Precision farming – consideration of reduced exposure in the pollinator risk assessment

Observed declines in the distribution and abundance of various insect species have moved the topic of biodiversity and the protection of honey bees, an insect species of particular economic interest, into the focus of public attention. This also resulted in an increasing public pressure to reform the European agricultural policy and as part of this to minimise the amount of synthetic plant protection products used. In this context, so-called ‘precision farming’ offers a considerable potential for a reduced application of plant protection products by using precision application techniques that allow to adjust applications to the actual scale of target distribution within a field. Is however currently not possible to exactly quantify the subsequent decrease of exposure of non-target organisms. Focusing on honey bees, the authors are therefore in a first step proposing a field study design to quantify the direct and indirect exposure of honey bees and their colonies in relation to the ratio of treated to untreated field area and the application pattern used. Furthermore, parameters of the bee risk assessment scheme are discussed that could be suitable to describe exposure reduction by precision application.Observed declines in the distribution and abundance of various insect species have moved the topic of biodiversity and the protection of honey bees, an insect species of particular economic interest, into the focus of public attention. This also resulted in an increasing public pressure to reform the European agricultural policy and as part of this to minimise the amount of synthetic plant protection products used. In this context, so-called ‘precision farming’ offers a considerable potential for a reduced application of plant protection products by using precision application techniques that allow to adjust applications to the actual scale of target distribution within a field. Is however currently not possible to exactly quantify the subsequent decrease of exposure of non-target organisms. Focusing on honey bees, the authors are therefore in a first step proposing a field study design to quantify the direct and indirect exposure of honey bees and their colonies in relation to the ratio of treated to untreated field area and the application pattern used. Furthermore, parameters of the bee risk assessment scheme are discussed that could be suitable to describe exposure reduction by precision application

Cytokeratin 18 expression in immature Sertoli cells: co-localization with interstitial lymphocytic infiltrates.

Although multiple interactions of seminiferous tubules and the interstitial testicular tissue are known, correlation of cytokeratin 18 expressing Sertoli cells with interstitial changes has still not yet been reported. Considering this fact, we focused our investigation on changes of the adjacent interstitial tissue. A total sample of 51 testicular biopsies (from infertile patients) showing mixed atrophy was examined immunohistochemically with antibodies against cytokeratin 18, vimentin, L26/CD20, CD4 and CD8. Twenty-one of the 51 cases showed single seminiferous tubules with Sertoli cells expressing cytokeratin 18. These 21 tubules consistently exhibit either spermatogenic arrest at the level of spermatogonia or only immature Sertoli cells. In the adjacent interstitial tissue of 8 of the 21 cytokeratin 18 positive tubules (39%) striking inflammatory infiltrates--predominantly expressing L26/CD20 typical for B lymphocytes and CD8 typical for T suppressor lymphocytes--were detected. These findings underline that tubules with cytokeratin 18 expressing Sertoli cells exhibit early spermatogenic arrest or only few remaining Sertoli cells. Additionally, we observed a remarkable co-localization of these tubules with lymphocytic infiltrates of the adjacent interstitial tissue

Reduced Acquisition Time [18F]GE-180 PET Scanning Protocol Replaces Gold-Standard Dynamic Acquisition in a Mouse Ischemic Stroke Model

Aim Understanding neuroinflammation after acute ischemic stroke is a crucial step on the way to an individualized post-stroke treatment. Microglia activation, an essential part of neuroinflammation, can be assessed using [ 18 F]GE-180 18 kDa translocator protein positron emission tomography (TSPO-PET). However, the commonly used 60–90 min post-injection (p.i.) time window was not yet proven to be suitable for post-stroke neuroinflammation assessment. In this study, we compare semi-quantitative estimates derived from late time frames to quantitative estimates calculated using a full 0–90 min dynamic scan in a mouse photothrombotic stroke (PT) model. Materials and Methods Six mice after PT and six sham mice were included in the study. For a half of the mice, we acquired four serial 0–90 min scans per mouse (analysis cohort) and calculated standardized uptake value ratios (SUVRs; cerebellar reference) for the PT volume of interest (VOI) in five late 10 min time frames as well as distribution volume ratios (DVRs) for the same VOI. We compared late static 10 min SUVRs and the 60–90 min time frame of the analysis cohort to the corresponding DVRs by linear fitting. The other half of the animals received a static 60–90 min scan and was used as a validation cohort. We extrapolated DVRs by using the static 60–90 min p.i. time window, which were compared to the DVRs of the analysis cohort. Results We found high linear correlations between SUVRs and DVRs in the analysis cohort for all studied 10 min time frames, while the fits of the 60–70, 70–80, and 80–90 min p.i. time frames were the ones closest to the line of identity. For the 60–90 min time window, we observed an excellent linear correlation between SUVR and DVR regardless of the phenotype (PT vs . sham). The extrapolated DVRs of the validation cohort were not significantly different from the DVRs of the analysis group. Conclusion Simplified quantification by a reference tissue ratio of the late 60–90 min p.i. [ 18 F]GE-180 PET image can replace full quantification of a dynamic scan for assessment of microglial activation in the mouse PT model

Can Radiomics Provide Additional Information in [F-18]FET-Negative Gliomas?

