EDV) and end-systolic volume (ESV) as well as a significantly reduced left ventricular ejection fraction (LVEF) both in gated MPS and gated FDG PET imaging. In the RC and the DC SPECT and PET showed good agreement and generally high linear correlations with regard to left ventricular volumes and LVEF. In the combined cohort (RC and DC) increasing amounts of LVMD were associated with increasing left ventricular volumes as well as a decreasing LVEF. The association was strongest for the dyssynchrony parameter Entropy. CONCLUSIONS: We demonstrated that gated SPECT and gated PET are useful tools in the evaluation of left ventricular function in patients with LVMD as detected by gated MPS. Increasing amounts of dyssynchrony were associated with an increasingly reduced myocardial function. For repeated measurements or therapy monitoring, the methods should not be used interchangeably.

Clinically focused multi-cohort benchmarking as a tool for external validation of artificial intelligence algorithm performance in basic chest radiography analysis.

Artificial intelligence (AI) algorithms evaluating [supine] chest radiographs ([S]CXRs) have remarkably increased in number recently. Since training and validation are often performed on subsets of the same overall dataset, external validation is mandatory to reproduce results and reveal potential training errors. We applied a multicohort benchmarking to the publicly accessible (S)CXR analyzing AI algorithm CheXNet, comprising three clinically relevant study cohorts which differ in patient positioning ([S]CXRs), the applied reference standards (CT-/[S]CXR-based) and the possibility to also compare algorithm classification with different medical experts' reading performance. The study cohorts include [1] a cohort, characterized by 563 CXRs acquired in the emergency unit that were evaluated by 9 readers (radiologists and non-radiologists) in terms of 4 common pathologies, [2] a collection of 6,248 SCXRs annotated by radiologists in terms of pneumothorax presence, its size and presence of inserted thoracic tube material which allowed for subgroup and confounding bias analysis and [3] a cohort consisting of 166 patients with SCXRs that were evaluated by radiologists for underlying causes of basal lung opacities, all of those cases having been correlated to a timely acquired computed tomography scan (SCXR and CT within < 90 min). CheXNet non-significantly exceeded the radiology resident (RR) consensus in the detection of suspicious lung nodules (cohort [1], AUC AI/RR: 0.851/0.839, p = 0.793) and the radiological readers in the detection of basal pneumonia (cohort [3], AUC AI/reader consensus: 0.825/0.782, p = 0.390) and basal pleural effusion (cohort [3], AUC AI/reader consensus: 0.762/0.710, p = 0.336) in SCXR, partly with AUC values higher than originally published ("Nodule": 0.780, "Infiltration": 0.735, "Effusion": 0.864). The classifier "Infiltration" turned out to be very dependent on patient positioning (best in CXR, worst in SCXR). The pneumothorax SCXR cohort [2] revealed poor algorithm performance in CXRs without inserted thoracic material and in the detection of small pneumothoraces, which can be explained by a known systematic confounding error in the algorithm training process. The benefit of clinically relevant external validation is demonstrated by the differences in algorithm performance as compared to the original publication. Our multi-cohort benchmarking finally enables the consideration of confounders, different reference standards and patient positioning as well as the AI performance comparison with differentially qualified medical readers.

Modulation of Rxrα Expression in Mononuclear Phagocytes Impacts on Cardiac Remodeling after Ischemia-Reperfusion Injury.

Retinoid X receptors (RXRs), as members of the steroid/thyroid hormone superfamily of nuclear receptors, are crucial regulators of immune response during health and disease. RXR subtype expression is dependent on tissue and cell type, RXRα being the relevant isoform in monocytes and macrophages. Previous studies have assessed different functions of RXRs and positive implications of RXR agonists on outcomes after ischemic injuries have been described. However, the impact of a reduced Rxrα expression in mononuclear phagocytes on cardiac remodeling after myocardial infarction (MI) has not been investigated to date. Here, we use a temporally controlled deletion of Rxrα in monocytes and macrophages to determine its role in ischemia-reperfusion injury. We show that reduced expression of Rxrα in mononuclear phagocytes leads to a decreased phagocytic activity and an accumulation of apoptotic cells in the myocardium, reduces angiogenesis and cardiac macrophage proliferation in the infarct border zone/infarct area, and has an impact on monocyte/macrophage subset composition. These changes are associated with a greater myocardial defect 30 days after ischemia/reperfusion injury. Overall, the reduction of Rxrα levels in monocytes and macrophages negatively impacts cardiac remodeling after myocardial infarction. Thus, RXRα might represent a therapeutic target to regulate the immune response after MI in order to improve cardiac remodeling.

Implications of the uncertainty of postoperative functional parameters for the preoperative planning of total hip arthroplasty.

