355-nm direct-detection Doppler wind lidar for vertical atmospheric motion measurement.

A compact and simple 355-nm direct-detection Doppler wind lidar (DDDWL) was developed to measure the line-of-sight (LOS) wind speed of the background atmosphere from atmospheric molecule return signals with and without aerosols and clouds. A receiver design with a Fabry-Perot etalon interferometer (FPEI) without an inside deposited step coating or fiber coupling is considered for the DDDWL using the double-edge technique. The receiver with the double-edge technique uses a FPEI and wedge prism to form a double-edge filter. The development of the double-edge filter in this combination is, to the best of our knowledge, an improvement at 355-nm wavelength. Considerations for the DDDWL receiver with a FPEI revealed that a full-angle light beam divergence into the FPEI and a working FPEI aperture are significant factors for the receiver design. Preliminary experimental evaluation demonstrated that the DDDWL had the potential of LOS wind speed measurements with a random error of less than 1 m/s when the signal-to-noise ratio was approximately 300. The DDDWL-measured vertical LOS wind speed profile was consistent with that of a 2-µm coherent Doppler wind lidar within the measurement error range. The preliminary experimental LOS wind measurement results demonstrated the capability of the DDDWL to measure low LOS wind speeds.

[Development of Body Phantom for Evaluation of Appropriate Administered Radioactivities and Image Quality on 99mTc-DMSA Scintigraphy in Pediatric Nuclear Medicine].

PURPOSE: We conducted a field survey about pediatric nuclear medicine. As a result, it was suggested that 99mTc-DMSA scintigraphy was performed at many institutions, whereas various examinations such as image acquisition and processing are not carried out using the renal phantom. Therefore, we developed the body phantom for the evaluation of appropriate administered radioactivities and image quality with renal scintigraphy in pediatric nuclear medicine. METHODS: We created three differently sized body phantoms (1-, 5-, and 20-year-old models). These pediatric body phantoms were filled with a 99mTc solution based on the consensus guideline of pediatric radiopharmaceutical administered radioactivity in Japan. The planar image was evaluated using acquisition count, uniformity and defect contrast. SPECT images were evaluated with a recovery coefficient (RC). RESULTS: The acquisition counts for pediatric body phantoms were relatively corresponded to the clinical study. The appropriate acquisition counts and the pixel size for the planar image were approximately 140 counts per pixel and 1.23-1.35 mm at 5 min acquisition times in 1- and 5-year-old pediatric body phantom studies, respectively. Although the uniformity and the cold contrast did not depend on pixel size and body size, the cold contrast was affected by body size. The RC for SPECT images depended on the performance of SPECT systems, the resolution recovery algorithm and body phantom size. CONCLUSION: The developed pediatric body phantom could allow us to establish optimal image acquisition and more evidence on renal scintigraphy in pediatric nuclear medicine.

Precise measurement of laser power using an optomechanical system.

This paper shows a novel method to precisely measure the laser power using an optomechanical system. By measuring a mirror displacement caused by the reflection of an amplitude modulated laser beam, the number of photons in the incident continuous-wave laser can be precisely measured. We have demonstrated this principle by means of a prototype experiment uses a suspended 25 mg mirror as an mechanical oscillator coupled with the radiation pressure and a Michelson interferometer as the displacement sensor. A measurement of the laser power with an uncertainty of less than one percent (1σ) is achievable.

Reduction of thermal fluctuations in a cryogenic laser interferometric gravitational wave detector.

The thermal fluctuation of mirror surfaces is the fundamental limitation for interferometric gravitational wave (GW) detectors. Here, we experimentally demonstrate for the first time a reduction in a mirror's thermal fluctuation in a GW detector with sapphire mirrors from the Cryogenic Laser Interferometer Observatory at 17 and 18 K. The detector sensitivity, which was limited by the mirror's thermal fluctuation at room temperature, was improved in the frequency range of 90 to 240 Hz by cooling the mirrors. The improved sensitivity reached a maximum of 2.2×10(-19) m/√Hz at 165 Hz.

Direct measurement of thermal fluctuation of high-Q pendulum.

We have achieved a direct measurement of the thermal fluctuation of a pendulum in an off-resonant and wide frequency region using a laser interferometric gravitational-wave detector. These measurements have been well identified for over one decade by an agreement with a theoretical prediction, which is derived by a fluctuation-dissipation theorem. Thermal fluctuation was dominated by the contribution of resistances in coil-magnet actuator circuits. When we tuned these resistances, the noise spectrum also changed according to a theoretical prediction. The measured thermal noise level corresponds to a high quality factor on the order of 10(5) of the pendulum.

