Future Prospects of Positron Emission Tomography-Magnetic Resonance Imaging Hybrid Systems and Applications in Psychiatric Disorders.

A positron emission tomography (PET)-magnetic resonance imaging (MRI) hybrid system has been developed to improve the accuracy of molecular imaging with structural imaging. However, the mismatch in spatial resolution between the two systems hinders the use of the hybrid system. As the magnetic field of the MRI increased up to 7.0 tesla in the commercial system, the performance of the MRI system largely improved. Several technical attempts in terms of the detector and the software used with the PET were made to improve the performance. As a result, the high resolution of the PET-MRI fusion system enables quantitation of metabolism and molecular information in the small substructures of the brainstem, hippocampus, and thalamus. Many studies on psychiatric disorders, which are difficult to diagnose with medical imaging, have been accomplished using various radioligands, but only a few studies have been conducted using the PET-MRI fusion system. To increase the clinical usefulness of medical imaging in psychiatric disorders, a high-resolution PET-MRI fusion system can play a key role by providing important information on both molecular and structural aspects in the fine structures of the brain. The development of high-resolution PET-MR systems and their potential roles in clinical studies of psychiatric disorders were reviewed as prospective views in future diagnostics.

Topographic connectivity and cellular profiling reveal detailed input pathways and functionally distinct cell types in the subthalamic nucleus.

The subthalamic nucleus (STN) controls psychomotor activity and is an efficient therapeutic deep brain stimulation target in individuals with Parkinson's disease. Despite evidence indicating position-dependent therapeutic effects and distinct functions within the STN, the input circuit and cellular profile in the STN remain largely unclear. Using neuroanatomical techniques, we construct a comprehensive connectivity map of the indirect and hyperdirect pathways in the mouse STN. Our circuit- and cellular-level connectivities reveal a topographically graded organization with three types of indirect and hyperdirect pathways (external globus pallidus only, STN only, and collateral). We confirm consistent pathways into the human STN by 7 T MRI-based tractography. We identify two functional types of topographically distinct glutamatergic STN neurons (parvalbumin [PV+/-]) with synaptic connectivity from indirect and hyperdirect pathways. Glutamatergic PV+ STN neurons contribute to burst firing. These data suggest a complex interplay of information integration within the basal ganglia underlying coordinated movement control and therapeutic effects.

In vivo 3D Reconstruction of the Human Pallidothalamic and Nigrothalamic Pathways With Super-Resolution 7T MR Track Density Imaging and Fiber Tractography.

The output network of the basal ganglia plays an important role in motor, associative, and limbic processing and is generally characterized by the pallidothalamic and nigrothalamic pathways. However, these connections in the human brain remain difficult to elucidate because of the resolution limit of current neuroimaging techniques. The present study aimed to investigate the mesoscopic nature of these connections between the thalamus, substantia nigra pars reticulata, and globus pallidus internal segment using 7 Tesla (7T) magnetic resonance imaging (MRI). In this study, track-density imaging (TDI) of the whole human brain was employed to overcome the limitations of observing the pallidothalamic and nigrothalamic tracts. Owing to the super-resolution of the TD images, the substructures of the SN, as well as the associated tracts, were identified. This study demonstrates that 7T MRI and MR tractography can be used to visualize anatomical details, as well as 3D reconstruction, of the output projections of the basal ganglia.

Air-stable and ultrasensitive solution-cast SWIR photodetectors utilizing modified core/shell colloidal quantum dots.

InGaAs-based photodetectors have been generally used for detection in the short-wave infrared (SWIR) region. However, the epitaxial process used to grow these materials is expensive; therefore, InGaAs-based photodetectors are limited to space exploration and military applications. Many researchers have expended considerable efforts to address the problem of SWIR photodetector development using lead sulfide (PbS) quantum dots (QDs). Along with their cost-efficient solution processability and flexible substrate compatibility, PbS QDs are highly interesting for the quantum-size-effect tunability of their bandgaps, spectral sensitivities, and wide absorption ranges. However, the performance of PbS QD-based SWIR photodetectors is limited owing to inefficient carrier transfer and low photo and thermal stabilities. In this study, a simple method is proposed to overcome these problems by incorporating CdS in PbS QD shells to provide efficient carrier transfer and enhance the long-term stability of SWIR photodetectors against oxidation. The SWIR photodetectors fabricated using thick-shell PbS/CdS QDs exhibited a high on/off (light/dark) ratio of 11.25 and a high detectivity of 4.0 × 1012 Jones, which represents a greater than 10 times improvement in these properties relative to those of PbS QDs. Moreover, the lifetimes of thick-shell PbS/CdS QD-based SWIR photodetectors were significantly improved owing to the self-passivation of QD surfaces.

