The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) play a pivotal role in neurotransmission and neuronal function. However, the effects of age and sex on AMPAR distribution in the living human brain and their associations with cognitive function remain unclear. The purpose of this study was to characterize age- and sex-dependent changes in brain AMPAR density and their relationships with cognitive performance in healthy individuals. Using a positron emission tomography tracer for AMPAR, [11C]K-2, we imaged 143 healthy participants aged 20–79 years. AMPAR density was evaluated using standard uptake value ratios with white matter as a reference. Age- and sex-related changes in AMPAR density were assessed across the brain, hierarchical clustering was used to characterize sex-dependent regional patterns of age-related change, and associations with cognitive performance were examined using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Age-dependent differences in cell-surface AMPAR density was observed across most brain regions. Females in their 50 s showed a surge in the upregulation of AMPAR density across brain. Hierarchical clustering revealed five distinct age-related trajectories, featuring marked sex-dependent regional patterns. AMPAR density was positively associated with cognitive performance; delayed memory correlated with whole-brain AMPAR density in both sexes, whereas other cognitive domains showed sex-specific regional associations. These findings demonstrated age- and sex-related alteration of AMPAR distribution and propose a model of AMPAR related synaptic aging in the living human brain over the life span. Furthermore, they may help to elucidate the pathophysiology of neurodegenerative disorders.

We propose a chest lesion case classification method for FDG-PET images using an attention-based Multiple Instance Learning (MIL) framework that effectively works in the commonly clinical situation with a small amount of strong teacher labeled (voxel-wise annotated) data and a larger amount of weakly labeled (cancer vs. normal) data. To detect small lesions in the large 3D PET images, the proposed method integrates multi-angle Maximum Intensity Projection (MIP) analysis with patch-based instance learning. 3D FDG-PET images are transformed into 2D MIP images from multiple observation directions. An attention-based MIL model is applied to each directional MIP image to enhance lesion-relevant instance features. Outputs from different directions are integrated via a 2.5D processing strategy, enabling the approximation of 3D lesion assessment at reduced computational cost. This design leverages MIP-based dimensionality reduction and attention mechanisms to achieve stable learning under weak supervision. Experimental results show that the proposed method achieved an average lesion case classification AUC of 0.892, outperforming both single-direction MIP-based analysis and a ResNet-50-based multi-angle MIP image analysis. In addition, attention-score heatmaps consistently highlighted lesion regions, indicating the potential for three-dimensional lesion localization through multi-directional attention integration. These results demonstrate that the proposed method has the potential to be an effective and efficient framework for lesioned FDG-PET image classification and lesion detection. The result also shows that the proposed method is suitable for developing an AI image diagnosis system with limited strong teacher labeled data.

AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and play a central role in synaptic function, with accumulating evidence in psychiatric disorders. Using [11C]K-2 PET to assess AMPAR-related signals in vivo, we examined whether regional standardized uptake value ratio (SUVR) patterns show diagnosis-aligned neighborhood organization beyond label-permutation chance. We analyzed the 219-participant cohort previously reported by Hatano et al., comprising healthy controls and individuals with autism spectrum disorder, bipolar disorder, major depressive disorder, or schizophrenia. Data were parcellated into 75-dimensional SUVR vectors using white-matter (WM) referencing (SUVR-WM) or whole-brain normalization (SUVR-WB). Uniform Manifold Approximation and Projection (UMAP) was applied unsupervised and with minimal supervision. Weakly supervised embeddings were compared with 1000 label-permuted embeddings using Calinski–Harabasz Index, Davies–Bouldin Index, and Silhouette scores with Bonferroni correction. Covariate associations were visualized. With minimal supervision, SUVR-WB produced diagnosis-aligned organization among the five groups and large improvements over permuted-label embeddings. SUVR-WM formed a horseshoe manifold aligned with mean SUVR-WM and age, with limited diagnostic clustering; age/sex residualization did not alter this geometry. These exploratory findings suggest that multiregional [11C]K-2 PET SUVR patterns show diagnosis-associated organization within a transdiagnostic sample, while emphasizing that normalization critically shapes visualization and that this approach is not an individual diagnostic test.

