RESUMEN
Organic material-based thermal switch is drawing much attention as one of the key thermal management devices in organic electronic devices. This study aims at tuning the switching temperature (TS) of thermal conductivity by using liquid crystalline block copolymers (BCs) with different order-order transition temperature (Ttr) related to the types of mesogens in the side chain. The BC films with low Ttr of 363 K and high Ttr of 395 K exhibit reversible thermal conductivity switching behaviors at TS of â¼360 K and â¼390 K, respectively. The BC films also exhibit thermal conductivity variation originating from the anisotropy of the internal structures: poly(ethylene oxide) domains and liquid crystals. These results demonstrate that the switching behavior is attributed to an order-order transition between BC films with vertically arranged cylinder domains and the ones with ordered sphere domains. This highlights that BCs become a promising thermal conductivity switching material with tailored TS.
RESUMEN
Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a "redox map". The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging.
Asunto(s)
Antioxidantes/metabolismo , Encéfalo/metabolismo , Espectroscopía de Resonancia por Spin del Electrón/métodos , Glutatión/metabolismo , Animales , Ácido Ascórbico/metabolismo , Encéfalo/diagnóstico por imagen , Óxidos N-Cíclicos/administración & dosificación , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacocinética , Glutatión/antagonistas & inhibidores , Imagen por Resonancia Magnética/métodos , Masculino , Maleatos/administración & dosificación , Maleatos/farmacología , Ratones Endogámicos C57BL , Estructura Molecular , Oxidación-Reducción/efectos de los fármacos , Distribución TisularRESUMEN
A low impedance transceiver circuit consisting of a transmit-receive switch circuit, a class-D amplifier and a transimpedance amplifier (TIA) was newly designed and tested for a nitrogen-14 NQR. An NQR signal at 1.37MHz from imidazole was successfully observed with the dead time of ~85µs under the high Q transmission (Q~120) and reception (Q~140). The noise performance of the low impedance TIA with an NQR probe was comparable with a commercial low noise 50Ω amplifier (voltage input noise: 0.25 nV/Hz) which was also connected to the probe. The protection voltage for the pre-amplifier using the low impedance transceiver was ~10 times smaller than that for the pre-amplifier using a 50Ω conventional transceiver, which is suitable for NQR remote sensing applications.
RESUMEN
This study describes a technique to clean amplitude modulation (AM) noise of RF transmission waves, which is used to observe the sub-GHz CW-EPR spectrum. An RF transmitter amplifier that has the function of cleaning AM noise has been developed. Cleaning of the AM noise was owing to saturation of the output at the amplifier. Three stages of the amplifiers in series could effectively suppress the AM noise to about -176 dBc/Hz and -183 dBc/Hz at offset frequency of 10 kHz and 100 kHz, respectively at the carrier frequency of 750 MHz and the output power of 29 dBm. Since phase modulation (PM) noise is suppressed by phase sensitive detection, the AM noise in the transmission is dominant cause of the noise in the sub-GHz CW-EPR absorption spectrum using a reflection bridge, which depends on the quality factor of the resonator and the power of the RF transmission. The additive phase modulation (PM) noise of this amplifier was -171 dBc/Hz at an offset frequency of 100 kHz, which indicated that the frequency modulation (FM) of the transmission wave was not distorted with this amplifier. Therefore, conventional CW-EPR spectrometers that typically require FM for automatic frequency control or automatic tunning control can use this technique to increase sensitivity.
