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Background: The diagnostic accuracy of colon capsule endoscopy (CCE) depends on a well-cleansed bowel. Evaluating the cleansing quality can be difficult with a substantial interobserver variation. Objectives: Our primary aim was to establish a standard of agreement for bowel cleansing in CCE based on evaluations by expert readers. Then, we aimed to investigate the interobserver agreement on bowel cleansing. Design: We conducted an interobserver agreement study on bowel cleansing quality. Methods: Readers with different experience levels in CCE and colonoscopy evaluated bowel cleansing quality on the Leighton–Rex scale and Colon Capsule CLEansing Assessment and Report (CC-CLEAR), respectively. All evaluations were reported on an image level. A total of 24 readers rated 500 images on each scale. Results: An expert opinion-based agreement standard could be set for poor and excellent cleansing but not for the spectrum in between, as the experts agreed on only a limited number of images representing fair and good cleansing. The overall interobserver agreement on the Leighton–Rex full scale was good (intraclass correlation coefficient (ICC) 0.84, 95% CI (0.82–0.85)) and remained good when stratified by experience level. On the full CC-CLEAR scale, the overall agreement was moderate (ICC 0.62, 95% CI (0.59–0.65)) and remained so when stratified by experience level. Conclusion: The interobserver agreement was good for the Leighton–Rex scale and moderate for CC-CLEAR, irrespective of the reader’s experience level. It was not possible to establish an expert-opinion standard of agreement for cleansing quality in CCE images. Dedicated training in using the scales may improve agreement and enable future algorithm calibration for artificial intelligence supported cleansing evaluation. Trial registration: All included images were derived from the CAREforCOLON 2015 trial (Registered with The Regional Health Research Ethics Committee (Registration number: S-20190100), the Danish data protection agency (Ref. 19/29858), and ClinicalTrials.gov (registration number: NCT04049357)).

Background and Purpose: The feasibility of acquiring diffusion-weighted imaging (DWI) images on an MR-Linac for quantitative response assessment during radiotherapy was explored. DWI data obtained with a Spin Echo Echo Planar Imaging sequence adapted for a 0.35 T MR-Linac were examined and compared with DWI data from a conventional 3 T scanner. Materials and Methods: Apparent diffusion coefficient (ADC) measurements and a distortion correction technique were investigated using DWI-calibrated phantoms and in the brains of seven volunteers. All DWI utilized two phase-encoding directions for distortion correction and off-resonance field estimation. ADC maps in the brain were analyzed for automatically segmented normal tissues. Results: Phantom ADC measurements on the MR-Linac were within a 3 % margin of those recorded by the 3 T scanner. The maximum distortion observed in the phantom was 2.0 mm prior to correction and 1.1 mm post-correction on the MR-Linac, compared to 6.0 mm before correction and 3.6 mm after correction at 3 T. In vivo, the average ADC values for gray and white matter exhibited variations of 14 % and 4 %, respectively, for different selections of b-values on the MR-Linac. Distortions in brain images before correction, estimated through the off-resonance field, reached 2.7 mm on the MR-Linac and 12 mm at 3 T. Conclusion: Accurate ADC measurements are achievable on a 0.35 T MR-Linac, both in phantom and in vivo. The selection of b-values significantly influences ADC values in vivo. DWI on the MR-Linac demonstrated lower distortion levels, with a maximum distortion reduced to 1.1 mm after correction.

Abstract The USP19 deubiquitinase is found in a locus associated with Parkinson’s Disease (PD), interacts with chaperonins, and promotes secretion of α-synuclein (α-syn) through the misfolding-associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of α-syn aggregates in PD, we inactivated USP19 (KO) in mice expressing the A53T mutation of α-syn and in whom α-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. This improvement was associated with less activation of microglia and improved performance in a tail-suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF nor propagation of aggregates in the cultured neurons. We conclude that USP19 instead modulates intracellular dynamics of aggregates. At an early time following PFF injection when the number of pSyn-positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from WT and KO brains with antibodies to pSyn showed higher levels of ubiquitinated oligomeric species in the KO samples. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of α-syn complexes.

Abstract Altered intrinsic brain connectivity of patients with anorexia nervosa has been observed in the acute phase of the disorder, but it remains unclear to what extent these alterations recover during weight normalization. In this study, we used functional imaging data from three time points to probe longitudinal changes in intrinsic connectivity patterns in patients with severe anorexia nervosa (BMI ≤ 15.5 kg/m2) over the course of weight normalization. At three distinct stages of inpatient treatment, we examined resting-state functional connectivity in 27 women with severe anorexia nervosa and 40 closely matched healthy controls. Using network-based statistics and graph-theoretic measures, we examined differences in global network strength, subnetworks with altered intrinsic connectivity, and global network topology. Patients with severe anorexia nervosa showed weakened intrinsic connectivity and altered network topology which did not recover during treatment. The persistent disruption of brain networks suggests sustained alterations of information processing in weight-recovered severe anorexia nervosa.

