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Objective: The quantity of ultra-high field MRI neuroimaging studies has rapidly increased. This study tests function, safety, and image artifacts of two frequently implanted programmable ventriculo-peritoneal (VP) shunt valves in a 7T MRI system., Methods: All tests were performed using a whole-body 7T MRI system. Three proGAV 2.0 and 3 CODMAN CERTAS® Plus programmable VP-shunt valves were tested in three steps. 1) Deflection angle tests close to the bore opening at the location of a static magnetic field gradient of 3-5 T/m. 2) Valves were fixed on a spherical phantom in 3 positions (a. lateral, b. cranial, c. cranial with 22.5° tilt anteriorly) and assessed for keeping the programmed pressure setting and reprogrammability. 3) Valves were fixed on the phantom and positioned lateral in a radiofrequency head coil. MRI scans were performed for both models, including MPRAGE, GRE and SE sequences., Results: Deflection angles were moderate (13°, 14°, 13°) for the proGAV valves and close to critical (43°, 43°, 41°) for the CODMAN valves at the test location. Taking a scaling factor of 2-3 for the maximum spatial magnetic field gradient accessible to a patient within the magnet bore into account renders both valves MR unsafe regarding ferromagnetic attraction. The proGAV valves kept the pressure settings in all positions and were reprogrammable in positions a. and b. In position c., reprogrammability was lost. The CODMAN valves changed their pressure setting and reprogrammability was lost in all positions. MR image signal homogeneity was unaltered in the phantom center, artifacts limit the assessability of structures in close vicinity to the valves., Conclusion: Both tested programmable VP-shunt valves are MR unsafe for 7T systems. Novel programming mechanisms using permanent magnets with sufficient magnetic coercivity or magnet-free mechanisms may allow the development of programmable VP-shunt valves that are conditional for 7T MR systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The correct estimation of fibre orientations is a crucial step for reconstructing human brain tracts. Bayesian Estimation of Diffusion Parameters Obtained using Sampling Techniques (bedpostx) is able to estimate several fibre orientations and their diffusion parameters per voxel using Markov Chain Monte Carlo (MCMC) in a whole brain diffusion MRI data, and it is capable of running on GPUs, achieving speed-up of over 100 times compared to CPUs. However, few studies have looked at whether the results from the CPU and GPU algorithms differ. In this study, we compared CPU and GPU bedpostx outputs by running multiple trials of both algorithms on the same whole brain diffusion data and compared each distribution of output using Kolmogorov-Smirnov tests., Results: We show that distributions of fibre fraction parameters and principal diffusion direction angles from bedpostx and bedpostx_gpu display few statistically significant differences in shape and are localized sparsely throughout the whole brain. Average output differences are small in magnitude compared to underlying uncertainty., Conclusions: Despite small amount of differences in output between CPU and GPU bedpostx algorithms, results are comparable given the difference in operation order and library usage between CPU and GPU bedpostx., Competing Interests: The authors have declared that no competing interests exist.

Alzheimer's disease (AD) is the leading cause of dementia in the elderly, but therapeutic options are lacking. Despite long being able to effectively treat the ill-effects of pathology present in various rodent models of AD, translation of these strategies to the clinic has so far been disappointing. One potential contributor to this situation is the fact that the vast majority of AD patients have other dementia-contributing comorbid pathologies, the most common of which are vascular in nature. This situation is modeled relatively infrequently in basic AD research, and almost never in preclinical studies. As part of our efforts to develop small molecule, anti-inflammatory therapeutics for neurological injury and disease, we have recently been exploring potentially promising treatments in preclinical multi-morbidity contexts. In the present study, we generated a mouse model of mixed amyloid and hyperhomocysteinemia (HHcy) pathology in which to test the efficacy of one of our anti-inflammatory compounds, MW151. HHcy can cause cerebrovascular damage and is an independent risk factor for both AD dementia and vascular contributions to cognitive impairment and dementia. We found that MW151 was able to partially rescue hippocampal-dependent spatial memory and learning deficits in this comorbidity context, and further, that the benefit is associated with a normalization of hippocampal metabolites detectable via magnetic resonance spectroscopy. These findings provide evidence that MW151 in particular, and potentially anti-inflammatory treatment more generally, may be beneficial in AD patients with comorbid vascular pathology., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: LVE and DMW are inventors on the following patents covering MW151: “Pyridazine compound composition and method of use in medicine: 8063047, 8367672, 8933076, 9527819, 9663493” “Lead compounds for neurodegeneration and neuroinflammation: 8158627, 9408845”. LVE is a scientific founder of ImmunoChem Therapeutics (ICT), LLC, a small virtual biotech company that has licensed these patents from Northwestern University. No funding has been received from ICT. This also does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The utility of intravoxel incoherent motion (IVIM) related parameters in differentiation of hypovascular liver lesions is still unknown., Purpose: The purpose of this study was to evaluate the value of IVIM related parameters in comparison to apparent diffusion coefficient (ADC) for differentiation among intrahepatic mass-forming cholangiocarcinoma (IMC), and hypovascular liver metastases (HLM)., Methods: Seventy-four prospectively enrolled patients (21 IMC, and 53 HLM) underwent 1.5T magnetic resonance examination with IVIM diffusion-weighted imaging using seven b values (0-800 s/mm2). Two independent readers performed quantitative analysis of IVIM-related parameters and ADC. Interobserver reliability was tested using a intraclass correlation coefficient. ADC, true diffusion coefficient (D), perfusion-related diffusion coefficient (D*), and perfusion fraction (ƒ) were compared among the lesions using Kruskal-Wallis H test. The diagnostic accuracy of each parameter was assessed by receiver operating characteristic (ROC) curve analysis., Results: The interobserver agreement was good for ADC (0.802), and excellent for D, D*, and ƒ (0.911, 0.927, and 0.942, respectively). ADC, and D values were significantly different among IMC and HLM (both p < 0.05), while there was no significant difference among these lesions for ƒ and D* (p = 0.101, and p = 0.612, respectively). ROC analysis showed higher diagnostic performance of D in comparison to ADC (AUC = 0.879 vs 0.821)., Conclusion: IVIM-derived parameters in particular D, in addition to ADC, could help in differentiation between most common hypovascular malignant liver lesions, intrahepatic mass-forming cholangiocarcinoma and hypovascular liver metastases., Competing Interests: The authors have declared that no competing interests exist.

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults., Competing Interests: The authors have declared that no competing interests exist.

Soccer is the most popular sport in the world and, since it is a contact sport, players are at risk for head injury, including concussion. Here, we proposed to investigate the association of heading and concussion with macroscopic brain structure among adult amateur soccer players. For this study, 375 amateur soccer players (median age 23 years) completed HeadCount-12m to estimate heading over the 12 months prior to MRI and lifetime concussion. T1-weighted 3D magnetization prepared rapid acquisition gradient echo (MP-RAGE) MRI was performed at 3 Tesla. Parcellation was performed using Freesurfer to extract regional gray and white matter volumes as well as regional cortical thickness and total intracranial volume. Regional cortical brain volumes were normalized by total intracranial volume. We categorized heading into quartiles and concussion as 0, 1 or 2 or more. Generalized linear regressions were used to test the association of heading or concussion with each brain morphometry metric, including age and sex, as covariates. Neither heading nor concussion were associated with reduced brain volume or cortical thickness. We observed that greater heading was associated with greater gray matter volume in the left inferior parietal area, which may reflect effects related to training., Competing Interests: The authors have declared that no competing interests exist.

