Impact of inadequate bowel cleansing in sigmoidoscopy screening.

BACKGROUND AND STUDY AIMS: Long-time follow-up of sigmoidoscopy screening trials has shown reduced incidence and mortality of colorectal cancer (CRC), but inadequate bowel cleansing may hamper efficacy. The aim of this study was to assess the impact of bowel cleansing quality in sigmoidoscopy screening. PATIENTS AND METHODS: Individuals 50 to 74 years old who had a screening sigmoidoscopy in a population-based Norwegian, randomized trial between 2012 and 2019, were included in this cross-sectional study. The bowel cleansing quality was categorised as excellent, good, partly poor, or poor. The effect of bowel cleansing quality on adenoma detection rate (ADR) and referral to colonoscopy was evaluated by fitting multivariable logistic regression models. RESULTS: 35,710 individuals were included. The bowel cleansing at sigmoidoscopy was excellent in 20,934 (58.6%) individuals, good in 6580 (18.4%), partly poor in 7097 (19.9%) and poor in 1099 (3.1%). The corresponding ADRs were 17.0%, 16.6%, 14.5%, and 13.0%. Compared to participants with excellent bowel cleansing, those with poor bowel cleansing had an odds ratio for adenoma detection of 0.66 (95% confidence interval 0.55-0.79). We found substantial differences in the assessment of bowel cleansing quality among endoscopists. CONCLUSIONS: Inadequate bowel cleansing reduces the efficacy of sigmoidoscopy screening, by lowering ADR. A validated rating scale and improved bowel preparation are needed to make sigmoidoscopy an appropriate screening method.Trial registration Clinicaltrials.gov (NCT01538550).

Multiple choice as formative assessment in dental education.

INTRODUCTION: The effectiveness of multiple-choice questions (MCQs) in dental education is pivotal to student performance and knowledge advancement. However, their optimal implementation requires exploration to enhance the benefits. MATERIALS AND METHODS: An educational tool incorporating MCQs was administered from the 5th to the 10th semester in a dental curriculum. The students filled out a questionnaire after the MCQ, which was linked to the learning management system. Four cohorts of four semesters generated 2300 data points analysed by Spearmen correlation and mixed model regression analysis. RESULTS: Demonstrated a significant correlation between early exam preparation and improved student performance. Independent study hours and lecture attendance emerged as significant predictors, accounting for approximately 10.27% of the variance in student performance on MCQs. While the number of MCQs taken showed an inverse relationship with study hours, the perceived clarity of these questions positively correlated with academic achievement. CONCLUSION: MCQs have proven effective in enhancing student learning and knowledge within the discipline. Our analysis underscores the important role of independent study and consistent lecture attendance in positively influencing MCQ scores. The study provides valuable insights into using MCQs as a practical tool for dental student learning. Moreover, the clarity of assessment tools, such as MCQs, remains pivotal in influencing student outcomes. This study underscores the multifaceted nature of learning experiences in dental education and the importance of bridging the gap between student expectations and actual performance.

Students' perceptions of post-exam feedback in oral radiology-A comparative study from two dental hygienist educational settings.

INTRODUCTION: The aim of this study was to investigate how students perceive the benefit of participating in a teacher-organised session providing feedback on exams, termed post-exam feedback, in two dental hygienist programmes. METHODS: The study was based on interviews with 22 participants, including 18 students and 4 faculty teachers. The data were approached on the basis of thematic analysis, allowing us to generate insights on how the participants reflected on their participation in the post-exam feedback sessions and how they perceived this arrangement as learners. RESULTS: The findings from the study suggest that motivated students consider post-exam feedback to be beneficial in clearing up uncertainties and deepening their understanding of issues not fully understood during the exam, as well as supporting their further learning. Less motivated students mainly consider post-exam feedback to be relevant for students who do not pass the exams. CONCLUSIONS: Organised in a student-centred way and with attentiveness to student learning preferences, the results suggest that post-exam feedback can be valuable for enhancing assessment and supporting student learning related to exams.

Biomechanical Effects of Chronic Ankle Instability on the Talar Cartilage Matrix: The Value of T1ρ Relaxation Mapping Without and With Mechanical Loading.