Development of a displacement- and frequency-noise-free interferometer in a 3D configuration for gravitational wave detection.

The displacement- and frequency-noise-free interferometer (DFI) is a multiple laser interferometer array for gravitational-wave detection free from both the displacement noise of optics and laser frequency noise. So far, partial experimental demonstrations of the DFI have been done in 2D table top experiments. In this Letter, we report the complete demonstration of a 3D DFI. The DFI consists of four Mach-Zehnder interferometers with four mirrors and two beam splitters The attained maximum suppression of the displacement noise of both mirrors and beam splitters was 40 dB at about 50 MHz. The nonvanishing DFI response to a gravitational wave was successfully confirmed using multiple electro-optic modulators and computing methods.

Improved breast cancer detection of prone breast fluorodeoxyglucose-PET in 118 patients.

OBJECTIVE: To prospectively evaluate the breast cancer detection of prone breast positron emission tomography (PET) images in comparison with supine whole-body PET images. MATERIAL AND METHODS: One hundred and eighteen female patients (age range 28-91 years) with 122 lesions suspected of having breast cancer underwent fluorine-18 fluorodeoxyglucose PET for preoperative staging. After the whole-body image was acquired, prone breast PET imaging was performed. The findings from both images were compared with the histopathologic results. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), and accuracy were used to compare the diagnostic accuracy of prone breast PET images with that of whole-body PET images. RESULTS: Sensitivity, specificity, positive predictive value, NPV, and accuracy of whole-body PET images were 83, 50, 97, 17, and 80%, and of prone breast PET images they were 95, 50, 96, 43, and 93%. Ten of 114 breast cancerous lesions (8.8%) were detected on prone breast PET images alone. Statistical difference was found between the sensitivity, accuracy, and NPV of prone breast PET images and those of whole-body PET images (P<0.0001 for sensitivity and accuracy and P<0.0009 for NPV). CONCLUSION: Our data about the 122 lesions, suspected of breast cancer, with regard to the usefulness of prone breast PET imaging indicate that prone breast PET images are effective in detecting breast cancer.

[Development of automatic analysis for dynamic renal function study using computed tomographic (CT) images].

Determination of the region of interest (ROI) for dynamic renal function has been highly discordant among operators because of the dependence on factors such as the rate of injection of radioactive medicines, constitution, and renal function. To simplify this problem, we developed a computer algorithm that provides automatic analysis for both localization of the kidney and automatic determination of ROIs using computed tomographic (CT) images. The bilateral kidneys were extracted from enhanced CT images, and the CT pixel size was adjusted to dynamic renal function images. The template-matching technique was used for these images, and the kidney renal location was analyzed on additional functional images constructed by dynamic renal function images. As a result, we were able to obtain time-activity curves of both renal function and quantified glomerular filtration rate (GFR). In conclusion, the computer algorithm we developed was considered to provide reliable results, apart from the variability among operators, because of its good reproducibility.

[Development of automatic analyses for star-shot images using computed radiography (CR)].

Recent progress in radiation therapy has been greatly enhanced in many facilities by the development of new machines for treatment, improved computer technology for radiotherapy treatment planning systems (RTPs), increased accuracy of radiation therapy such as stereotactic irradiation, and intensity-modulated radiation therapy (IMRT). Quality control (QC) of the isocenter, which has consisted of gantry rotation and limiting the radiation field, is important for greater accuracy of these radiation therapy technologies. Star-shot analyses using computed radiography (CR) for evaluation of the isocenter were employed in this study. Devices to support CR were created, and a method of automatically analyzing images obtained by the star-shot technique, which calculated the error (distance) from the isocenter and the incident beam angle, were developed. In terms of the accuracy of our method, the average maximum error was 0.33 mm (less than 2 pixels: 0.35 mm), the average absolute error and incident beam angle errors were 0.3 mm and 0.4 degrees at maximum and at one standard deviation (SD), respectively. In this study, the processing times were 16 sec at minimum, 152 sec at maximum, 18 sec at most frequencies, and 23.6 sec on average. In conclusion, it was considered that our newly developed method for analyzing star-shot images using CR enabled immediate, quantitative evaluation of the isocenter.

No regional differences of cytochrome P450 expression in the liver of Cynomolgus monkeys (Macaca fascicularis).

