Microglia shapes and states:Exploring microglia's path from homeostasis to disease

Microglia are immune cells in the central nervous system responsible for maintaining brain health and homeostasis. They constantly monitor their surroundings for danger signals and can become reactive, changing their shape and releasing inflammatory molecules when they detect threats. One of their important functions is phagocytosis, which involves clearing apoptotic cells, debris, and pathogens. Dysregulation of microglial functions is linked to aging and neurodegenerative diseases. With age, microglia become less efficient at clearing debris and misfolded proteins, leading to the accumulation of toxic aggregates and chronic inflammation in the brain. Chronic microglial activation can cause neuroinflammation, damaging neurons and excessive synapse pruning, ultimately contributing to neurodegeneration. This thesis explores microglial phenotypes in various disease conditions and aging, aiming to understand how microglia acquire these disease-associated characteristics. In chapter 2, we demonstrated that treatment with minocycline to inhibit microgliosis at an early-stage prevented cognitive impairment in a mouse model of Alzheimer's disease. In chapter 3, we identified a set of genes that potentially reflects the initial response of microglia to amyloid. In chapter 4, we determined potential regulators of microglia acquiring a primed phenotype, which is associated with aging and neurodegenerative diseases. In chapter 5, we revealed that radiation induces persistent upregulation of microglia priming genes as well as exaggerated immune responses with a subsequent peripheral stimulus. Overall, the thesis delves into the microglial functions in different disease contexts and aging, shedding light on their contributions to neuroinflammation and neurodegeneration

Mechanistic evidence for the remote π-aryl participation in acidcatalyzed ring opening of homobenzoquinone epoxides

The acid-induced reaction of bis(p-chlorophenyl)homobenzoquinone epoxide gave the dual ipso/ortho intramolecular SE2-Ar products associated with the π-aryl participated oxirane ring opening, whereas bis(p-tolyl)- and diphenyl-substituted homologues provided only the ortho products

Requisite role of vasohibin‐2 in spontaneous gastric cancer formation and accumulation of cancer‐associated fibroblasts

The vasohibin (VASH) family consists of two genes, VASH1 and VASH2. VASH1 is mainly expressed in vascular endothelial cells and suppresses angiogenesis in an autocrine manner, whereas VASH2 is mainly expressed in cancer cells and exhibits pro‐angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we recently reported on the role of Vash2 in the spontaneous formation of intestinal tumors. In this study, we used K19‐Wnt1/C2mE (Gan) mice and examined the role of Vash2 in spontaneous gastric cancer formation. Gan mice spontaneously develop gastric tumors by activation of Wnt and prostaglandin E2 signaling pathways in gastric mucosa after 30 weeks of age. Expression of Vash2 mRNA was significantly increased in gastric tumor tissues compared with normal stomach tissues. When Gan mice were crossed with the Vash2‐deficient (Vash2 LacZ/LacZ) strain, gastric cancer formation was significantly suppressed in Vash2 LacZ/LacZ Gan mice. Normal composition of gastric mucosa was partially maintained in Vash2 LacZ/LacZ Gan mice. Knockout of Vash2 caused minimal reduction of tumor angiogenesis but a significant decrease in cancer‐associated fibroblasts (CAF) in tumor stroma. DNA microarray analysis and real‐time RT‐PCR showed that mRNA levels of epiregulin (Ereg) and interleukin‐11 (Il11) were significantly downregulated in gastric tumors of Vash2 LacZ/LacZ Gan mice. Furthermore, conditioned medium of gastric cancer cells stimulated migration of and α‐smooth muscle actin expression in fibroblasts, whereas conditioned medium of VASH2 knockdown cells attenuated these effects in vitro. These results suggest that VASH2 plays an important role in gastric tumor progression via the accumulation of CAF accompanying upregulation of EREG and IL‐11 expression

[N355] Experimental and Numerical Study of Spatial Coherence of Surface Pressure on a Square Cylinder for Numerical Aerodynamic Noise Prediction

Aerodynamic noises from building exterior subsidiaries such as balusters or louver fins exposed to strong winds give serious psychological impact to inhabitants. To reduce required resources for three-dimensional aeroacoustic source computation of such two-dimensional bodies, an estimationmethod of full-span acoustic intensity from a partial-span computation has been formerlypresented by one of the authors. The method has stood on an unproved assumption that the real part of complex coherence of surface pressure as function of spanwise distance obeys Gaussian function, which is examined experimentally and computationally in this investigation.The experiments are conducted in a low-noise wind tunnel using a square-cylindrical test body in which surface pressure sensors are embedded. In computations, a Large Eddy Simulation with the standard Smagorinsky model is employed. Reynolds numbers range from 4620 to 9240 and the angles of attack from 0 to 30 degrees. The results tell that in all cases the real parts of complex coherences fit well with Gaussian function especially at K´arm´an frequencies. Although coherent structures also agreed qualitatively between experiments and computations, large discrepancies are found in coherent lengths. The investigation of the cause remains as future work.会議名称：The 32nd International Congress and Exposition on Noise Control Engineering主催学会：KSNVE/AS

