A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism.

Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.

Genome editing iPSC to purposing enhancement of induce CD8 killer T cell function for regenerative immunotherapy.

In recent years, immunotherapy has become a standard cancer therapy, joining surgery, chemotherapy, and radiation therapy. This therapeutic approach involves the use of patient-derived antigen-specific T cells or genetically modified T cells engineered with chimeric antigen receptors (CAR) or T cell receptors (TCR) that specifically target cancer antigens. However, T cells require ex vivo stimulation for proliferation when used in therapy, and the resulting "exhaustion," which is characterized by a diminished proliferation capacity and anti-tumor activity, poses a significant challenge. As a solution, we reported "rejuvenated" CD8 + T cells that possess high proliferation capacity from induced pluripotent stem cells (iPSCs) in 2013. This review discusses the status and future developments in immunotherapy using iPSC-derived T cells, drawing insights from our research to overcome the exhaustion associated with antigen-specific T cell therapy.

Near-Infrared Photoimmunotherapy Using a Protein Mimetic for EGFR-Positive Salivary Gland Cancer.

Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer therapy based on a monoclonal antibody (mAb) conjugated to a photosensitizer (IR700Dye). The conjugate can be activated by near-infrared light irradiation, causing necrotic cell death with high selectivity. In this study, we investigated NIR-PIT using a small protein mimetic (6-7 kDa, Affibody) which has more rapid clearance and better tissue penetration than mAbs for epidermal growth factor receptor (EGFR)-positive salivary gland cancer (SGC). The level of EGFR expression was examined in vitro using immunocytochemistry and Western blotting. Cell viability was analyzed using the alamarBlue assay. In vivo, the volume of EGFR-positive tumors treated with NIR-PIT using the EGFR Affibody-IR700Dye conjugate was followed for 43 days. It was found that NIR-PIT using the EGFR Affibody-IR700Dye conjugate induced the selective destruction of EGFR-positive SGC cells and restricted the progression of EGFR-positive tumors. We expect that NIR-PIT using the EGFR Affibody-IR700Dye conjugate can efficiently treat EGFR-positive SGC and preserve normal salivary function.

Improved anti-solid tumor response by humanized anti-podoplanin chimeric antigen receptor transduced human cytotoxic T cells in an animal model.

Recently, research has been conducted with chimeric antigen receptor (CAR)-T cells to improve efficacy against solid tumors. Humanized CAR improved the long-term survival of CAR-T cells in patients' peripheral blood, resulting in increased therapeutic efficacy. Therefore, the humanization of the CAR-gene sequence is considered an effective method. Podoplanin (PDPN) is a glycosylated transmembrane protein that is highly expressed in solid tumors and is associated with poor prognosis in patients with cancer. Therefore, PDPN is considered a biomarker and good target for cancer treatment with CAR-T cells. Previously, an anti-PDPN CAR was generated from a conventional nonhumanized antibody-NZ-1, the only anti-PDPN antibody for which a CAR was produced. In this study, we investigated other anti-PDPN CARs from the antibody NZ-27, or humanized NZ-1, to enhance the therapeutic potential of CAR-T cells. The CAR signal intensity was enhanced by the efficient expression of CAR proteins on the T-cell surface of NZ-27 CAR-T cells, which show tumor-specific cytotoxicity, proinflammatory cytokine production, and anti-tumor activity against PDPN-expressing tumor xenografts in mice that were significantly better than those in nonhumanized NZ-1 CAR-T cells.

Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy.

Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose. The near-infrared camera system LIGHTVISION was used to image IR700 during PIT treatment. IR700 showed a sharp decrease in fluorescence intensity in the early stage of treatment and almost reached a plateau at an irradiation dose of 40 J/cm. Cetuximab-PIT for A431 xenografts was performed at multiple doses from 0-100 J/cm. A significant antitumor effect was observed at 40 J/cm compared to no irradiation, and there was no significant difference between 40 J/cm and 100 J/cm. These results suggest that the rate of decay of the tumor fluorescence intensity correlates with the antitumor effect by real-time fluorescence imaging during PIT. In addition, when the fluorescence intensity of the tumor plateaued in real-time fluorescence imaging, it was assumed that the laser dose was necessary for treatment.