Simple Summary Amino acid positron emission tomography (PET) complements standard magnetic resonance imaging (MRI) since it directly visualizes the increased amino acid transport into tumor cells. Amino acid PET using O-(2-[F-18]fluoroethyl)-L-tyrosine ([F-18]FET) has proven to be relevant, for example, for glioma classification, identification of tumor progression or recurrence, or for the delineation of tumor extent. Nevertheless, a relevant proportion of low-grade gliomas (30%) and few high-grade gliomas (5%) were found to show no or even decreased amino acid uptake by conventional visual analysis of PET images. Advanced image analysis with the extraction of radiomic features is known to provide more detailed information on tumor characteristics than conventional analyses. Hence, this study aimed to investigate whether radiomic features derived from dynamic [F-18]FET PET data differ between [F-18]FET-negative glioma and healthy background and thus provide information that cannot be extracted by visual read. The purpose of this study was to evaluate the possibility of extracting relevant information from radiomic features even in apparently [F-18]FET-negative gliomas. A total of 46 patients with a newly diagnosed, histologically verified glioma that was visually classified as [F-18]FET-negative were included. Tumor volumes were defined using routine T2/FLAIR MRI data and applied to extract information from dynamic [F-18]FET PET data, i.e., early and late tumor-to-background (TBR5-15, TBR20-40) and time-to-peak (TTP) images. Radiomic features of healthy background were calculated from the tumor volume of interest mirrored in the contralateral hemisphere. The ability to distinguish tumors from healthy tissue was assessed using the Wilcoxon test and logistic regression. A total of 5, 15, and 69% of features derived from TBR20-40, TBR5-15, and TTP images, respectively, were significantly different. A high number of significantly different TTP features was even found in isometabolic gliomas (after exclusion of photopenic gliomas) with visually normal [F-18]FET uptake in static images. However, the differences did not reach satisfactory predictability for machine-learning-based identification of tumor tissue. In conclusion, radiomic features derived from dynamic [F-18]FET PET data may extract additional information even in [F-18]FET-negative gliomas, which should be investigated in larger cohorts and correlated with histological and outcome features in future studies

Cerebrovascular risk factors in cerebral amyloid angiopathy – modifier or bystander?

Goal: Cerebral amyloid angiopathy (CAA) is a frequent cause of atypical intracerebral hemorrhage (ICH) in the elderly. Stroke risk factors such as arterial hypertension (AHT), atrial fibrillation (AFib), diabetes mellitus (DM), and renal dysfunction (RD) are increasingly apparent in these patients. In this retrospective study, we analyzed the presence of these stroke risk factors in different initial CAA presentations comprising cerebral microbleeds (CMB), acute ischemic stroke (AIS), cortical superficial hemosiderosis (cSS), or lobar ICH (LICH) and evaluated their influence on the initial clinical presentation of patients with CAA. Material and Methods: We identified patients with at least possible CAA defined by the modified Boston criteria admitted to the Department of Neurology or Neurosurgery from 2002 to 2018. Findings: In the overall cohort of 209 patients, we analyzed the correlation between the number of stroke risk factors and the initial clinical presentation of patients with CAA and could show the high multimorbidity of the collective. There are large differences between the subgroups with different initial clinical presentations, e.g., patients with CMB as initial CAA presentation have the highest number of cerebrovascular risk factors and recurrent AIS, whereas AFib is more frequent in the Neurosurgery Department. Conclusion: There is a distinct overlap between the subgroups of CAA manifestations and stroke risk factors that need to be verified in larger patient collectives. Since these comorbidities are likely to influence the clinical course of CAA, they represent possible targets for secondary prevention until specific treatment for CAA becomes available

Feasibility of radiomic feature harmonization for pooling of [18F]FET or [18F]GE-180 PET images of gliomas

Introduction: Large datasets are required to ensure reliable non-invasive glioma assessment with radiomics-based machine learning methods. This can often only be achieved by pooling images from different centers. Moreover, trained models should perform with high accuracy when applied to data from different centers. In this study, the impact of reconstruction settings and segmentation methods on radiomic features derived from amino acid and TSPO PET images of glioma patients was examined. Additionally, the ability to model and thus reduce feature differences was investigated.Methods: [(18)FJFET and [(18)FJGE-180 PET data were acquired from 19 glioma patients. For each acquisition, 10 reconstruction settings and 9 segmentation methods were included to emulate multicentric data. Statistical robustness measures were calculated before and after ComBat harmonization. Differences between features due to setting variations were assessed using Friedman test, coefficient of variation (CV) and inter-rater reliability measures, including intraclass and Spearman's rank correlation coefficients and Fleiss' Kappa.Results: According to Friedman analyses, most features (>60%) showed significant differences. Yet, CV and interrater reliability measures indicated higher robustness. ComBat resulted in almost complete harmonization (>87%) according to Friedman test and little to no improvement according to CV and inter-rater reliability measures. [(18)FJGE-180 features were more sensitive to reconstruction settings than [(18)FJFET features.Conclusions: According to Friedman test, feature distributions could be successfully aligned using ComBat. However, depending on settings, changes in patient ranks were observed for some features and could not be eliminated by harmo-nization. Thus, for clinical utilization it is recommended to exclude affected features