Objective: The definition of an in vivo nodal anatomical baseline is crucial for validation of representative lymph node dissections and accompanying pathology reports of pelvic cancers, as well as for assessing a potential therapeutic effect of extended lymph node dissections. Therefore the number, size and distribution of lymph nodes in the pelvis were assessed with high-resolution, large field-of-view, 7 Tesla (T) magnetic resonance imaging (MRI) with frequency-selective excitation., Materials and Methods: We used 7 T MRI for homogeneous pelvic imaging in 11 young healthy volunteers. Frequency-selective imaging of water and lipids was performed to detect nodal structures in the pelvis. Number and size of detected nodes was measured and size distribution per region was assessed. An average volunteer-normalized nodal size distribution was determined., Results: In total, 564 lymph nodes were detected in six pelvic regions. Mean number was 51.3 with a wide range of 19-91 lymph nodes per volunteer. Mean diameter was 2.3 mm with a range of 1 to 7 mm. 69% Was 2 mm or smaller. The overall size distribution was very similar to the average volunteer-normalized nodal size distribution., Conclusions: The amount of in vivo visible lymph nodes varies largely between subjects, whereas the normalized size distribution of nodes does not. The presence of many small lymph nodes (≤2mm) renders representative or complete removal of pelvic lymph nodes to be very difficult. 7T MRI may shift the in vivo detection limits of lymph node metastases in the future., Competing Interests: The authors have declared that no competing interests exist.

The impact of a method for MR-based respiratory motion correction of PET data on lesion visibility and quantification in patients with oncologic findings in the lung was evaluated. Twenty patients with one or more lesions in the lung were included. Hybrid imaging was performed on an integrated PET/MR system using 18F-FDG as radiotracer. The standard thoracic imaging protocol was extended by a free-breathing self-gated acquisition of MR data for motion modelling. PET data was acquired simultaneously in list-mode for 5-10 mins. One experienced radiologist and one experienced nuclear medicine specialist evaluated and compared the post-processed data in consensus regarding lesion visibility (scores 1-4, 4 being best), image noise levels (scores 1-3, 3 being lowest noise), SUVmean and SUVmax. Motion-corrected (MoCo) images were additionally compared with gated images. Non-motion-corrected free-breathing data served as standard of reference in this study. Motion correction generally improved lesion visibility (3.19 ± 0.63) and noise ratings (2.95 ± 0.22) compared to uncorrected (2.81 ± 0.66 and 2.95 ± 0.22, respectively) or gated PET data (2.47 ± 0.93 and 1.30 ± 0.47, respectively). Furthermore, SUVs (mean and max) were compared for all methods to estimate their respective impact on the quantification. Deviations of SUVmax were smallest between the uncorrected and the MoCo lesion data (average increase of 9.1% of MoCo SUVs), while SUVmean agreed best for gated and MoCo reconstructions (MoCo SUVs increased by 1.2%). The studied method for MR-based respiratory motion correction of PET data combines increased lesion sharpness and improved lesion activity quantification with high signal-to-noise ratio in a clinical setting. In particular, the detection of small lesions in moving organs such as the lung and liver may thus be facilitated. These advantages justify the extension of the PET/MR imaging protocol by 5-10 minutes for motion correction., Competing Interests: Matthias Fenchel, PhD, is employee of Siemens Healthcare GmbH, Erlangen, Germany. Inki Hong, PhD, is employee of Siemens Medical Solutions Inc, Knoxville, USA. This does not alter our adherence to PLOS ONE policies on sharing data and materials”.

With continuing advances in MRI techniques and the emergence of higher static field strengths, submillimetre spatial resolution is now possible in human functional imaging experiments. This has opened up the way for more specific types of analysis, for example investigation of the cortical layers of the brain. With this increased specificity, it is important to correct for the geometrical distortions that are inherent to echo planar imaging (EPI). Inconveniently, higher field strength also increases these distortions. The resulting displacements can easily amount to several millimetres and as such pose a serious problem for laminar analysis. We here present a method, Recursive Boundary Registration (RBR), that corrects distortions between an anatomical and an EPI volume. By recursively applying Boundary Based Registration (BBR) on progressively smaller subregions of the brain we generate an accurate whole-brain registration, based on the grey-white matter contrast. Explicit care is taken that the deformation does not break the topology of the cortical surface, which is an important requirement for several of the most common subsequent steps in laminar analysis. We show that RBR obtains submillimetre accuracy with respect to a manually distorted gold standard, and apply it to a set of human in vivo scans to show a clear increase in spacial specificity. RBR further automates the process of non-linear distortion correction. This is an important step towards routine human laminar fMRI for large field of view acquisitions. We provide the code for the RBR algorithm, as well as a variety of functions to better investigate registration performance in a public GitHub repository, https://github.com/TimVanMourik/OpenFmriAnalysis, under the GPL 3.0 license., Competing Interests: The authors have declared that no competing interests exist.

γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter, is challenging to measure using proton spectroscopy due to its relatively low concentration, J-coupling and overlapping signals from other metabolites. Currently, the prevalent methods for detecting GABA at ultrahigh field strengths (≥ 7 T) are GABA-editing and model fitting of non-editing single voxel spectra. These two acquisition approaches have their own advantages: the GABA editing approach directly measures the GABA resonance at 3 ppm, whereas the fitting approach on the non-editing spectrum allows the detection of multiple metabolites, and has an SNR advantage over longer echo time (TE) acquisitions. This study aims to compare these approaches for estimating GABA at 7 T. We use an interleaved sequence of semi-LASER (sLASER: TE = 38 ms) and MEGA-sLASER (TE = 80 ms). This simultaneous interleaved acquisition minimizes the differential effect of extraneous factors, and enables an accurate comparison of the two acquisition methods. Spectra were acquired with an 8 ml isotropic voxel at six different brain regions: anterior-cingulate cortex, dorsolateral-prefrontal cortex, motor cortex, occipital cortex, posterior cingulate cortex, and precuneus. Spectral fitting with LCModel quantified the GABA to total Cr (tCr: Creatine + Phosphocreatine) concentration ratio. After correcting the T2 relaxation time variation, GABA/tCr ratios were similar between the two acquisition approaches. GABA editing showed smaller spectral fitting error according to Cramér-Rao lower bound than the sLASER approach for all regions examined. We conclude that both acquisition methods show similar accuracy but the precision of the MEGA-editing approach is higher for GABA measurement. In addition, the 2.28 ppm GABA resonance was found to be important for estimating GABA concentration without macromolecule contamination in the GABA-edited acquisition, when utilizing spectral fitting with LCModel., Competing Interests: The authors have declared that no competing interests exist.