Interaction between Hydrophilic Ionic Liquid and Phospholipid/Cholesterol Mixed Film.

Surface pressure (π)-area (A) isotherms were studied to analyze the interactions between a hydrophilic ionic liquid (IL) (ethyl(2-hydroxyethyl)dimethylammonium methanesulfonate) and a pure dipalmitoylphosphatidylcholine (DPPC) film or a DPPC-cholesterol mixed film. When the hydrophilic IL was added to an underlayer solution, the isotherm shifted toward higher areas. Intriguingly, when the hydrophilic IL was added, the packing of the film materials became loose and the elastic modulus decreased, resulting in increased flexibility. This phenomenon was most evident under a cholesterol mole fraction of 0.2. This composition resembles that of cell membranes, which typically comprise phospholipids and cholesterol, suggesting that this hydrophilic IL may be able to interact significantly with biological membranes.

Generation of hypoimmunogenic T cells from genetically engineered allogeneic human induced pluripotent stem cells.

Avoiding the immune rejection of transplanted T cells is central to the success of allogeneic cancer immunotherapies. One solution to protecting T-cell grafts from immune rejection involves the deletion of allogeneic factors and of factors that activate cytotoxic immune cells. Here we report the generation of hypoimmunogenic cancer-antigen-specific T cells derived from induced pluripotent stem cells (iPSCs) lacking ß2-microglobulin, the class-II major histocompatibility complex (MHC) transactivator and the natural killer (NK) cell-ligand poliovirus receptor CD155, and expressing single-chain MHC class-I antigen E. In mouse models of CD20-expressing leukaemia or lymphoma, differentiated T cells expressing a CD20 chimeric antigen receptor largely escaped recognition by NKG2A+ and DNAM-1+ NK cells and by CD8 and CD4 T cells in the allogeneic recipients while maintaining anti-tumour potency. Hypoimmunogenic iPSC-derived T cells may contribute to the creation of off-the-shelf T cell immunotherapies.

Resting-State Functional Connectivity Estimated With Hierarchical Bayesian Diffuse Optical Tomography.

Resting-state functional connectivity (RSFC) has been generally assessed with functional magnetic resonance imaging (fMRI) thanks to its high spatial resolution. However, fMRI has several disadvantages such as high cost and low portability. In addition, fMRI may not be appropriate for people with metal or electronic implants in their bodies, with claustrophobia and who are pregnant. Diffuse optical tomography (DOT), a method of neuroimaging using functional near-infrared spectroscopy (fNIRS) to reconstruct three-dimensional brain activity images, offers a non-invasive alternative, because fNIRS as well as fMRI measures changes in deoxygenated hemoglobin concentrations and, in addition, fNIRS is free of above disadvantages. We recently proposed a hierarchical Bayesian (HB) DOT algorithm and verified its performance in terms of task-related brain responses. In this study, we attempted to evaluate the HB DOT in terms of estimating RSFC. In 20 healthy males (21-38 years old), 10 min of resting-state data was acquired with 3T MRI scanner or high-density NIRS on different days. The NIRS channels consisted of 96 long (29-mm) source-detector (SD) channels and 56 short (13-mm) SD channels, which covered bilateral frontal and parietal areas. There were one and two resting-state runs in the fMRI and fNIRS experiments, respectively. The reconstruction performances of our algorithm and the two currently prevailing algorithms for DOT were evaluated using fMRI signals as a reference. Compared with the currently prevailing algorithms, our HB algorithm showed better performances in both the similarity to fMRI data and inter-run reproducibility, in terms of estimating the RSFC.

Transgelin-1 (SM22α) interacts with actin stress fibers and podosomes in smooth muscle cells without using its actin binding site.

