一般口演（Oral）

Oral Brain Activity Measurement 一般口演脳活動測定法

7月25日（木）14:40～14:55　第8会場（朱鷺メッセ　3F　303+304） 1O-08a1-1 磁性ナノプローブを用いたカルシウム応答型fMRI Satoshi Okada（岡田智）^1,2，Benjamin B Bartelle（Bartelle B Benjamin）³，Nan Li（Li Nan）³，Vincent Breton-Provencher（Breton-Provencher Vincent）^4,5，Jiyoung J Lee（Lee J Jiyoung）³，Elisenda Rodriguez（Rodriguez Elisenda）³，James Melican（Melican James）³，Mriganka Sur（Sur Mriganka）^4,5，Alan Jasanoff（Jasanoff Alan）^3,4,6 ¹産総研健康工学 ²JSTさきがけ ³Dept Bio Eng, MIT, Cambridge, USA ⁴Dept Brain Cog Sci, MIT, Cambridge, USA ⁵Picower Inst for Learn Mem, MIT, Cambridge, USA ⁶Dept Nuc Sci Eng, MIT, Cambridge, USA Fluctuations in extracellular calcium ions (Ca²⁺) are closely locked to neural activity because of the influx of Ca²⁺ into presynaptic neurons during synaptic transmission in the brain. An extracellular calcium probe could therefore become a useful tool for resolving spatiotemporal patterns of neural activity, while bypassing limitations of conventional functional magnetic resonance imaging (fMRI) readouts based on blood flow. Here we present magnetic calcium-responsive nanoparticles (MaCaReNas) that can be detected by MRI. The MaCaReNa probe consists of two components: one is an anionic lipid coated magnetic nanoparticle, which can be detected at nanomolar levels by T₂-weighted MRI; the other is a C2 domain of synaptotagmin, which is a component of the synaptic neurotransmitter-release machinery that responds to sub-millimolar changes in [Ca²⁺]. C2 domains promote tethering the anionic lipid surface of the magnetic nanoparticles in a calcium-dependent manner. The consequent clustering of the nanoparticles causes substantial enhancement in T₂ relaxation, making them appear darker in T₂-weighted MRI. Atomic force microscopy and dynamic light scattering directly revealed calcium-dependent changes in the clustering state of the probe. A titration curve of T₂ relaxation rate vs. [Ca²⁺] demonstrates MaCaReNas respond to [Ca²⁺] changes in the 0.1-1.0 mM range, suitable for monitoring extracellular calcium signaling processes in the brain. Responses are reversible and relatively fast, taking place with a time constant of about 5 s. To validate the probes in vivo, they were injected into the dorsal striatum of rats in conjunction with manipulations designed to test calcium sensitivity. Chemically-induced brain stimulation in the presence of the probe produced nearly 20% of signal changes, consistent with the results obtained in vitro. Signal changes were not observed in the presence of non-functional probe analogs or mock stimulation conditions. MaCaReNas also permit detection of striatal responses to electrical stimulation of medial forebrain bundle, which is a part involved in reward. These results constitute the first demonstration of calcium-dependent fMRI in the living brain, and establish a precedent for application of nanoparticle-based MRI probes to functional neuroimaging.		7月25日（木）14:55～15:10　第8会場（朱鷺メッセ　3F　303+304） 1O-08a1-2 IDH変異型グリオーマにおけるMRSによる2HG測定 Manabu Natsumeda（棗田学）¹，Hironaka Igarashi（五十嵐博中）²，Kunio Motohashi（Motohashi Kunio）^1,2，Akiyoshi Kakita（柿田明美）³，Tsutomu Nakada（中田力）²，Yukihiko Fujii（藤井幸彦）¹ ¹新潟大学　脳研究所　脳神経外科 ²新潟大学　脳研究所　統合脳機能研究所 ³新潟大学　脳研究所　病理学分野 Introduction. Accumulation of 2-hydroxyglutarate (2HG) is known to occur in isocitrate dehydrogenase (IDH)-mutant gliomas. Detection 2HG is possible by 3.0-tesla single voxel magnetic resonance spectroscopy (SVMRS), thus making non-invasive diagnosis of IDH-mutant gliomas possible. We set out to determine whether reliable detection of 2HG is feasible in IDH-mutant World Health Organization (WHO) grade 2 through 4 gliomas. Methods. A total of 110 patients harboring WHO grade 2 through 4 gliomas underwent preoperative MRS evaluation to detect 2HG and other metabolites. MRI/1H-MRS analysis was performed using a 3.0-tesla system (Signa LX, General Electric). First, proton density images (Fast Spin Echo; TR/TE = 5000/40; FOV: 20 x 20 mm; matrix: 256 x 256; slice thickness: 5 mm; inter slice gap: 2.5 mm) were taken. The slice with the largest depiction of tumor on proton density images was selected for SVMRS. A point-resolved spectroscopic sequence (PRESS), with chemical-shift-selective water suppression was used with the following parameters: (TR: 1.5 s; TE: 30 ms; data point 512; spectral width 1000 Hz; number of acquisitions: 128 -196; volume of interest (VOI): 12-20 x 12-20 x 12-20 mm). Presence of IDH-mutations was determined by IDH1 R132H immunohistochemical analysis and DNA sequencing of surgically obtained tissues. Results. Thirty seven out of 66 (56.1%) grade 2/3 gliomas and 6 out of 44 (13.6%) GBs were IDH-mutant. IDH-mutant gliomas exhibited significantly higher accumulation of 2HG (median 5.029mM for grade 2/3 gliomas, 3.191 mM for GBs vs. 0.000 mM for IDH-wildtype grade 2/3 and GBs, both p <0.0001, Mann-Whitney test). Also, lower levels of Glx (the sum of Glutamine and Glutamate) were detected in IDH-mutant grade 2 through 4 gliomas and Glutathione in IDH-mutant grade 2/3 gliomas. A cutoff of 2HG = 1.489 mM achieved 100% sensitivity and 68.4% specificity and 83.3% sensitivity and 92.6% specificity in determining IDH-mutation in grade 2/3 gliomas and GBs, respectively. Grade 2/3 gliomas with high 2HG accumulation had significantly longer overall survival than those with low 2HG accumulation (p = 0.02, Log Rank test). Discussion. Non-invasive and reliable detection of 2HG in IDH-mutant grade 2 though 4 gliomas was possible by 3.0-tesla SVMRS.

7月25日（木）15:10～15:25　第8会場（朱鷺メッセ　3F　303+304） 1O-08a1-3 大脳皮質を透過する静磁界を用いた非侵襲的脳信号計測技術の開発 Osamu Hiwaki（樋脇治），Tatsuhiko Masuda（増田達彦），Tatsuro Esaki（江崎達朗）広島市立大学情報科学研究科 Noninvasive techniques to measure brain activity are still unsatisfactory for revealing the human brain functions. Conventional techniques for noninvasive measurement of brain activity are burdened by critical limitations in spatial or temporal resolution. In this study, we propose a noninvasive brain function measurement with high spatiotemporal resolution using a static magnetic field emitted from a magnet, which we term as transcranial magnetoencephalography (TME). A ferrite magnet with a diameter of 5 mm and a thickness of 2 mm was placed on the head. A magnetic field irradiated from the magnet, which passes across the cerebral cortex under the skull, was measured by a highly sensitive magnetometer at a distance of 25 mm from the magnet on the surface of the head. We made a 16-channel TME system. In order to confirm the validity of the TME technique, we tried to measure the somatosensory evoked signals with the TME system following stimulation of the median nerve. An electrical stimulation was applied to the median nerve of the left wrist. The somatosensory evoked TME signals were obtained by an average of 300 responses. The TME signals were measured at 16 points with the 16-channel TME system. The midpoint between each magnet and magnetometer was adopted as the measurement point. The somatosensory evoked TME signals were successfully obtained. The largest signal was observed at CP4 of the international 10-20 system, overlying the hand area of the somatosensory cortex contralateral to the stimulated side when the magnetic field was directed from the anterior to the posterior. This somatosensory evoked TME signal at CP4 began to deviate with a latency of about 30 ms and the maximum amplitude was about 5 nT, whereas the amplitude of the signal at the same location with the magnetic field in the opposite direction was about 1 nT. The results indicate that TME signal response is not only fast and localized but also vectorial. This study is the first finding that the dynamic brain signals can be detected noninvasively by measuring the static magnetic field passing across the cerebral cortex. It is expected that the TME technique becomes a breakthrough as a noninvasive imaging technique of human brain activity with high spatial and temporal resolution.		7月25日（木）15:25～15:40　第8会場（朱鷺メッセ　3F　303+304） 1O-08a1-4 針状ダイヤモンド電極による局所薬物動態の生体内実時間マイクロセンシングシステム Genki Ogata（緒方元気）¹，Kai Asai（浅井開）²，Seishiro Sawamura（澤村晴志朗）¹，Hiroyuki Kusuhara（楠原洋之）³，Yasuaki Einaga（栄長泰明）²，Hiroshi Hibino（日比野浩）¹ ¹新潟大院医歯分子生理 ²慶應大理工化学 ³東京大院薬分子薬物動態 In neuroscience studies, it is crucial to detect local concentrations of systemically administered drugs in different organs or tissues of live animals. Conventional methods do not accomplish this real-time monitoring because they require considerable analyte quantities and have low sampling rates. They also cannot pursue changes of functions in target cells or tissues over time. To address this subject, we developed a system equipped with two different sensors. One is composed of a needle-type of boron-doped diamond electrode with tip diameter ~40 μm. This sensor electrochemically detects behavior of drug concentrations with a time resolution of ~5 seconds. The other is a glass microelectrode that is regularly used for electrophysiological experiments. We first tested bumetanide, a diuretic that antagonizes Na⁺,K⁺,2Cl^--cotransporter and is sometimes applied to patients with epilepsy. This drug can induce deafness as an adverse event. In the guinea-pig cochlea, changes of bumetanide concentration and the extracellular potential underlying hearing were simultaneously measured in real time. We further examined an antiepileptic drug lamotrigine, which blocks Na⁺ channel, in the rat brain, and tracked its kinetics and at the same time the local field potentials elicited by neuronal activity. The actions of an anticancer drug, doxorubicin, was also monitored in vivo. Our microsensing system may detect pharmacological and physiological responses of other chemical compounds and contribute not only to advances in basic neuroscience research but also to the development of effective medical therapies for neuronal diseases.