The functional parameters pelvic tilt (PT) and hip joint force (HJF) are required to calculate patient-specific target zones based on the range of motion (ROM) and implant loading for preoperative planning of total hip arthroplasty (THA). Both functional parameters may change after THA. The preoperative prediction of the postoperative PT and HJF is associated with a specific amount of uncertainty. The prediction uncertainty has to be considered in the preoperative planning process to avoid a suboptimal implantation. So far, very little attention has been paid to the necessary reduction of patient-specific target zones by the prediction uncertainties of postoperative functional parameters. Prediction models for the postoperative PT in standing position and for the HJF during one-leg stance as a surrogate for the peak force phase during level walking were used to quantify the reduction of the ROM- and load-based target zones of 196 Japanese THA patients. The prediction uncertainty was about 14° for the postoperative standing PT and ranged from 17% body weight to 37% body weight for the components of the HJF. On average, the prosthetic ROM-based target zone had to be significantly reduced by 43% and the load-based target zone by 39%. This led to a median reduction of the combined prosthetic ROM- and load-based target zone of 96%. The study sharpens the awareness for the substantial reduction of ROM- and load-based target zones by prediction uncertainties of the postoperative PT and HJF and highlights the importance of further research to improve prediction models for both functional parameters.

Comparison of transient and permanent LAD ligation in mice using 18F-FDG PET imaging.

OBJECTIVE: Animal models for myocardial injuries represent important cornerstones in cardiovascular research to monitor the pathological processes and therapeutic approaches. We investigated the association of 18F-FDG derived left ventricular metabolic volume (LVMV), defect area and cardiac function in mice after permanent or transient ligation of the left anterior descending artery (LAD). METHODS: Serial non-invasive ECG-gated 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) after permanent or transient LAD ligation enabled a longitudinal in vivo correlation of 18F-FDG derived left ventricular metabolic volume to functional parameters and myocardial defect. RESULTS: The LVMV shows a more prominent drop after permanent than transient LAD ligation and recovers after 30 days. The loss of LVMV correlates with the defect area assessed by QPS software. Cardiac function parameters (e.g., EDV, ESV, SV) by the QGS software positively correlate with LVMV after permanent and transient LAD ligation. CONCLUSIONS: This study provides novel insight into 18F-FDG derived LVMV after permanent and transient LAD ligation by longitudinal in 18F-FDG PET imaging and underlines the associations of the FDG derived parameter and cardiac function.

Detection of cardiac apoptosis by [18F]ML-10 in a mouse model of permanent LAD ligation.

PURPOSE: The loss of viable cardiac cells and cell death by myocardial infarction (MI) is still a significant obstacle in preventing deteriorating heart failure. Imaging of apoptosis, a defined cascade to cell death, could identify areas at risk. PROCEDURES: Using 2-(5-[18F]fluoropentyl)-2-methyl-malonic acid ([18F]ML-10) in autoradiography and positron emission tomography (PET) visualized apoptosis in murine hearts after permanent ligation of the left anterior descending artery (LAD) inducing myocardial infarction (MI). 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET imaging localized the infarct area after MI. Histology by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining validated apoptosis in the heart. RESULTS: Accumulation of [18F]ML-10 was evident in the infarct area after permanent ligation of the LAD in autoradiography and PET imaging. Detection of apoptosis by [18F]ML-10 is in line with the defect visualized by [18F]FDG and the histological approach. CONCLUSION: [18F]ML-10 could be a suitable tracer for apoptosis imaging in a mouse model of permanent LAD ligation.

Biocompatible Gas Plasma Treatment Affects Secretion Profiles but Not Osteogenic Differentiation in Patient-Derived Mesenchymal Stromal Cells.

Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen and nitrogen species, is suggested to provide advantages in regenerative medicine. Intraoperative CPP therapy targeting pathologies related to diminished bone quality could be promising in orthopedic surgery. Assessment of a clinically approved plasma jet regarding cellular effects on primary bone marrow mesenchymal stromal cells (hBM-MSCs) from relevant arthroplasty patient cohorts is needed to establish CPP-based therapeutic approaches for bone regeneration. Thus, the aim of this study was to derive biocompatible doses of CPP and subsequent evaluation of human primary hBM-MSCs' osteogenic and immunomodulatory potential. Metabolic activity and cell proliferation were affected in a treatment-time-dependent manner. Morphometric high content imaging analyses revealed a decline in mitochondria and nuclei content and increased cytoskeletal compactness following CPP exposure. Employing a nontoxic exposure regime, investigation on osteogenic differentiation did not enhance osteogenic capacity of hBM-MSCs. Multiplex analysis of major hBM-MSC cytokines, chemokines and growth factors revealed an anti-inflammatory, promatrix-assembling and osteoclast-regulating secretion profile following CPP treatment and osteogenic stimulus. This study can be noted as the first in vitro study addressing the influence of CPP on hBM-MSCs from individual donors of an arthroplasty clientele.