Transgelin-1 (SM22α) has been recognized as a smooth muscle marker and a tumor suppressor, but many details of the working mechanisms remain unclear. Transgelin-1 belongs to the calponin family of actin-binding proteins with an N-terminal calponin homology domain (CH-domain) and a C-terminal calponin-like module (CLIK23). Here, we demonstrate that transgelin-1 interacts with actin stress fibers and podosomes in smooth muscle cells via its type-3 CH-domain, while CLIK23 is dispensable for the binding to the actin structures. We further suggest that the EF-hand motif in transgelin-1 contributes to proper folding of the CH-domain and in turn to the interaction with the actin structures. These results are in contrast to the ones reported in in vitro studies that demonstrated CLIK23 was necessary for the transgelin-1-actin binding, while the CH-domain was not. Besides, within cells, transgelin-1 phosphorylation at Ser181 in CLIK23 did not affect its colocalization with the actin structures, while the same phosphorylation was reported in in vitro studies to negatively regulate actin binding. Thus, our results suggest the molecular basis of intracellular interaction between transgelin-1 and actin, distinct from that in vitro. The actin binding capability intrinsic to CLIK23 may not appear within cells probably because of the weaker competition for actin binding compared to other actin binding molecules.

Cerebral Hemodynamic Responses During Dynamic Posturography: Analysis with a Multichannel Near-Infrared Spectroscopy System.

To investigate cortical roles in standing balance, cortical hemodynamic activity was recorded from the right hemisphere using near-infrared spectroscopy (NIRS) while subjects underwent the sensory organization test (SOT) protocol that systematically disrupts sensory integration processes (i.e., somatosensory or visual inputs or both). Eleven healthy men underwent the SOT during NIRS recording. Group statistical analyses were performed based on changes in oxygenated hemoglobin concentration in 10 different cortical regions of interest and on a general linear analysis with NIRS statistical parametric mapping. The statistical analyses indicated significant activation in the right frontal operculum (f-Op), right parietal operculum (p-Op), and right superior temporal gyrus (STG), right posterior parietal cortex (PPC), right dorsal and ventral premotor cortex (PMC), and the supplementary motor area (SMA) under various conditions. The activation patterns in response to specific combinations of SOT conditions suggested that (1) f-Op, p-Op, and STG are essential for sensory integration when standing balance is perturbed; (2) the SMA is involved in the execution of volitional action and establishment of new motor programs to maintain postural balance; and (3) the PPC and PMC are involved in the updating and computation of spatial reference frames during instances of sensory conflict between vestibular and visual information.

Selective Medial Prefrontal Cortex Responses During Live Mutual Gaze Interactions in Human Infants: An fNIRS Study.

To investigate the role of the prefrontal cortex (PFC) in processing multimodal communicative ostensive signals in infants, we measured cerebral hemodynamic responses by using near-infrared spectroscopy (NIRS) during the social interactive play "peek-a-boo", in which both visual (direct gaze) and auditory (infant-directed speech) stimuli were presented. The infants (mean age, around 7 months) sat on their mother's lap, equipped with an NIRS head cap, and looked at a partner's face during "peek-a-boo". An eye-tracking system simultaneously monitored the infants' visual fixation patterns. The results indicate that, when the partner presented a direct gaze, rather than an averted gaze, toward an infant during social play, the infant fixated on the partner's eye region for a longer duration. Furthermore, hemodynamic activity increased more prominently dorsomedial prefrontal cortex (mPFC) in response to social play with a partner's direct gaze compared to an averted gaze. In contrast, hemodynamic activity increased in the right dorsolateral prefrontal cortex (R-lPFC) regardless of a partner's eye gaze direction. These results indicate that a partner's direct gaze shifts an infant's attention to the partner's eyes for interactive communication, and specifically activates the mPFC. The differences in hemodynamic responses between the mPFC and R-lPFC suggest functional differentiation within the PFC, and a specific role of the mPFC in the perception of face-to-face communication, especially in mutual gaze, which is essential for social interaction.

Brain-machine interfaces for assistive smart homes: A feasibility study with wearable near-infrared spectroscopy.