Excessive Astrocytic GABA Causes Cortical Hypometabolism and Impedes Functional Recovery after Subcortical Stroke.

Glucose hypometabolism in cortical structures after functional disconnection is frequently reported in patients with white matter diseases such as subcortical stroke. However, the molecular and cellular mechanisms have been poorly elucidated. Here we show, in an animal model of internal capsular infarct, that GABA-synthesizing reactive astrocytes in distant cortical areas cause glucose hypometabolism via tonic inhibition of neighboring neurons. We find that reversal of aberrant astrocytic GABA synthesis, by pharmacological inhibition and astrocyte-specific gene silencing of MAO-B, reverses the reduction in cortical glucose metabolism. Moreover, induction of aberrant astrocytic GABA synthesis by cortical injection of putrescine or adenovirus recapitulates cortical hypometabolism. Furthermore, MAO-B inhibition causes a remarkable recovery from post-stroke motor deficits when combined with a rehabilitation regimen. Collectively, our data indicate that cortical glucose hypometabolism in subcortical stroke is caused by aberrant astrocytic GABA and MAO-B inhibition and that attenuating cortical hypometabolism can be a therapeutic approach in subcortical stroke.

Development of Positron Emission Tomography With Wobbling and Zooming for High Sensitivity and High-Resolution Molecular Imaging.

Demands for in-vivo human molecular imaging with high resolution and high sensitivity in positron emission tomography (PET) require several new design formulae. A classical problem of the PET design, however, was the trade-off between sensitivity and resolution. To satisfy both requirements, the brain-body convertible PET with wobbling and zooming is proposed. The features of this new proposed system are wobble sampling for high-resolution imaging and zooming mode for high sensitivity, especially for the brain dedicated imaging. For the high resolution, wobbling with a linear interpolation and line spread function (LSF) deconvolution reconstruction algorithm was introduced. The result of the proposed system provided resolution up to 1.56 mm full width at half maximum (FWHM) in the brain mode and resulting in the detector-to-resolution ratio (DRR) was 2.47. For both brain phantom and in-vivo rat brain imaging, the proposed system demonstrated superior image quality compared with the commercial PET systems. The newly designed PET with wobbling and zooming also demonstrated the possibility of developing practically usable high-resolution human brain PET-MRI fusion system, especially for the neuroscience research.

Al atomistic surface modulation on colloidal gradient quantum dots for high-brightness and stable light-emitting devices.

Quantum-dot (QD) light-emitting devices (QLEDs) have been attracting considerable attention owing to the unique properties of process, which can control the emission wavelength by controlling the particle size, narrow emission bandwidth, and high brightness. Although there have been rapid advances in terms of luminance and efficiency improvements, the long-term device stability is limited by the low chemical stability and photostability of the QDs against moisture and air. In this study, we report a simple method, which can for enhance the long-term stability of QLEDs against oxidation by inserting Al into the shells of CdSe/ZnS QDs. The Al coated on the ZnS shell of QDs act as a protective layer with Al2O3 owing to photo-oxidation, which can prevents the photodegradation of QD with prolonged irradiation and stabilize the device during a long-term operation. The QLEDs fabricated using CdSe/ZnS/Al QDs exhibited a maximum luminance of 57,580 cd/m2 and current efficiency of 5.8 cd/A, which are significantly more than 1.6 times greater than that of CdSe/ZnS QDs. Moreover, the lifetimes of the CdSe/ZnS/Al-QD-based QLEDs were significantly improved owing to the self-passivation at the QD surfaces.

Characterization of Tetrodes Coated with Au Nanoparticles (AuNPs) and PEDOT and Their Application to Thalamic Neural Signal Detection in vivo.

Tetrodes, consisting of four twisted micro-wires can simultaneously record the number of neurons in the brain. To improve the quality of neuronal activity detection, the tetrode tips should be modified to increase the surface area and lower the impedance properties. In this study, tetrode tips were modified by the electrodeposition of Au nanoparticles (AuNPs) and dextran (Dex) doped poly (3,4-ethylenedioxythiophene) (PEDOT). The electrochemical properties were measured using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A decrease in the impedance value from 4.3 MΩ to 13 kΩ at 1 kHz was achieved by the modified tetrodes. The cathodic charge storage capacity (CSCC) of AuNPs-PEDOT deposited tetrodes was 4.5 mC/cm2, as determined by CV measurements. The tetrodes that were electroplated with AuNPs and PEDOT exhibited an increased surface area, which reduced the tetrode impedance. In vivo recording in the ventral posterior medial (VPM) nucleus of the thalamus was performed to investigate the single-unit activity in normal rats. To evaluate the recording performance of modified tetrodes, spontaneous spike signals were recorded. The values of the L-ratio, isolation distance and signal-to-noise (SNR) confirmed that electroplating the tetrode surface with AuNPs and PEDOT improved the recording performance, and these parameters could be used to effectively quantify the spikes of each cluster.