Non-human primates are frequently used in toxicological studies the result of which are extrapolated to humans, but background data on drug metabolism ability among monkeys derived from different countries has not been published, especially on the key enzyme, cytochrome P450 (CYP450). We assessed the amounts of hepatic CYP450 obtained from cynomolgus monkeys of different ages and from different countries in this study. There were no regional differences of total P450 content, as well as major CYP450 isozymes (CYP 1A, 2A, 2B, 2C, 2D, 2E1 and 3A4) in cynomolgus monkeys by westernblot analysis. Similarly, there were no significant differences with hybrid cynomolgus monkeys, but variations in individual values were large. As for aging, total P450 contents declined in old cynomolgus monkeys (12-32 years of age). These results indicate the usefulness of basic data of hepatic CYP450 obtained from cynomolgus monkeys of different ages and from different countries.

[Research on time-course differential imaging by bone scintigraphy].

The temporal image subtraction technique was applied to bone scintigraphy, using Photoshop (commercially available image processing software) and Morpher (public domain warping software). For the temporal subtraction images, 81 subtraction images (19 cases) were prepared by a method used to subtract the previous images from the current ones. Registration of the current and previous images was performed by manual operation using Photoshop, and warping was done using the warping function of Morpher. In addition, difference images prepared after correcting the distributions of radioactive isotopes of the current and previous images using the count of the pelvic region were also examined. Compared with manual operation, alignment of images by warping improved registration and reduced the generation of pseudo-images of subtraction images. The rate of identification of abnormal accumulation-enhanced regions and subjective evaluation by doctors was improved for warping more than for manual operation. Furthermore, abnormal hot regions, which are difficult to find in film images, could be found in three subtraction images. In addition, it was confirmed that abnormal hot regions become more visible in many cases by preparing subtraction images after correcting the count between images using the count of the pelvic region. Thus, it is suggested that the temporal image subtraction technique in bone scintigraphy enables more accurate observation of enhancement of or changes in abnormal hot regions, which will support diagnostic reading. It is considered that enhancement of or changes in abnormal hot regions will be more accurately understood through further detailed discussion in the future.

Cryopreservation and primary culture of cerebral neurons from cynomolgus monkeys (Macaca fascicularis).

We established the procedures for cryopreservation and primary culture of fetal cerebral neurons of cynomolgus monkeys (Macaca fascicularis). Three developmental stages of fetuses (80, 93, and 102 days of gestation) were compared to determine the optimal stage of cerebrum development for primary culture. Among the three fetuses, the 80-day-old fetus produced the most process-rich neurons with the highest survival. The number of total recovery cells from the cryopreserved 80-day-old fetus corresponded to 83.4% of that from fresh tissue. Besides, synchronous oscillations of intracellular calcium were first seen in primate cerebral neurons, which suggested the formation of synapse-networks. Cultured neurons expressed synaptophysin protein. Successful cryopreservation and subsequent cell culture of primate neurons would be useful tools for neuroscience research with species specificity.

Study on the usefulness of whole body SPECT coronal image, MIP image in 67Ga scintigraphy.

In this study, we examined the usefulness of whole body coronal images and whole body cine display MIP images (CMIP) upon which image processing was carried out after whole body SPECT in comparison to the usefulness of whole body images (WB/SC) compensated by scattered radiation in tumor/inflammation scintigraphy with 67Ga-citrate (67Ga). Image interpretation was performed for the 120 patients with confirmed diagnoses, and the accuracy of their diagnoses was studied by three nuclear medical physicians and two clinical radiological technologists by means of sensitivity, specificity and ROC analysis. The resultant data show that sensitivity, specificity, accuracy and the area under the ROC curve Az in the WB/SC were approximately 65%, 86%, 74% and 0.724, respectively, whereas sensitivity, specificity, accuracy and Az of the image reading system in which CMIP is combined with whole body coronal images reconstructed by the OS-EM method were approximately 93%, 95%, 94% and 0.860, respectively. Furthermore, coronal images reconstructed by the OS-EM method tended to be superior to those produced by the FBP method in both diagnostic accuracy and ROC analysis. In conclusion, the image reading system in which CMIP is combined with whole body coronal images reconstructed by the OS-EM method was shown to be superior in diagnostic accuracy and ROC analysis. Our data suggest that whole body SPECT is an excellent technique as an alternative to WB/SC.

Renal function tests on diabetes-induced and non-induced APA hamsters.

