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Optic nerve injury (ONI) induces retinal ganglion cell (RGC) death and optic nerve atrophy that lead to visual loss. Apoptosis signal-regulating kinase 1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase (MAPK) kinase kinase and has an important role in stress-induced RGC apoptosis. In this study, we found that ONI-induced p38 activation and RGC loss were suppressed in ASK1-deficient mice. Sequential in vivo retinal imaging revealed that post-ONI treatment with a p38 inhibitor into the eyeball was effective for RGC protection. ONI-induced monocyte chemotactic protein-1 production in RGCs and microglial accumulation around RGCs were suppressed in ASK1-deficient mice. In addition, the productions of tumor necrosis factor and inducible nitric oxide synthase in microglia were decreased when the ASK1-p38 pathway was blocked. These results suggest that ASK1 activation in both neural and glial cells is involved in neural cell death, and that pharmacological interruption of ASK1-p38 pathways could be beneficial in the treatment of ONI. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the feasibility of estimating functional ischemia information from coronary artery computed tomography (CACT) data (i.e., morphological information). Fifty-five suspected ischemic heart disease patients were included in this study. To calculate the ischemic myocardium percentage (LV myocardial territories volume of distal portion the stenotic lesion/total LV myocardial volume) from CACT data with "coronary territories analysis, Ziostation2", and compared with the ischemic LV myocardium percentage and the functional flow reserve (FFR). The results showed that ischemic LV myocardium percentage was correlated with the FFR (r=-0.57). The median ischemic LV myocardium percentage of the FFR-positive group (n=33) was 37.1% (interquartile range [IQR] 33, 41.4%) and that of the FFR-negative group (n=22) was 24.8% (IQR 19.6, 30.6%). The ischemic LV myocardium percentage was significantly higher in the FFR-positive group (p<0.01) than in the FFR-negative group. The receiver operating characteristic (ROC) curve showed that the cutoff value for the ischemic LV myocardium percentage was 30%, with the sensitivity of 90.9% and the specificity of 77.3%. In conclusion, myocardial ischemia to diagnosis of FFR may occur when ischemic LV myocardium percentage is over than 30% and is unlikely to occur when it is less than 30%. This study suggests that the analysis of CACT data may contribute to the diagnosis of functional ischemia.

Background: Fractional flow reserve (FFR) is used to evaluate the need for percutaneous coronary intervention (PCI) in cases of moderate stenosis of the coronary artery. Recently, diagnostic imaging support with computational fluid dynamics (CFD) analysis has been garnering attention. This study defines the relationship between FFR conducted for cardiac catheterization and CFD analyses conducted using coronary computed tomography (CT) for moderate stenosis, in addition to considering whether wall pressure (WP) and wall shear stress (WSS) can be used to evaluate ischemia. Methods and Results: Cases in which FFR was measured via coronary CT and cardiac catheterization was performed within 3 months were collected retrospectively. In the CFD analysis, WP and WSS were calculated and compared with FFR. Three groups were created to compare results of CFD analysis and FFR values according to the location of the stenosis: the right coronary artery, the left anterior descending artery, and the left circumflex artery. There was a correlation between FFR and WSS according to CFD analysis for moderate stenosis of the coronary artery, with a cut-off value for treatment able to be calculated. Conclusions: The results of this study suggest that ischemia can be evaluated by conducting CFD analysis (WSS) using coronary CT., Competing Interests: There is no conflict of interest to disclose., (Copyright © 2020, THE JAPANESE CIRCULATION SOCIETY.)

It is important to optimize the exposure dose when conducting interventional radiology, but optimization is difficult for medical centers to achieve independently. In 2005, we administered a questionnaire on the measurement of dose rates and awareness of exposure reduction when performing percutaneous coronary intervention. Ten years later, we conducted a follow-up survey of the same 31 centers to determine the current situation and identify trends. The results of the survey showed that the mean fluoroscopy dose rate decreased to 55% of the 2005 value, from 28.2 to 15.6 mGy/min, and the mean radiography dose rate decreased to 71% of the 2005 value, from 4.2 to 3.0 mGy/s. Dose rates for both fluoroscopy and radiography decreased by 84% of facilities. The results also indicated greater cooperation by physicians compared to 10 years ago. In particular, there was a considerable increase in the exchange of ideas with physicians regarding exposure, suggesting a stronger level of interest in exposure. The overall score for questionnaire items was 33% higher than that in the previous survey. These results show that in the past 10 years, awareness of exposure reduction has improved, and dose optimization has been a major factor in the downward trend in dose rates in radiography and fluoroscopy.