Background: Quantifying reproducibility of native T1 and T2 mapping over a long period (> 1 year) is necessary to assess whether changes in T1 and T2 over repeated sessions in a longitudinal study are associated with variability due to underlying tissue composition or technical confounders., Objectives: To carry out a single-center phantom study to 1) investigate measurement reproducibility of slice-interleaved T1 (STONE) and T2 mapping over 20 months, 2) quantify sources of variability, and 3) compare reproducibility and measurements against reference spin-echo measurements., Methods: MR imaging was performed on a 1.5 Tesla Philips Achieva scanner every 2-3 weeks over 20 months using the T1MES phantom. In each session, slice-interleaved T1 and T2 mapping was repeated 3 times for 5 slices, and maps were reconstructed using both 2-parameter and 3-parameter fit models. Reproducibility between sessions, and repeatability between repetitions and slices were evaluated using coefficients of variation (CV). Different sources of variability were quantified using variance decomposition analysis. The slice-interleaved measurement was compared to the spin-echo reference and MOLLI., Results: Slice-interleaved T1 had excellent reproducibility and repeatability with a CV < 2%. The main sources of T1 variability were temperature in 2-parameter maps, and slice in 3-parameter maps. Superior between-session reproducibility to the spin-echo T1 was shown in 2-parameter maps, and similar reproducibility in 3-parameter maps. Superior reproducibility to MOLLI T1 was also shown. Similar measurements to the spin-echo T1 were observed with linear regression slopes of 0.94-0.99, but slight underestimation. Slice-interleaved T2 showed good reproducibility and repeatability with a CV < 7%. The main source of T2 variability was slice location/orientation. Between-session reproducibility was lower than the spin-echo T2 reference and showed good measurement agreement with linear regression slopes of 0.78-1.06., Conclusions: Slice-interleaved T1 and T2 mapping sequences yield excellent long-term reproducibility over 20 months., Competing Interests: The author RN is an inventor of patents for MRI involving multislice T1 and T2 mapping (System and method for tissue characterization using multislice magnetic resonance imaging, US20150323630A1; Method and apparatus for multi-slice imaging of T2-relaxation time; US10191132B2). The rest of the authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: The principal excitatory neurotransmitter glutamate plays an important role in many central nervous system disorders. Because glutamate resides predominantly in glutamatergic neurons, its relaxation properties reflect the intracellular environment of glutamatergic neurons. This study developed an improved echo time-independent technique for measuring transverse relaxation time and demonstrated that this radio frequency (RF)-driven longitudinal steady state technique can reliably measure glutamate transverse relaxation in the frontal cortex, where structural and functional abnormalities have been associated with psychiatric symptoms., Method: Bloch and Monte Carlo simulations were performed to improve and optimize the RF-driven, longitudinal, steady-state (MARzss) technique to significantly shorten scan time and increase measurement precision. Optimized four-flip angle measurements at 0°,12°, 24°, and 36° with matched repetition time were used in nine human subjects (6F, 3M; 27-49 years old) at 7 Tesla. Longitudinal and transverse relaxation rates for glutamate were measured from a 2 x 2 x 2 cm3 voxel placed in three different brain regions: gray matter-dominated medial prefrontal lobe, white matter-dominated left frontal lobe, and gray matter-dominated occipital lobe., Results: Compared to the original MARzss technique, the scan time per voxel for measuring glutamate transverse relaxation was shortened by more than 50%. In the medial frontal, left frontal, and occipital voxels, the glutamate T2 was found to be 117.5±12.9 ms (mean ± standard deviation, n = 9), 107.3±12.1 (n = 9), and 124.4±16.6 ms (n = 8), respectively., Conclusions: The improvements described in this study make the MARZSS technique a viable tool for reliably measuring glutamate relaxation from human subjects in a typical clinical setting. It is expected that this improved technique can be applied to characterize the intracellular environment of glutamatergic neurons in a variety of brain disorders., Competing Interests: The authors have declared that no competing interests exist.

Selective breeding of laboratory rats resulted in changes of their behavior. Concomitantly, the albino strains developed vision related pathologies. These alterations certainly occurred on the background of modifications in brain morphology. The aim of the study was to assess and compare volumes of major structures in brains of wild-captive, laboratory albino and laboratory pigmented rats. High resolution T2-weighted images of brains of adult male Warsaw Wild Captive Pisula-Stryjek rats (WWCPS, a model of wild type), laboratory pigmented (Brown Norway strain, BN) and albino rats (Wistar strain, WI) were obtained with a 7T small animal-dedicated magnetic resonance tomograph. Volume quantification of whole brains and 50 brain structures within each brain were performed with the digital Schwarz rat brain atlas and a custom-made MATLAB/SPM8 scripts. Brain volumes were scaled to body mass, whereas volumes of brain structures were normalized to individual brain volumes. Normalized brain volume was similar in WWCPS and BN, but lower in WI. Normalized neocortex volume was smaller in both laboratory strains than in WWCPS and the visual cortex was smaller in albino WI rats than in WWCPS and BN. Relative volumes of phylogenetically older structures, such as hippocampus, amygdala, nucleus accumbens and olfactory nuclei, also displayed certain strain-related differences. The present data shows that selective breeding of laboratory rats markedly affected brain morphology, the neocortex being most significantly altered. In particular, albino rats display reduced volume of the visual cortex, possibly related to retinal degeneration and the development of blindness., Competing Interests: The authors have declared that no competing interests exist.

There is converging evidence that distinct neuronal processes leave distinguishable footprints in the laminar BOLD response. However, even though the achievable spatial resolution in functional MRI has much improved over the years, it is still challenging to separate signals arising from different cortical layers. In this work, we propose a new method to extract laminar signals. We use a spatial General Linear Model in combination with the equivolume principle of cortical layers to unmix laminar signals instead of interpolating through and integrating over a cortical area: thus reducing partial volume effects. Not only do we provide a mathematical framework for extracting laminar signals with a spatial GLM, we also illustrate that the best case scenarios of existing methods can be seen as special cases within the same framework. By means of simulation, we show that this approach has a sharper point spread function, providing better signal localisation. We further assess the partial volume contamination in cortical profiles from high resolution human ex vivo and in vivo structural data, and provide a full account of the benefits and potential caveats. We eschew here any attempt to validate the spatial GLM on the basis of fMRI data as a generally accepted ground-truth pattern of laminar activation does not currently exist. This approach is flexible in terms of the number of layers and their respective thickness, and naturally integrates spatial regularisation along the cortex, while preserving laminar specificity. Care must be taken, however, as this procedure of unmixing is susceptible to sources of noise in the data or inaccuracies in the laminar segmentation., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The aim of this study was to evaluate and quantify the effect of improved attenuation correction (AC) including bone segmentation and truncation correction on 18F-Fluordesoxyglucose cardiac positron emission tomography/magnetic resonance (PET/MR) imaging., Methods: PET data of 32 cardiac PET/MR datasets were reconstructed with three different AC-maps (1. Dixon-VIBE only, 2. HUGE truncation correction and bone segmentation, 3. MLAA). The Dixon-VIBE AC-maps served as reference of reconstructed PET data. 17-segment short-axis polar plots of the left ventricle were analyzed regarding the impact of each of the three AC methods on PET quantification in cardiac PET/MR imaging. Non-AC PET images were segmented to specify the amount of truncation in the Dixon-VIBE AC-map serving as a reference. All AC-maps were evaluated for artifacts., Results: Using HUGE + bone AC results in a homogeneous gain of ca. 6% and for MLAA 8% of PET signal distribution across the myocardium of the left ventricle over all patients compared to Dixon-VIBE AC only. Maximal relative differences up to 18% were observed in segment 17 (apex). The body volume truncation of -12.7 ± 7.1% compared to the segmented non-AC PET images using the Dixon-VIBE AC method was reduced to -1.9 ± 3.9% using HUGE and 7.8 ± 8.3% using MLAA. In each patient, a systematic overestimation in AC-map volume was observed when applying MLAA. Quantitative impact of artifacts showed regional differences up to 6% within single segments of the myocardium., Conclusions: Improved AC including bone segmentation and truncation correction in cardiac PET/MR imaging is important to ensure best possible diagnostic quality and PET quantification. The results exhibited an overestimation of AC-map volume using MLAA, while HUGE resulted in a more realistic body contouring. Incorporation of bone segmentation into the Dixon-VIBE AC-map resulted in homogeneous gain in PET signal distribution across the myocardium. The majority of observed AC-map artifacts did not significantly affect the quantitative assessment of the myocardium., Competing Interests: The authors have declared that no competing interests exist.

Purpose: The trend towards faster acquisition protocols in whole-body positron emission tomography/magnetic resonance (PET/MR) arises the question of whether short PET data acquisition protocols in a whole-body multi-station context allow for reduced PET acquisition times while providing adequate PET image quality and accurate quantification parameters. The study goal is to investigate how reducing PET acquisition times affects PET image quality and quantification in whole-body PET/MR in patients with oncologic findings., Methods: Fifty-one patients with different oncologic findings underwent a clinical whole-body 18F-Fluorodeoxyglucose PET/MR examination. PET data was reconstructed with 4, 3, 2, and 1 min/bed time intervals for each patient to simulate the effect of reduced PET acquisition times. The 4-minute PET reconstructions served as reference standard. All whole-body PET data sets were analyzed regarding image quality, lesion detectability, PET quantification and standardized uptake values., Results: A total of 91 lesions were detected in the 4-minute PET reconstructions. The same number of congruent lesions was also noticed in the 3 and 2 minutes-per-bed (mpb) reconstructed images. A total of 2 lesions in 2 patients was not detected in the 1 minute PET data reconstructions due to poor image quality. Image noise in the blood pool increased from 22.2% (4 mpb) to 42.1% (1 mpb). Signal-to-noise ratio declined with shorter timeframes from 13.1 (4 mpb) to 9.3 (1 mpb). SUVmean and SUVmax showed no significant changes between 4 and 1 mpb reconstructed timeframes., Conclusions: Reconstruction of PET data with different time intervals has shown that 2 minutes acquisition time per bed position instead of 4 minutes is sufficient to provide accurate lesion detection and adequate image quality in a clinical setting, despite the trends to lower image quality with shorter PET acquisition times. This provides latitude for potential reduction of PET acquisition times in fast PET/MR whole-body examinations., Competing Interests: The authors have declared that no competing interests exist.

