The comprehension of the glymphatic system, a postulated mechanism responsible for the removal of interstitial solutes within the central nervous system (CNS), has witnessed substantial progress ...recently. While direct measurement techniques involving fluorescence and contrast agent tracers have demonstrated success in animal studies, their application in humans is invasive and presents challenges. Hence, exploring alternative noninvasive approaches that enable glymphatic research in humans is imperative. This review primarily focuses on several noninvasive magnetic resonance imaging (MRI) techniques, encompassing perivascular space (PVS) imaging, diffusion tensor image analysis along the PVS, arterial spin labeling, chemical exchange saturation transfer, and intravoxel incoherent motion. These methodologies provide valuable insights into the dynamics of interstitial fluid, water permeability across the blood-brain barrier, and cerebrospinal fluid flow within the cerebral parenchyma. Furthermore, the review elucidates the underlying concept and clinical applications of these noninvasive MRI techniques, highlighting their strengths and limitations. It addresses concerns about the relationship between glymphatic system activity and pathological alterations, emphasizing the necessity for further studies to establish correlations between noninvasive MRI measurements and pathological findings. Additionally, the challenges associated with conducting multisite studies, such as variability in MRI systems and acquisition parameters, are addressed, with a suggestion for the use of harmonization methods, such as the combined association test (COMBAT), to enhance standardization and statistical power. Current research gaps and future directions in noninvasive MRI techniques for assessing the glymphatic system are discussed, emphasizing the need for larger sample sizes, harmonization studies, and combined approaches. In conclusion, this review provides invaluable insights into the application of noninvasive MRI methods for monitoring glymphatic system activity in the CNS. It highlights their potential in advancing our understanding of the glymphatic system, facilitating clinical applications, and paving the way for future research endeavors in this field. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.
Purpose
The purpose of this study was to investigate recent trends in work-style reform and the use of information and communication technology (ICT) among board-certified diagnostic radiologists in ...Japan.
Materials and methods
We conducted online questionnaire surveys of board-certified radiologists of the Japan Radiological Society (JRS) and registered training institutions. Completed surveys were obtained from 1192 radiologists and 275 training institutions (response rates of 25.5% and 38.1%, respectively). Respondents were assured of confidentiality.
Results
13.5% (134/991) of full-time radiologists and 56.7% (89/157) of part-time radiologists had shifted some of their work to teleradiology at home. In addition, 52.9% (83/157) of part-time radiologists and 27.3% (12/44) of board-certified individuals who had stopped working as radiologists responded that they would consider starting full-time work in hospitals, if teleradiology at home was permitted as part of full-time work. Furthermore, 16.7% of training institutions (46/275) had introduced teleradiology systems for radiologists, and 47.2% (108/229) of the remaining training institutions wanted to introduce teleradiology systems in the future.
Conclusion
Teleradiology using ICT is already a part of Japanese radiologists’ workload. Work-style reform may progress with the use of ICT, such as part-time radiologists, and board-certified individuals who stop working as radiologists, becoming full-time radiologists.
Systemically administered lipid nanoparticles (LNPs) are complexed with Apolipoprotein E (ApoE) in the bloodstream, and the complex is subsequently largely taken up by hepatocytes. Based on a ...previous report showing that, like blood, lymph fluid also contains ApoE, and that LECs, in turn, expresses a low density-lipoprotein receptor (LDLR), which is the receptor responsible for the ApoE-bound LNP, we hypothesized that subcutaneously administered LNPs would be taken up by LECs via an ApoE-LDLR pathway. Our in vitro studies using immortal LECs that we established in a previous study showed that LEC indeed took up LNPs in an ApoE-dependent manner. We then reported on the development of LNPs that target the lymphatic endothelium for in vivo siRNA delivery after subcutaneous administration. The key to success for in vivo LEC targeting is that the surface needs to be modified with a high density of polyethylene glycol (PEG)-conjugated lipids with short acyl chains (C14). The LNPs were drained into the lymphatic system, and then accumulated in lymphatic endothelial cells in an ApoE-dependent manner, most likely after the release of the PEG-lipid. Subcutaneous administration of optimized LNPs containing encapsulated siRNA against VEGFR3, a marker of LECs, significantly inhibited the expression of VEGFR3. These findings are the first report of a simple straightforward strategy for targeting lymphatic endothelial cells by using ionizable lipid-formulated LNPs.