Accuracy, repeatability, and reproducibility of T1 and T2 relaxation times measurement by 3D magnetic resonance fingerprinting with different dictionary resolutions

[Objectives] To assess the accuracy, repeatability, and reproducibility of T₁ and T₂ relaxation time measurements by three-dimensional magnetic resonance fingerprinting (3D MRF) using various dictionary resolutions. [Methods] The ISMRM/NIST phantom was scanned daily for 10 days in two 3 T MR scanners using a 3D MRF sequence reconstructed using four dictionaries with varying step sizes and one dictionary with wider ranges. Thirty-nine healthy volunteers were enrolled: 20 subjects underwent whole-brain MRF scans in both scanners and the rest in one scanner. ROI/VOI analyses were performed on phantom and brain MRF maps. Accuracy, repeatability, and reproducibility metrics were calculated. [Results] In the phantom study, all dictionaries showed high T₁ linearity to the reference values (R² > 0.99), repeatability (CV 0.98), repeatability (CV < 6%), and reproducibility (CV ≤ 4%) for T₂ measurement. The volunteer study demonstrated high T1 reproducibility of within-subject CV (wCV) < 4% by all dictionaries with the same ranges, both in the brain parenchyma and CSF. Yet, reproducibility was moderate for T₂ measurement (wCV < 8%). In CSF measurement, dictionaries with a smaller range showed a seemingly better reproducibility (T₁, wCV 3%; T₂, wCV 8%) than the much wider range dictionary (T₁, wCV 5%; T₂, wCV 13%). Truncated CSF relaxometry values were evident in smaller range dictionaries. [Conclusions] The accuracy, repeatability, and reproducibility of 3D MRF across various dictionary resolutions were high for T₁ and moderate for T₂ measurements. A lower-resolution dictionary with a well-defined range may be adequate, thus significantly reducing the computational load. [Key Points] • A lower-resolution dictionary with a well-defined range may be sufficient for 3D MRF reconstruction. • CSF relaxation times might be underestimated due to truncation by the upper dictionary range. • Dictionary with a higher upper range might be advisable, especially for CSF evaluation and elderly subjects whose perivascular spaces are more prominent

Clinical Application of MPRAGE Wave Controlled Aliasing in Parallel Imaging (Wave-CAIPI): A Comparative Study with MPRAGE GRAPPA

PURPOSE: To compare reliability and elucidate clinical application of magnetization-prepared rapid gradient-echo (MPRAGE) with 9-fold acceleration by using wave-controlled aliasing in parallel imaging (Wave-CAIPI 3 × 3) in comparison to conventional MPRAGE accelerated by using generalized autocalibrating partially parallel acquisition (GRAPPA) 2 × 1. METHODS: A total of 26 healthy volunteers and 33 patients were included in this study. Subjects were scanned with two MPRAGEs, GRAPPA 2 × 1 and Wave-CAIPI 3 × 3 acquired in 5 min 21 s and 1 min 42 s, respectively, on a 3T MR scanner. Healthy volunteers underwent additional two MPRAGEs (CAIPI 3 × 3 and GRAPPA 3 × 3). The image quality of the four MPRAGEs was visually evaluated with a 5-point scale in healthy volunteers, and the SNR of four MPRAGEs was also calculated by measuring the phantom 10 times with each MPRAGE. Based on the results of the visual evaluation, voxel-based morphometry (VBM) analyses, including subfield analysis, were performed only for GRAPPA 2 × 1 and Wave-CAIPI 3 × 3. Correlation of segmentation results between GRAPPA 2 × 1 and Wave-CAIPI 3 × 3 was assessed. RESULTS: In visual evaluations, scores for MPRAGE GRAPPA 2 × 1 (mean rank: 4.00) were significantly better than those for Wave-CAIPI 3 × 3 (mean rank: 3.00), CAIPI 3 × 3 (mean rank: 1.83), and GRAPPA 3 × 3 (mean rank: 1.17), and scores for Wave-CAIPI 3×3 were significantly better than those for CAIPI 3 × 3 and GRAPPA 3 × 3. Image noise was evident at the center for additional MPRAGE CAIPI 3 × 3 and GRAPPA 3 × 3. The correlation of segmentation results between GRAPPA 2 × 1 and Wave-CAIPI 3 × 3 was higher than 0.85 in all VOIs except globus pallidus. Subfield analysis of hippocampus also showed a high correlation between GRAPPA 2 × 1 and Wave-CAIPI 3 × 3. CONCLUSION: MPRAGE Wave-CAIPI 3 × 3 shows relatively better contrast, despite of its short scan time of 1 min 42 s. The volumes derived from automated segmentation of MPRAGE Wave-CAIPI are considered to be reliable measures