Lack of insight is a core feature of non-affective psychosis and has been associated with poorer outcomes. Brain abnormalities underlying lack of insight have been suggested, mostly in the frontal lobe, although previous research showed mixed results. We used a voxel-based morphometry (VBM) analysis in 108 first-episode non-affective psychosis patients to investigate the pattern of brain structural abnormalities related to lack of insight. In addition, 77 healthy volunteers were compared with the patients classified as having poor and good insight. The shortened version of the Scale to Assess Unawareness of Mental Disorder was used to evaluate insight. Patients with poor insight (n = 68) compared with patients with good insight (n = 40) showed a single significant cluster (kc = 5834; PcFWE = 0.001) of reduced grey matter volume (GMV) in the right occipital lobe extending to its lateral and medial surfaces, the cuneus, and the middle temporal gyrus. In addition, GMV at this cluster showed a negative correlation with the score of the SUMD (r = -0.305; p = 0.001). When comparing patients with poor insight with healthy subjects overall reductions of GMV were found, mainly in frontal and occipital lobes. Hence, poor insight in non-affective psychosis seems to be associated with specific brain abnormalities in the right occipital and temporal cortical regions. Dysfunction in any combination of these areas may contribute to lack of insight in non-affective psychosis. Specifically, the 'right' hemisphere dysfunction underlying impaired insight in our sample is consistent with previously reported similarities between lack of insight in psychosis and anosognosia in neurological disorders., Competing Interests: The authors have declared that no competing interests exist.

The use of online-communication applications including messengers (e.g. WhatsApp) or social networking services (e.g. Facebook) on the smartphone has turned into daily practice for billions of people, for example during waiting times. An increasing number of individuals show diminished control over their usage of these applications despite negative consequences in everyday life. This can be referred to as Internet-communication disorder (ICD). The current study investigated the effect of boredom proneness on symptoms of an ICD. It further examined the mediating role of cognitive and affective mechanisms, namely expectancies to avoid negative feelings online and cue-induced craving. The results of a structural equation model (N = 148) illustrate that boredom proneness is a risk factor for the development and maintenance of an ICD as it had a significant direct effect on ICD symptoms. Furthermore, boredom proneness predicted avoidance expectancies as well as cue-induced craving. Both in turn enhanced the risk of developing ICD tendencies. Moreover, both variables mediated the effect of boredom proneness on ICD and interacted among each other. In summary, the results demonstrate that people who have a higher susceptibility to experience boredom show higher expectancies to avoid negative emotions online, which promotes higher craving reactions when being confronted with specific cues (e.g. an incoming message), and could result in ICD tendencies.

Objectives: The aim of this study was to investigate and compare the feasibility as well as potential impact of altered magnetic field properties on image quality and potential artifacts of 1.5 Tesla, 3 Tesla and 7 Tesla non-enhanced abdominal MRI., Materials and Methods: Magnetic Resonance (MR) imaging of the upper abdomen was performed in 10 healthy volunteers on a 1.5 Tesla, a 3 Tesla and a 7 Tesla MR system. The study protocol comprised a (1) T1-weighted fat-saturated spoiled gradient-echo sequence (2D FLASH), (2) T1-weighted fat-saturated volumetric interpolated breath hold examination sequence (3D VIBE), (3) T1-weighted 2D in and opposed phase sequence, (4) True fast imaging with steady-state precession sequence (TrueFISP) and (5) T2-weighted turbo spin-echo (TSE) sequence. For comparison reasons field of view and acquisition times were kept comparable for each correlating sequence at all three field strengths, while trying to achieve the highest possible spatial resolution. Qualitative and quantitative analyses were tested for significant differences., Results: While 1.5 and 3 Tesla MRI revealed comparable results in all assessed features and sequences, 7 Tesla MRI yielded considerable differences in T1 and T2 weighted imaging. Benefits of 7 Tesla MRI encompassed an increased higher spatial resolution and a non-enhanced hyperintense vessel signal at 7 Tesla, potentially offering a more accurate diagnosis of abdominal parenchymatous and vasculature disease. 7 Tesla MRI was also shown to be more impaired by artifacts, including residual B1 inhomogeneities, susceptibility and chemical shift artifacts, resulting in reduced overall image quality and overall image impairment ratings. While 1.5 and 3 Tesla T2w imaging showed equivalently high image quality, 7 Tesla revealed strong impairments in its diagnostic value., Conclusions: Our results demonstrate the feasibility and overall comparable imaging ability of T1-weighted 7 Tesla abdominal MRI towards 3 Tesla and 1.5 Tesla MRI, yielding a promising diagnostic potential for non-enhanced Magnetic Resonance Angiography (MRA). 1.5 Tesla and 3 Tesla offer comparably high-quality T2w imaging, showing superior diagnostic quality over 7 Tesla MRI.

Background: Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability., Methods: In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration., Results: In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age., Conclusion: Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.

GPR116 (ADGRF5) and ELTD1 (ADGRL4) belong to different subfamilies of the adhesion G-protein-coupled receptor group but are both expressed in endothelial cells. We therefore analyzed their functions in mice lacking these receptors. While loss of GPR116 or ELTD1 alone had no obvious effect on cardiovascular or kidney function, mice lacking both, GPR116 and ELTD1, showed malformations of the aortic arch arteries and the cardiac outflow tract leading to perinatal lethality in about 50% of the mutants. In addition to cardiovascular malformations, surviving mice developed renal thrombotic microangiopathy as well as hemolysis and splenomegaly, and their lifespan was significantly reduced. Loss of GPR116 and ELTD1 specifically in endothelial cells or neural crest-derived cells did not recapitulate any of the phenotypes observed in GPR116-ELTD1 double deficient mice, indicating that loss of GPR116 and ELTD1 expressed by other cells accounts for the observed cardiovascular and renal defects.

Background/aims: Since the degeneration of the nigrostriatal dopaminergic pathway in Parkinson's disease (PD) is associated with the inflammation process and decreased levels of cyclic nucleotides, inhibition of up-regulated cyclic nucleotide phosphodiesterases (PDEs) appears to be a promising therapeutic strategy. We used ibudilast (IBD), a non-selective PDE3,4,10,11 inhibitor, due to the abundant PDE 4 and 10 expression in the striatum. The present study for the first time examined the efficacy of IBD in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD., Methods: IBD [0, 20, 30, 40, or 50 mg/kg] was injected b.i.d. subcutaneously for nine days to three-month-old male C57Bl/10Tar mice, beginning two days prior to MPTP (60 mg/kg) intoxication. High-pressure liquid chromatography, Western blot analysis, and real time RT-PCR methods were applied., Results: Our study demonstrated that chronic administration of IBD attenuated astroglial reactivity and increased glial cell-derived neurotrophic factor (GDNF) production in the striatum. Moreover, IBD reduced TNF-α, IL-6, and IL-1β expression., Conclusion: IBD had a well-defined effect on astroglial activation in the mouse model of PD; however, there was no protective effect in the acute phase of injury. Diminished inflammation and an increased level of GDNF may provide a better outcome in the later stages of neurodegeneration.