Although it has been said that Syrian hamsters of the APA strain (APA hamsters) spontaneously develop glomerulosclerosis with age, more prominent and severe glomerulosclerosis with proteinuria as well as arteriosclerosis is induced in diabetic APA hamsters. In this study, in order to supply new information on APA hamsters, tests on renal function and histology were done on non-diabetic and streptozotocin (SZ)-induced diabetic APA hamsters (APA-N and APA-D, respectively), and the data were compared with those of normal Syrian (golden) hamsters (GOL). At 4, 8, 12, 20, and 32 weeks of age, the markers indicating renal function, serum urea nitrogen and creatinine levels and the urinary total protein level were measured and thereafter histological studies were done. Although there were no remarkable differences between APA-N and GOL in serum urea nitrogen and creatinine levels, APA-N excreted more urinary total protein from the early weeks of age. In APA-D, an apparent worsening in these markers indicating renal function was detected and diabetic nephropathy in this model was confirmed also in terms of renal function. In the histological studies, the major lesion observed in APA-D was diffuse glomerulosclerosis. This may mean that renal dysfunction in APA-D was mainly caused by the glomerular change and that it is similar to other experimental diabetic animals and human diabetic patients. These data show that the diabetic APA hamster is a desirable model of human diabetic nephropathy.

Expression of lipoprotein receptors in the aortic walls of diabetic APA hamsters.

Syrian hamsters of the APA strain (APA hamsters) have recently been demonstrated to develop atheromatous lesions in the aortic arches under the diabetic condition induced by a single injection of streptozotocin (SZ). Various lipoprotein receptors are reported to play important roles in atherogenesis mainly in vitro, while there are few reports on the relative expressions of these receptors in vivo. In this study, we therefore examined messenger RNA (mRNA) expressions of several lipoprotein receptors on the aortic arches of diabetic APA hamsters at 6, 14 and 26 weeks after the injection (WAI) of SZ. In semi-quantitative RT-PCR, scavenger receptor (SR)-AI, macrosialin (MS)/CD68, and receptor for advanced glycation end-products (RAGE) mRNAs showed significant increases at 6 WAI of SZ, and SR-AI and CD36 mRNA obviously increased until 26 WAI, as compared with the control. Low-density lipoprotein receptor mRNA showed a significant decrease at 14 and 26 WAI, and SR-BI mRNA significantly decreased at 6 and 14 WAI, as compared with the control. Very low-density lipoprotein receptor mRNA was at the same level as the control. By means of in situ hybridization, SR-AI, MS/CD68 and RAGE mRNA were detected in the foam cells of the fatty streaks at 6 WAI, which suggested that SR-AI, MS/CD68 and RAGE play crucial roles in the formation of the fatty streaks, the initial lesions of atherogenesis in diabetic APA hamsters. SR-AI and CD36 were also believed to be related to the progression of atherogenesis in this model.

Cryopreservation of brain tissue for primary culture.

Factors affecting recovery of brain cells from cryopreserved cerebral tissues of fetal rats were examined based on yields of viable cells on cell culture. Favorable preservation was obtained with freezing small pieces (less than 1 mm cube) of brain tissues rather than whole tissues or dissociated single cells, and use of 10% dimethylsulfoxide as a cryoprotectant in liquid nitrogen. As for cell preparation procedures, cell survival was improved when tissues were heated at 32 degrees C during papain digestion and centrifugation. Under favorable conditions, the number of brain cells recovered from cryopreserved tissues corresponded to 20-30% of those from fresh control tissues. Immunocytochemical characteristics of cultured neurons, astrocytes, and oligodendrocytes from cryopreserved and fresh tissues were indistinguishable. Semi-quantitive analyses of microtubule-associated protein-2 (MAP-2) and synaptophysin revealed that there was no difference in the amounts of these markers between cultures from both fresh and cryopreserved tissues. These results suggest that most of all cell types including neurons were equally susceptible to the cryopreservation procedures. We concluded that cryopreservation in liquid nitrogen is an effective method for preservation of embryonic brain tissues for later use in cell culture studies.

Functional and histochemical analysis on pancreatic islets of APA hamsters with SZ-induced hyperglycemia and hyperlipidemia.

To clarify how Syrian hamsters of the APA strain (APA hamsters) keep a diabetic condition for a long period, the functional and histochemical changes in the pancreatic islets of diabetic APA hamsters were examined. By glucose tolerance test, no glucose-induced insulin secretion was seen in the diabetic APA hamsters. By immunohistochemistry, it was revealed that at 24 hr after SZ-injection, the number of islets had decreased and that remnant islets had become markedly smaller. The islets had hardly any insulin-immunoreactive cells and consisted of cells stained by anti-glucagon and somatostatin antibodies. One, three and six months after SZ-injection, a small number of cells with vacuolative changes, which were positive for PAS staining, were observed in most islets and the vacuolated cells were stained mainly by anti-insulin antibody. In addition, a number of PCNA-positive cells were observed, especially in the periphery of the vacuolated cells, while TUNEL-positive cells were not detected. This data suggests that beta-cells proliferating as a result of the replication of the resident beta-cells in islets had fallen into degeneration and necrosis by a stress, such as the glycogen deposition in hyperglycemia and hyperlipidemia. Consequently, secretion of insulin was maintained at low levels, which allowed the hamsters to live without insulin therapy in the diabetic condition for over 6 months.