Abstract This prospective study aimed to present, compare, and evaluate the suitability of five different magnetic resonance imaging (MRI) protocols (3D double-echo steady-state (DESS), 3D fast spin echo short-tau inversion recovery (SPACE-STIR), 3D fast spin echo spectral attenuated inversion recovery (SPACE-SPAIR), volumetric interpolated breath-hold examination (T1-VIBE-Dixon), and ultrashort echo time (UTE)) and for orthopantomogram (OPG)-like MRI reconstructions using a novel mandibular coil. Three readers assessed MR-OPGs of 21 volunteers regarding technical image quality (4, excellent; 0, severely reduced), susceptibility to artifacts (3, absence; 0, massive), and visualization of anatomical structures in the oral cavity and surrounding skeletal structures (4, fine details visible; 0, no structures visible). Average image quality was good (3.29 ± 0.83) for all MRI protocols, with UTE providing the best image quality (3.52 ± 0.62) and no to minor artifacts (2.56 ± 0.6). Full diagnostic interpretability of the osseous structures is best in VIBE-Dixon and UTE MR-OPGs. DESS provided excellent visualization of the finest details of the nervous tissue (3.95 ± 0.22). Intra-reader and inter-reader agreement between the readers was good to excellent for all protocols (ICCs 0.812–0.957). MR-OPGs provide indication-specific accurate imaging of the oral cavity and could contribute to the early detection of pathologies, staging, and radiological follow-up of oral and maxillofacial diseases.

Background: The diagnostic accuracy of colon capsule endoscopy (CCE) depends on a well-cleansed bowel. Evaluating the cleansing quality can be difficult with a substantial interobserver variation. Objectives: Our primary aim was to establish a standard of agreement for bowel cleansing in CCE based on evaluations by expert readers. Then, we aimed to investigate the interobserver agreement on bowel cleansing. Design: We conducted an interobserver agreement study on bowel cleansing quality. Methods: Readers with different experience levels in CCE and colonoscopy evaluated bowel cleansing quality on the Leighton–Rex scale and Colon Capsule CLEansing Assessment and Report (CC-CLEAR), respectively. All evaluations were reported on an image level. A total of 24 readers rated 500 images on each scale. Results: An expert opinion-based agreement standard could be set for poor and excellent cleansing but not for the spectrum in between, as the experts agreed on only a limited number of images representing fair and good cleansing. The overall interobserver agreement on the Leighton–Rex full scale was good (intraclass correlation coefficient (ICC) 0.84, 95% CI (0.82–0.85)) and remained good when stratified by experience level. On the full CC-CLEAR scale, the overall agreement was moderate (ICC 0.62, 95% CI (0.59–0.65)) and remained so when stratified by experience level. Conclusion: The interobserver agreement was good for the Leighton–Rex scale and moderate for CC-CLEAR, irrespective of the reader's experience level. It was not possible to establish an expert-opinion standard of agreement for cleansing quality in CCE images. Dedicated training in using the scales may improve agreement and enable future algorithm calibration for artificial intelligence supported cleansing evaluation. Trial registration: All included images were derived from the CAREforCOLON 2015 trial (Registered with The Regional Health Research Ethics Committee (Registration number: S-20190100), the Danish data protection agency (Ref. 19/29858), and ClinicalTrials.gov (registration number: NCT04049357)). [ABSTRACT FROM AUTHOR]

An important tactile function is the active detection of small-scale features, such as edges or asperities, which depends on fine hand motor control. Using a resting-state fMRI paradigm, we sought to identify the functional connectivity of the brain network engaged in mapping tactile inputs to and from regions engaged in motor preparation and planning during active touch. Human participants actively located small-scale tactile features that were rendered by a computer-controlled tactile display. To induce rapid perceptual learning, the contrast between the target and the surround was reduced whenever a criterion level of success was achieved, thereby raising the task difficulty. Multiple cortical and subcortical neural connections within a parietal-cerebellar-frontal network were identified by correlating behavioral performance with changes in functional connectivity. These cortical areas reflected perceptual, cognitive, and attention-based processes required to detect and use small-scale tactile features for hand dexterity.

Abstract Quantitative susceptibility mapping (QSM) is a novel processing method for gradient-echo magnetic resonance imaging (MRI). Higher magnetic susceptibility in cortical veins have been observed on susceptibility maps in the ischemic hemisphere of stroke patients, indicating an increased oxygen extraction fraction (OEF). Our goal was to investigate susceptibility in veins of stroke patients after successful recanalization in order to analyze the value of QSM in predicting tissue prognosis and clinical outcome. We analyzed MR images of 23 patients with stroke due to unilateral middle cerebral artery (MCA)-M1/M2 occlusion acquired 24–72 h after successful thrombectomy. The susceptibilities of veins were obtained from QSM and compared between the stroke territory, the ipsilateral non-ischemic MCA territory and the contralateral MCA territory. As outcome variables, early infarct size and functional disability (modified Rankin Scale, mRS) after 3–5 months was used. The median susceptibility value of cortical veins in the ischemic core was 41% lower compared to the ipsilateral non-ischemic MCA territory and 38% lower than on the contralateral MCA territory. Strikingly, in none of the patients prominent vessels with high susceptibility signal were found after recanalization. Venous susceptibility values within the infarct did not correlate with infarct volume or functional disability after 3–5 months. Low venous susceptibility within the infarct core after successful recanalization of the occluded vessel likely indicates poor oxygen extraction arising from tissue damage. We did not identify peri-infarct tissue with increased susceptibility values as potential surrogate of former penumbral areas. We found no correlation of QSM parameters with infarct size or outcome.