Background: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis. Although mechanistic pathways could link Lipoprotein(a) with myocardial fibrosis, whether the two are related has not been previously explored. In this study, we investigated whether elevated Lipoprotein(a) was associated with the presence of myocardial replacement fibrosis., Methods: A total of 110 patients with mild, moderate and severe aortic stenosis were assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance to identify fibrosis. Mann Whitney U tests were used to assess for evidence of an association between Lp(a) and the presence or absence of myocardial fibrosis and aortic stenosis severity and compared to controls. Univariable and multivariable linear regression analysis were undertaken to identify possible predictors of Lp(a)., Results: Thirty-six patients (32.7%) had no LGE enhancement, 38 (34.6%) had midwall enhancement suggestive of midwall fibrosis and 36 (32.7%) patients had subendocardial myocardial fibrosis, typical of infarction. The aortic stenosis patients had higher Lp(a) values than controls, however, there was no significant difference between the Lp(a) level in mild, moderate or severe aortic stenosis. No association was observed between midwall or infarction pattern fibrosis and Lipoprotein(a), in the mild/moderate stenosis (p = 0.91) or severe stenosis patients (p = 0.42)., Conclusion: There is no evidence to suggest that higher Lipoprotein(a) leads to increased myocardial midwall or infarction pattern fibrosis in patients with aortic stenosis.

Background: Efforts are continuously made to detect and investigate the pivotal processes and interplay between the response of sentinel lymph node and malignant cells from a primary tumor. Conversely, some frequently used tumor animal models, such as human cancer xenografts, rarely feature metastasis. Therefore, lymph node alterations are seldom assessed. We consider that studying lymph node response could contribute to the understanding of host reaction to cancer. In the present study, we explored the presence of regional lymph node alterations in parallel with tumor growth using a pancreatic tumor xenograft model which does not develop metastasis., Methods and Findings: We established an animal cancer model by the subcutaneous inoculation of PANC-1 (a metastatic human pancreatic cancer cell line) in the left upper flank of athymic nude mice. Tumor animals, along with controls (n = 7 / group) were subjected to Magnetic Resonance Imaging (MRI) in order to follow tumor growth and brachial and axillary lymph nodes alterations over several weeks. Further histological analyses were performed at the end of the study. The individual average of the different lymph nodes sizes was 15-40% larger in the tumor animals compared to control animals at week 8 to week 20. The tumor size and lymph node size were not correlated. Histological analysis of the lymph nodes showed paracortical histiocytosis. No metastasis to lymph nodes could be detected by histology. In tumor bearing animals, histiocytosis was associated with isolated apoptotic bodies and migration of human tumoral cells was confirmed by specific immunostaining of human origin markers., Conclusions: The lack of metastasis as well as the pathological manifestation of the lymph node alteration in this pre-clinical model established here parallels findings in patients with sinus histiocytosis that is correlated with improved survival.

Despite different treatments and courses of illness, depressive symptoms appear similar in bipolar disorder (BD) and major depressive disorder (MDD), causing BD with an onset of depressive episode being frequently misdiagnosed as MDD, and leading to inappropriate treatment and poor clinical outcomes. Therefore, there is an urgent need to explore underlying neural basis to distinguish BD from MDD. The medical records of 80 first-episode, drug-naïve depressive patients with an initial diagnosis of MDD and illness duration of at least 5 years were reviewed retrospectively for this study. Fourteen bipolar depressed patients with a diagnosis conversion from MDD to BD, 14 patients with diagnosis of MDD, and 14 healthy subjects demographically matched with the BD group, were selected to participate in the study. Firstly, we examined whether there were differences among the three groups in whole brain fALFF during resting state. Secondly, clusters showing group differences in fALFF in any two groups were chosen as regions of interest (ROI) and then correlation between clinical features and fALFF values of ROIs were calculated. The BD group showed increased fALFF in bilateral putamen relative to both the MDD group and controls, while the MDD group exhibited decreased fALFF in left superior frontal gyrus (SFG) relative to both the BD group and controls (p < 0.05, corrected). Positive correlations between abnormality in the putamen and symptom severity were observed (significant for the MDD group, p = 0.043; marginally significant for the BD group, p = 0.060/0.076). These results implicate that abnormalities of key regions in the striatum and prefrontal areas may be trait markers for BD and MDD.

Introduction: The objective of this study was to assess the diagnostic value of integrated 11C- methionine PET/MRI for suspected primary brain tumors, in comparison to MRI alone., Material and Methods: Forty-eight consecutive patients with suspected primary brain tumor were prospectively enrolled for an integrated 11C-methionine PET/MRI. Two neuro-radiologists separately evaluated the MRI alone and the integrated PET/MRI data sets regarding most likely diagnosis and diagnostic confidence on a 5-point scale. Reference standard was histopathology or follow-up imaging., Results: Fifty-one suspicious lesions were detected: 16 high-grade glioma and 25 low-grade glioma. Ten non-malignant cerebral lesions were described by the reference standard. MRI alone and integrated PET/MRI each correctly classified 42 of the 51 lesions (82.4%) as neoplastic lesions (WHO grade II, III and IV) or non-malignant lesions (infectious and neoplastic lesions). Diagnostic confidence for all lesions, low-grade astrocytoma and high-grade astrocytoma (3.7 vs. 4.2, 3,1 vs. 3.8, 4.0 vs. 4,7) were significantly (p < 0.05) better with integrated PET/MRI than in MRI alone., Conclusions: The present study demonstrates the high potential of integrated 11C-methionine-PET/MRI for the assessment of suspected primary brain tumors. Although integrated methionine PET/MRI does not lead to an improvement of correct diagnoses, diagnostic confidence is significantly improved., Competing Interests: The authors have declared that no competing interests exist.

Alterations to myelin may be a core pathological feature of neurodegenerative diseases. Although white matter microstructural differences have been described in Parkinson's disease (PD), it is unknown whether such differences include alterations of the brain's myelin content. Thus, the objective of the current study is to measure and compare brain myelin content between PD patients and age-matched controls. In this cross-sectional study, 63 participants from the Longitudinal MRI in Parkinson's Disease study underwent brain MRI, Unified Parkinson's Disease Rating Scale (UPDRS) scoring, and cognitive asessments. Subjects were imaged with the mcDEPSOT (multi-component driven equilibrium single pulse observation of T1 and T2), a multicomponent relaxometry technique that quantifies longitudinal and transverse relaxation rates (R1 and R2, respectively) and the myelin water fraction (VFM), a surrogate for myelin content. A voxel-wise approach was used to compare R1, R2, and VFM measures between PD and control groups, and to evaluate relationships with age as well as disease duration, UPDRS scores, and daily levodopa equivalent dose. PD subjects had higher VFM than controls in frontal and temporal white matter and bilateral thalamus. Greater age was strongly associated with lower VFM in both groups, while an age-by-group interaction suggested a slower rate of VFM decline in the left putamen with aging in PD. Within the PD group, measures of disease severity, including UPDRS, daily levodopa equivalent dose, and disease duration, were observed to be related with myelin content in diffuse brain regions. The age-by-group interaction suggests that either PD or dopaminergic therapies allay observed age-related myelin changes. The relationships between VFM and disease severity measures suggests that VFM may provide a surrogate marker for microstructural changes related to Parkinson's disease., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study is to evaluate the ability of quantitative magnetic resonance imaging (MRI) to discriminate between skin biopsies from individuals with osteogenesis imperfecta (OI) and skin biopsies from individuals without OI. Skin biopsies from nine controls (unaffected) and nine OI patients were imaged to generate maps of five separate MR parameters, T1, T2, km, MTR and ADC. Parameter values were calculated over the dermal region and used for univariate and multiparametric classification analysis. A substantial degree of overlap of individual MR parameters was observed between control and OI groups, which limited the sensitivity and specificity of univariate classification. Classification accuracies ranging between 39% and 67% were found depending on the variable of investigation, with T2 yielding the best accuracy of 67%. When several MR parameters were considered simultaneously in a multivariate analysis, the classification accuracies improved up to 89% for specific combinations, including the combination of T2 and km. These results indicate that multiparametric classification by quantitative MRI is able to detect differences between the skin of OI patients and of unaffected individuals, which motivates further study of quantitative MRI for the clinical diagnosis of OI.