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Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). Human colon cancer HCT116 xenografts were used in the mice. We used 3-carbamoyl-PROXYL (3CP) as a paramagnetic and redox status probe for the EPRI of tumors. The first EPRI was followed by the intraperitoneal administration of buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, or X-ray irradiation of the tumor. A second EPRI was performed on the following day. Autoradiography was performed after the second EPRI. After imaging, the tumor sections were evaluated by histological analysis and the amount of reducing substances in the tumor was measured. BSO treatment and X-ray irradiation significantly decreased the rate of 3CP reduction in tumors. Redox maps of tumors obtained from EPRI can be compared with tissue sections of approximately the same cross section. BSO treatment reduced glutathione levels in tumors, whereas X-ray irradiation did not alter the levels of any of the reducing substances. Comparison of the redox map with the autoradiography of [18F]FDG revealed that regions with high reducing power in the tumor were active in glucose metabolism; however, this correlation disappeared after X-ray irradiation. These results suggest that the novel compact and portable EPRI device is suitable for multimodal imaging, which can be used to study tumor redox status and therapeutic efficacy in cancer, and for combined analysis with other imaging modalities.
Asunto(s)
Estudios de Factibilidad , Fluorodesoxiglucosa F18 , Glucosa , Imagen Multimodal , Oxidación-Reducción , Animales , Humanos , Ratones , Fluorodesoxiglucosa F18/metabolismo , Glucosa/metabolismo , Imagen Multimodal/métodos , Espectroscopía de Resonancia por Spin del Electrón/métodos , Butionina Sulfoximina/farmacología , Autorradiografía , Células HCT116 , Neoplasias del Colon/metabolismo , Neoplasias del Colon/diagnóstico por imagen , Neoplasias del Colon/patología , Radiofármacos/metabolismo , Tomografía de Emisión de Positrones/métodos , Ensayos Antitumor por Modelo de Xenoinjerto , Glutatión/metabolismo , Ratones DesnudosRESUMEN
2,2,6,6-Tetramethylpiperidin-N-oxyl (TEMPO)-type nitroxides are susceptible to bioreduction, leading to a loss of radical properties. Although it has been reported that the steric and electronic environments around the N-O moiety of nitroxides affect the reduction, how the relative configuration of nitroxide derivatives alters it is unclear. In this study, we investigated the effect of diastereomers on the radical properties of C2- and C4-disubstituted TEMPO-type nitroxides. We succeeded in isolating the diastereomers of the studied nitroxides for the first time. In addition, we compared the reactivities of nitroxide derivatives with different substituents at the C2 and C4 positions toward ascorbate reduction. We found that the bulky substituents at both C2 and C4 and the electronic effect of C4 affected the reduction of the isomers. C2- and C4-disubstituted nitroxides were administered to mice for electron spin resonance imaging to assess bioreduction in the brain. Similar to the reactivity to reduction in vitro, a difference in the bioreduction of diastereomers was observed in brain tissues. Our research strongly indicates that bioreduction can be controlled by changing the relative configuration, which can be used in the design of nitroxide derivatives for biological applications.
Asunto(s)
Ácido Ascórbico , Óxidos N-Cíclicos , Ratones , Animales , Espectroscopía de Resonancia por Spin del Electrón/métodos , Óxidos de Nitrógeno , Marcadores de Spin , Oxidación-ReducciónRESUMEN
The performance of rectangular radio frequency (RF) coils capable of being used to detect nuclear quadrupole resonance (NQR) signals from blister packs of medicines has been compared. The performance of a fixed-pitch RF coil was compared with that from two variable-pitch coils, one based on a design in the literature and the other optimized to obtain the most homogeneous RF field over the whole volume of the coil. It has been shown from (14)N NQR measurements with two medicines, the antibiotic ampicillin (as trihydrate) and the analgesic medicine Paracetamol, that the latter design gives NQR signal intensities almost independent of the distribution of the capsules or pills within the RF coil and is therefore more suitable for quantitative analysis.