Easy-to-Fabricate and High-Sensitivity LSPR Type Specific Protein Detection Sensor Using AAO Nano-Pore Size Control.

In this study, we developed a pore size/pore area-controlled optical biosensor-based anodic aluminum oxide (AAO) nanostructure. As the pore size of AAO increases, the unit cell of AAO increases, which also increases the non-pore area to which the antibody binds. The increase in the number of antibodies immobilized on the surface of the AAO enables effective detection of trace amounts of antigen, because increased antigen-antibody bonding results in a larger surface refractive index change. High sensitivity was thus achieved through amplification of the interference wave of two vertically-incident reflected waves through the localized surface plasmon resonance phenomenon. The sensitivity of the fabricated sensor was evaluated by measuring the change in wavelength with the change in the refractive index of the device surface, and sensitivity was increased with increasing pore-size and non-pore area. The sensitivity of the fabricated sensor was improved and up to 11.8 ag/mL serum amyloid A1 antigen was detected. In addition, the selectivity of the fabricated sensor was confirmed through a reaction with a heterogeneous substance, C-reactive protein antigen. By using hard anodization during fabrication of the AAO, the fabrication time of the device was reduced and the AAO chip was fabricated quickly and easily.

Efficient exciton generation in atomic passivated CdSe/ZnS quantum dots light-emitting devices.

We demonstrate the first-ever surface modification of green CdSe/ZnS quantum dots (QDs) using bromide anions (Br-) in cetyl trimethylammonium bromide (CTAB). The Br- ions reduced the interparticle spacing between the QDs and induced an effective charge balance in QD light-emitting devices (QLEDs). The fabricated QLEDs exhibited efficient charge injection because of the reduced emission quenching effect and their enhanced thin film morphology. As a result, they exhibited a maximum luminance of 71,000 cd/m2 and an external current efficiency of 6.4 cd/A, both significantly better than those of their counterparts with oleic acid surface ligands. In addition, the lifetime of the Br- treated QD based QLEDs is significantly improved due to ionic passivation at the QDs surface.

Remodeling of Neuronal Circuits After Reach Training in Chronic Capsular Stroke.

BACKGROUND: Subcortical capsular stroke has a poor prognosis, and it is not yet fully understood how and under what circumstances reach training contributes to motor recovery. Objective This study was performed to investigate changes in neuronal circuits and motor recovery in a chronic capsular stroke model in the presence or absence of reach training. METHOD: We generated photothrombotic capsular lesions in 42 Sprague-Dawley rats and evaluated motor recovery with or without daily training in a single-pellet reaching task (SPRT). We used 2-deoxy-2-[18F]-fluoro-D-glucose-microPET (positron emission tomography) to assess remodeling of neuronal circuits. RESULTS: SPRT training was selectively beneficial only for the group with incomplete capsular destruction (P < .05), suggesting the relevance of plasticity in the remaining capsular fibers for motor recovery. Groups that did not receive SPRT training showed no motor recovery at all. The microPET analysis demonstrated that motor recovery was correlated with a reduction in cortical diaschisis in ipsilesional motor and sensory cortices and in the contralesional sensory cortex (Pearson's correlation, P < .05). We also observed training-dependent subcortical activation in the contralesional red nucleus, the internal capsule, and the ventral hippocampus (P < .0025; false discovery rate q < 0.05). The groups without reach training did not show the same degree of reduction in diaschisis or activation of the red nucleus. CONCLUSIONS: Our results suggest that motor recovery and remodeling of neuronal circuits after capsular stroke depend on the magnitude of the capsular lesion and on the presence or absence of reach training. Task-specific training is strongly indicated only when there is incomplete destruction of the capsular fibers.

Low Dark-Current, High Current-Gain of PVK/ZnO Nanoparticles Composite-Based UV Photodetector by PN-Heterojunction Control.

We propose a solution-processable ultraviolet (UV) photodetector with a pn-heterojunction hybrid photoactive layer (HPL) that is composed of poly-n-vinylcarbazole (PVK) as a p-type polymer and ZnO nanoparticles (NPs) as an n-type metal oxide. To observe the effective photo-inducing ability of the UV photodetector, we analyzed the optical and electrical properties of HPL which is controlled by the doping concentration of n-type ZnO NPs in PVK matrix. Additionally, we confirmed that the optical properties of HPL dominantly depend on the ZnO NPs from the UV-vis absorption and the photoluminescence (PL) spectral measurements. This HPL can induce efficient charge transfer in the localized narrow pn-heterojunction domain and increases the photocurrent gain. It is essential that proper doping concentration of n-type ZnO NPs in polymer matrix is obtained to improve the performance of the UV photodetector. When the ZnO NPs are doped with the optimized concentration of 3.4 wt.%, the electrical properties of the photocurrent are significantly increased. The ratio of the photocurrent was approximately 10³ higher than that of the dark current.

Enhanced Performance of Light-Emitting Diodes by Surface Ligand Modification on Quantum Dots.

The electrical characteristics of quantum dots (QDs) can vary depending on the surface modulation, which can change the luminance and efficiency of electroluminescent devices. Thus, understanding surface ligand is essential in improving the performance of QDs-based light-emitting diodes (LEDs). We analyzed the performance of QDs-based LEDs with respect to the QD surface volume. On the QD surfaces, the 1.1 nm-long tryoctylphosphine oxide (TOPO) ligand with three neck-type structure was replaced with a 1.7 nm-long oleic acid (OA) ligand with a one neck-type structure to evaluate the dependence of the LED properties on the ligand length. With all other conditions being identical, the luminance and efficiency of the QDs-based LEDs with an OA ligand were approximately 1,000 cd/m2 greater and 1.5 times higher, respectively, than those of the QDs-based LEDs with a TOPO ligand. These results show that if the physical length of the surface ligand is relatively long, decreasing the surface area would result in increased injection of electrons and holes into the QDs, increasing the luminance and efficiency.

Solution Processable CdSe/ZnS Quantum Dots Light-Emitting Diodes Using ZnO Nanocrystal as Electron Transport Layer.

In this paper, we propose interface engineering between cadmium selenide/zinc sulfide (CdSe/ZnS) quantum dots (QDs) as the emissive layer (EML) and ZnO nanocrystals (NCs) as the electron transport layer (ETL) for reducing the potential barrier in QDs based light-emitting diode (QLED). The n-type ZnO NCs were effective in confining charge to the QDs EML because of their wide band gap. The ZnO NCs were synthesized using a modified sol-gel process and were applied as the ETL in QLED. For comparison, a standard QLED with Tris(8-hydroxyquinolinato)aluminium as the ETL was also fabricated. The standard QLED was shown to have a luminance of 11,240 cd/m2 and current efficiency of 2.3 cd/A. However, QLED with ZnO NCs showed a higher luminance of 28,760 cd/m2 and current efficiency of 4.9 cd/A than the reference structure, and so has more efficient charge transport. Thus, QLED with ZnO NCs not only simplified the process, but also enhanced the luminance and current efficiency by factor of two.

Au-Polypyrrole Framework Nanostructures for Improved Localized Surface Plasmon Resonance Volatile Organic Compounds Gas Sensing.

In this paper, we propose an Au-polypyrrole (Ppy) nanorod gas sensor for the detection of volatile organic compound (VOC) gases. This gas sensor operates on the principle of localized surface plasmon resonance (LSPR). The Au-Ppy nanorods used in this experiment were synthesized using an anodic aluminum oxide template by the electrochemical deposition method. Using field emission scanning electron microscopy, we confirmed that the Au-Ppy nanorod arrays were successfully fabricated with a uniform size. By depositing gold, the Au-Ppy nanorods exhibited both optical and LSPR interference. The gas sensing properties of the fabricated nanorods were tested for VOCs such as acetic acid, benzene, and toluene with a short response time (~1 min). Moreover, the proposed VOC gas sensing system was tested with three types of VOC gases over a wide concentration range from 10 to 100 ppm. Highest sensitivity was observed for acetic acid gas, which had a linear relation with the gas concentration, indicating that the system can be used as a gas sensor.

Response characterization of a fiber optic sensor array with dye-coated planar waveguide for detection of volatile organic compounds.