D-galactosamine induced hepatocyte apoptosis is inhibited in vivo and in cell culture by a calcium calmodulin antagonist, chlorpromazine, and a calcium channel blocker, verapamil.

Studies were conducted in C57BL/6N Crj male mice and in cultured hepatocytes to clarify the relationship between galactosamine (GaIN) induced apoptosis and [Ca2+]i kinetics. Chlorpromazine (CPZ), a Ca(2+)-calmodulin antagonist, and verapamil (VR), a Ca(2+)-channel blocker each inhibited GaIN-induced DNA fragmentation and the appearance of apoptotic bodies. The kinetics of calcium uptake were evaluated using a calcium analyzer with the acetoxymethyl ester of fura-PE3 (fura-PE3/AM, 2.5 microM) as the calcium reporter. An increase in [Ca2+]i was detected in the cultured hepatocytes within 3 hours after treatment with 20 mM GaIN; this increase was inhibited by pretreatment with either 20 microM CPZ or 30 microM VR. Ca2+ imaging by confocal laser scanning microscopy showed that increase in [Ca2+]i after treatment with GaIN was initially localized around nuclei, while [Ca2+]i signals were later diffuse and observed throughout the cytoplasm. The activities of lactate dehydrogenase (LDH) and serum glutamate-pyruvate transaminase (sGPT), used as indicators of plasma membrane damage and leakage, however, were not reduced by pretreatment with CPZ or VR. From these findings, we infer that the DNA fragmentation in GaIN-induced hepatocyte apoptosis is associated with an elevation in the perinuclear concentration of Ca2+, but GaIN-induced necrotic cell death is triggered through pathway(s) that are insensitive to blockage of Ca2+ influx and therefore appear to occur independently of elevation in [Ca2+]i. These results help to clarify the role of calcium flux in hepatocyte apoptosis and necrosis induced by exposure to hepatotoxins in vivo and in vitro.

Differences between BALB/c and C57BL/6 mice in mouse hepatitis virus replication in primary hepatocyte culture.

We previously showed that an intraperitoneal infection with mouse hepatitis virus (MHV) resulted in acute hepatic failure accompanying extremely elevated viral growth in the liver in interferon-gamma-deficient BALB/c (BALB-GKO), but not C57BL/6 (B6-GKO) mice. To examine the basis of the strain difference against MHV infection in interferon-gamma-deficient mice, viral replication in primary hepatocyte cultures from BALB/c and B6 mice with or without the IFN-gamma gene was compared in vitro. The MHV replication in BALB/c hepatocytes with or without the IFN-gamma gene was significantly higher than that in B6 hepatocytes with or without the IFN-gamma gene, suggesting that there is a strain difference in MHV replication in hepatocytes. Since a significant difference in MHV replication in hepatocytes was not observed between wild type and IFN-gamma-deficient mice of the same genetic background, the phenomenon is thought to be independent of IFN-gamma. However, pretreatment of hepatocytes with recombinant mouse interferon-gamma inhibited MHV replication in a dose-dependent fashion. The results are discussed with respect to the pathology of MHV infection in mice with or without the IFN-gamma gene.

The effect of probucol on atherosclerosis in streptozotocin-induced diabetic-hyperlipidemic APA hamsters in different stages of atherosclerosis.

We investigated the effect of probucol (PB) on atherosclerosis in streptozotocin (SZ)-induced diabetic-hyperlipidemic APA hamsters in three different stages, the early, middle and late stages of atherosclerosis. Male APA hamsters were injected intraperitoneally with SZ or vehicle alone (citrate buffer; CB) as a control at the age of 8 weeks. At 6 weeks after injection (WAI) of SZ or CB (the early stage), 14 WAI (the middle stage) and 26 WAI (the late stage), animals were assigned to PB treated- or non-treated groups (CBPB, SZPB, CB, SZ). After 8 weeks of PB administration with diet, the aorta was taken from each animal for assessment of atheromatous lesions and blood samples were subjected to serum biochemical analysis and the measurement of blood lipid peroxide (LPO). In the middle stage, PB treatment significantly decreased serum total cholesterol level, slightly decreased LPO, and also tended to reduce the lesion area, although no statistical difference was seen. There was no marked effect of PB treatment in the early and late stages. These findings suggest that single use of PB has little effect on atherosclerosis of a hyperglycemia-hyperlipidemia animal model.