Asunto(s)
Acetaminofén/química , Ampicilina/química , Embalaje de Medicamentos , Espectroscopía de Resonancia Magnética/instrumentación , Ondas de Radio , Medicamentos Falsificados/químicaRESUMEN
The pulsed nuclear quadrupole resonance method was used to search for the NQR frequencies of (14)N in methamphetamine hydrochloride based on quantum chemical estimates. The NQR spectrum peaks were observed at ν(+)=1.217 MHz and ν(-)=0.654 MHz. The temperature dependences of the NQR frequencies and relaxation properties were investigated for the purpose of stand-off sensing of illicit drugs. The NQR frequency shifts for ν(+) and ν(-) were approximately 0.22 kHz/K and 0.10 kHz/K, respectively, around room temperature. The spin-lattice relaxation times and spin-phase memory times were 8.3 ms-10.0 ms and 0.65 ms -0.86 ms, respectively.
RESUMEN
A simulation method to estimate the detection efficiency of nuclear quadrupole resonance (NQR) was proposed for optimizing a sensing probe operating at radio frequencies (RFs). It first calculates the transmitted magnetic field from the probe coil to the target sample. The nuclei make quadrupole resonance by it. We considered this nonlinear reaction to estimate NQR emission by the nuclei. Then the received NQR signal intensity from the sample at the probe coil. We calculated the efficiency by testing two different probe types (solenoid and gradiometer) and by changing the relative positions of the probe and sample. The simulation results were in good agreement with the experimental results.
RESUMEN
Electron paramagnetic resonance imaging using nitroxides is a powerful method for visualizing the redox status modulated by oxidative stress in vivo. Typically, however, data acquisition times have been too slow to obtain a sufficient number of projections for three-dimensional images, when using continuous wave-electron paramagnetic resonance imager in small rodents, using nitroxides with comparatively short T(2) and a half-life values. Because of improvements in imagers that enable rapid data-acquisition, the feasibility of three-dimensional electron paramagnetic resonance imaging with good quality in mice was tested with nitroxides. Three-dimensional images of mice were obtained at an interval of 15 sec under field scanning of 0.3 sec and with 46 projections in the case of strong electron paramagnetic resonance signals. Three-dimensional electron paramagnetic resonance images of a blood brain barrier-permeable nitroxide, 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl, in the mouse head clearly showed that 3-hydroxymethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl was distributed within brain tissues, and this was confirmed by MRI observations. Based on the pharmacokinetics of nitroxides in mice, half-life mapping was demonstrated in an ischemia-reperfusion model mouse brain. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in mouse head under oxidative stress by the improved continuous wave-electron paramagnetic resonance imager noninvasively.
Asunto(s)
Infarto Cerebral/metabolismo , Modelos Animales de Enfermedad , Espectroscopía de Resonancia por Spin del Electrón/métodos , Imagenología Tridimensional/métodos , Imagen por Resonancia Magnética/métodos , Pirrolidinas/farmacocinética , Especies Reactivas de Oxígeno/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Infarto Cerebral/patología , Humanos , Masculino , Ratones , Ratones Endogámicos ICR , Oxidación-Reducción , Estrés Oxidativo , Distribución TisularRESUMEN
Toward searching for illegal drugs, we investigated the pulsed nuclear quadrupole resonance (NQR) response of 14N in (1R,2S)-(-)-norephedrine, based on the predictions of quantum chemical calculations. Two pairs of spectral lines (ν+=3.089, 3.093 MHz and ν-=2.594, 2.608 MHz) were observed despite its molecule structure having only a single nitrogen atom. This indicates that the molecular crystal has two nonequivalent nitrogen atoms in the unit cell. The temperature dependence of the NQR frequencies and relaxation properties were investigated for the purpose of accurate remote sensing of the drugs. The NQR frequency shift was approximately 0.23 kHz/K around room temperature. The spin-lattice relaxation and spin-phase memory times were 5.2-10.2 ms and 0.6-1.5 ms, respectively.
Asunto(s)
Espectroscopía de Resonancia Magnética/métodos , Fenilpropanolamina/química , Bases de Datos Factuales , Drogas Ilícitas/síntesis química , Isomerismo , Teoría Cuántica , Temperatura , Factores de TiempoRESUMEN
Nitroxide compounds have been used as redox-sensitive imaging probes by electron paramagnetic resonance (EPR) for assessing oxidative stress in vivo. Fast redox reactions of nitroxide radicals are favorable for assessment of higher redox sensitivity; however, a variety of nitroxides have not been trialed for use as imaging probes due to their very rapid in vivo reduction, which cannot be captured at the slow operation speed of existing EPR imagers. To overcome this limitation, we improved our EPR system to provide a stable and highly sensitive imaging operation. We challenged the improved EPR imager to perform three-dimensional (3D) EPR imaging of mouse brain using two useful nitroxide imaging probes, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) and 2,6-dispiro-4',4"-dipyrane-piperidine-4-one-N-oxyl (DiPy). The second-order rate constant of DiPy with ascorbic acid is 10 times larger than that of Tempol. The improved EPR imager obtained clear 3D EPR images of mouse brain and demonstrated that Tempol could exist with an unpaired electron. The imager also successfully obtained 3D EPR images of mouse head after administration of DiPy. As 126 projections can be acquired in a period of 6 s, 3D EPR imaging can visualize the sequential process of DiPy entering the brain, being distributed within the brain, and being reduced within the brain. These improvements to the EPR imager will enable useful nitroxide imaging probes that were previously unsuitable as imaging probes due to their rapid reduction to be considered for use for sensitive redox assessment in an in vivo system.
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Ácido Ascórbico , Óxidos de Nitrógeno , Animales , Encéfalo/diagnóstico por imagen , Óxidos N-Cíclicos , Espectroscopía de Resonancia por Spin del Electrón/métodos , Ratones , Oxidación-ReducciónRESUMEN
Alzheimer's disease (AD) is a common neurodegenerative disease that causes progressive cognitive decline. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by the generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and is known to occur early in its course. Several reports have suggested a relationship between changes in redox status and AD pathology, including progressive Aß deposition, glial cell activation, and inflammation. In the present study, we employed a newly designed three-dimensional continuous-wave digital electron paramagnetic resonance (EPR) imager with a blood-brain barrier (BBB)-permeable redox-sensitive piperidine nitroxide probe, 4-oxo-2,2,6,6-tetramethyl-piperidine-d16-1-oxyl, for early detection of changed brain redox status. Using this system, we noninvasively compared age-matched 7-month-old AD model mice with normal littermates (WT mice). The obtained brain redox images of AD and WT mice clearly showed impaired brain redox status of AD mice compared to WT, suggesting that oxidative damage had already increased in 7-month-old AD mice compared with age-matched WT mice. The pathological changes in 7-month-old mice in this study were detected earlier than in previous studies in which only AD mice older than 9 months of age could be imaged. Since EPR images suggested that oxidative damage was already increased in 7-month-old AD mice compared to age-matched WT mice, we also evaluated antioxidant levels and the activity of superoxide dismutase (SOD) in brain tissue homogenates of 7-month-old AD and WT mice. Compared to WT mice, decreased levels of glutathione and mitochondrial SOD activity were found in AD mice, which supports the EPR imaging results indicating impaired brain redox status. These results indicate that the EPR imaging method developed in this study is useful for early noninvasive detection of altered brain redox status due to oxidative disease.