The formation of transient networks in response to external stimuli or as a reflection of internal cognitive processes is a hallmark of human brain function. However, its identification in fMRI data of the human brain is notoriously difficult. Here we propose a new method of fMRI data analysis that tackles this problem by considering large-scale, task-related synchronisation networks. Networks consist of nodes and edges connecting them, where nodes correspond to voxels in fMRI data, and the weight of an edge is determined via task-related changes in dynamic synchronisation between their respective times series. Based on these definitions, we developed a new data analysis algorithm that identifies edges that show differing levels of synchrony between two distinct task conditions and that occur in dense packs with similar characteristics. Hence, we call this approach "Task-related Edge Density" (TED). TED proved to be a very strong marker for dynamic network formation that easily lends itself to statistical analysis using large scale statistical inference. A major advantage of TED compared to other methods is that it does not depend on any specific hemodynamic response model, and it also does not require a presegmentation of the data for dimensionality reduction as it can handle large networks consisting of tens of thousands of voxels. We applied TED to fMRI data of a fingertapping and an emotion processing task provided by the Human Connectome Project. TED revealed network-based involvement of a large number of brain areas that evaded detection using traditional GLM-based analysis. We show that our proposed method provides an entirely new window into the immense complexity of human brain function.

Background: The aim of this study was to assess the applicability of a fast MR-protocol for whole-body staging of lymphoma patients using an integrated PET/MR system., Methods: A total of 48 consecutive lymphoma patients underwent 52 clinically indicated PET/CT and subsequent PET/MRI examinations with the use of 18F-FDG. For PET/MR imaging, a fast whole-body MR-protocol was implemented. A radiologist and a nuclear medicine physician interpreted MRI and PET/MRI datasets in consensus and were instructed to identify manifestations of lymphoma on a site-specific analysis. The accuracy for the identification of active lymphoma disease was calculated and the tumor stage for each examination was determined. Furthermore, radiation doses derived from administered tracer activities and CT protocol parameters were estimated and the mean scan duration of PET/CT and PET/MR imaging was determined. Statistical analysis was performed to compare the diagnostic performance of PET/MRI and MRI alone. The results of PET/CT imaging, all available histopathological samples as well as results of prior examinations and follow-up imaging were used for the determination of the reference standard., Results: Active lymphoma disease was present in 28/52 examinations. PET/MRI revealed higher values of diagnostic accuracy for the identification of active lymphoma disease in those 52 examinations in comparison to MRI, however, results of the two ratings did not differ significantly. On a site specific analysis, PET/MRI showed a significantly higher accuracy for the identification of nodal manifestation of lymphoma (p<0.05) if compared to MRI, whereas ratings for extranodal regions did not reveal a significant difference. In addition, PET/MRI enabled correct identification of lymphoma stage in a higher percentage of patients than MRI (94% vs. 83%). Furthermore, SUVs derived from PET/MRI were significantly higher than in PET/CT, however, there was a strong positive correlation between SUVmax and SUVmean of the two imaging modalities (R = 0.91 p<0.001 and R = 0.87, p<0.001). Average scan duration of whole-body PET/CT and PET/MRI examinations amounted to 17.3±1.9 min and 27.8±3.7 min, respectively. Estimated mean effective-dose for whole-body PET/CT scans were 64.4% higher than for PET/MRI., Conclusions: Our results demonstrate the usefulness of 18F-FDG PET data as a valuable additive to MRI for a more accurate evaluation of patients with lymphomas. With regard to patient comfort related to scan duration and a markedly reduced radiation exposure, fast PET/MRI may serve as a powerful alternative to PET/CT for a diagnostic workup of lymphoma patients.

Background: Ventral intermediate nucleus thalamotomy is an effective treatment for Parkinson's disease tremor. However, its mechanism is still unclear., Purpose: We used resting-state fMRI to investigate short-term ReHo changes after unilateral thalamotomy in tremor-dominant PD, and to speculate about its possible mechanism on tremor suppression., Methods: 26 patients and 31 healthy subjects (HS) were recruited. Patients were divided into two groups according to right- (rPD) and left-side (lPD) thalamotomy. Tremor was assessed using the 7-item scale from the Unified Parkinson's disease rating scale motor score (mUPDRS). Patients were scanned using resting state fMRI after 12h withdrawal of medication, both preoperatively (PDpre) and 7- day postoperatively (PDpost), whereas healthy subjects were scanned once. The regions associated with tremor and altered ReHo due to thalamic ablation were examined., Results: The impact of unilateral VIM thalamotomy was characterized in the frontal, parietal, temporal regions, basal ganglia, thalamus, and cerebellum. Compared with PDpre, significantly reduced ReHo was found in the left cerebellum in patients with rPDpost, and slightly decreased ReHo in the cerebellum vermis in patients with lPDpost, which was significantly higher than HS. We demonstrated a positive correlation between the ReHo values in the cerebellum (in rPD, peak coordinate [-12, -54, -21], R = 0.64, P = 0.0025, and peak coordinate [-9, -54, -18], R = 0.71, P = 0.0025; in lPD, peak coordinate [3, -45, -15], R = 0.71, P = 0.004) in the pre-surgical condition, changes of ReHo induced by thalamotomy (in rPD, R = 0.63, P = 0.021, R = 0.6, P = 0.009; in lPD, R = 0.58, P = 0.028) and tremor scores contralateral to the surgical side, respectively., Conclusion: The specific area that may be associated with PD tremor and altered ReHo due to thalamic ablation is the cerebellum. The neural basis underlying thalamotomy is complex; cerebellum involvement is far beyond cerebello-thalamic tract breakage.

Objectives: T1 mapping allows quantitative myocardial assessment, but its value in clinical routine remains unclear. We investigated, whether the average native myocardial T1 value can be used as a diagnostic classifier between healthy and diffuse diseased myocardium., Methods: Native T1 mapping was performed in 54 persons with healthy hearts and in 150 patients with diffuse myocardial pathologies (coronary artery disease (CAD): n = 76, acute myocarditis: n = 19, convalescent myocarditis: n = 26, hypertrophic cardiomyopathy (HCM): n = 12, dilated cardiomyopathy (DCM): n = 17) at 1.5 Tesla in a mid-ventricular short axis slice using a modified Look-Locker inversion recovery (MOLLI) sequence. The average native myocardial T1 value was measured using dedicated software for each patient. The mean as well as the range of the observed average T1 values were calculated for each group, and compared using t-test. The ability of T1 mapping to differentiate between healthy and diffuse diseased myocardium was assessed using receiver operating characteristic analysis (ROC)., Results: The mean T1 value of the group "healthy hearts" (955±34ms) differed significantly from that of the groups DCM (992±37ms, p<0.001), HCM (980±44ms, p = 0.035), and acute myocarditis (974±36ms, p = 0.044). No significant difference was observed between the groups "healthy hearts" and CAD (951±37ms, p = 0.453) or convalescent myocarditis (965±40ms, p = 0.240). The average native T1 value varied considerably within all groups (range: healthy hearts, 838-1018ms; DCM, 882-1034ms; HCM, 897-1043ms; acute myocarditis, 925-1025ms; CAD, 867-1082ms; convalescent myocarditis, 890-1071ms) and overlapped broadly between all groups. ROC analysis showed, that the average native T1 value does not allow for differentiating between healthy and diffuse diseased myocardium, except for the subgroup of DCM., Conclusions: The average native T1 value in cardiac MR imaging does not allow differentiating between healthy and diffusely diseased myocardium in individual cases.

Schizophrenia (SZ) and bipolar disorder (BD) share clinical features, genetic risk factors and neuroimaging abnormalities. There is evidence of disrupted connectivity in resting state networks in patients with SZ and BD and their unaffected relatives. Resting state networks are known to undergo reorganization during youth coinciding with the period of increased incidence for both disorders. We therefore focused on characterizing resting state network connectivity in youth at familial risk for SZ or BD to identify alterations arising during this period. We measured resting-state functional connectivity in a sample of 106 youth, aged 7-19 years, comprising offspring of patients with SZ (N = 27), offspring of patients with BD (N = 39) and offspring of community control parents (N = 40). We used Independent Component Analysis to assess functional connectivity within the default mode, executive control, salience and basal ganglia networks and define their relationship to grey matter volume, clinical and cognitive measures. There was no difference in connectivity within any of the networks examined between offspring of patients with BD and offspring of community controls. In contrast, offspring of patients with SZ showed reduced connectivity within the left basal ganglia network compared to control offspring, and they showed a positive correlation between connectivity in this network and grey matter volume in the left caudate. Our findings suggest that dysconnectivity in the basal ganglia network is a robust correlate of familial risk for SZ and can be detected during childhood and adolescence.

Objective: Chronic recurrent multifocal osteomyelitis/ chronic non-bacterial osteomyelitis (CRMO/ CNO) is a rare auto-inflammatory disease and typically manifests in terms of musculoskeletal pain. Because of a high frequency of musculoskeletal disorders in children/ adolescents, it can be quite challenging to distinguish CRMO/ CNO from nonspecific musculoskeletal pain or from malignancies. The purpose of this study was to evaluate the visibility of CRMO lesions in a whole-body diffusion-weighted imaging (WB-DWI) technique and its potential clinical value to better characterize MR-visible lesions., Material and Methods: Whole-body imaging at 3T was performed in 16 patients (average: 13 years) with confirmed CRMO. The protocol included 2D Short Tau Inversion Recovery (STIR) imaging in coronal and axial orientation as well as diffusion-weighted imaging in axial orientation. Visibility of lesions in DWI and STIR was evaluated by two readers in consensus. The apparent diffusion coefficient (ADC) was measured for every lesion and corresponding reference locations., Results: A total of 33 lesions (on average 2 per patient) visible in STIR and DWI images (b = 800 s/mm2 and ADC maps) were included, predominantly located in the long bones. With a mean value of 1283 mm2/s in lesions, the ADC was significantly higher than in corresponding reference regions (782 mm2/s). By calculating the ratio (lesion to reference), 82% of all lesions showed a relative signal increase of 10% or higher and 76% (25 lesions) showed a signal increase of more than 15%. The median relative signal increase was 69%., Conclusion: This study shows that WB-DWI can be reliably performed in children at 3T and predominantly, the ADC values were substantially elevated in CRMO lesions. WB-DWI in conjunction with clinical data is seen as a promising technique to distinguish benign inflammatory processes (in terms of increased ADC values) from particular malignancies.

It has been suggested that incongruence between signals for motor intention and sensory input can cause pain and other sensory abnormalities. This claim is supported by reports that moving in an environment of induced sensorimotor conflict leads to elevated pain and sensory symptoms in those with certain painful conditions. Similar procedures can lead to reports of anomalous sensations in healthy volunteers too. In the present study, we used mirror visual feedback to investigate the effects of sensorimotor incongruence on responses to stimuli that arise from sources external to the body, in particular, touch. Incongruence between the sensory and motor signals for the right arm was manipulated by having the participants make symmetrical or asymmetrical movements while watching a reflection of their left arm in a parasagittal mirror, or the left hand surface of a similarly positioned opaque board. In contrast to our prediction, sensitivity to the presence of gaps in tactile stimulation of the right forearm was not reduced when participants made asymmetrical movements during mirror visual feedback, as compared to when they made symmetrical or asymmetrical movements with no visual feedback. Instead, sensitivity was reduced when participants made symmetrical movements during mirror visual feedback relative to the other three conditions. We suggest that small discrepancies between sensory and motor information, as they occur during mirror visual feedback with symmetrical movements, can impair tactile processing. In contrast, asymmetrical movements with mirror visual feedback may not impact tactile processing because the larger discrepancies between sensory and motor information may prevent the integration of these sources of information. These results contrast with previous reports of anomalous sensations during exposure to both low and high sensorimotor conflict, but are nevertheless in agreement with a forward model interpretation of perceptual modulations during goal directed movement.

Individual differences in mind and behavior are believed to reflect the functional variability of the human brain. Due to the lack of a large-scale longitudinal dataset, the full landscape of variability within and between individual functional connectomes is largely unknown. We collected 300 resting-state functional magnetic resonance imaging (rfMRI) datasets from 30 healthy participants who were scanned every three days for one month. With these data, both intra- and inter-individual variability of six common rfMRI metrics, as well as their test-retest reliability, were estimated across multiple spatial scales. Global metrics were more dynamic than local regional metrics. Cognitive components involving working memory, inhibition, attention, language and related neural networks exhibited high intra-individual variability. In contrast, inter-individual variability demonstrated a more complex picture across the multiple scales of metrics. Limbic, default, frontoparietal and visual networks and their related cognitive components were more differentiable than somatomotor and attention networks across the participants. Analyzing both intra- and inter-individual variability revealed a set of high-resolution maps on test-retest reliability of the multi-scale connectomic metrics. These findings represent the first collection of individual differences in multi-scale and multi-metric characterization of the human functional connectomes in-vivo, serving as normal references for the field to guide the use of common functional metrics in rfMRI-based applications.

Hypertension is an independent risk factor for the progression of chronic renal failure, and oxidative stress plays a critical role in hypertensive renal damage. Forkbox O1(FoxO1) signaling protects cells against oxidative stress and may be a useful target for treating oxidative stress-induced hypertension. Tongxinluo is a traditional Chinese medicine with cardioprotective and renoprotective functions. Therefore, this study aimed to determine the effects of Tongxinluo in hypertensive renal damage in spontaneously hypertensive rats(SHRs)and elucidate the possible involvement of oxidative stress and FoxO1 signaling in its molecular mechanisms. SHRs treated with Tongxinluo for 12 weeks showed a reduction in systolic blood pressure. In addition to increasing creatinine clearance, Tongxinluo decreased urinary albumin excretion, oxidative stress injury markers including malondialdehyde and protein carbonyls, and expression of nicotinamide adenine dinucleotide phosphate oxidase subunits and its activity in SHR kidneys. While decreasing phosphorylation of FoxO1, Tongxinluo also inhibited the phosphorylation of extracellular signal-regulated kinase1/2 and p38 and enhanced manganese superoxide dismutase and catalase activities in SHR kidneys. Furthermore, histology revealed attenuation of glomerulosclerosis and renal podocyte injury, while Tongxinluo decreased the expression of α-smooth muscle actin, extracellular matrixprotein, transforming growth factor β1 and small mothers against decapentaplegic homolog 3,and improved tubulointerstitial fibrosis in SHR kidneys. Finally, Tongxinluo inhibited inflammatory cell infiltration as well as expression of tumor necrosis factor-α and interleukin-6. In conclusion, Tongxinluo protected SHRs against hypertension-induced renal injury by exerting antioxidant, antifibrotic, and anti-inflammatory activities. Moreover, the underlying mechanisms of these effects may involve inhibition of oxidative stress and functional activation of FoxO1 signaling.

The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB.