The quality of the present day fluoroscopic images is sufficiently high for use as exposure images depending on the environment where the fluoroscopic images are recorded. In some facilities which use fluoroscopic images as exposure images they are recorded with a radiological x-ray diagnostic device equipped with a fluoroscopic storage function. There are, however, cases where fluoroscopic images cannot be used as exposure images because the quality of the fluoroscopic image cannot be assured in the environment where the fluoroscopic images are recorded. This poses problems when stored fluoroscopic images are used in place of exposure images without any clearly established standard. In the present study, we establish that stored fluoroscopic images can be used as exposure images by using gray values obtained from profile curves. This study finds that replacement of stored fluoroscopic images with exposure images requires 20.1 or higher gray scale value differences between the background and signal, using a 20 cm thick acrylic phantom (here an adult abdomen as representing the human body) as the specific geometry. This suggests the conclusion that the gray value can be considered a useful index when using stored fluoroscopic images as exposure images., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: We conducted a multicenter study to investigate the current status of difference between the actual values at the patient entrance reference point (PERP) and display air kerma., Methods: We exposure dose and fluoroscopy dose were measured by 32 apparatuses at 32 member institutions of the Japanese Society of Circulation Imaging Technology (CITEC) under unified conditions, and the actual measured values and display air kerma were compared. We entrance doses during fluoroscopy and imaging were measured at the PERP, with focus detector distance (FDD) 110 cm, a copper plate of 3.5 mm in thickness adhered to the front face of flat panel detector (FPD) as absorber, field-of-view (FOV) 18 cm, and the frame rate of 15 f/s, excluding the bed. Display air kerma were recorded at the same time. JIS (Z 4751-2-43: 2012) specify "The reference air kerma rate and the cumulative reference air kerma shall not deviate from their respective display air kerma by more than ±35% over the range of 6 mGy/min and 100 mGy to the maximum value." The number of apparatuses display air kerma deviated from this condition and its percentage were obtained., Results: The mean difference percentage between actual measured values and display air kerma in 32 apparatuses was approximately 15.6%, with some apparatuses showing substantially different display air kerma., Conclusion: In order to estimate patients' skin exposure dose from display air kerma more accurately, it is necessary to perform calibration of the apparatus by regular dose measurement or convert values.

In recent years, reports have been made that predict the state of aneurysm by performing computational fluid dynamics (CFD) analysis using cerebral aneurysm blood flow analysis software. However, analysis results are not constant and there are various opinions, and it is conceivable that the image quality and analysis conditions of medical images used for CFD analysis are not standardized. In this study, CFD analysis of cerebral aneurysm phantom was performed, and image quality and analysis conditions were standardized. Then, we investigated whether increase of cerebral aneurysm and prediction of rupture are possible. From this study, stable results of wall shear stress analysis were obtained under slice thickness 1.0 mm or less, CT value 400 HU or more, reconstruction function as soft part function, image SD under 10 HU. In addition, as the size of the cerebral aneurysm became larger, wall shear stress tended to be lower, and the same tendency was shown also in clinical cases. Although CFD analysis using software dedicated to blood flow analysis did not reach the prediction of rupture, it can be evaluated based on the quantitative values for the aneurysm increase at the preceding stage and plays an important role in prediction there is a possibility.