Quiet Diffusion-weighted MR Imaging of the Brain for Pediatric Patients with Moyamoya Disease

PURPOSE: Diffusion-weighted MRI (DWI) is an essential sequence for evaluating pediatric patients with moyamoya disease (MMD); however, acoustic noise associated with DWI may lead to motion artifact. Compared with conventional DWI (cDWI), quiet DWI (qDWI) is considered less noisy and able to keep children more relaxed and stable. This study aimed to evaluate the suitability of qDWI compared with cDWI for pediatric patients with MMD. METHODS: In this observational study, MR examinations of the brain were performed either with or without sedation in pediatric patients with MMD between September 2017 and August 2018. Three neuroradiologists independently evaluated the images for artifacts and restricted diffusion in the brain. The differences between qDWI and cDWI were compared statistically using a chi-square test. RESULTS: One-hundred and six MR scans of 56 patients with MMD (38 scans of 15 sedated patients: 6 boys and 9 girls; mean age, 5.2 years; range, 1-9 years; and 68 scans of 42 unsedated patients: 19 boys and 23 girls; mean age, 10.7 years; range, 7-16 years) were evaluated. MR examinations were performed either with or without sedation (except in one patient). In sedated patients, no artifact other than susceptibility was observed on qDWI, whereas four artifacts were observed on cDWI (P = .04). One patient awoke from sedation during cDWI scanning, while no patient awoke from sedation during qDWI acquisition. For unsedated patients, three scans showed artifacts on qDWI, whereas two scans showed artifacts on cDWI (P = .65). Regarding restricted diffusion, qDWI revealed three cases, while two cases were found on cDWI (P = .66). CONCLUSION: qDWI induced fewer artifacts compared with cDWI in sedated patients, and similar frequencies of artifacts were induced by qDWI and by cDWI in unsedated patients. qDWI showed restricted diffusion comparable to cDWI

Signal Intensity and Volume of Pituitary and Thyroid Glands in Preterm and Term Infants

[Background]: Hypothalamic–pituitary–thyroid (HPT) maturation has not been extensively evaluated using neonatal MRI, even though both structures are visualized on MRI. [Hypothesis]: That signal intensity and volume of pituitary and thyroid (T) glands on MRI in neonates may be interrelated. [Study Type]: Retrospective. [Subjects]: In all, 102 participants. [Field Strength/Sequence]: 3.0T, T₁‐weighted pointwise encoding time reduction with radial acquisition (PETRA).[ Assessment]: The volume of interest of the anterior pituitary (AP), posterior pituitary (PP), and T on MRI were defined on T₁‐PETRA by two radiologists, and volumes of AP (AP_vol) and thyroid (T_vol) were calculated. Gestational age (GA), chronological age (CA), GA+CA, birth weight (BW), and thyroid function were recorded. Mean and maximum signal intensities of AP, PP, and T were normalized using signals from the pons and spinal cord as follows: signal ratio of anterior pituitary/pons (AP/pons), signal ratio of posterior pituitary/pons (PP/pons), and signal ratio of thyroid/cord (T/cord) T/cord, respectively. [Statistical Tests]: Correlations between signal intensity and volume measures and GA, CA, GA+CA, and BW were assessed using Pearson's correlation coefficient or Spearman's rank correlation coefficient. Thyroid function analysis and Tmean/cord, Tmax/cord, and T_vol were evaluated using the Steel–Dwass test. Results: APmean/pons correlated positively with GA (ρ = 0.62, P < 0.001) and BW (ρ = 0.74, P < 0.001), and negatively with CA (ρ = −0.86, P < 0.001) and GA+CA (ρ = −0.46, P < 0.001). PPmean/pons correlated positively with GA (ρ = 0.49, P < 0.001) and BW (ρ = 0.63, P < 0.001), and negatively with CA (ρ = −0.70, P < 0.001) and GA+CA (r = −0.38, P < 0.001). Tmean/cord correlated positively with GA (ρ = 0.48, P < 0.001) and BW (ρ = 0.55, P < 0.001), and negatively with CA (ρ = −0.59, P < 0.001) and GA+CA (ρ = −0.22, P = 0.03). AP_vol correlated positively with GA (ρ = 0.68, P < 0.001) and BW (ρ = 0.73, P < 0.001), and negatively with CA (ρ = −0.72, P < 0.001). T_vol correlated positively with GA (ρ = 0.50, P < 0.001) and BW (ρ = 0.61, P < 0.001), and negatively with CA (ρ = −0.54, P < 0.001). APmean/pons correlated positively with Tmean/cord (ρ = 0.61, P < 0.001). [Data Conclusion]: Signal and volume of pituitary and thyroid glands correlated positively with GA and BW, and negatively with CA in neonates. [Level of Evidence]: 4 [Technical Efficacy Stage]: