Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET.

PURPOSE: According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively. METHODS: Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied. RESULTS: TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97). CONCLUSION: The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.

Concept Development of an On-Chip PET System.

Organs-on-Chips (OOCs), microdevices mimicking in vivo organs, find growing applications in disease modeling and drug discovery. With the increasing number of uses comes a strong demand for imaging capabilities of OOCs. Positron Emission Tomography (PET) would be ideal for OOC imaging, however, current PET systems have insufficient spatial resolution for this task. In this work, we propose the concept of an On-Chip PET system capable of imaging OOCs. Our system consists of four detectors arranged around the OOC device. Each detector is made of two monolithic Lutetium-yttrium oxyorthosilicate (LYSO) crystals and covered with Silicon photomultipliers (SiPMs) on multiple surfaces. We use a Convolutional Neural Network (CNN) trained with data from a Monte Carlo Simulation (MCS) to predict the first gamma-ray interaction position inside the detector from the light patterns that are recorded by the SiPMs on the detector's surfaces. With the Line of Responses (LORs) created by the predicted interaction positions, we reconstruct with Simultaneous Algebraic Reconstruction Technique (SART). The CNN achieves a mean average prediction error of 0.78 mm in the best configuration. We use the trained network to reconstruct an image of a grid of 21 point sources spread across the field-of-view and obtain a mean spatial resolution of 0.53 mm. We demonstrate that it is possible to achieve a spatial resolution of almost 0.5 mm in a PET system made of multiple monolithic LYSO crystals by directly predicting the scintillation position from light patterns created with SiPMs. We observe that CNNs from the ResNet family perform better than those from the EfficientNet family and that certain surfaces encode significantly more information for the scintillation-point prediction than others.

Opening up a tailored tutor qualification program for medical students to other healthcare students - a mixed-method study.

BACKGROUND: Peer-led tutorials are widely used in medical education to promote practical skills acquisition and support faculty staff. Typically, student tutors are custom trained for this specific task. We investigated whether opening up an existing medical tutor qualification program to other degree programs is successful in terms of acceptance among students, acquisition of tutor-specific and interprofessional competencies, and which factors contribute to success or failure. METHODS: We developed a two-day tutor qualification program and conducted it annually from 2016 to 2020 with medical and other healthcare students. At the end of each course, we administered a written survey in which the participants rated the following items: their attitudes towards interprofessional learning (using the UWE-IP-D Interprofessional Learning Scale), the interprofessional learning setting, the teaching approach, and their competency acquisition (each on a five-point Likert scale; 1 = strongly agree, 5 = strongly disagree). Furthermore, we assessed participants' qualitative feedback in free-text fields and performed inductive content analyses. RESULTS: The study participation rate was high (response rate 97%; medical students: n = 75; healthcare students: n = 22). Participants stated high levels of competency acquisition (total M = 1.59, individual items' M's ranging from 1.20 to 2.05) and even higher satisfaction with the teaching approach (total M = 1.28, individual items' M's ranging from 1.43 to 1.05). Overall satisfaction with the training was M = 1.22; SD = 0.58. No significant differences in ratings were found between the student groups. The qualitative results showed that students appreciated the interprofessional setting and experienced it as enriching. The most positive feedback was found in didactics/teaching methods on role-plays and group work; most suggestions for improvement were found in the area of structure and organisation on breaks and time management. CONCLUSIONS: Opening up an existing medical tutor qualification program to other student groups can be seen as fruitful to teach not only tutor-related aspects but also interprofessional competencies. The results demonstrate the importance of detailed planning that considers group composition and contextual conditions and provides interactive teaching methods to promote interprofessional experiences. This study offers important information about prerequisites and methodological implementation that could be important for the interprofessional redesign of existing training programs.

Assessment of dietary protein supplementation on milk productivity of commercial organic dairy farms during the grazing season.