Spherical deconvolution (SD) methods are widely used to estimate the intra-voxel white-matter fiber orientations from diffusion MRI data. However, while some of these methods assume a zero-mean Gaussian distribution for the underlying noise, its real distribution is known to be non-Gaussian and to depend on many factors such as the number of coils and the methodology used to combine multichannel MRI signals. Indeed, the two prevailing methods for multichannel signal combination lead to noise patterns better described by Rician and noncentral Chi distributions. Here we develop a Robust and Unbiased Model-BAsed Spherical Deconvolution (RUMBA-SD) technique, intended to deal with realistic MRI noise, based on a Richardson-Lucy (RL) algorithm adapted to Rician and noncentral Chi likelihood models. To quantify the benefits of using proper noise models, RUMBA-SD was compared with dRL-SD, a well-established method based on the RL algorithm for Gaussian noise. Another aim of the study was to quantify the impact of including a total variation (TV) spatial regularization term in the estimation framework. To do this, we developed TV spatially-regularized versions of both RUMBA-SD and dRL-SD algorithms. The evaluation was performed by comparing various quality metrics on 132 three-dimensional synthetic phantoms involving different inter-fiber angles and volume fractions, which were contaminated with noise mimicking patterns generated by data processing in multichannel scanners. The results demonstrate that the inclusion of proper likelihood models leads to an increased ability to resolve fiber crossings with smaller inter-fiber angles and to better detect non-dominant fibers. The inclusion of TV regularization dramatically improved the resolution power of both techniques. The above findings were also verified in human brain data.

The recent blood flow and magnetization transfer (MT) technique termed alternate ascending/descending directional navigation (ALADDIN) achieves the contrast using interslice blood flow and MT effects with no separate preparation RF pulse, thereby potentially overcoming limitations of conventional methods. In this study, we examined the signal characteristics of ALADDIN as a simultaneous blood flow and MT imaging strategy, by comparing it with pseudo-continuous ASL (pCASL) and conventional MT asymmetry (MTA) methods, all of which had the same bSSFP readout. Bloch-equation simulations and experiments showed ALADDIN perfusion signals increased with flip angle, whereas MTA signals peaked at flip angle around 45°-60°. ALADDIN provided signals comparable to those of pCASL and conventional MTA methods emulating the first, second, and third prior slices of ALADDIN under the same scan conditions, suggesting ALADDIN signals to be superposition of signals from multiple labeling planes. The quantitative cerebral blood flow signals from a modified continuous ASL model overestimated the perfusion signals compared to those measured with a pulsed ASL method. Simultaneous mapping of blood flow, MTA, and MT ratio in the whole brain is feasible with ALADDIN within a clinically reasonable time, which can potentially help diagnosis of various diseases.

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

3,4-Methylenedioxymethamphetamine (MDMA), also known as "Ecstasy", is a common recreational drug of abuse. Several previous studies have attributed the central serotonergic neurotoxicity of MDMA to distal axotomy, since only fine serotonergic axons ascending from the raphe nucleus are lost without apparent damage to their cell bodies. However, this axotomy has never been visualized directly in vivo. The present study examined the axonal integrity of the efferent projections from the midbrain raphe nucleus after MDMA exposure using in vivo manganese-enhanced magnetic resonance imaging (MEMRI). Rats were injected subcutaneously six times with MDMA (5 mg/kg) or saline once daily. Eight days after the last injection, manganese ions (Mn2+) were injected stereotactically into the raphe nucleus, and a series of MEMRI images was acquired over a period of 38 h to monitor the evolution of Mn2+-induced signal enhancement across the ventral tegmental area, the medial forebrain bundle (MFB), and the striatum. The MDMA-induced loss of serotonin transporters was clearly evidenced by immunohistological staining consistent with the Mn2+-induced signal enhancement observed across the MFB and striatum. MEMRI successfully revealed the disruption of the serotonergic raphe-striatal projections and the variable effect of MDMA on the kinetics of Mn2+ accumulation in the MFB and striatum.

The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the ultrasound probe, highly correlated with total flow determined by MRI, R = 0.89 and P = 10-7. Linear regression yielded a slope of 1.2 and a y-axis intercept of 259 mL/min. The mean total volume of the investigated muscle tissue corresponds to an offset perfusion of 4.7mL/(min ⋅ 100cm3). The DCE-MRI technique presented here uses a blood pool contrast medium in combination with a two-compartment tracer kinetic model and allows absolute quantification of low-perfused non-cerebral organs such as muscles.

Background: Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI)., Methods: Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured., Results: DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05)., Conclusion: After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

Neuroimaging studies have demonstrated that patients with Alzheimer's disease presented disconnection syndrome. However, little is known about the alterations of interhemispheric functional interactions and underlying structural connectivity in the AD patients. In this study, we combined resting-state functional MRI and diffusion tensor imaging (DTI) to investigate interhemispheric functional and structural connectivity in 16 AD, 16 mild cognitive impairment (MCI), as well as 16 cognitive normal healthy subjects (CN). The pattern of the resting state interhemispheric functional connectivity was measured with a voxel-mirrored homotopic connectivity (VMHC) method. Decreased VMHC was observed in AD and MCI subjects in anterior brain regions including the prefrontal cortices and subcortical regions with a pattern of AD

Objective: Diffuse axonal injury (DAI) is a specific type of traumatic brain injury caused by shearing forces leading to widespread tearing of axons and small vessels. Traumatic microbleeds (TMBs) are regarded as a radiological marker for DAI. This study aims to compare DAI-associated TMBs at 3 Tesla (T) and 7 T susceptibility weighted imaging (SWI) to evaluate possible diagnostic benefits of ultra-high field (UHF) MRI., Material and Methods: 10 study participants (4 male, 6 female, age range 20-74 years) with known DAI were included. All MR exams were performed with a 3 T MR system (Magnetom Skyra) and a 7 T MR research system (Magnetom 7 T, Siemens AG, Healthcare Sector, Erlangen, Germany) each in combination with a 32-channel-receive coil. The average time interval between trauma and imaging was 22 months. Location and count of TMBs were independently evaluated by two neuroradiologists on 3 T and 7 T SWI images with similar and additionally increased spatial resolution at 7 T. Inter- and intraobserver reliability was assessed using the interclass correlation coefficient (ICC). Count and diameter of TMB were evaluated with Wilcoxon signed rank test., Results: Susceptibility weighted imaging revealed a total of 485 TMBs (range 1-190, median 25) at 3 T, 584 TMBs (plus 20%, range 1-262, median 30.5) at 7 T with similar spatial resolution, and 684 TMBs (plus 41%, range 1-288, median 39.5) at 7 T with 10-times higher spatial resolution. Hemorrhagic DAI appeared significantly larger at 7 T compared to 3 T (p = 0.005). Inter- and intraobserver correlation regarding the counted TMB was high and almost equal 3 T and 7 T., Conclusion: 7 T SWI improves the depiction of small hemorrhagic DAI compared to 3 T and may be supplementary to lower field strengths for diagnostic in inconclusive or medicolegal cases.

When performing non-enhanced time-of-flight MR angiography of the lower extremity arteries at 7 T with cardiac triggering, the acquisition time is a crucial consideration. Therefore, in previous studies, saturation RF pulses were applied only every second TR. In the axial source images a slight artifact with an appearance similar to aliasing could be observed. The purpose of this study was to investigate the origin of this artifact. The reason for the artifact is supposed to be related to the two effective TRs during acquisition caused by the sparsely applied saturation RF pulse. Several sequence variants were simulated and implemented within the sequence source code to examine this hypothesis. An adaptation of the excitation flip angles for each TR as well as a correction factor for the k-space data was calculated. Additionally, a different ordering of the k-space data during acquisition was implemented as well as the combination of the latter with the k-space correction factor. The observations from the simulations were verified using both a static and a flow phantom and, finally, in a healthy volunteer using the same measurement setup as in previous volunteer and patient studies. Of all implemented techniques, only the reordering of the k-space was capable of suppressing the artifact almost completely at the cost of creating a ringing artifact. The phantom measurements showed the same results as the simulations and could thus confirm the hypothesis regarding the origin of the artifact. This was additionally verified in the healthy volunteer. The origin of the artifact could be confirmed to be the periodic signal variation caused by two effective TRs during acquisition.

The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer's disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD.

Background: Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging., Methods: A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity., Results: Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores., Conclusion: Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI.