Magnetic particle imaging (MPI) is a novel tracer-based in vivo imaging modality allowing quantitative measurements of the spatial distributions of superparamagnetic iron oxide (SPIO) nanoparticles ...in three dimensions (3D) and in real time using electromagnetic fields. However, MPI lacks the detection of morphological information which makes it difficult to unambiguously assign spatial SPIO distributions to actual organ structures. To compensate for this, a preclinical highly integrated hybrid system combining MPI and Magnetic Resonance Imaging (MRI) has been designed and gets characterized in this work. This hybrid MPI-MRI system offers a high grade of integration with respect to its hard- and software and enables sequential measurements of MPI and MRI within one seamless study and without the need for object repositioning. Therefore, time-resolved measurements of SPIO distributions acquired with MPI as well as morphological and functional information acquired with MRI can be combined with high spatial co-registration accuracy. With this initial phantom study, the feasibility of a highly integrated MPI-MRI hybrid systems has been proven successfully. This will enable dual-modal in vivo preclinical investigations of mice and rats with high confidence of success, offering the unique feature of precise MPI FOV planning on the basis of MRI data and vice versa.
The hepatic content of amyloid beta (Aβ) decreases drastically in human and rodent cirrhosis highlighting the importance of understanding the consequences of Aβ deficiency in the liver. This is ...especially relevant in view of recent advances in anti‐Aβ therapies for Alzheimer's disease (AD). Here, it is shown that partial hepatic loss of Aβ in transgenic AD mice immunized with Aβ antibody 3D6 and its absence in amyloid precursor protein (APP) knockout mice (APP‐KO), as well as in human liver spheroids with APP knockdown upregulates classical hallmarks of fibrosis, smooth muscle alpha‐actin, and collagen type I. Aβ absence in APP‐KO and deficiency in immunized mice lead to strong activation of transforming growth factor‐β (TGFβ), alpha secretases, NOTCH pathway, inflammation, decreased permeability of liver sinusoids, and epithelial‐mesenchymal transition. Inversely, increased systemic and intrahepatic levels of Aβ42 in transgenic AD mice and neprilysin inhibitor LBQ657‐treated wild‐type mice protect the liver against carbon tetrachloride (CCl4)‐induced injury. Transcriptomic analysis of CCl4‐treated transgenic AD mouse livers uncovers the regulatory effects of Aβ42 on mitochondrial function, lipid metabolism, and its onco‐suppressive effects accompanied by reduced synthesis of extracellular matrix proteins. Combined, these data reveal Aβ as an indispensable regulator of cell–cell interactions in healthy liver and a powerful protector against liver fibrosis.
Hepatic deficiency of Amyloid beta (Aβ) leads to liver fibrosis reflected by increased cleavage of NOTCH, activation of hepatic stellate cells (HSC), decreased permeability of endothelial cells (LSEC), and epithelial‐mesenchymal transition (EMT) of hepatocytes. High hepatic Aβ levels provide powerful protection against liver fibrosis by reversing the aforementioned processes.
Intertemporal choice involves deciding between smaller, sooner and larger, later rewards. People tend to prefer smaller rewards that are available earlier to larger rewards available later, a ...phenomenon referred to as temporal or delay discounting. Despite its ubiquity in human and non-human animals, temporal discounting is subject to considerable individual differences. Here, we provide a critical narrative review of this literature and make suggestions for future work. We conclude that temporal discounting is associated with key socio-economic and health-related variables. Regarding personality, large-scale studies have found steeper temporal discounting to be associated with higher levels of self-reported impulsivity and extraversion; however, effect sizes are small. Temporal discounting correlates negatively with future-oriented cognitive styles and inhibitory control, again with small effect sizes. There are consistent associations between steeper temporal discounting and lower intelligence, with effect sizes exceeding those of personality or cognitive variables, although socio-demographic moderator variables may play a role. Neuroimaging evidence of brain structural and functional correlates is not yet consistent, neither with regard to areas nor directions of effects. Finally, following early candidate gene studies, recent Genome Wide Association Study (GWAS) approaches have revealed the molecular genetic architecture of temporal discounting to be more complex than initially thought. Overall, the study of individual differences in temporal discounting is a maturing field that has produced some replicable findings. Effect sizes are small-to-medium, necessitating future hypothesis-driven work that prioritizes large samples with adequate power calculations. More research is also needed regarding the neural origins of individual differences in temporal discounting as well as the mediating neural mechanisms of associations of temporal discounting with personality and cognitive variables.
To explore the typical magnetic resonance imaging (MRI) pattern of osteoblastoma (OB) after radiofrequency ablation (RFA) treatment and to identify signs indicating treatment success or relapse.
...Forty-four follow-up MRI examinations of 15 patients with OB who had undergone 19 RFA procedures were analyzed retrospectively. An early follow-up group (1-4 months after RFA) and a late follow-up group (8-131 months after RFA) were established. The groups were further subdivided according to treatment success. Images were analyzed for the presence of central nidus enhancement (CNE), peripheral nidus enhancement (PNE), perifocal bone marrow edema (PBME) and fatty nidus conversion (FNC).
The early follow-up MRI image from every patient in the treatment success group exhibited a target-like appearance with negative CNE and positive PNE or PBME. PNE and PBME were observed in 93% and 71% of the early follow-up images, respectively. A target-like appearance was observed in 25% of the late follow-up images, and PNE and PBME were each observed in 20% of these images. FNC was not observed in the early follow-up images, but was seen in 55% of the late follow-up images. All three MRI images of the patients exhibiting clinical recurrence demonstrated strong CNE, PNE and extensive PMBE, which was in contrast to the images of the patients exhibiting treatment success.
A target-like appearance of OB in early follow-up MRI examination indicates treatment success. PNE and PBME typically reduce over time and can lead to FNC in successfully treated patients. CNE recurrence, PNE and extensive PBME are signs of relapse.
Since the mpox outbreak in 2022, it was unclear if and how often infections with mpox virus (MPXV) were clinically inapparent, i.e. not presenting to clinical care with mpox symptoms. Moreover, it ...was hypothesized that MPXV circulated in the affected communities before the outbreak was officially detected. We retrospectively tested rectal and urethral swabs, and pooled samples for presence of MPXV. Samples were obtained from routine STI testing of three anonymous Community Based Voluntary Counselling and Testing (CBVCT) centres in Berlin, in 2022 and 2023. Testing results were linked to anonymously provided behavioural data. Overall, 9,053 samples from 6,600 client visits were included. Clinically inapparent MPXV infections were detectable in 1.1% of the samples. We did not find MPXV infections in the month before the first cases appeared in Berlin or between October 2022 and January 2023 when case numbers were low in Germany. However, during the outbreak period in 2022, we found clinically inapparent MPXV infections among 2.2% of the clients and during summer/autumn 2023 among 0.3%. The number of condomless anal/vaginal intercourse partners within the previous 6 months and PrEP use were identified as predictors of clinically inapparent MPXV infection. Clinically inapparent MPXV infections occurred during the mpox outbreak in Berlin in 2022 and post-outbreak in summer/autumn 2023. Unrecognized MPXV circulation in Berlin before the recognition of the outbreak in May 2022 appears unlikely. However, low-level sustained circulation of clinically inapparent MPXV infections need to be acknowledged in mpox prevention strategies.
The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and ...correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (
= 0.001, c-index 0.72), the speed of growth of the fastest growing FL (
= 0.003, c-index 0.75), the DI score (DIS,
= 0.014, c-index 0.67), and its dynamic over time (DIS dynamic,
< 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (
= 0.016 and
= 0.022). DIS correlated with decrease of hemoglobin (
< 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL-OL; DIS-hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future.
Purpose
To evaluate the utility of delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping in evaluation of type II osteochondral lesions (OCLs) of the talus and ...define cutoff values for identifying patients with good/poor clinical outcomes.
Materials and Methods
28 patients (mean age, 42.3 years) underwent T2 mapping and dGEMRIC at least 1.5 years (mean duration, 3.5 years) after microfracture (n = 12) or conservative (n = 16) treatment for type II OCL. Clinical outcomes were considered good with an American Orthopedic Foot and Ankle Society score ≥80. The T1/T2‐values and indices of repair tissue (RT; cartilage above the OCL) were compared to those of the adjacent normal cartilage (NC) by region‐of‐interest analysis. The ability of the two methods to discriminate RT from NC was determined by area under the receiver operating characteristics curve (AUC) analysis. The Youden index was maximized for T1/T2 measures for identifying cutoff values indicative of good/poor clinical outcomes.
Results
Repair tissue exhibited lower dGEMRIC values (629.83 vs. 738.51 msec) and higher T2 values (62.07 vs. 40.69 msec) than NC (P < 0.001). T2 mapping exhibited greater AUC than dGEMRIC (0.88 vs. 0.69; P = 0.0398). All T1 measures exhibited higher maximized Youden indices than the corresponding T2 measures. The highest maximized Youden index for T1difference was observed at a cutoff value of 84 msec (sensitivity, 78%; specificity, 83%).
Conclusion
While T2 mapping is superior to dGEMRIC in discriminating RT, the latter better identifies good/poor clinical outcomes in patients with type II talar OCL.
Level of Evidence: 2
Technical Efficacy: Stage 3
J. Magn. Reson. Imaging 2017;46:1601–1610.
This study investigated the ability of T2 mapping to assess the glenoid labrum and to differentiate between healthy labral substances and superior labral anterior posterior (SLAP) lesions using ...arthroscopy as the gold standard. Eighteen patients (mean age: 52.4 ± 14.72 years, 12 men) with shoulder pain were examined using 3-Tesla T2 mapping. All the patients underwent shoulder arthroscopy. Using morphological sequences for correlation, regions of interest covering the entire labral substance were placed in the corresponding T2 maps. The diagnostic cutoff values, sensitivities, and specificities, as well as the inter-reader correlation coefficients (ICCs) determined by two independent radiologists, were calculated. The mean T2 value was 20.8 ± 2.4 ms for the healthy labral substances and 37.7 ± 10.63 ms in the patients with SLAP lesions. The maximum T2 value in normal labrum (21.2 ms) was lower than the minimum T2 value in the patients with SLAP lesions (27.8 ms), leading to sensitivities, specificities, and positive and negative predictive values of 100% (95% CI 54.1-100.0) for all the cutoff values between 21.2 and 27.8 ms. The ICCs ranged from 0.91 to 0.99. In summary, the data suggest that evaluation and quantification of the labral (ultra)structural integrity using T2 mapping may allow discrimination between arthroscopically confirmed SLAP lesions and a healthy glenoid labrum. T2 mapping may therefore be helpful in diagnosing patients with suspected labral damage.
In the present study, an ultra-sensitive and highly reproducible novel SERS-based capillary platform was developed and utilized for the trace detection of tetrahydrocannabinol (THC). The approach ...combines the advantages of microwave-assisted nanoparticle synthesis, plasmonics and capillary forces. By employing a microwave-assisted preparation method, glass capillaries were reproducibly coated with silver nanoparticles in a batch fabrication process that required a processing time of 3 min without needing to use any pre-surface modifications or add surfactants. The coated capillaries exhibited an excellent SERS activity with a high reproducibility and enabled the detection of low concentrations of target molecules. At the same time, only a small amount of analyte and a short and simple incubation process was required. The developed platform was applied to the spectroscopic characterization of tetrahydrocannabinol (THC) and its identification at concentration levels down to 1 nM. Thus, a highly efficient detection system for practical applications, e.g., in drug monitoring/detection, is introduced, which can be fabricated at low cost by using microwave-assisted batch synthesis techniques.
In the present study, an ultra-sensitive and highly reproducible novel SERS-based capillary platform was developed. By utilizing microwave-assisted synthesis, glass capillaries were coated with silver nanoparticles in a batch fabrication process with a 3 minute processing time. The capillary-based platform exhibits a high point-to-point and batch-to-batch SERS reproducibility. Finally, the platform was applied to the spectroscopic characterization of tetrahydrocannabinol (THC) and its identification at concentration levels down to 1 nM. Display omitted
•An ultra-sensitive and highly reproducible novel SERS-based capillary platform.•Glass capillaries were coated with Ag nanoparticles by utilizing microwave-assisted synthesis in a batch fabrication process.•A high point-to-point and batch-to-batch SERS reproducibility.•1 nM of tetrahydrocannabinol (THC) is detected.
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