We have developed a multi-array side-polished optical-fiber gas sensor for the detection of volatile organic compound (VOC) gases. The side-polished optical-fiber coupled with a polymer planar waveguide (PWG) provides high sensitivity to alterations in refractive index. The PWG was fabricated by coating a solvatochromic dye with poly(vinylpyrrolidone). To confirm the effectiveness of the sensor, five different sensing membranes were fabricated by coating the side-polished optical-fiber using the solvatochromic dyes Reinhardt's dye, Nile red, 4-aminophthalimide, 4-amino-N-methylphthalimide, and 4-(dimethylamino)cinnamaldehyde, which have different polarities that cause changes in the effective refractive index of the sensing membrane owing to evanescent field coupling. The fabricated gas detection system was tested with five types of VOC gases, namely acetic acid, benzene, dimethylamine, ethanol, and toluene at concentrations of 1, 2,…,10 ppb. Second-regression and principal component analyses showed that the response properties of the proposed VOC gas sensor were linearly shifted bathochromically, and each gas showed different response characteristics.

Seven-Tesla magnetic resonance images of the substantia nigra in Parkinson disease.

OBJECTIVE: To investigate anatomical changes in the substantia nigra (SN) of Parkinson disease (PD) patients with age-matched controls by using ultra-high field magnetic resonance imaging (MRI). METHODS: We performed 7T MRI in 10 PD and 10 age-matched control subjects. Magnetic resonance images of the SN were obtained from a 3-dimensional (3D) T(2)*-weighted gradient echo sequence. Region of interest-based 3D shape analysis was performed to quantitatively compare images from the 2 groups. RESULTS: The boundary between the SN and crus cerebri was not smooth in PD subjects. Undulation in the lateral surface of the SN appeared more intense in the side contralateral to that with the more severe symptoms, and more prominent at the rostral level of the SN than at the intermediate or caudal levels. In addition to the lateral surface, there was a striking difference in the dorsomedial aspects of the SN between PD and control subjects. In control subjects, a brighter signal region was observed along the dorsomedial surface of the lateral portion of SN, whereas in PD subjects, this region was observed as a dark region containing a hypointense signal in T(2)*-weighted images. The measurement of SN volumes, normalized to the intracranial volumes, showed higher values in PD subjects than in control subjects. INTERPRETATION: This study demonstrates that 3D 7T MRI can definitively visualize anatomical alterations occurring in the SN of PD subjects. Further pathological studies are required to elucidate the nature of these anatomical alterations.

Highly sensitive nano-porous lattice biosensor based on localized surface plasmon resonance and interference.

We propose a design for a highly sensitive biosensor based on nanostructured anodized aluminum oxide (AAO) substrates. A gold-deposited AAO substrate exhibits both optical interference and localized surface plasmon resonance (LSPR). In our sensor, application of these disparate optical properties overcomes problems of limited sensitivity, selectivity, and dynamic range seen in similar biosensors. We fabricated uniform periodic nanopore lattice AAO templates by two-step anodizing and assessed their suitability for application in biosensors by characterizing the change in optical response on addition of biomolecules to the AAO template. To determine the suitability of such structures for biosensing applications, we immobilized a layer of C-reactive protein (CRP) antibody on a gold coating atop an AAO template. We then applied a CRP antigen (Ag) atop the immobilized antibody (Ab) layer. The shift in reflectance is interpreted as being caused by the change in refractive index with membrane thickness. Our results confirm that our proposed AAO-based biosensor is highly selective toward detection of CRP antigen, and can measure a change in CRP antigen concentration of 1 fg/ml. This method can provide a simple, fast, and sensitive analysis for protein detection in real-time.

MOSFET-BJT hybrid mode of the gated lateral bipolar junction transistor for C-reactive protein detection.

In this study, we propose a novel biosensor based on a gated lateral bipolar junction transistor (BJT) for biomaterial detection. The gated lateral BJT can function as both a BJT and a metal-oxide-semiconductor field-effect transistor (MOSFET) with both the emitter and source, and the collector and drain, coupled. C-reactive protein (CRP), which is an important disease marker in clinical examinations, can be detected using the proposed device. In the MOSFET-BJT hybrid mode, the sensitivity, selectivity, and reproducibility of the gated lateral BJT for biosensors were evaluated in this study. According to the results, in the MOSFET-BJT hybrid mode, the gated lateral BJT shows good selectivity and reproducibility. Changes in the emitter (source) current of the device for CRP antigen detection were approximately 0.65, 0.72, and 0.80 µA/decade at base currents of -50, -30, and -10 µA, respectively. The proposed device has significant application in the detection of certain biomaterials that require a dilution process using a common biosensor, such as a MOSFET-based biosensor.