BACKGROUND: T1ρ mapping has been proposed for the detection of early cartilage degeneration associated with chronic ankle instability (CAI). However, there are limited data surrounding the influence of ankle loading on T1ρ relaxation. PURPOSE: To evaluate T1ρ relaxation times of talar cartilage, as an indicator of early degenerative changes, associated with CAI and to investigate the influence of acute axial in situ loading on T1ρ values in CAI patients and healthy controls. STUDY TYPE: Prospective. SUBJECTS: A total of 9 patients (age = 21.8 ± 2.5 years, male/female = 2/7) with chronic ankle instability and 18 healthy control subjects (age = 22.8 ± 3.6 years, male/female = 5/13). FIELD STRENGTH: 3 T. SEQUENCE: 3D gradient echo fast low-angle shot (FLASH) sequence augmented with a variable spin-lock preparation period. ASSESSMENT: Ankle T1ρ mapping was performed without and with axial loading of 500 N. The talar cartilage was segmented in five coronal slices covering the central talocrural joint. Median talar T1ρ values were separately calculated for the medial and lateral facets. STATISTICAL TESTS: Mann-Whitney U and Wilcoxon signed-rank tests, significance level: P < 0.05. RESULTS: For the combined cohorts, the statistical analysis yielded significantly lower T1ρ values with loading compared to the no-load measurement for both the lateral (no load: [51.0 ± 4.0] msec, load: [49.5 ± 5.4] msec) as well as the medial compartment (no load: [50.0 ± 5.4] msec, load: [47.8 ± 6.8] msec). In the unloaded scans, the CAI patients showed significantly increased talar T1ρ values ([53.0 ± 7.4] mse ) compared to the healthy control subjects ([48.8 ± 4.1] msec) in the medial compartment. DATA CONCLUSION: Increased talar T1ρ relaxation times in CAI patients compared to healthy controls suggest that T1ρ relaxation is a sensitive biomarker for CAI-induced early-stage cartilage degeneration. However, the load-induced T1ρ change did not prove to be a viable marker for the altered biomechanical properties of the hyaline talar cartilage. LEVEL OF EVIDENCE: 2 LEVEL OF EFFICACY: Stage 2.

Time-Resolved Quantification of Patellofemoral Cartilage Deformation in Response to Loading and Unloading via Dynamic MRI With Prospective Motion Correction.

BACKGROUND: In vivo cartilage deformation has been studied by static magnetic resonance imaging (MRI) with in situ loading, but knowledge about strain dynamics after load onset and release is scarce. PURPOSE: To measure the dynamics of patellofemoral cartilage deformation and recovery in response to in situ loading and unloading by using MRI with prospective motion correction. STUDY TYPE: Prospective. SUBJECTS: Ten healthy male volunteers (age: [31.4 ± 3.2] years). FIELD STRENGTH/SEQUENCE: T1-weighted RF-spoiled 2D gradient-echo sequence with a golden angle radial acquisition scheme, augmented with prospective motion correction, at 3 T. ASSESSMENT: In situ knee loading was realized with a flexion angle of approximately 40° using an MR-compatible pneumatic loading device. The loading paradigm consisted of 2 minutes of unloaded baseline followed by a 5-minute loading bout with 50% body weight and an unloading period of 38 minutes. The cartilage strain was assessed as the mean distance between patellar and femoral bone-cartilage interfaces as a percentage of the initial (pre-load) distance. STATISTICAL TESTS: Wilcoxon signed-rank tests (significance level: P < 0.05), Pearson correlation coefficient (r). RESULTS: The cartilage compression and recovery behavior was characterized by a viscoelastic response. The elastic compression ([-12.5 ± 3.1]%) was significantly larger than the viscous compression ([-7.6 ± 1.5]%) and the elastic recovery ([10.5 ± 2.1]%) was significantly larger than the viscous recovery ([6.1 ± 1.8]%). There was a significant residual offset strain ([-3.6 ± 2.3]%) across the cohort. A significant negative correlation between elastic compression and elastic recovery was observed (r = -0.75). DATA CONCLUSION: The in vivo cartilage compression and recovery time course in response to loading was successfully measured via dynamic MRI with prospective motion correction. The clinical relevance of the strain characteristics needs to be assessed in larger subject and patient cohorts. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

Application of gas diffusion electrodes in bioeconomy: An update.