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•Areal parcellation identified dorsal and ventral areas in the right ventral IFC activated during response inhibition.•The ventral area demonstrated a positive correlation between centrality and ...brain activity, whereas the dorsal area did not.•The ventral area also exhibited a significant correlation between brain activity and behavioral indices.•The functional dissociation in centrality within the vIFC raises the need to investigate the vIFC in greater spatial detail.
The human right inferior frontal cortex (IFC) plays a critical role in response inhibition. It has also been demonstrated that the IFC is heterogeneous and that the ventral part of the IFC (vIFC) is more critical to inhibition of prepotent response tendency. Recent areal parcellation analyses based on resting-state functional connectivity have revealed that the right vIFC consists of multiple functional areas. In the present study, we characterized the parcellated areas (parcels) in the right vIFC using graph theory analysis, which characterizes local connectivity properties of a brain network by referring to its global structure of functional connectivity. Functional magnetic resonance imaging (MRI) scans were obtained during performance of a stop-signal task and during resting state. The cerebral cortex was parcellated into areas using resting-state functional connectivity. The parcels were then subjected to graph theory analysis to reveal central areas. Two parcels, ventral and dorsal, in the posterior part of the vIFC, exhibited significant brain activity during response inhibition. The ventral parcel exhibited a positive correlation between betweenness centrality and brain activity while the dorsal parcel did not. Correlations were significantly stronger in the ventral parcel. Moreover, the ventral parcel exhibited a negative correlation between brain activity during response inhibition and stop-signal reaction time (SSRT), a behavioral measure used to evaluate stopping performance. These dissociation results suggest that the ventral region in the vIFC plays a more central role in the brain network by increasing brain activity, which may further predict better performance of response inhibition.
Purpose
To reveal that a computed tomography surveillance program (CT-surveillance) could demonstrate the epidemiologic features of COVID-19 infection and simultaneously investigate the type and ...frequency of CT findings using clinical CT data.
Materials and methods
We targeted individuals with possible CT findings of viral pneumonia. Using an online questionnaire, we asked Japanese board-certified radiologists to register their patients’ information including patient age and sex, the CT examination date, the results of PCR test for COVID-19 infection, CT findings, and the postal code of the medical institution that performed the CT. We compared the diurnal patient number and the cumulative regional distribution map of registrations in CT-surveillance to those of the PCR-positive patient surveillance (PCR-surveillance).
Results
A total of 637 patients was registered from January 1 to April 17, 2020 for CT-surveillance. Their PCR test results were positive (
n
= 62.5–398%), negative (
n
= 8.9–57%), unknown (
n
= 26.2–167%), and other disease (
n
= 2.4–15%). An age peak at 60–69 years and male dominance were observed in CT-surveillance. The most common CT finding was bilaterally distributed ground-glass opacities. The diurnal number and the cumulative regional distribution map by CT-surveillance showed tendencies that were similar to those revealed by PCR-surveillance.
Conclusion
Using clinical CT data, CT-surveillance program delineated the epidemiologic features of COVID-19 infection.
Linear polarization of high-energy gamma-rays (10MeV–100GeV) can be detected by measuring the azimuthal angle of electron–positron pairs and observing the modulation of the azimuthal distribution. To ...demonstrate the gamma-ray polarization sensitivity of emulsion, we conducted a test using a polarized gamma-ray beam (0.8–2.4GeV) at SPring-8/LEPS. Emulsion tracks were reconstructed using scanning data, and gamma-ray events were selected automatically. Using an optical microscope, out of the 2381 gamma-ray conversions that were observed, 1372 remained after event selection, on the azimuthal angle distribution of which we measured the modulation. From the distribution of the azimuthal angles of the selected events, a modulation factor of 0.21+0.11−0.09 was measured, from which the detection of a non-zero modulation was established with a significance of 3.06σ. This attractive polarimeter will be applied to the GRAINE project, a balloon-borne experiment that observes 10–100GeV cosmic gamma-rays with an emulsion-based pair conversion telescope.