Smart houses for elderly or physically challenged people need a method to understand residents' intentions during their daily-living behaviors. To explore a new possibility, we here developed a novel brain-machine interface (BMI) system integrated with an experimental smart house, based on a prototype of a wearable near-infrared spectroscopy (NIRS) device, and verified the system in a specific task of controlling of the house's equipments with BMI. We recorded NIRS signals of three participants during typical daily-living actions (DLAs), and classified them by linear support vector machine. In our off-line analysis, four DLAs were classified at about 70% mean accuracy, significantly above the chance level of 25%, in every participant. In an online demonstration in the real smart house, one participant successfully controlled three target appliances by BMI at 81.3% accuracy. Thus we successfully demonstrated the feasibility of using NIRS-BMI in real smart houses, which will possibly enhance new assistive smart-home technologies.

Cerebral functional imaging using near-infrared spectroscopy during repeated performances of motor rehabilitation tasks tested on healthy subjects.

To investigate the relationship between the frontal and sensorimotor cortices and motor learning, hemodynamic responses were recorded from the frontal and sensorimotor cortices using functional near infrared spectroscopy (NIRS) while healthy subjects performed motor learning tasks used in rehabilitation medicine. Whole-head NIRS recordings indicated that response latencies in the anterior dorsomedial prefrontal cortex (aDMPFC) were shorter than in other frontal and parietal areas. Furthermore, the increment rate of the hemodynamic responses in the aDMPFC across the eight repeated trials significantly correlated with those in the other areas, as well as with the improvement rate of task performance across the 8 repeated trials. In the second experiment, to dissociate scalp- and brain-derived hemodynamic responses, hemodynamic responses were recorded from the head over the aDMPFC using a multi-distance probe arrangement. Six probes (a single source probe and 5 detectors) were linearly placed 6 mm apart from each of the neighboring probes. Using independent component analyses of hemodynamic signals from the 5 source-detector pairs, we dissociated scalp- and brain-derived components of the hemodynamic responses. Hemodynamic responses corrected for scalp-derived responses over the aDMPFC significantly increased across the 8 trials and correlated with task performance. In the third experiment, subjects were required to perform the same task with and without transcranial direct current stimulation (tDCS) of the aDMPFC before the task. The tDCS significantly improved task performance. These results indicate that the aDMPFC is crucial for improved performance in repetitive motor learning.

Neurofeedback using real-time near-infrared spectroscopy enhances motor imagery related cortical activation.

Accumulating evidence indicates that motor imagery and motor execution share common neural networks. Accordingly, mental practices in the form of motor imagery have been implemented in rehabilitation regimes of stroke patients with favorable results. Because direct monitoring of motor imagery is difficult, feedback of cortical activities related to motor imagery (neurofeedback) could help to enhance efficacy of mental practice with motor imagery. To determine the feasibility and efficacy of a real-time neurofeedback system mediated by near-infrared spectroscopy (NIRS), two separate experiments were performed. Experiment 1 was used in five subjects to evaluate whether real-time cortical oxygenated hemoglobin signal feedback during a motor execution task correlated with reference hemoglobin signals computed off-line. Results demonstrated that the NIRS-mediated neurofeedback system reliably detected oxygenated hemoglobin signal changes in real-time. In Experiment 2, 21 subjects performed motor imagery of finger movements with feedback from relevant cortical signals and irrelevant sham signals. Real neurofeedback induced significantly greater activation of the contralateral premotor cortex and greater self-assessment scores for kinesthetic motor imagery compared with sham feedback. These findings suggested the feasibility and potential effectiveness of a NIRS-mediated real-time neurofeedback system on performance of kinesthetic motor imagery. However, these results warrant further clinical trials to determine whether this system could enhance the effects of mental practice in stroke patients.

Cerebral hemodynamic responses induced by specific acupuncture sensations during needling at trigger points: a near-infrared spectroscopic study.