The transition of today's fossil fuel based chemical industry toward sustainable production requires improvement of established production processes as well as development of new sustainable and bio-based synthesis routes within a circular economy. Thereby, the combination of electrochemical and biotechnological advantages in such routes represents one important keystone. For the electrochemical generation of reactants from gaseous substrates such as O2 or CO2 , gas diffusion electrodes (GDE) represent the electrodes of choice since they overcome solubility-based mass transport limitations. Within this article, we illustrate the architecture, function principle and fabrication of GDE. We highlight the application of GDE for conversion of CO2 using abiotic catalysts for subsequent biosynthesis as well as the application of microbial catalysts at GDE for CO2 conversion. The reduction of oxygen at GDE is summarized for the application of oxygen depolarized cathodes in microbial fuel cells and generation of H2 O2 to drive enzymatic reactions. Finally, engineering aspects such as scale-up and the modeling of GDE-based processes are described. This review presents an update on the application of GDE in bio-based production systems and emphasizes their large potential for sustainable development of new pathways in bioeconomy.

Diagnostic yield for video capsule endoscopy in gastrointestinal graft- versus -host disease: a systematic review and metaanalysis.

BACKGROUND: The gastrointestinal tract is the second most involved organ for graft-versus-host disease where involvement of the small intestine is present in 50% of the cases. Therefore, the use of a non-invasive investigation i.e., video capsule endoscopy (VCE) seems ideal in the diagnostic work-up, but this has never been systematically evaluated before. OBJECTIVE: The aim of this systematic review was to determine the efficacy and safety of VCE, in comparison with conventional endoscopy in patients who received hematopoietic stem cell transplantation. METHOD: Databases searched were PubMed, Scopus, EMBASE, and Cochrane CENTRAL. All databases were searched from their inception date until June 17, 2022. The search identified 792 publications, of which 8 studies were included in our analysis comprising of 232 unique patients. Efficacy was calculated in comparison with the golden standard i.e., histology. Risk of bias assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: The pooled sensitivity was higher for VCE at 0.77 (95% CI: 0.60-0.89) compared to conventional endoscopy 0.62 (95% CI: 0.47-0.75) but the difference was not statistically significant (p = 0.155, Q = 2.02). Similarly, the pooled specificity was higher for VCE at 0.68 (95% CI: 0.46-0.84) than for conventional endoscopy at 0.58 (95% CI: 0.40-0.74) but not statistically significant (p = 0.457, Q = 0.55). Moreover, concern for adverse events such as intestinal obstruction or perforation was not justified since none of the capsules were retained in the small bowel and no perforations occurred in relation to VCE. A limitation to the study is the retrospective approach seen in 50% of the studies. CONCLUSION: The role of video capsule endoscopy in diagnosing or dismissing graft-versus-host disease is not yet established and requires further studies. However, the modality appears safe in this cohort.

Exploring the potential of incremental feature selection to improve genomic prediction accuracy.

BACKGROUND: The ever-increasing availability of high-density genomic markers in the form of single nucleotide polymorphisms (SNPs) enables genomic prediction, i.e. the inference of phenotypes based solely on genomic data, in the field of animal and plant breeding, where it has become an important tool. However, given the limited number of individuals, the abundance of variables (SNPs) can reduce the accuracy of prediction models due to overfitting or irrelevant SNPs. Feature selection can help to reduce the number of irrelevant SNPs and increase the model performance. In this study, we investigated an incremental feature selection approach based on ranking the SNPs according to the results of a genome-wide association study that we combined with random forest as a prediction model, and we applied it on several animal and plant datasets. RESULTS: Applying our approach to different datasets yielded a wide range of outcomes, i.e. from a substantial increase in prediction accuracy in a few cases to minor improvements when only a fraction of the available SNPs were used. Compared with models using all available SNPs, our approach was able to achieve comparable performances with a considerably reduced number of SNPs in several cases. Our approach showcased state-of-the-art efficiency and performance while having a faster computation time. CONCLUSIONS: The results of our study suggest that our incremental feature selection approach has the potential to improve prediction accuracy substantially. However, this gain seems to depend on the genomic data used. Even for datasets where the number of markers is smaller than the number of individuals, feature selection may still increase the performance of the genomic prediction. Our approach is implemented in R and is available at https://github.com/FelixHeinrich/GP_with_IFS/ .

Outcome of self-expandable metal stents placement for obstructive colorectal cancer: 7 years' experience from a Swedish tertiary center.

BACKGROUND AND STUDY AIMS: Self expandable metal stents (SEMS) is an alternative to emergency surgery to treat malignant large bowel obstruction. It can be used either for palliation or as a bridge to curative surgery. Our study aims to review the outcomes of SEMS treatment in a tertiary center and to find predictors for the clinical outcome. PATIENT AND METHODS: We retrospectively analyzed data from SEMS insertion at Sahlgrenska University Hospital, a referral center in Western Sweden (1.7 million inhabitants), between 2014 and 2020. Data collected were age, the intent of intervention, tumor localization, complication rate, technical and clinical success, 30- and 90-days mortality as well as long-term survival for the indication bridge to surgery. RESULTS: We identified 265 SEMS insertions (mean age 72, female 49.4%). Most SEMS were used for palliation (90.2%). The malign obstruction was most often located in the left colon (71.7%). Technical success was achieved in 259 (97.7%) cases and clinical success in 244 (92.1%) cases. Post-operative complications occurred in 11 cases (4.2%). The 30-days mortality rate was 11.7% and the 90-day was 31.7%. In our analysis the tumor site was not associated with adverse outcomes and bridge to surgery indication was a positive prognostic factor for the 90-day mortality. CONCLUSIONS: We found that SEMS is an effective and safe treatment for patients with acute obstructive colorectal cancer.

Ethanol Kinetics in the Human Brain Determined by Magnetic Resonance Spectroscopy.

In many parts of the world, ethanol is a widely consumed substance that displays its effect in the brain, the target organ for desired, but also negative impact. In a previous study, the ethanol concentrations were analyzed in different regions of the brain by magnetic resonance spectroscopy (MRS). In this study, the same method is used to demonstrate the kinetics of the ethanol concentration in the human brain after oral ethanol uptake. A drinking study was performed with 10 healthy participants. After the uptake of ethanol in a calculated amount leading to a plasma ethanol concentration of 0.92 g/L (19.95 mM corresponding to a blood ethanol concentration of 0.7 g/kg), brain ethanol concentrations were continuously measured by means of MRS on a 3 Tesla human magnetic resonance imaging (MRI) system. For the data acquisition a single-voxel sLASER sequence was used, with the volume of interest located in the occipital cortex. Intermittently, blood samples were taken and plasma was analyzed for ethanol using headspace gas chromatography with flame ionization detection (HS-GC-FID). The obtained MRS brain ethanol curves showed distinct inter-individual differences; however, a good intra-individual correlation of plasma and brain ethanol concentrations was observed. The results suggest a rapid equilibration between blood and brain. The ethanol concentrations measured in the brain were substantially lower than the measured plasma ethanol results, suggesting an MRS visibility of about 63% for ethanol in brain tissue. The maximum individual ethanol concentrations in the brain (normalized to water content) ranged between 7.1 and 14.1 mM across the cohort, while the highest measured plasma concentrations were in the range between 0.35 g/L (9.41 mM) and 0.95 g/L (20.52 mM).

Articular Cartilage-From Basic Science Structural Imaging to Non-Invasive Clinical Quantitative Molecular Functional Information for AI Classification and Prediction.

This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to image the structure and associated functions of articular cartilage but, instead, to devise methods for generating non-invasive, function-depicting images with quantitative information that is useful for detecting the early, pre-clinical stage of diseases such as primary or post-traumatic osteoarthritis (OA/PTOA). In this context, this review summarizes (a) the structure and function of articular cartilage as a molecular imaging target, (b) quantitative MRI for non-invasive assessment of articular cartilage composition, microstructure, and function with the current state of medical diagnostic imaging, (c), non-destructive imaging methods, (c) non-destructive quantitative articular cartilage live-imaging methods, (d) artificial intelligence (AI) classification of degeneration and prediction of OA progression, and (e) our contribution to this field, which is an AI-supported, non-destructive quantitative optical biopsy for early disease detection that operates on a digital tissue architectural fingerprint. Collectively, this review shows that articular cartilage imaging has undergone profound changes in the purpose and expectations for which cartilage imaging is used; the image is becoming an AI-usable biomarker with non-invasive quantitative functional information. This may aid in the development of translational diagnostic applications and preventive or early therapeutic interventions that are yet beyond our reach.