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Enfermedad de Alzheimer , Enfermedades Neurodegenerativas , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides , Animales , Encéfalo/diagnóstico por imagen , Modelos Animales de Enfermedad , Espectroscopía de Resonancia por Spin del Electrón , Ratones , Ratones Transgénicos , Oxidación-ReducciónRESUMEN
This paper shows the design of a radio-frequency transceiver coil for landmine detection in Colombia by nuclear quadrupole resonance (NQR). The radio-frequency transceiver coil is of great importance as it is responsible for exciting the target explosive and for picking up the weak NQR signal; however, little detail is found on the literature about its design. The strategy followed on this work consisted on constructing and experimentally comparing five different radio-frequency transceiver coils, whose dimensions were selected according to four design parameters: noise rejection, magnetic flux density, coil sensitivity, and quality factor; taking into account the characteristics of landmines in Colombia, the second country most affected by anti-personnel mines in the world. The constructed coils were experimentally compared using a portable system and with three of them, the system was capable of detecting 200 g ammonium nitrate (the main substance used in Colombian landmines) up to 3 cm from the coil within 12 s, with a steady-state free precession pulse sequence. Conclusions from this work could help to guide RF coil design in other works that apply NQR for remote detection of substances in non-shielded environments and to direct future research about landmine detection in Colombia.
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This technical note reports a continuous-wave electron paramagnetic resonance (CW-EPR) imager that can visualize the distribution of free radicals with a half-life of subminutes in three-dimensional (3D) space. A total of 46 EPR spectra under magnetic field gradients, called projections, were obtained for image reconstruction at an interval of 3.6 s. A shortened data-acquisition time was achieved with the use of analog signals that drove field gradient coils in the imager. 3D mapping of the half-lives of nitroxyl radicals (4-hydroxyl-2,2,6,6-tetramethyl-piperidinyl-1-oxyl) was demonstrated in their reduction reaction with ascorbic acid. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in a sample tube.
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Espectroscopía de Resonancia por Spin del Electrón/métodos , Imagenología Tridimensional/métodos , Óxidos de Nitrógeno/análisis , Ácido Ascórbico/metabolismo , Espectroscopía de Resonancia por Spin del Electrón/economía , Espectroscopía de Resonancia por Spin del Electrón/instrumentación , Diseño de Equipo , Semivida , Imagenología Tridimensional/economía , Imagenología Tridimensional/instrumentación , Óxidos de Nitrógeno/metabolismo , Oxidación-Reducción , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
A method of post-processing to enhance the image resolution of the distribution of free radical molecules obtained with continuous-wave electron paramagnetic resonance (CW-EPR) imaging is reported. The low spatial resolution of EPR imaging, which has created difficulties in biomedical applications, was overcome by the method of resolution-recovery for EPR imaging. High spatial resolution images for the distribution of free radical molecules with a very short relaxation time were obtained with this method. The method's two-step postprocessing consists of conventional deconvolution and filtered back-projection and a process of iterative deconvolution. The resolution-recovery method was demonstrated with three-dimensional (3D) imaging of stable nitroxyl radicals in mouse head. In phantom experiments with a solution of triarylmethyl (TAM) radicals, the spatial resolution was improved by a factor of 7 with the resolution-recovery method.
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Algoritmos , Espectroscopía de Resonancia por Spin del Electrón/métodos , Radicales Libres/análisis , Imagen de Cuerpo Entero/métodos , Animales , Masculino , Ratones , Ratones Endogámicos ICR , Distribución TisularRESUMEN
The development of a digital console for in-vivo rapid scan electron paramagnetic resonance (RS-EPR) spectroscopy and imaging is described in detail. The console was build using field programmable gate array (FGPA) technology that permits real-time control of the resonator and scanning magnetic fields during the measurements. Automatic resonator tuning and matching are achieved by implementing a digital feedback control system and using voltage-tunable capacitors. A band-pass subsampling method is used to directly digitize EPR signals at the carrier frequencies of about 1.2â¯GHz. The magnetic field scan waveforms, excitation EPR frequency, and sampling clock are all internally synchronized. Full-cycle RS-EPR signals are accumulated in the FPGA in real time without any time gaps. The result is the elimination of the re-arm time, during which data are not acquired. The proposed design in this manuscript has a small footprint and is relatively low cost. The FPGA-based RS-EPR system was tested using standard LiNc-BuO and tempone-d16 samples. The RS-EPR linewidth of the LiNc-BuO sample was consistent with an independent pulsed EPR measurement.