Acupuncture stimulation at specific points, or trigger points (TPs), elicits sensations called "de-qi". De-qi sensations relate to the clinical efficacy of the treatment. However, it is neither clear whether de-qi sensations are associated with TPs, nor clear whether acupuncture effects on brain activity are associated with TPs or de-qi. We recorded cerebral hemodynamic responses during acupuncture stimulation at TPs and non-TPs by functional near-infrared spectroscopy. The acupuncture needle was inserted into both TPs and non-TPs within the right extensor muscle in the forearm. Typical acupuncture needle manipulation was conducted eight times for 15 s. The subjects pressed a button if they felt a de-qi sensation. We investigated how hemodynamic responses related to de-qi sensations induced at TPs and non-TPs. We observed that acupuncture stimulations producing de-qi sensations significantly decreased the Oxy-Hb concentration in the supplementary motor area (SMA), pre-supplementary motor area, and anterior dorsomedial prefrontal cortex regardless of the point stimulated. The hemodynamic responses were statistically analyzed using a general linear model and a boxcar function approximating the hemodynamic response. We observed that hemodynamic responses best fit the boxcar function when an onset delay was introduced into the analyses, and that the latency of de-qi sensations correlated with the onset delay of the best-fit function applied to the SMA. Our findings suggest that de-qi sensations favorably predict acupuncture effects on cerebral hemodynamics regardless of the type of site stimulated. Also, the effect of acupuncture stimulation in producing de-qi sensation was partly mediated by the central nervous system including the SMA.

Development of a new rehabilitation system based on a brain-computer interface using near-infrared spectroscopy.

We describe the set-up for an electrical muscle stimulation device based on near-infrared spectroscopy (NIRS), designed for use as a brain-computer interface (BCI). Employing multi-channel NIRS, we measured evoked cerebral blood oxygenation (CBO) responses during real motor tasks and motor-imagery tasks. When a supra-threshold increase in oxyhemoglobin concentration was detected, electrical stimulation (50 Hz) of the biceps brachii muscle was applied to the side contralateral to the hand grasping task or ipsilateral to the motor-imagery task. We observed relatively stable and reproducible CBO responses during real motor tasks with an average accuracy of 100%, and during motor imagery tasks with an average accuracy of 61.5%. Flexion movement of the arm was evoked in all volunteers in association with electrical muscle stimulation and no adverse effects were noted. These findings suggest that application of the electrical muscle stimulation system based on a NIRS-BCI is non-invasive and safe, and may be useful for the physical training of disabled patients.

Brain cortical mapping by simultaneous recording of functional near infrared spectroscopy and electroencephalograms from the whole brain during right median nerve stimulation.

To investigate relationships between hemodynamic responses and neural activities in the somatosensory cortices, hemodynamic responses by near infrared spectroscopy (NIRS) and electroencephalograms (EEGs) were recorded simultaneously while subjects received electrical stimulation in the right median nerve. The statistical significance of the hemodynamic responses was evaluated by a general linear model (GLM) with the boxcar design matrix convoluted with Gaussian function. The resulting NIRS and EEGs data were stereotaxically superimposed on the reconstructed brain of each subject. The NIRS data indicated that changes in oxy-hemoglobin concentration increased at the contralateral primary somatosensory (SI) area; responses then spread to the more posterior and ipsilateral somatosensory areas. The EEG data indicated that positive somatosensory evoked potentials peaking at 22 ms latency (P22) were recorded from the contralateral SI area. Comparison of these two sets of data indicated that the distance between the dipoles of P22 and NIRS channels with maximum hemodynamic responses was less than 10 mm, and that the two topographical maps of hemodynamic responses and current source density of P22 were significantly correlated. Furthermore, when onset of the boxcar function was delayed 5-15 s (onset delay), hemodynamic responses in the bilateral parietal association cortices posterior to the SI were more strongly correlated to electrical stimulation. This suggests that GLM analysis with onset delay could reveal the temporal ordering of neural activation in the hierarchical somatosensory pathway, consistent with the neurophysiological data. The present results suggest that simultaneous NIRS and EEG recording is useful for correlating hemodynamic responses to neural activity.

Fast (100-175 ms) components elicited bilaterally by language production as measured by three-wavelength optical imaging.

Optical imaging has been gradually utilized to investigate language functions in the brain. The majority of hemodynamic response (slow signal) measurements have been applied to receptive and productive language processing, while several event-related optical signal (EROS) measurements on neuronal response (fast signal) have focused on receptive language processing. Therefore, an investigation of language production based on fast signal measurement is yet to be realized. Using a continuous-wave near-infrared spectroscopic (CW-NIRS) method with three long wavelengths in close ranges (780, 805, and 830 nm), which are suitable for the detection of fast optical signals, the current work investigated whether absorbance-based EROS components during overt language production might be elicited bilaterally in each wavelength with a 25 ms sampling time. Healthy adult subjects read aloud Japanese noun phrases (NP) presented on a computer screen. Two conditions (short/long-vowel duration) included either initial [s]- or [k]-phoneme types in the first words of the NP. The cognitive subtraction method achieved by deducting short-duration from long-duration conditions showed that in both phoneme types, reliable fast optical components with a peak latency of about 100-175 ms post initial-consonant onset were bilaterally elicited by long vowels. This result suggests that the present CW-NIRS methodology can clearly detect such early optical signals with good temporal resolution and with a good signal-to-noise ratio (SNR) obtained from a small number of stimuli. The fact that optical absorbance values at all three wavelengths had the same positive deflections during the initial-syllable production demonstrates that the elicitation of fast optical components may directly represent neuronal activity.

Quantification of cerebral blood flow and oxygen metabolism with 3-dimensional PET and 15O: validation by comparison with 2-dimensional PET.

UNLABELLED: Quantitative PET with (15)O provides absolute values for cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF), which are used for assessment of brain pathophysiology. Absolute quantification relies on physically accurate measurement, which, thus far, has been achieved by 2-dimensional PET (2D PET), the current gold standard for measurement of CBF and oxygen metabolism. We investigated whether quantitative (15)O study with 3-dimensional PET (3D PET) shows the same degree of accuracy as 2D PET. METHODS: 2D PET and 3D PET measurements were obtained on the same day on 8 healthy men (age, 21-24 y). 2D PET was performed using a PET scanner with bismuth germanate (BGO) detectors and a 150-mm axial field of view (FOV). For 3D PET, a 3D-only tomograph with gadolinium oxyorthosilicate (GSO) detectors and a 156-mm axial FOV was used. A hybrid scatter-correction method based on acquisition in the dual-energy window (hybrid dual-energy window [HDE] method) was applied in the 3D PET study. Each PET study included 3 sequential PET scans for C(15)O, (15)O(2), and H(2)(15)O (3-step method). The inhaled (or injected) dose for 3D PET was approximately one fourth of that for 2D PET. RESULTS: In the 2D PET study, average gray matter values (mean +/- SD) of CBF, CBV, CMRO(2), and OEF were 53 +/- 12 (mL/100 mL/min), 3.6 +/- 0.3 (mL/100 mL), 3.5 +/- 0.5 (mL/100 mL/min), and 0.35 +/- 0.06, respectively. In the 3D PET study, scatter correction strongly affected the results. Without scatter correction, average values were 44 +/- 6 (mL/100 mL/min), 5.2 +/- 0.6 (mL/100 mL), 3.3 +/- 0.4 (mL/100 mL/min), and 0.39 +/- 0.05, respectively. With the exception of OEF, values differed between 2D PET and 3D PET. However, average gray matter values of scatter-corrected 3D PET were comparable to those of 2D PET: 55 +/- 11 (mL/100 mL/min), 3.7 +/- 0.5 (mL/100 mL), 3.8 +/- 0.7 (mL/100 mL/min), and 0.36 +/- 0.06, respectively. Even though the 2 PET scanners with different crystal materials, data acquisition systems, spatial resolution, and attenuation-correction methods were used, the agreement of the results between 2D PET and scatter-corrected 3D PET was excellent. CONCLUSION: Scatter coincidence is a problem in 3D PET for quantitative (15)O study. The combination of both the present PET/CT device and the HDE scatter correction permits quantitative 3D PET with the same degree of accuracy as 2D PET and with a lower radiation dose. The present scanner is also applicable to conventional steady-state (15)O gas inhalation if inhaled doses are adjusted appropriately.

Adaptive optics instrumentation in submillimeter/terahertz spectroscopy with a flexible polyvinylidene fluoride cladding hollow waveguide.

A simple instrument has been developed to carry out temperature dependent submillimeter/terahertz-wave spectroscopy using a polyvinylidene fluoride flexible hollow waveguide and an eggplant-shape launching lens.