The use of post-exam feedback in oral radiology: A survey study of dental and dental hygienist schools in Europe.

INTRODUCTION: A combination of summative assessments and post-exam feedback can create a formative environment to support student learning. It remains unknown to what extent feedback sessions are conducted after exams in oral radiology courses for dental and dental hygienist students in Europe. This survey study aimed to explore whether post-exam feedback sessions were conducted, and if so, in what format. MATERIALS AND METHODS: A questionnaire was distributed to 76 dental schools in 26 countries and 34 dental hygienist schools in 14 countries in Europe. The questions addressed whether feedback was provided after exams in oral radiology, the feedback format, and whether feedback sessions were formalised or performed for other reasons. RESULTS: Questionnaire responses were received from 33 dental schools in 18 countries, and 20 dental hygienist schools in 11 countries. Information about grades was provided in 23-30% of the schools. Post-exam feedback sessions including opportunities for discussion was provided at 39% of the schools, all with guidelines stating that these sessions should be carried out. The remaining schools provided feedback either on request by individual students or as written examples of correct answers. CONCLUSION: Almost one third of the dental schools announced grades without providing any post-exam feedback that could support learning. Two fifth utilised feedback sessions to assist students in gaining knowledge and sorting out misconceptions, all according to guidelines. Given the possible learning potential in post-exam feedback with opportunity to discuss, further studies of this format would be valuable, including the role and use of feedback guidelines.

Characteristics of nonparticipants in a randomised colorectal cancer screening trial comparing sigmoidoscopy and faecal immunochemical testing.

Public health systems should guarantee universal access to health care services, including cancer screening. We assessed whether certain population subgroups were underrepresented among participants in colorectal cancer screening with sigmoidoscopy and faecal immunochemical testing (FIT). Between 2012 and 2019, about 140 000 individuals aged 50 to 74 years were randomly invited to once-only sigmoidoscopy or first round of FIT screening. Our study included 46 919 individuals invited to sigmoidoscopy and 70 019 to FIT between 2012 and 2017. We used logistic regression models to evaluate if demographic and socioeconomic factors and use of certain drugs were associated with participation. Twenty-four thousand one hundred and fifty-nine (51.5%) individuals attended sigmoidoscopy and 40 931 (58.5%) FIT screening. Male gender, young age, low education and income, being retired or unemployed, living alone, being an immigrant, long driving time to screening centre, and use of antidiabetic and psychotropic drugs were associated with low participation in both screening groups. Many of these factors also predicted low acceptance of colonoscopy after positive FIT. While male gender, young age and living alone were more strongly associated with nonparticipation in FIT than sigmoidoscopy, low education and income, being retired or immigrant and long driving time were more strongly associated with nonparticipation in sigmoidoscopy than FIT. In conclusion, participation was lower in sigmoidoscopy than FIT. Predictors of nonparticipation were similar between arms. However, low socioeconomic status, being an immigrant and long driving time affected participation more in sigmoidoscopy screening, suggesting that FIT may guarantee more equal access to screening services than sigmoidoscopy.

Colorectal Cancer Screening With Repeated Fecal Immunochemical Test Versus Sigmoidoscopy: Baseline Results From a Randomized Trial.