Various types of transgenic mice carrying either class I or II human leukocyte antigen (HLA) molecules are readily available, and reports describing their use in a variety of studies have been ...published for more than 30 years. Examples of their use include the discovery of HLA-specific antigens against viral infection as well as the reproduction of HLA-mediated autoimmune diseases for the development of therapeutic strategies. Recently, HLA transgenic mice have been used to reproduce HLA-mediated idiosyncratic drug toxicity (IDT), a rare and unpredictable adverse drug reaction that can result in death. For example, abacavir-induced IDT has successfully been reproduced in HLA-B*57:01 transgenic mice. Several reports using HLA transgenic mice for IDT have proven the utility of this concept for the evaluation of IDT using various HLA allele combinations and drugs. It has become apparent that such models may be a valuable tool to investigate the mechanisms underlying HLA-mediated IDT. This review summarizes the latest findings in the area of HLA transgenic mouse models and discusses the current challenges that must be overcome to maximize the potential of this unique animal model.
Despite differences in the pathogenesis and treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), it remains difficult to distinguish them. In this study, we aimed ...to discriminate between MS and NMOSD using diffusion tensor imaging (DTI), free water (FW) imaging, and neurite orientation dispersion and density imaging (NODDI).
Thirty patients with relapsing-remitting (RR) MS, 18 NMOSD patients with positive anti-aquaporin-4 immunoglobulin G seroreactivity, and 20 age- and sex- matched currently healthy subjects underwent MRI. The differences in the DTI (fractional anisotropy FA, axial diffusivity AD, mean diffusivity MD, and radial diffusivity RD), FW and FW-corrected DTI, and NODDI indices between the three groups were evaluated using tract-based spatial statistics (TBSS) and region-of-interest (ROI) analyses.
The ROI analysis of lesions indicated that the RRMS group had significantly higher AD, MD, RD, ISO and FW-corrected AD, and MD; and lower intracellular volume fraction (ICVF) than the NMOSD group. TBSS analysis showed increased water content in RRMS patients compared to NMOSD patients. Compared with healthy controls (HCs) using TBSS and ROI analysis, the changes in FW imaging indices were more limited than those of in DTI in RRMS patients.
FW imaging and NODDI were useful for identifying the etiology of neurodegeneration- and neuroinflammation-related microstructural changes in RRMS and NMOSD patients.
•We evaluated MS and NMOSD using DTI, FW imaging and NODDI.•RRMS group had significantly higher diffusivity in lesions.•RRMS group had significantly lower intracellular volume fraction in lesions.•TBSS analysis showed increased water content in RRMS group.•These results may reflect microstructural changes in MS and NMOSD.
Early-phase pathologies of Alzheimer's disease (AD) are attracting much attention after clinical trials of drugs designed to remove beta-amyloid (Aβ) aggregates failed to recover memory and cognitive ...function in symptomatic AD patients. Here, we show that phosphorylation of serine/arginine repetitive matrix 2 (SRRM2) at Ser1068, which is observed in the brains of early phase AD mouse models and postmortem end-stage AD patients, prevents its nuclear translocation by inhibiting interaction with T-complex protein subunit α. SRRM2 deficiency in neurons destabilized polyglutamine binding protein 1 (PQBP1), a causative gene for intellectual disability (ID), greatly affecting the splicing patterns of synapse-related genes, as demonstrated in a newly generated PQBP1-conditional knockout model. PQBP1 and SRRM2 were downregulated in cortical neurons of human AD patients and mouse AD models, and the AAV-PQBP1 vector recovered RNA splicing, the synapse phenotype, and the cognitive decline in the two mouse models. Finally, the kinases responsible for the phosphorylation of SRRM2 at Ser1068 were identified as ERK1/2 (MAPK3/1). These results collectively reveal a new aspect of AD pathology in which a phosphorylation signal affecting RNA splicing and synapse integrity precedes the formation of extracellular Aβ aggregates and may progress in parallel with tau phosphorylation.
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