An accurate diagnostic method using biological indicators is critically needed for bipolar disorder (BD) and major depressive disorder (MDD). The excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) is a crucial regulator of synaptic function, and its dysregulation may play a central role in the pathophysiology of psychiatric disorders. Our recently developed positron emission tomography (PET) tracer, [11C]K-2, enables the quantitative visualization of AMPAR distribution and is considered useful for characterizing synaptic phenotypes in patients with psychiatric disorders. This study aimed to develop a machine learning-based method to differentiate bipolar disorder from major depressive disorder using AMPAR density. Sixteen patients with BD and 27 patients with MDD, all in depressive episodes, underwent PET scans with [11C]K-2 and structural magnetic resonance imaging. AMPAR density was estimated using the standardized uptake value ratio from 30 to 50 min after tracer injection, normalized to whole brain radioactivity. A partial least squares model was trained to predict diagnoses based on AMPAR density, and its performance was evaluated using a leave-one-pair-out cross-validation. Significant differences in AMPAR density were observed in the parietal lobe, cerebellum, and frontal lobe, notably the dorsolateral prefrontal cortex between patients with BD and patients with MDD during a depressive episode. The model achieved an area under the curve of 0.80, sensitivity of 75.0%, and specificity of 77.8%. These findings suggest that AMPAR density measured with [11C]K-2 can effectively distinguish BD from MDD and may aid diagnosis, especially in patients with ambiguous symptoms or incomplete clinical presentation.

This paper presents improved design of a singlelayer dual-band and wideband multi-ring microstrip antenna (MR-MSA) fed by an L-probe with outer separated L-shaped elements. The proposed MSA is composed of two outer separated L-shaped patches, an inner rectangular split ring patch, and a feeding L-shaped probe (L-probe) arranged on a single-layer dielectric substrate with a relatively large thickness of approximately 0.1 wavelengths. The outer patches and the inner patch are designed for lower and higher bands around 9.5 GHz and 13 GHz, respectively. The L-probe is used to excite the both patches as well as to obtain wideband performance together with the thick substrate. In order to realize wideband characteristics for the two bands, structural parameters of the proposed MSA are tuned by using an electromagnetic simulator ANSYS HFSS. The simulated results reveal that $\mathbf{2 0. 1 \%}$ and $\mathbf{1 8. 3 \%}$ fractional bandwidths less than -10 dB reflection for the lower and higher bands are achieved by the proposed MSA, respectively. It is also confirmed by the simulation that stable unidirectional radiation pattern and good broadside gain characteristics are also obtained.

Long COVID primarily presents with persistent cognitive impairment (Cog-LC), imposing a substantial and lasting global burden. Even after the pandemic, there remains a critical global need for diagnostic and therapeutic strategies targeting Cog-LC. Nevertheless, the underlying neural mechanisms remain poorly understood. Given the central role of synapses in brain function, investigation of synaptic molecular changes may provide vital insights into Cog-LC pathophysiology. In this study, we used [11C]K-2 PET to characterize the density of AMPA receptors (AMPARs) on the post-synaptic cell surface, which are crucial synaptic components in brain signalling. Statistical parametrical mapping was used to spatially normalize and apply independent t-test for a voxel-based comparison. We selected patients with Cog-LC (n = 30) based on Repeatable Battery for the Assessment of Neuropsychological Status assessed persistent cognitive impairment and healthy controls (n = 80) with no diagnosed neuropsychiatric disorders. The primary objective was to compare [11C]K-2 standardized uptake value ratio with white matter (SUVRWM) as a reference region between patients with Cog-LC and healthy controls, and to define the regional extent of differences. The secondary objective was to examine associations between [11C]K-2 SUVRWM and plasma concentrations of cytokines or chemokines. As an exploratory objective, we tested whether [11C]K-2 PET data could distinguish Cog-LC from healthy controls using a partial least squares based classification algorithm. A voxel-based comparison (P < 0.05, T > 1.66, one-tailed, false discovery rate control) and a volume of interests analysis (P < 0.05, Bonferroni multiple comparison) demonstrated that increased index of AMPAR density in large parts of the brains of patients with Cog-LC compared with that in healthy controls. A voxel-based correlation analysis also showed the brain regions where [11C]K-2 SUVRWM correlated positively with plasma TNFSF12 and negatively with plasma CCL2 concentrations. A partial least squares model trained on the index of AMPAR density data demonstrated high diagnostic accuracy, achieving 100% sensitivity and 91.2% specificity. [11C]K-2 PET signal represents the index of AMPAR density on the post-synaptic neural cell surface, not on the glial cell surface. A systemic increase in synaptic AMPARs across the brain may drive abnormal information processing in Cog-LC and, through excessive excitatory signalling, pose a risk of excitotoxic neuronal damage. We derived the hypothesis that [11C]K-2 PET would be helpful in establishing a diagnostic framework for Cog-LC and that antagonists for cell surface AMPARs, such as perampanel, would be a potential therapeutic target. These hypotheses should be investigated in future large-scale clinical studies.

This paper presents the design of a low-profile wideband ring microstrip antenna (MSA) fed by two L-probes with a rat-race coupler. The proposed antenna is composed of a square ring patch, two feeding L-shaped probes (L-probes), and a rat-race coupler on the ground plane. Since the two L-probes are excited by the rat-race coupler out-of-phase each other, unwanted radiation from the vertical portions of the two L-probes are suppressed. Therefore, cross polarization in H-plane pattern of the wideband MSA fed by an L-probe can be reduced. The design frequency of the proposed MSA is around 0.6 GHz. The rat-race coupler is miniaturized by folding the microstrip lines of the rat-race coupler so that the size of the rat-race coupler is smaller than the ring patch. In order to achieve wideband characteristics as well as low profile design, the structural parameters of the proposed MSA are tuned by using the electromagnetic simulator IE3D. The height of the designed wideband MSA is 62.0 mm. The simulated results reveal that 34.5% fractional bandwidth less than -7.4 dB reflection is achieved by the designed MSA. Very low cross polarization in H-plane pattern below -30 dB is also observed by the simulation.

Although the alteration of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) distribution is believed to underlie physiologic and pathologic neuronal function, there has been no modality to evaluate AMPARs in a living human. [11C]K-2, the PET tracer we previously developed, is the first and only technology, to the best of our knowledge, to visualize AMPAR densities in the living human brain. Despite its favorable kinetics as a PET tracer, the short half-life of 11C limits the potential of [11C]K-2. We recently developed an 18F-labeled PET tracer, [18F]K-40, which demonstrated AMPAR-specific binding properties and brain distribution similar to that of [11C]K-2 in preclinical studies. The purpose of this first-in-human study is to evaluate the properties of [18F]K-40 in humans and to compare the kinetics and PET images of [18F]K-40 with those of [11C]K-2. Methods: Five healthy volunteers were enrolled and underwent dynamic PET imaging using [18F]K-40 and [11C]K-2. The nondisplaceable binding potential (BPND) with white matter as the reference was calculated by Logan graphical analysis using tissue time-activity curves (TACs), and the total distribution volume of [18F]K-40 was calculated using plasma TACs. The intraindividual correlation between BPND values obtained for [18F]K-40 and [11C]K-2 was examined. To optimize the time window for PET scanning, BPND and SUV ratio were evaluated. Results: The tissue TACs of [18F]K-40 showed curves similar to those of [11C]K-2. Logan graphical analysis using plasma TACs revealed reversible binding of [18F]K-40. The BPND obtained with [18F]K-40 and [11C]K-2 significantly correlated in each corresponding region and showed very good correlation, which indicated that K-40, as observed with K-2, can provide PET images that reflect the amount of AMPARs. A good linear relationship was observed between BPND and the summation image of SUV ratios between 40 and 50 min after radiotracer injection. Conclusion: [18F]K-40, as with [11C]K-2, has favorable binding properties as an AMPAR PET tracer. Thus, [18F]K-40 could characterize AMPAR distribution in pathophysiologic conditions of the brain and facilitate the development of novel diagnostics of neuropsychiatric disorders.

Through a retrospective analysis of existing FDG PET-MRI images, we recently demonstrated that metformin increases the accumulation of FDG in the intestinal lumen, suggesting that metformin stimulates glucose excretion into the intestine. However, the details of this phenomenon remain unclear. We here investigate the detailed dynamics of intestinal glucose excretion, including the rate of excretion and the metabolism of excreted glucose, in both the presence and absence of metformin. We quantified intestinal glucose excretion using newly developed FDG PET-MRI-based bioimaging in individuals with type 2 diabetes, both treated and untreated with metformin. The metabolism of excreted glucose was analyzed through mass spectrometry of fecal samples from mice intravenously injected with 13C-labeled glucose. Continuous FDG PET/MRI image taking reveals that FDG is initially observed in the jejunum, suggesting its involvement in FDG excretion. Metformin-treated individuals excrete a significant amount of glucose (~1.65 g h–1 per body) into the intestinal lumen. In individuals not receiving metformin, a certain amount of glucose (~0.41 g h–1per body) is also excreted into the intestinal lumen, indicating its physiological importance. Intravenous injection of 13C-labeled glucose in mice increases the content of 13C in short-chain fatty acids (SCFAs) extracted from feces, and metformin increased the incorporation of 13C into SCFAs. A previously unrecognized, substantial flux of glucose from the circulation to the intestinal lumen exists, which likely contributes to the symbiosis between gut microbiota and the host. This flux represents a potential target of metformin’s action in humans. People with diabetes have high levels of a specific sugar, glucose, in the blood, which can cause health problems. Metformin is one of the most widely prescribed drugs to treat diabetes. However, it remains unclear how metformin works. We investigated metformin’s effect on glucose movement within the body. We found that more glucose moves inside the intestine in individuals taking metformin. The glucose is then digested by gut microbiota. These findings help us not only understand how metformin works but also reveal a relationship between humans and the gut microbiota which could be helpful for further development of diabetes treatments. Sakaguchi, Sugawara, Hosokawa, Ito, Morita, et al. quantify the effect of metformin on intestinal glucose excretion using fluorodeoxyglucose PET-MRI based bioimaging in individuals with type 2 diabetes. A substantial amount of glucose is excreted into the intestinal lumen, a process augmented by metformin, which is metabolized by gut microbiota into short-chain fatty acids.

This paper presents the design of a single-layer dual-polarized dual-band wideband ring microstrip antenna (MSA) fed by two L-probes with an inner folded patch. The proposed MSA consists of an outer square ring patch, an inner folded X-shaped ring patch, and two feeding L-shaped probes (L-probes) placed on a single-layer thick dielectric substrate. The two L-probes are orthogonally arranged to excite two orthogonal modes of the outer and inner patches independently. The design frequency bands are around 9.0 GHz and 13.0 GHz. A relative permittivity and a thickness of the substrate is 2.6 and 3.2 mm, respectively. The structural parameters are tuned by using ANSYS HFSS so that dual-band and wideband performance is achieved at the two design bands. The simulated results reveal that the -10 dB impedance fractional bandwidths are 9.3% for the lower band (8.6-9.4 GHz) and 23.7% for the upper band (11.5-14.5 GHz), with more than 10.6 dB port-to-port isolation. The radiation patterns are stable and unidirectional in both bands. These results verify that the proposed MSA provides good dual-polarized dual-band and wideband performance in a simple single-layer configuration.

Objective. Temporal changes in volumetric breast density (VBD) may serve as prognostic biomarkers for predicting the risk of future breast cancer development. However, accurately measuring VBD from archived x-ray mammograms remains challenging. In a previous study, we proposed a method to estimate volumetric breast density using imaging parameters (tube voltage, tube current, and exposure time) and patient age. This approach, based on a multiple regression model, achieved a determination coefficient (R2) of 0.868.Approach. In this study, we developed and applied machine learning models-Random Forest, XG-Boost-and the deep learning model Residual Network (ResNet) to the same dataset. Model performance was assessed using several metrics: determination coefficient, correlation coefficient, root mean square error, mean absolute error, root mean square percentage error, and mean absolute percentage error. A five-fold cross-validation was conducted to ensure robust validation.Main results. The best-performing fold resulted in R2values of 0.895, 0.907, and 0.918 for Random Forest, XG-Boost, and ResNet, respectively, all surpassing the previous study's results. ResNet consistently achieved the lowest error values across all metrics.Significance. These findings suggest that ResNet successfully achieved the task of accurately determining VBD from past mammography-a task that has not been realised to date. We are confident that this achievement contributes to advancing research aimed at predicting future risks of breast cancer development by enabling high-accuracy time-series analyses of retrospective VBD.

This paper presents the design of a double-layered varactor-loaded dual-band microstrip antenna (MSA) fed by an L-probe with a miniaturized shorted and slitted element. The proposed antenna consists of a miniaturized shorted and slitted patch on the top layer and a feeding L-probe arranged on the bottom layer of a double-layered dielectric substrate. Two varactor diodes are mounted on the patch near the short-circuited via hole and over the slit at the center, respectively. The bias circuit is located on the backside of the ground plane and is connected to the patch with another via. The frequency-tunable performance as well as radiation properties of the proposed MSA are simulated by the electromagnetic simulator Ansys HFSS. The simulated results reveal that two resonant frequencies of the proposed MSA are controlled in the range of 4.02 to 6.18 GHz for the lower mode and in the range of 6.80 to 9.06 GHz for the higher mode, respectively, when the capacitance of the two varactor is varied from 0.2 to 0.75 pF.

This paper presents the design of a single-layer dual-polarized dual-band and wideband microstrip antenna (MSA) fed by two L-probe with separated outer elements. The proposed MSA is composed of four separated outer L-shaped patches, an inner square patch, and two feeding L-shaped probe (L-probe) arranged orthogonally on a single-layer dielectric substrate with a relatively large thickness of approximately 0.1 wavelengths. The separated outer patches and the inner patch are designed for lower and higher bands around 9.5 GHz and 13 GHz, respectively. The two L-probes are used to excite two orthogonal modes of the outer and inner patches as well as to obtain wideband performance together with the thick substrate. In order to achieve dual-band and wideband characteristics, the structural parameters such as the sizes and spacings of the patches and the L-probes are tuned by using ANSYS HFSS. The simulated results reveal that 16.2% and 21.4% fractional bandwidths less than -10 dB reflection for the lower and higher bands are obtained by the proposed MSA, respectively. It is also confirmed by the simulation that sufficient port-to-port isolation characteristics more than 11.7 dB and stable unidirectional radiation patterns are observed for both bands.

Since the approval of disease-modifying drugs for Alzheimer's disease, the demand for amyloid positron emission tomography (PET) scans, which are crucial for determining treatment eligibility, is expected to increase significantly. We thus investigated the ability of an algorithm to predict amyloid accumulation from 18 F-fluorodeoxyglucose (FDG)-PET images for use in amyloid PET screening. We analyzed the images of 194 subjects with cognitive disorders who had undergone brain FDG-PET, amyloid PET using Pittsburgh compound-B ( 11 C-PiB), and MRI scans at Kindai University Hospital between 2011 and 2018. Among them, 108 subjects showed positive amyloid accumulation; the other 86 did not. For the 108 positive cases, the input values were the region of interest-based calculated from the automatic anatomical labeling template, which divides the brain into 120 regions, applied to the anatomically standardized FDG-PET images of each subject. We then used a support-vector machine (SVM) machine learning algorithm and conducted a 10-fold cross-validation to assess the algorithm's accuracy for predicting amyloid accumulation from FDG-PET images. We observed 81.5% accuracy, 78.5% sensitivity, 84.6% specificity, and an area under the curve (AUC) of 0.846 during training. The validation results for the trained model revealed 85.9% accuracy, 88.4% sensitivity, 81.0% specificity, and an AUC of 0.918. The performance of our algorithm to predict amyloid accumulation in subjects with cognitive disorders from 18 FDG-PET images is adequate for use in amyloid PET scan screenings.

This paper presents the design of a microstrip antenna (MSA) array fed by inclined slots on the broad wall of a rectangular waveguide with standing-wave excitation for 45degree inclined linear polarization. In order to suppress grating lobes radiated from an inclined slot array arranged at a spacing of one guided wavelength on the broad wall of the waveguide, it is proposed to place dual-ring parallelogram MSAs with a circumference of approximately 5 wavelengths on the inclined slot array with a dielectric substrate. In this paper, a 3-element standing-wave excitation array with the dual-ring parallelogram MSAs excited by the inclined slots on the broad wall of the waveguide for a 45-degree inclined linearly polarization is designed by using ANSYS HFSS. The design frequency is 11.2 GHz and an X-band standard rectangular waveguide is assumed for the array. The simulated results reveal that 45-degree linearly polarized radiation as well as a sharp main beam pattern with suppressed grating lobes can be obtained at the design frequency.

This paper introduces a compact and lightweight Microstrip Antenna (MSA) designed for GNSS systems operating in the L1 and L5 bands. The proposed antenna is a right-hand circularly polarized antenna with two feed points. To realize dual-resonance operation, a lumped-element circuit was implemented on the antenna element, in which a printed coil was employed as one of the components. It was confirmed by simulation results that the zenith gain is effectively improved by using a printed coil with a higher Qfactor compared to conventional lumped elements. Due to its small size and lightweight design, the proposed antenna is well-suited for GNSS applications in automobiles and drones.

This paper presents design of a circularly dual-polarized wideband microstrip antenna (MSA) fed by two orthogonally-arranged L-probes and a two-section hybrid coupler. The proposed antenna consists of a single-layer dual-polarized wideband MSA fed by two orthogonally-arranged L-probes and a two-section branch-line hybrid coupler arranged on the backside of the ground plane. In order to obtain wideband circularly dual-polarized performance, the structural parameters of the proposed MSA are tuned by using the electromagnetic simulator Mentor IE3D. Consequently, the single-layer dual-polarized wideband MSA with a center frequency of 4.00 GHz and the two-section hybrid coupler with a center frequency of 5.25 GHz are combined. The simulated results reveal that 24.2% fractional bandwidth of the proposed MSA with less than -10 dB reflection, more than 10 dB port-to-port isolation, and less than 3 dB broadside axial ratio characteristics is obtained. Good wideband and circularly-polarized performance of the proposed antenna is confirmed by the simulation.

This paper presents design of a wideband microstrip antenna (MSA) fed by an L-probe with double-layered radiation elements. The proposed antenna consists of double-layered square radiating patches and a feeding L-shaped probe (L-probe) above the ground plane. Air layers are assumed between the top patches and the ground plane. The radiating patches are excited by the L-probe with electromagnetic coupling. The design frequency of the proposed antenna is around 0.6 GHz. The structural dimensions such as the size and the height of the two patches and L-probe are tuned by using the electromagnetic simulator. The total height of the proposed antenna is set to 50 mm. The simulated results reveal that triple resonance characteristics with a fractional bandwidth of 43.0% of less than -7.4 dB reflection (VSRW = 2.5) are observed. In comparison with the conventional MSA with a single-layer radiating patch and almost the same height, the fractional bandwidth and the broadside gain in the above bandwidth are improved by approximately 5.6% and by at most 0.6 dBi, respectively. It is also confirmed by the simulation that the cross polarization of the H-plane pattern is reduced by about 3 dB at the lower frequency in the bandwidth.

This paper presents design of a wideband ring microstrip antenna (MSA) fed by two L-probes with a rat-race coupler. The proposed antenna consists of a square ring patch, two feeding L-shaped probes (L-probes) to excite the ring patch, and a rat-race coupler on the ground plane. The two L-probes are fed by the rat-race coupler differentially and unwanted radiations from the vertical portions of the two L-probes are cancelled out each other. Therefore, cross polarization in H-plane pattern of the proposed antenna, which is a typical phenomenon of the wideband MSA fed by an L-probe, can be reduced. The design frequency of the proposed MSA is around 0.6 GHz. In order to make the ring patch and the rat-race coupler equal in size, the rat-race coupler is miniaturized by bending the rat-race circuit. To achieve wideband characteristics at around the design frequency, dimensions of the proposed antenna are tuned by using electromagnetic simulator IE3D. It is confirmed by the simulation that fractional bandwidth less than -7.4 dB reflection is approximately 34%. Very low cross polarization in H-plane pattern below -30 dB is also confirmed by the simulation.