National Institutes for Quantum and Radiological Science and Technology
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Native receptor–targeted chemogenetics elucidates the role of cerebellar mGlu1 in freely moving mice
No full textHigher brain functions such as learning and memory are governed by neurotransmitter receptors at synapses. Establishing causal links between receptor function and behavior requires tools that enable precise manipulation of endogenous receptors in vivo. Genetic loss-of-function approaches enable brain region- and cell-type-specific manipulation of receptor function. However, these approaches lack adequate temporal resolution for the analysis of receptor function and often cause severe phenotypes. In contrast, pharmacological approaches enable reversible and acute inhibition of receptor function but lack spatial specificity. To overcome these limitations, we develop a novel chemogenetic method that enables high spatiotemporal control of native receptors. This approach employs a designer inhibitor and an inhibitorinsensitive mutant receptor pair to enable transient and cell-type-specific inhibition of endogenous receptor signaling in vivo, while preserving intrinsic function of the target receptor.As a proof of concept, we focused on metabotropic glutamate receptor subtype 1 (mGlu1), a G protein–coupled receptor implicated in motor function. Previous mGlu1-knockout studies in mice have shown severe motor defects, precluding detailed behavioral analysis. Thus, a new strategy that enables selective and reversible inhibition of mGlu1 without disrupting its physiological function is required. Based on the X-ray crystal structure of mGlu1 in complex with FITM, an mGlu1-selective inhibitor, we designed FITM derivatives and mGlu1 mutants. Cell-based assays identified a designer inhibitor–mutant receptor pair that selectively inhibits wild-type mGlu1 without affecting the mutant receptor, while preserving its responsiveness to glutamate. To extend this strategy in vivo, we generated genetically modified mice that express the inhibitor-insensitive mutant mGlu1 throughout the brain but retain wild-type mGlu1 in cerebellar Purkinje cells. Administration of the designer inhibitor to these mice enabled selective inhibition of mGlu1 in Purkinje cells. Behavioral analyses using accelerated rotarod tests revealed that cerebellar mGlu1 is essential for motor learning during developmental stages. Taken together, these results demonstrate that this novel chemogenetic approach enables causal dissection of receptor function in defined neural circuits in vivo.NEURO2026conference poste
Safety of MRI Examinations Under Sedation: A Nationwide Survey in Japan.
No full textMRI is performed under sedation for patients requiring immobility or for those already sedated for clinical management. Although specialist guidelines advocate for anesthesiologist-led care, non-anesthesiologist-led adult sedation is a common practice worldwide. Furthermore, the increase in risk attributable to sedation has not been quantified.journal articl
Everything everywhere all at once: Exploring the richness of visual experience beyond words.
No full textOur visual experience feels rich and detailed, yet studies implied that it is limited to 3~4 items at a glance. These studies focus on small, easy-to-label details in the stimuli, without exhausting all we could experience. Here, we consider both semantic labels and perceptual qualities we have no words for. For each of 100 natural scenes, we synthesised an image with matched summary statistics. In Experiment 1 (N = 100), we collected semantic descriptions for each image, and evaluated whether each image pair is semantically-equivalent. Using the semantically-equivalent pairs, in registered Experiment 2, we will perform a perceptual task on online participants (N = 112-448) and in-lab participants with immersive displays (N = 28-112). Depending on the results, we will perform a control experiment (Experiment 3, N = 360) to characterise possible roles of gists in Experiment 2. Overall, we will investigate how rich our experience can be beyond words.journal articl
Deep-brain thermo-endomicroscopy
No full textSubtle deviations in biophysical parameters, particularly temperature, within deep-brain regions exert substantial effects on whole-body homeostasis and metabolism. However, the underlying mechanisms remain poorly understood because cellular-resolution measurements of these parameters in the deep brain have been technically inaccessible. Here, we present a lensless fiber-optic quantum-sensing endomicroscopy that enables cellular-resolution temperature mapping in the mouse deep brain. A microwire-coupled, lensless fiber bundle permits simultaneous temperature readout from optically detected magnetic resonance spectra of >50 fluorescent nanodiamonds, achieving cellular resolution (4.88 μm) with a precision of 0.49 ℃ (minimum precision, 0.18 ℃) within a 0.28 mm2 field of view. We demonstrated temperature mapping of multiple brain depths in head-fixed and vigorously behaving mice subjected to nociceptive stimulation, detecting lower temperatures during anesthesia compared to the awake state in ventromedial hypothalamic nucleus (VMH) at a 5 mm depth. These mappings reveal that spatio-temporal temperature distribution and its anesthesia-dependent reduction are heterogeneous rather than uniform in VMH. This endomicroscopy provides a promising platform to dissect how deviations in biophysical parameters modulate deep-brain function.journal articl
重粒⼦線治療装置⽤超電導シンクロトロンの開発
No full text近年、医療分野における放射線治療技術は⾶躍的な進化を遂げており、特に重粒⼦線や陽⼦線を⽤いた⾼精度な治療法は、がん治療における新たな選択肢として注⽬を集めている。これらの⾼度な治療技術を⽀える基盤として、加速器や照射装置の⾼性能化が不可⽋であり、その中でも「超電導技術」は、装置の⼩型化・省エネルギー化を実現する鍵として、極めて重要な役割を担っている。本発表では、放射線治療装置への超電導技術の応⽤に焦点を当て、最先端の研究成果を開発事例とともに広く紹介する。第4回超電導応⽤研究会シンポジウムconference presentatio
Progress on development of EC system for JT-60 SA, ITER and DEMO
No full textThe JT-60SA electron cyclotron (EC) system utilizes three frequencies: 138 GHz, 110 GHz, and 82 GHz, for plasma breakdown, heating, and current drive. During the first plasma operation campaign in 2023, plasma operation was performed using two EC systems, one with a single-frequency 110 GHz gyrotron and one with a triple-frequency gyrotron. From the next operation campaign, two more triple-frequency gyrotrons will be added, increasing the EC system to four systems. New high-voltage power supplies were procured from Europe for these new gyrotrons. These high-voltage power supplies consist of one main power supply and two sets of anode and body power supplies. Initial operation was conducted using the new triple-frequency gyrotrons, achieving simultaneous operations. Thus, four-system configuration has been completed, consisting of one new power supply and two existing power supplies. All four waveguide transmission lines are constructed with large-diameter waveguides with a diameter of 60.3 mm, with transmission distances of approximately 60 m or 110 m. The new two axis EC launchers consisting of two moving mirrors and one fixed mirror will be installed, enabling scanning at poloidal angles (-40° to +20°) and toroidal angles (-5° to +25°). Thus, the launchers will be connected to two transmission lines, making them possible to inject a total of more than 3 MW of power aiming at from the plasma center to the edge.For ITER EC system, QST has manufactured eight sets of 170 GHz/1 MW gyrotrons, completed factory acceptance tests, and shipped all of them to ITER. Assembly/installation works are currently underway inside ITER RF building, and two gyrotrons have been installed. One of the gyrotrons is currently being prepared for on-site acceptance test. ITER baseline has been upgraded, and the EC systems used for first plasma phase will be increased from the initial 24 systems to 48 systems. In future D-T operations, 80 systems will be utilized. QST will procure an additional 20 gyrotrons by the time of first plasma.Additionally, QST is conducting research activities using a multi-frequency gyrotron at 170 GHz, 203 GHz, and 236 GHz in preparation for a future DEMO.Korea-Japan Workshop on Physics and Technology of Heating and Current Driveconference presentatio
Comparison of supine and upright postures in carbon ion radiotherapy for pancreatic cancer: An in silico planning study
No full textBackground: Conducting carbon ion radiotherapy (CIRT) in upright posture has several technical advantages over that in conventional supine posture for pancreatic cancer treatment. However, few studies have investigated effects of upright positioning on anatomy and CIRT dose distributions.Purpose: This study compared anatomy and dose distributions in CIRT for pancreatic cancer between supine and upright postures.Methods: Fourteen pairs of computed tomography (CT) images obtained from asymptomatic volunteers in these postures were analyzed. Clinical target volume (CTV), organs-at-risk (OARs), and gastrointestinal gas contours were delineated within a planning volume for each CT image, and a CIRT dose distribution was calculated. The anatomical differences between these postures were evaluated by comparing volumes and 3D rendered images of the contours, while the dosimetric differences were assessed with 12 dosimetric metrics. Moreover, a proximal overlap volume of the OARs and possible change in water-equivalent path length due to gastrointestinal gas were calculated for all coplanar beam angles to compare ranges of applicable beam angles and potential range uncertainty between these postures.Results: The bowel contour volumes in the upright posture were more than 46% smaller than those in the supine posture because the bowel was shifted. The upright posture provided a smaller dose to the bowel and higher dose coverage to the CTV than the supine posture. The possible water-equivalent path length changes due to the stomach and duodenum gas decreased at most beam angles in the upright posture.Conclusions: The upright CIRT had several anatomical and dosimetric advantages for pancreatic cancer treatment over conventional supine CIRT. This technique will be useful in applying the patient-specific beam angle arrangement and precise dose delivery with reduced range uncertainty.journal articl
標的α線放出核種治療における抗腫瘍効果の分子メカニズム
No full textTargeted α-radionuclide therapy (TAT) is a systemic therapy for cancer with cancer-targeting compounds conjugated with α-emitters. Since the linear energy transfer (LET) of α-particle is high, relative biological effectiveness is higher than low LET radiation, such as X-ray and β-particle, and the damage to the normal tissues surrounding the tumor is minimal because path-length of α-particle is short (a few cells). TAT has demonstrated remarkable therapeutic effects in patients, attracting significant attention from physicians and researchers around the world. In particular, a paper published in 2016 has shown that disseminated tumors in a patient with castration-resistant prostate cancer disappeared following treatment with an 225Ac labeled prostate specific membrane antigen ligand. So how is the powerful antitumor effect of TAT induced? The molecular mechanism of the antitumor effect of radiation is well studied in external beam radiation therapy (EBRT). However, because EBRT and TAT are fundamentally different in terms of dose-rate, irradiation uniformity, and exposure time, it is difficult to extrapolate the knowledge of EBRT to TAT. Compared to research on the development of new TAT agents, studies focusing on the radiobiology of TAT are limited, and the detailed mechanisms of its antitumor effects remain poorly understood. We have developed α-emitting meta-[211At]astato-benzylguanidine ([211At]MABG) as a novel TAT agent, and investigated radiobiological responses caused by [211At]MABG using comprehensive gene expression analysis. Here, we would like to introduce the mechanism of antitumor effects on TAT based on our studies of [211At]MABG.journal articl
軟X線多層膜回折格子を用いた300～1100 eV域において高spectral fluxを呈する平面結像型回折格子分光器の開発
No full text軟X線平面結像型発光分光器の高分析感度を実現するためには，spectral flux と呼ばれる回折効率と光源から検出器に到達する光束の積で表される量を増加させる必要がある。このため，300～1100 eV領域を測定対象とするラミナー型の格子溝を持つの回折格子の表面にW/B4C多層膜構造した球面回折格子を設計製作し，回折効率を測定したので報告する．設計では刻線密度1/σを3600 本/mmと仮定した。最適化計算の結果，入射角 αは86.70°となった。この多層膜回折格子とほぼ同じエネルギー領域を対象に過去に設計した回折格子（1/σ︓2400本/mm， 表面︓Au，α: 88.65° ）の場合の計算による比較では、今回設計した多層膜回折格子のspectral fluxは、平均で約5倍増加していることが判った。発表ではKEK放射光実験施設(PF)の反射率測定ビームラインBL-12Aでの多層膜回折格子の絶対回折効率の測定についても述べる。第39回日本放射光学会年会・放射光科学合同シンポジウムconference presentatio
GATE 10 Monte Carlo particle transport simulation: I. Development and new features
No full textWe present GATE version 10, a major evolution of the open-source Monte Carlo simulationapplication for medical physics, built on Geant4. This release marks a transformative evolution,featuring a modern Python-based user interface, enhanced multithreading and multiprocessingcapabilities, the ability to be embedded as a library within other software, and a streamlined frameworkfor collaborative development. In this Part 1 paper, we outline GATE’s position among otherMonte Carlo codes, the core principles driving this evolution, and the robust development cycleemployed. We also detail the new features and improvements. Part 2 will focus on the architecturalinnovations and technical challenges. By combining an open, collaborative framework withcutting-edge features, such a Monte Carlo platform supports a wide range of academic and industrialresearch, solidifying its role as a critical tool for innovation in medical physics.journal articl