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Espectroscopía de Resonancia por Spin del Electrón/instrumentación , Algoritmos , Diseño de Equipo , Procesamiento de Señales Asistido por ComputadorRESUMEN
The high specificity of Nuclear Quadrupole Resonance (NQR) makes it very suited for the detection of antipersonnel mines, where the intensity of the signal spectrum around the resonance frequency of the target substance is the standard decision parameter; however, radiofrequency interference, soil effects on the search coil, landmine size, burial depth, and target temperature affect signal intensity. To overcome this, the use of spectral descriptors and a supervised classifier are proposed in this work, where an assembly of decision trees was trained with NQR data collected on places where a target filled with ammonium nitrate was present and where it was not. A statistical test, comparing the proposed classifier and the solution based solely on the intensity of the signal spectrum, showed with significant evidence that the proposed classifier outperforms the traditional solution. A final blind experiment was conducted in a rural region of Colombia, where five landmines of different size filled with ammonium nitrate were shallowly buried in an area of 1.9 × 1.52â¯m, and the system with the proposed classifier detected four of them with three false alarms. This work is also novel in detecting ammonium nitrate in antipersonnel mines, which are typical in Colombia, the second most mined country in the world.
RESUMEN
Glutathione (GSH) is an important antioxidant that can protect cells under oxidative stress. Thus, a non-invasive method to measure and map the distribution of GSH in live animals is needed. To image the distribution of GSH levels in specific brain regions, a new method using electron paramagnetic resonance (EPR) imaging with a nitroxide imaging probe was developed. Pixel-based mapping of brain GSH levels was successfully obtained by using the linear relationship between reduction rates for nitroxides in brains, measured by an in vivo EPR imager, and brain GSH levels, measured by an in vitro biochemical assay. The newly developed method was applied to a kindling mouse model induced with pentylenetetrazole (PTZ) to visualize changes in GSH levels in specific brain regions after seizure. The obtained map of brain GSH levels clearly indicated decreased GSH levels around the hippocampal region compared to control mice.
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Encéfalo/metabolismo , Óxidos N-Cíclicos/metabolismo , Espectroscopía de Resonancia por Spin del Electrón/métodos , Glutatión/metabolismo , Excitación Neurológica/metabolismo , Neuroimagen/métodos , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Pentilenotetrazol , Convulsiones/inducido químicamente , Convulsiones/metabolismoRESUMEN
Alzheimer's disease (AD) is a common neurodegenerative disease that progressively impairs memory and cognition. Deposition of amyloid-ß (Aß) peptides is the most important pathophysiological hallmark of AD. Oxidative stress induced by generation of reactive oxygen species (ROS) is a prominent phenomenon in AD and known to occur early in the course of AD. Several reports suggest a relationship between change in redox status and AD pathology including progressive Aß deposition, glial cell activation, and inflammation. Galantamine is an acetylcholinesterase inhibitor and has been reported to have an oxidative stress inhibitory function. In the present study, galantamine was administered orally to AD model mice from before the appearance of Aß plaques (preplaque phase), and in vivo change in redox status of the brain was measured using electron paramagnetic resonance (EPR) imaging. Administration of galantamine from the preplaque phase ameliorated memory decline in Morris water maze test and novel object recognition test. Monitoring of the redox status of the brain using EPR imaging showed that galantamine treatment improved the unbalanced redox state. Additionally, galantamine administration enhanced microglial function to promote Aß clearance, reducing the Aß-positive area in the cortex and amount of insoluble Aß in the brain. In contrast, galantamine treatment from the preplaque phase suppressed the production of proinflammatory cytokines through neurotoxic microglial activity. Therefore, galantamine administration from the preplaque phase may have the potential of clinical application for the prevention of AD. In addition, our results demonstrate the usefulness of EPR imaging for speedy and quantitative evaluation of the efficacy of disease-modifying drugs for AD.