Variability of protein and energy supply from pasture during the grazing season is a primary factor that can influence milk production of grazing organic dairy herds in the Northeast United States. This study evaluated the effects of altering the crude protein (CP) content of dietary supplements included in dairy rations fed to grazing organic dairy herds, on milk production and composition. Six commercial organic farms participated in a 6-wk trial, consisting of a 2-wk baseline period and 4-wk experimental period. Farms were paired by their summer 2017 milk urea nitrogen profile, and farms within each pair were assigned by restricted randomization to (1) continuation of their regular supplements (n = 3, control group, CON), or (2) supplement with altered CP as percentage of dry matter, formulated using an organic barley and roasted soybean mix (n = 3, treatment group, TRT). Throughout the 6-wk trial, individual milk samples were collected at 2 consecutive milkings weekly, while pasture and supplement samples, pasture measurements, and management information were collected twice weekly per farm. Data were statistically analyzed using the MIXED procedure of SAS (version 9.4, SAS Institute Inc.) for all parameters, and effects of treatment, week, and their interaction (treatment × week) were determined. The supplement CP (percentage of dry matter) during the baseline period was 13.5% for CON and 15.3% for TRT and 14.8% for CON and 19.3% for TRT during the experimental period. Milk production was 21% higher during the experimental period for TRT compared with CON (24.1 vs. 19.9 kg of milk per day, respectively). Milk production decreased for CON from wk 1 to wk 6 (23.6 vs. 20.4 kg of milk per day), whereas TRT maintained milked production from wk 1 to wk 6 (22.8 vs. 22.7 kg of milk per day). Milk composition was different between groups, with CON having higher fat percent (4.21 vs. 3.73%, respectively) and protein percent (3.15 vs. 3.05%, respectively) compared with TRT for the 6 wk. The milk urea nitrogen concentrations were similar between TRT and CON for the baseline period (11.9 vs. 12.1 mg/dL) and the final week of the experimental period (14.5 vs. 14.2 mg/dL). Although the effects of different diet CP fractions, particularly rumen undegradable protein and soluble protein, must be further delineated, these results indicate that altering the CP content of dietary supplements fed to grazing organic dairy cattle during the summer period in the Northeast US could be a useful mechanism to maintain milk production.

Prognostic impact of gross tumor volume during radical radiochemotherapy of locally advanced non-small cell lung cancer-results from the NCT03055715 multicenter cohort study of the Young DEGRO Trial Group.

BACKGROUND: In radical radiochemotherapy (RCT) of inoperable non-small-cell lung cancer (NSCLC) typical prognostic factors include T- and N-stage, while there are still conflicting data on the prognostic relevance of gross tumor volume (GTV) and particularly its changes during RCT. The NCT03055715 study of the Young DEGRO working group of the German Society of Radiation Oncology (DEGRO) evaluated the prognostic impact of GTV and its changes during RCT. METHODS: A total of 21 university centers for radiation oncology from five different European countries (Germany, Switzerland, Spain, Belgium, and Austria) participated in the study which evaluated n = 347 patients with confirmed (biopsy) inoperable NSCLC in UICC stage III A/B who received radical curative-intent RCT between 2010 and 2013. Patient and disease data were collected anonymously via electronic case report forms and entered into the multi-institutional RadPlanBio platform for central data analysis. GTV before RCT (initial planning CT, GTV1) and at 40-50 Gy (re-planning CT for radiation boost, GTV2) was delineated. Absolute GTV before/during RCT and relative GTV changes were correlated with overall survival as the primary endpoint. Hazard ratios (HR) of survival analysis were estimated by means of adjusted Cox regression models. RESULTS: GTV1 was found to have a mean of 154.4 ml (95%CI: 1.5-877) and GTV2 of 106.2 ml (95% CI: 0.5-589.5), resulting in an estimated reduction of 48.2 ml (p < 0.001). Median overall survival (OS) was 18.8 months with a median of 22.1, 20.9, and 12.6 months for patients with high, intermediate, and low GTV before RT. Considering all patients, in one survival model of overall mortality, GTV2 (2.75 (1.12-6.75, p = 0.03) was found to be a stronger survival predictor than GTV1 (1.34 (0.9-2, p > 0.05). In patients with available data on both GTV1 and GTV2, absolute GTV1 before RT was not significantly associated with survival (HR 0-69, 0.32-1.49, p > 0.05) but GTV2 significantly predicted OS in a model adjusted for age, T stage, and chemotherapy, with an HR of 3.7 (1.01-13.53, p = 0.04) per 300 ml. The absolute decrease from GTV1 to GTV2 was correlated to survival, where every decrease by 50 ml reduced the HR by 0.8 (CI 0.64-0.99, p = 0.04). There was no evidence for a survival effect of the relative change between GTV1 and GTV2. CONCLUSION: Our results indicate that independently of T stage, the re-planning GTV during RCT is a significant and superior survival predictor compared to baseline GTV before RT. Patients with a high absolute (rather than relative) change in GTV during RT show a superior survival outcome after RCT.

Rapid Design and Development of a Network Isolated DICOM Service Class Provider Device.

Integrating vendor equipment and instruments into a corporate pharmaceutical research environment can be challenging and in light of recently reported cyber-attacks across industries and ongoing threats, additional security measures add to the challenge. In theory, Windows 10-based equipment coupled with the Digital Imaging and Communications in Medicine (DICOM) protocol should make it easier for instrument integration. A challenge arose with the onboarding of 2 new Microsoft Windows 10, DICOM compliant, Pre-clinical Positron Emission Tomography and Computed Tomography (PET/CT) instruments post acquisition when we discovered that we were restricted from connecting them to our corporate network. These new instruments were scheduled to run studies the following week. The coordinating of PET studies is complex, so schedule disruption incurs costs and long-term scheduling impacts. The solution was to develop a DICOM Service Class Provider (SCP) device using a commodity beagleboard.org BeagleBone Black (BBB) Rev. C device, the Offis DCMTK open source toolkit, and automation code written in Python. The BBB device provides network and DICOM communication from the instrument to the BBB, it provides the corporate network connectivity needed to NFS mount the network attached storage (NAS) system, isolated the two networks, and moves the files to the appropriate NAS share. The design went from concept to production ready in less than 24 h, providing a cost-effective, reliable, robust, and easily supported solution. The device satisfies internal and best practice security concerns, and it isolates the instrument from the network adding a layer of cyber resilience protection for the instrument.

Quantitation of amino sugar stereoisomer and muramic acid biomarkers by hydrophilic interaction liquid chromatography-mass spectrometry.

A rapid separation and quantitation of the stereoisomer amino sugars glucosamine, galactosamine, and mannosamine, along with muramic acid, is needed. These compounds, when their quantities are accurate, can be used to understand the origin and fate of natural organic matter (NOM) in the environment. These target molecules are biomarkers of fungi and bacteria and allow the deconvolution of microbial transformations and degradation of NOM in a wide variety of environmental matrices. Analytical methods applied to this suite of biomarkers are needed to understand carbon and nitrogen biogeochemistry with a changing global climate. Traditional separations of these analytes by gas chromatography require sample derivatization, as does reverse phase liquid chromatography. In contrast, ion chromatography can separate the analytes directly, but requires a separate analytical method to quantify muramic acid. In this work we present a direct analysis of all these molecules using hydrophilic liquid interaction chromatography. Solvent composition, buffer strength, pH, flow rate, and column temperature were optimized. The method can separate these four compounds and the biopolymeric precursor molecule N-acetylglucosamine in a single run in under 8 min with equivalent resolution to the best previously reported separations that did not require derivatization prior to analysis. Detection of the analytes was performed by both tandem and time-of-flight mass spectrometry. The method was assessed for its quantitative capabilities through i) peak area assignment, ii) check standards with ratios of the target analytes likely to be present in real samples, iii) an injection internal standard, and iv) quantitative analysis of real soil hydrolysates by external calibration and standard addition approaches. Across their expected analytical ranges the response for each analyte was highly linear with good accuracy (<25%) and precision (<15%) over three orders of magnitude. Detection limits of 20 µg L-1 were found for galactosamine and 5 µg L-1 for the remainder of the analytes, comparable to the majority of other methods reported in the literature. Overall, this new approach can directly and rapidly quantify amino sugars recovered in environmental hydrolysates.

Increasing chloride concentration causes retention of mercury in melted Arctic snow due to changes in photoreduction kinetics.

Mercury (Hg) in the Arctic is a significant concern due to its bioaccumulative and neurotoxic properties, and the sensitivity of Arctic environments. Previous research has found high levels of Hg in snowpacks with high chloride (Cl-) concentrations. We hypothesised that Cl- would increase Hg retention by decreasing Hg photoreduction to Hg(0) in melted Arctic snow. To test this, changes in Hg photoreduction kinetics in melted Alert, NU snow were quantified with changing Cl- concentration and UV intensity. Snow was collected and melted in Teflon bottles in May 2014, spiked with 0-10µg/g Cl-, and irradiated with 3.52-5.78W·m-2 UV (280-400nm) radiation in a LuzChem photoreactor. Photoreduction rate constants (k) (0.14-0.59hr-1) had positive linear relationships with [Cl-], while photoreduced Hg amounts (Hg(II)red) had negative linear relationships with [Cl-] (1287-64pg in 200g melted snow). Varying UV and [Cl-] both altered Hg(II)red amounts, with more efficient Hg stabilisation by Cl- at higher UV intensity, while k can be predicted by Cl- concentration and/or UV intensity, depending on experimental parameters. Overall, with future projections for greater snowpack Cl- loading, our experimental results suggest that more Hg could be delivered to Arctic aquatic ecosystems by melted snow (smaller Hg(II)red expected), but the Hg in the melted snow that is photoreduced may do so more quickly (larger k expected).

IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.

Atopic dermatitis (AD) often precedes asthma and food allergy, indicating that epicutaneous sensitization to allergens may be important in the induction of allergic responses at other barrier surfaces. Thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 are two cytokines that may drive type 2 responses in the skin; both are potential targets in the treatment of allergic diseases. We tested the functional role of IL-33 and the interplay between IL-33 and TSLP in mouse models of atopic march and gastrointestinal (GI) allergy. IL-33-driven allergic disease occurred in a TSLP-independent manner. In contrast, mice lacking IL-33 signaling were protected from onset of allergic diarrhea in TSLP-driven disease. Epithelial-derived IL-33 was important in this model, as specific loss of IL-33 expression in the epithelium attenuated cutaneous inflammation. Notably, the development of diarrhea following sensitization with TLSP plus antigen was ameliorated even when IL-33 was blocked after sensitization. Thus, IL-33 has an important role during early cutaneous inflammation and during challenge. These data reveal critical roles for IL-33 in the "atopic march" that leads from AD to GI allergy.

IL-33 promotes gastrointestinal allergy in a TSLP-independent manner.

This corrects the article DOI: 10.1038/mi.2017.61.

Hypercementosis Associated with ENPP1 Mutations and GACI.

Mineralization of bones and teeth is tightly regulated by levels of extracellular inorganic phosphate (Pi) and pyrophosphate (PPi). Three regulators that control pericellular concentrations of Pi and PPi include tissue-nonspecific alkaline phosphatase (TNAP), progressive ankylosis protein (ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Inactivation of these factors results in mineralization disorders affecting teeth and their supporting structures. This study for the first time analyzed the effect of decreased PPi on dental development in individuals with generalized arterial calcification of infancy (GACI) due to loss-of-function mutations in the ENPP1 gene. Four of the 5 subjects reported a history of infraocclusion, overretained primary teeth, ankylosis, and/or slow orthodontic tooth movement, suggesting altered mineral metabolism contributing to disrupted tooth movement and exfoliation. All subjects had radiographic evidence of unusually protruding cervical root morphology in primary and/or secondary dentitions. High-resolution micro-computed tomography (micro-CT) analyses of extracted primary teeth from 3 GACI subjects revealed 4-fold increased cervical cementum thickness ( P = 0.00007) and a 23% increase in cementum density ( P = 0.009) compared to age-matched healthy control teeth. There were no differences in enamel and dentin densities between GACI and control teeth. Histology revealed dramatically expanded cervical cementum in GACI teeth, including cementocyte-like cells and unusual patterns of cementum resorption and repair. Micro-CT analysis of Enpp1 mutant mouse molars revealed 4-fold increased acellular cementum thickness ( P = 0.002) and 5-fold increased cementum volume ( P = 0.002), with no changes in enamel or dentin. Immunohistochemistry identified elevated ENPP1 expression in cementoblasts of human and mouse control teeth. Collectively, these findings reveal a novel dental phenotype in GACI and identify ENPP1 genetic mutations associated with hypercementosis. The sensitivity of cementum to reduced PPi levels in both human and mouse teeth establishes this as a well-conserved and fundamental biological process directing cementogenesis across species (ClinicalTrials.gov NCT00369421).

GM-CSF produced by the airway epithelium is required for sensitization to cockroach allergen.

Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization. Epithelial-derived GM-CSF was required for allergic sensitization and selectively restored Th2 responses in the absence of MyD88. Thus, we demonstrate that epithelial-derived GM-CSF is a critical early signal during allergic sensitization to CRA.

Critical role of TSLP-responsive mucosal dendritic cells in the induction of nasal antigen-specific IgA response.

Thymic stromal lymphopoietin (TSLP) is an interleukin-7 (IL-7)-like cytokine involved in T helper 2 type immune responses. The primary target of TSLP is myeloid dendritic cells (DCs), however, little is known about the mechanism by which TSLP elicits respiratory IgA immune responses upon mucosal immunization. Here, we found that the levels of TSLP and TSLPR were upregulated in the mucosal DCs of mice nasally immunized with pneumococcal surface protein A (PspA) plus cholera toxin (CT) compared with those immunized with PspA alone. PspA-specific IgA responses, but not IgG Ab responses were significantly reduced in both serum and mucosal secretions of TSLPR knockout mice compared with wild-type mice after nasal immunization with PspA plus CT. Furthermore, CD11c+ mucosal DCs isolated from TSLPR knockout mice nasally immunized with PspA plus CT were less activated and exhibited markedly reduced expression of IgA-enhancing cytokines (e.g., APRIL, BAFF, and IL-6) compared with those from equivalently immunized wild-type mice. Finally, exogenous TSLP promoted production of IgAs in an in vitro DC-B cell co-culture system as exhibited by enhanced IL-6 production. These results suggest that TSLP-TSLPR signaling is pivotal in the induction of nasal respiratory immunity against pathogenic pneumococcal infection.

Comparison between the impact of morning and evening doses of rivaroxaban on the circadian endogenous coagulation rhythm in healthy subjects.

UNLABELLED: ESSENTIALS: It is unknown whether single rivaroxaban doses should best be administered in the morning or evening. Circadian rhythm of coagulation/fibrinolysis was measured after morning or evening intake of rivaroxaban. Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations. Evening intake of rivaroxaban better matches the morning hypofibrinolysis. BACKGROUND: A circadian variation of the endogenous coagulation system exists with hypercoagulability and hypofibrinolysis and a corresponding peak of cardiovascular thromboembolic events in the morning. So far, no information is given as to whether single daily doses of the new oral anticoagulant drug rivaroxaban should best be administered in the morning or the evening. MATERIALS AND METHODS: Sixteen healthy male or female volunteers with a mean age of 26 ± 7 years were included in this randomized, controlled, analyst-blinded cross-over clinical trial. All subjects were given three morning and three evening single doses of 10 mg rivaroxaban. Circadian rhythms of prothrombin fragment 1 + 2, plasminogen activator inhibitor, and plasmin-antiplasmin complex were measured before any medication intake, as well as after morning or evening medication intake. Rivaroxaban concentrations were determined by an anti-activated factor X assay and liquid chromatography-mass spectrometry. MAIN RESULTS: Concentrations of rivaroxaban were higher 12 h after evening intake of rivaroxaban than 12 h after morning intake (53.3 ng mL(-1) [95% confidence interval 46.0-67.8] vs. 23.3 ng mL(-1) [19.4-29.1, respectively]). Rivaroxaban intake in the evening reduced morning F1+2 concentrations better at 8:00 AM than did administration on awakening (85 ± 25 nmol L(-1) vs. 106 ± 34 nmol L(-1) , CI: 9.4-32.1). In addition, this suppression effect was longer lasting after evening intake. CONCLUSIONS: Evening intake of rivaroxaban leads to prolonged exposure to rivaroxaban concentrations and better matches the morning hypofibrinolysis. These results might help to further improve the efficacy and safety of rivaroxaban treatment.

Non-invasive imaging of implanted peritoneal carcinomatosis in mice using PET and bioluminescence imaging.

BACKGROUND: Non-invasive imaging of peritoneal carcinomatosis remains challenging. The aim of this study was to compare positron emission tomography (PET) and bioluminescence imaging (BLI) for the early detection of peritoneal carcinomatosis in a mouse model. METHODS: Female nude mice were inoculated intraperitoneally with 1×10(7) HSC45-M2-luc gastric cancer cells. The cells were stably transfected with the gene coding for firefly luciferase. Tumour development was monitored using PET and BLI and in two subgroups, on days 3 and 4 or on days 6 and 7 after tumour cell inoculation. Tumour nodules found on post mortem examination served as the reference standard for evaluating the images. RESULTS: PET detected 58/82 lesions (sensitivity 71 %). This method detected all (100 %) nodules larger than 6 mm, 88 % of nodules in the range of >2-4 mm, and even 58 % of small nodules measuring only 1-2 mm. BLI identified a total of 40/82 lesions (sensitivity 49 %). The difference between PET and BLI was statistically significant at p < 0.05 (PET/BLI chi-square 8.2). CONCLUSIONS: PET was more sensitive than BLI for the detection of early peritoneal carcinomatosis in our mouse model. The sensitivity of BLI largely depended on the site of the lesions in relation to the imaging device.

CHERENCUBE: concept definition and implementation challenges of a Cherenkov-based detector block for PET.

PURPOSE: A new concept for a depth-of-interaction (DOI) capable time-of-flight (TOF) PET detector is defined, based only on the detection of Cherenkov photons. The proposed "CHERENCUBE" consists of a cubic Cherenkov radiator with position-sensitive photodetectors covering each crystal face. By means of the spatial distribution of the detected photons and their time of arrival, the point of interaction of the gamma-ray in the crystal can be determined. This study analyzes through theoretical calculations and Monte Carlo simulations the potential advantages of the concept toward reaching a Cherenkov-only detector for TOF-PET with DOI capability. Furthermore, an algorithm for the DOI estimation is presented and the requirements for a practical implementation of the proposed concept are defined. METHODS: The Monte Carlo simulations consisted of a cubic crystal with one photodetector coupled to each one of the faces of the cube. The sensitive area of the detector matched exactly the crystal size, which was varied in 1 mm steps between 1 × 1 × 1 mm(3) and 10 × 10 × 10 mm(3). For each size, five independent simulations of ten thousand 511 keV gamma-rays were triggered at a fixed distance of 10 mm. The crystal chosen was PbWO4. Its scintillation properties were simulated, but only Cherenkov photons were analyzed. Photodetectors were simulated having perfect photodetection efficiency and infinite time resolution. For every generated particle, the analysis considered its creation process, parent and daughter particles, energy, origin coordinates, trajectory, and time and position of detection. The DOI determination is based on the distribution of the emission time of all photons per event. These values are calculated as a function of the coordinates of detection and origin for every photon. The common origin is estimated by finding the distribution with the most similar emission time-points. RESULTS: Detection efficiency increases with crystal size from 8.2% (1 × 1 × 1 mm(3)) to 58.6% (10 × 10 × 10 mm(3)) and decreases applying a photon detection threshold of 5/10/20 photons to 6.3%/4.3%/0.7% and 49.3%/30.4%/2.8%, respectively. The detection rate in the six photodetectors is uniform due to the nearly isotropic cone emission. Most cones originated after a photoelectric effect interaction, with two dominating peaks for the kinetic energy of the electron at 422.99 and 441.47 keV. The detection distance between same-event photons defines the spatial resolution of the detector required for individual photon recognition, with 20% of the detected photons having their closest neighbor within a distance of 5% of the length of the cube. Same-event photons are detected within a time window whose width is determined by the crystal size, with values of 30 and 150 ps for a 1 × 1 × 1 mm(3) and a 10 × 10 × 10 mm(3) cube, respectively. The DOI reconstruction has an accuracy of approximately 23% of the length of the cube, with an average value of 2.2 mm for a 10 × 10 × 10 mm(3) CHERENCUBE. CONCLUSIONS: The proposed concept requires a detector with high photodetection efficiency. The structure of the sensitive surface of the detector should be a two dimensional array of microcells, able to provide individual detection coordinates and time stamps. The microcell size determines the ability to recognize individual photons, influencing detection efficiency. The 3D DOI recognition relies on the accuracy of the time stamps and detection coordinates, without the need for a recognition of the projected patterns of photons. The refractive index of the material defines a detector intrinsic energy-based rejection of scattered PET events at the cost of reduced sensitivity.

Mercury in Arctic snow: quantifying the kinetics of photochemical oxidation and reduction.

Controlled experiments were performed with frozen and melted Arctic snow to quantify relationships between mercury photoreaction kinetics, ultra violet (UV) radiation intensity, and snow ion concentrations. Frozen (-10°C) and melted (4°C) snow samples from three Arctic sites were exposed to UV (280-400 nm) radiation (1.26-5.78 W · m(-2)), and a parabolic relationship was found between reduction rate constants in frozen and melted snow with increasing UV intensity. Total photoreduced mercury in frozen and melted snow increased linearly with greater UV intensity. Snow with the highest concentrations of chloride and iron had larger photoreduction and photooxidation rate constants, while also having the lowest Hg(0) production. Our results indicate that the amount of mercury photoreduction (loss from snow) is the highest at high UV radiation intensities, while the fastest rates of mercury photoreduction occurred at both low and high intensities. This suggests that, assuming all else is equal, earlier Arctic snow melt periods (when UV intensities are less intense) may result in less mercury loss to the atmosphere by photoreduction and flux, since less Hg(0) is photoproduced at lower UV intensities, thereby resulting in potentially greater mercury transport to aquatic systems with snowmelt.

Impact of flexible body surface coil and patient table on PET quantification and image quality in integrated PET/MR.

AIM: The surface coils of the Biograph mMR integrated PET/MR system were optimised for PET, but are otherwise unaccounted for. The patient table is still more massive than those of PET/CT devices. The goal was to assess those hardware effects on quantification, count statistics, image quality and scan time both with phantoms and in patients and to investigate their clinical relevance. PATIENTS, MATERIAL, METHODS: PET phantom data were acquired with and without the patient table. Image noise was expressed as relative standard deviation and compared to a state-of-the-art PET/CT scanner. Protocols of the phantom/patient study regarding the surface coils were similar. Thoraces/abdomens of 11 patients were scanned with and without a coil (1 BP, 4 min). Mean uptake and standard deviation in a cubical VOI were derived and expressed as SUV. RESULTS: The patient table reduced the number of true coincidences (trues) by 19% (PET/MR) and by 11% (PET/CT). The scan duration for the mMR had to be increased by approximately 30% to achieve a noise level comparable to that of the PET/CT. Decreased SUVs with coil observed in the phantom were confirmed by the patient study. By removing the coil, the mean liver SUV increased by (6 ± 2)%. With (+3 ± 14)%, the average change was similar in lesions, but exceeded 20% in almost one fifth of them. The number of trues grew by (6 ± 1)% for the patients and by 7% for the phantom. CONCLUSION: Due to the additional attenuation caused by MR hardware, PET scan durations would have to be increased compared to current PET/CTs to provide similar image noise levels. The effect of the coils is mostly in the order of statistical fluctuations. In tumour lesions, it is more pronounced and shows a larger variability. Therefore, coils should be included in the attenuation correction to ensure accurate quantification and thus comparability across PET/MR and PET/CT scanners and within patient populations.

[[¹¹C]choline as a pharmacodynamic marker for docetaxel therapy. Response assessment in a LNCaP prostate cancer xenograft mouse model]. / Ansprechen auf eine Docetaxeltherapie im LNCaP-Prostatakarzinom-Xenograft-Mausmodell. Untersuchung mit der [¹¹C]Cholin-Kleintier-PET/CT.

UNLABELLED: The AIM of this study was to determine whether [¹¹C]choline can be used for docetaxel therapy response assessment in a LNCaP-prostate cancer xenograft mouse model using [¹¹C]choline small-animal PET/CT. ANIMALS, METHODS: The androgen-dependent human prostate cancer cell line LNCaP was implanted subcutaneously into the left flanks of 17 SCID-mice, 12.5 mg testosterone platelets were implanted in the neck wrinkle. All mice were injected 4-6 weeks after xenograft implantation with 37 MBq [¹¹C]choline via the tail vein. Dynamic imaging was performed for 60 minutes with a small-animal PET/CT scanner. After the first [¹¹C]choline PET/CT imaging 8 mice were subsequently injected intravenously with docetaxel twice (days 1 and 5) at a dose of 3 mg/kg body weight. 8 mice were treated with PBS as a control. [¹¹C]choline PET/CT imaging was performed on day 7, 14 and 21 after treatment. Image analysis was performed using tumor/muscle (T/M) ratios (ROI(T)/ROI(M) = T/M ratio). RESULTS: All LNCaP tumours could be visualized by [¹¹C]choline PET/CT. Before treatment the mean T/M ratio was 2.0 ± 0.2 in the docetaxel-treated group and 1.9 ± 0.2 in the control group (p = 0.837). There was a reduction in the mean [¹¹C]choline uptake after docetaxel treatment of the tumours of the LNCaP cell line as early as 1 week after initiation of therapy (T/M(mean) ratio 1.5 ± 0.2 after one week, 1.3 ± 0.2 after 2 weeks and 1.4 ± 0.2 after 3 weeks). There was no decrease in [¹¹C]choline uptake in the control group. CONCLUSION: Our results show that [¹¹C]choline has the potential for use in the early monitoring of the therapeutic effect of docetaxel in a LNCaP prostate cancer xenograft animal model.