BACKGROUND & AIMS: The comparative effectiveness of sigmoidoscopy and fecal immunochemical testing (FIT) for colorectal cancer (CRC) screening is unknown. METHODS: Individuals aged 50-74 years living in Southeast Norway were randomly invited between 2012 and 2019 to either once-only flexible sigmoidoscopy or FIT screening every second year. Colonoscopy was recommended after sigmoidoscopy if any polyp of ≥10 mm, ≥3 adenomas, any advanced adenomas, or CRC was found or, subsequent to, FIT >15 µg hemoglobin/g feces. Data for this report were obtained after complete recruitment in both groups and included 2 full FIT rounds and part of the third round. Outcome measures were participation, neoplasia detection, and adverse events. Age-standardized detection rates and age-adjusted odds ratios (ORs) were calculated. RESULTS: We included 139,291 individuals: 69,195 randomized to sigmoidoscopy and 70,096 to FIT. The participation rate was 52% for sigmoidoscopy, 58% in the first FIT round, and 68% for 3 cumulative FIT rounds. Compared to sigmoidoscopy, the detection rate for CRC was similar in the first FIT round (0.25% vs 0.27%; OR, 0.92; 95% confidence interval [CI], 0.75-1.13) but higher after 3 FIT rounds (0.49% vs 0.27%; OR, 1.87; 95% CI, 1.54-2.27). Advanced adenoma detection rate was lower in the first FIT round compared to sigmoidoscopy at 1.4% vs 2.4% (OR, 0.57; 95% CI, 0.53-0.62) but higher after 3 cumulative FIT rounds at 2.7% vs 2.4% (OR, 1.14; 95% CI, 1.05-1.23). There were 33 (0.05%) serious adverse events in the sigmoidoscopy group compared to 47 (0.07%) in the FIT group (P = .13). CONCLUSIONS: Participation was higher and more CRC and advanced adenomas were detected with repeated FIT compared to sigmoidoscopy. The risk of perforation and bleeding was comparable. Clinicaltrials.gov, Number: NCT01538550.

HPLC fluorescence assay for measuring the activity of diacylglycerol lipases and the action of inhibitors thereof.

1,2-Diacylglycerol lipases (DAGLs) are the most important enzymes for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), and their role in various pathophysiological conditions is currently under investigation. We synthesized a new 1,2-diacylglycerol substrate for these enzymes with a fluorogenic 4-(pyren-1-yl)butanoyl residue in sn-2 position. Using the fluorescent substrate, we measured DAGL activity in rat liver S9 fraction and brain microsomes. To this end, 2-acylglycerol release was directly determined via HPLC and fluorescence detection without further sample clean-up. The method was used to evaluate the action of several known DAGL inhibitors. These showed partly significant differences in their inhibitory effect on DAGLs in liver versus brain preparations. The method was verified by measuring the IC50 values for a subset of inhibitors by HPLC and single-quad MS detection using the deuterated natural DAGL substrate 1-stearoyl-2-arachidonoyl-sn-glycerol-d8. DAGL activity could also be measured with the new pyrene-labeled substrate by HPLC and UV instead of fluorescence detection, if larger quantities of the samples were injected into the HPLC system. Furthermore, using intact human sperm, we show that the substrate is also converted by DAGL enzymes in human cells.

Non-linear transformation of enzyme-linked immunosorbent assay (ELISA) measurements allows usage of linear models for data analysis.

BACKGROUND: In research questions such as in resistance breeding against the Beet necrotic yellow vein virus it is of interest to compare the virus concentrations of samples from different groups. The enzyme-linked immunosorbent assay (ELISA) counts as the standard tool to measure virus concentrations. Simple methods for data analysis such as analysis of variance (ANOVA), however, are impaired due to non-normality of the resulting optical density (OD) values as well as unequal variances in different groups. METHODS: To understand the relationship between the OD values from an ELISA test and the virus concentration per sample, we used a large serial dilution and modelled its non-linear form using a five parameter logistic regression model. Furthermore, we examined if the quality of the model can be increased if one or several of the model parameters are defined beforehand. Subsequently, we used the inverse of the best model to estimate the virus concentration for every measured OD value. RESULTS: We show that the transformed data are essentially normally distributed but provide unequal variances per group. Thus, we propose a generalised least squares model which allows for unequal variances of the groups to analyse the transformed data. CONCLUSIONS: ANOVA requires normally distributed data as well as equal variances. Both requirements are not met with raw OD values from an ELISA test. A transformation with an inverse logistic function, however, gives the possibility to use linear models for data analysis of virus concentrations. We conclude that this method can be applied in every trial where virus concentrations of samples from different groups are to be compared via OD values from an ELISA test. To encourage researchers to use this method in their studies, we provide an R script for data transformation as well as the data from our trial.

Flexible MEGA editing scheme with asymmetric adiabatic pulses applied for T2 measurement of lactate in human brain.

PURPOSE: A flexible MEGA editing scheme which decouples the editing efficiency from TE is proposed and the utility of asymmetric adiabatic pulses for this new technique is explored. It is demonstrated that the method enables robust T2 measurement of lactate in healthy human brain. METHODS: The proposed variation of the MEGA scheme applies editing pulses in both acquired spectra, ensuring that the difference in J-evolution of the target resonance leads to maximal signal yield in the difference spectrum for arbitrary TE. A MEGA-sLASER sequence is augmented with asymmetric adiabatic editing pulses for enhanced flexibility and immunity to B1+ miscalibration and inhomogeneities. The technique is validated and optimized for flexible lactate editing via a simple analytical model, numerical simulations and in vitro experiments. The T2 relaxation constant of lactate is determined in vivo via multiple-TE measurements with the proposed method and a dedicated postprocessing and quantification approach. RESULTS: Asymmetric adiabatic editing pulses improve robustness and facilitate efficient J-editing in sequences or protocols with strong timing constraints. Single voxel measurements using the proposed MEGA scheme in the occipital cortex of six healthy subjects yield a relaxation constant of T2=171±19  ms for the methyl resonance of lactate at a field strength of 3T. CONCLUSIONS: The proposed MEGA editing scheme allows for novel kinds of J-editing experiments and promises to be an asset to robust T2 measurement of lactate and potentially other J-coupled metabolites in vivo.

Three-dimensional spatially resolved phase graph framework.

PURPOSE: An open-source spatially resolved phase graph framework is proposed for simulating arbitrary pulse sequences in the presence of piece-wise constant gradients with arbitrary orientations in three dimensions. It generalizes the extended phase graph algorithm for analysis of nonperiodic sequences while preserving its efficiency, and is able to estimate the signal modulation in the 3D spatial domain. METHODS: The framework extends the recursive magnetization-evolution algorithm to account for anisotropic diffusion and exploits a novel 3D k-space grid-merging method to balance the computational effort and memory requirements against acceptable simulation errors. A new postsimulation module is proposed to track and visualize the signal evolution both in the k-space and in the image domain, which can be used for simulating image artifacts or finding frequency-response profiles. To illustrate the developed technique, three examples are presented: (1) fast off-resonance calculation for dictionary building in MR fingerprinting, (2) validation of a steady-state sequence with quasi-isotropic diffusion weighting, and (3) investigation of the magnetization evolution in PRESS-based spectroscopic imaging. RESULTS: The grid-merging algorithm of the proposed framework demonstrates high calculation efficiency exemplified by frequency-response simulation of pseudo steady-state or diffusion-weighted steady-state sequences. It further helps to visualize the signal evolution in PRESS-based sequences. CONCLUSIONS: The proposed simulation framework has been validated based on several different example applications for analyzing signal evolution in the frequency and spatial domain.

Localized singlet-filtered MRS in vivo.

MR is a prominent technology to investigate diseases, with millions of clinical procedures performed every year. Metabolic dysfunction is one common aspect associated with many diseases. Thus, understanding and monitoring metabolic changes is essential to develop cures for many illnesses, including for example cancer and neurodegeneration. MR methodologies are especially suited to study endogenous metabolites and processes within an organism in vivo, which has led to many insights about physiological functions. Advancing metabolic MR techniques is therefore key to further understand physiological processes. Here, we introduce an approach based on nuclear spin singlet states to specifically filter metabolic signals and particularly show that singlet-filtered glutamate can be observed distinctly in the hippocampus of a living mouse in vivo. This development opens opportunities to make use of the singlet spin phenomenon in vivo and besides its use as a filter to provide scope for new contrast agents.

The CRCbiome study: a large prospective cohort study examining the role of lifestyle and the gut microbiome in colorectal cancer screening participants.

BACKGROUND: Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions. METHODS: The CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period. DISCUSSION: The CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538550 .