Late-stage Anle138b treatment ameliorates tau pathology and metabolic decline in a mouse model of human Alzheimer's disease tau

BackgroundAugmenting the brain clearance of toxic oligomers with small molecule modulators constitutes a promising therapeutic concept against tau deposition. However, there has been no test of this concept in animal models of Alzheimer's disease (AD) with initiation at a late disease stage. Thus, we aimed to investigate the effects of interventional late-stage Anle138b treatment, which previously indicated great potential to inhibit oligomer accumulation by binding of pathological aggregates, on the metabolic decline in transgenic mice with established tauopathy in a longitudinal F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) study.MethodsTwelve transgenic mice expressing all six human tau isoforms (hTau) and ten controls were imaged by FDG-PET at baseline (14.5months), followed by randomization into Anle138b treatment and vehicle groups for 3months. FDG-PET was repeated after treatment for 3months, and brains were analyzed by tau immunohistochemistry. Longitudinal changes of glucose metabolism were compared between study groups, and the end point tau load was correlated with individual FDG-PET findings.ResultsTau pathology was significantly ameliorated by late-stage Anle138b treatment when compared to vehicle (frontal cortex -53%, p<0.001;hippocampus -59%, p<0.005). FDG-PET revealed a reversal of metabolic decline during Anle138b treatment, whereas the vehicle group showed ongoing deterioration. End point glucose metabolism in the brain of hTau mice had a strong correlation with tau deposition measured by immunohistochemistry (R=0.92, p<0.001).ConclusionLate-stage oligomer modulation effectively ameliorated tau pathology in hTau mice and rescued metabolic function. Molecular imaging by FDG-PET can serve for monitoring effects of Anle138b treatment

3D Monte Carlo bone marrow dosimetry for Lu-177-PSMA therapy with guidance of non-invasive 3D localization of active bone marrow via Tc-99m-anti-granulocyte antibody SPECT/CT

Background: The bone marrow (BM) is a main risk organ during Lu-177-PSMA ligand therapy of metastasized castration-resistant prostate cancer (mCRPC) patients. So far, BM dosimetry relies on S values, which are pre-computed for reference anatomies, simplified activity distributions, and a physiological BM distribution. However, mCRPC patients may show a considerable bone lesion load, which leads to a heterogeneous and patient-specific activity accumulation close to BM-bearing sites. Furthermore, the patient-specific BM distribution might be significantly altered in the presence of bone lesions. The aim was to perform BM absorbed dose calculations through Monte Carlo (MC) simulations and to investigate the potential value of image-based BM localization. This study is based on 11 Lu-177-PSMA-617 therapy cycles of 10 patients (10 first cycles), who obtained a pre-therapeutic Ga-68-PSMA-11 PET/CT; quantitative Lu-177 SPECT acquisitions of the abdomen 24 (+CT), 48, and 72 h p.i.; and a Lu-177 whole-body planar acquisition at 24 h post-therapy. Patient-specific 3D volumes of interest were segmented from the Ga-68-PSMA-11 PET/CT, filled with activity information from the Lu-177 data, and imported into the FLUKA MC code together with the patient CT. MC simulations of the BM absorbed dose were performed assuming a physiological BM distribution according to the ICRP 110 reference male (MC1) or a displacement of active BM from the direct location of bone lesions (MC2). Results were compared with those from S values (SMIRD). BM absorbed doses were correlated with the decrease of lymphocytes, total white blood cells, hemoglobin level, and platelets. For two patients, an additional pre-therapeutic Tc-99m-anti-granulocyte antibody SPECT/CT was performed for BM localization. Results: Median BM absorbed doses were 130, 37, and 11 mGy/GBq for MC1, MC2, and SMIRD, respectively. Significant strong correlation with the decrease of platelet counts was found, with highest correlation for MC2 (MC1: r = − 0.63, p = 0.04; MC2: r = − 0.71, p = 0.01; SMIRD: r = − 0.62, p = 0.04). For both investigated patients, BM localization via Tc-99m-anti-granulocyte antibody SPECT/CT indicated a displacement of active BM from the direct location of lesions similar to model MC2 and led to a reduction in the BM absorbed dose of 40 and 41% compared to MC1. Conclusion: Higher BM absorbed doses were observed for MC-based models; however, for MC2, all absorbed doses were still below 2 Gy. MC1 resulted in critical values for some patients, but is suspected to yield strongly exaggerated absorbed doses by neglecting bone marrow displacement. Image-based BM localization might be beneficial, and future studies are recommended to support an improvement for the prediction of hematoxicities