Following recent rapid advances in devices and treatment technology, indications for percutaneous peripheral intervention (PPI) have been expanded to include complex lesions (long-segment lesions, completely obstructed chronic lesions, etc.) and even lesions of the superficial femoral artery and arteries distal to the popliteal artery. However, when PPI is used for treatment of complete obstruction, treatment can take a long time or its outcome can be less satisfactory for reasons such as difficulty in assessing the vascular distribution/arrangement or the direction of calcification in the obstructed area or excessively long lesions. In the present study, we conducted three-dimensional image processing of CT data from leg arteries conventionally used for preoperative diagnosis. Using this processing technique, we created virtual images of the blood vessels of the completely obstructed area and mapped these virtual vessel images onto the fluoroscopic monitor image during catheter treatment. The usefulness of this technique for PPI was then evaluated. We succeeded in creating virtual vessel images of the completely obstructed parts of leg arteries with the use of preoperative CT images of leg arteries that we then mapped onto the fluoroscopic monitor images during treatment. We were successful in mapping virtual images onto the abdominal aorta in 96.8% of cases and in 95.7% with the common iliac artery. This technique is thus able to supply reliable information on vascular distribution/arrangement, suggesting that it can enable the surgeon to advance the treatment device precisely along the vessels, making it useful for treatment with PPI. The study additionally showed that differences in the angle of imaging affect the manual mapping of the CT images onto angiograms.

Dock3, a new member of the guanine nucleotide exchange factor family, causes cellular morphological changes by activating the small GTPase Rac1. Overexpression of Dock3 in neural cells promotes neurite outgrowth through the formation of a protein complex with Fyn and WAVE downstream of brain-derived neurotrophic factor (BDNF) signaling. Here, we report a novel Dock3-mediated BDNF pathway for neurite outgrowth. We show that Dock3 forms a complex with Elmo and activated RhoG downstream of BDNF-TrkB signaling and induces neurite outgrowth via Rac1 activation in PC12 cells. We also show the importance of Dock3 phosphorylation in Rac1 activation and show two key events that are necessary for efficient Dock3 phosphorylation: membrane recruitment of Dock3 and interaction of Dock3 with Elmo. These results suggest that Dock3 plays important roles downstream of BDNF signaling in the central nervous system where it stimulates actin polymerization by multiple pathways., (© 2012 The Authors Journal compilation © 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.)

(123)I-MIBG Heart-to-Mediastinum activity ratio (H/M) is commonly used as an indicator of relative myocardial (123)I-MIBG uptake. H/M ratios reflect myocardial sympathetic nerve function, therefore it is a useful parameter to assess regional myocardial sympathetic denervation in various cardiac diseases. However, H/M ratio values differ by site, gamma camera system, position and size of region of interest (ROI), and collimator. In addition to these factors, 529 keV scatter component may also affect (123)I-MIBG H/M ratio. In this study, we examined whether the H/M ratio shows correlation between two different gamma camera systems and that sought for H/M ratio calculation formula. Moreover, we assessed the feasibility of (123)I Dual Window (IDW) method, which is a scatter correction method, and compared H/M ratios with and without IDW method. H/M ratio displayed a good correlation between two gamma camera systems. Additionally, we were able to create a new H/M calculation formula. These results indicated that the IDW method is a useful scatter correction method for calculating (123)I-MIBG H/M ratios.

Gangliosides, sialic acid-containing glycosphingolipids, have been considered to play roles as neurotrophic factors. Exogenous gangliosides added to the culture medium of neuronal cells or injected in artificially injured sites of nerve tissues actually showed neurotrophic factor-like effects such as neurite extension and alleviation of nerve tissue deterioration. In this study, neuroregeneration in the mutant mice lacking complex gangliosides was examined. To determine whether the nervous system maintains regenerative activity in the long-term absence of complex gangliosides, we analyzed hypoglossal nerve regeneration after axotomy in the mutant mice of GM2/GD2 synthase. These mice exhibited marked impairment of regenerative activity both in the number of surviving neurons and in the number of peroxidase-positive neurons. Moreover, reduced levels of gene expression of neurotrophic factors and their receptors including CNTF, p75 NTR, TrkB, and others in hypoglossal neurons were observed in real-time reverse transcription-polymerase chain reaction combined with laser capture microdissection, suggesting that these molecules are, at least partly, involved in the regeneration of lesioned nerves and that their expression levels are precisely controlled in the presence of intact expression of complex gangliosides.

GM2/GD2 synthase gene knockout mice lack all complex gangliosides, which are abundantly expressed in the nervous systems of vertebrates. In turn, they have increased precursor structures GM3 and GD3, probably replacing the roles of the depleted complex gangliosides. In this study, we found that 9-O-acetyl GD3 is also highly expressed as one of the major glycosphingolipids accumulating in the nervous tissues of the mutant mice. The identity of the novel component was confirmed by neuraminidase treatment, thin layer chromatography-immunostaining, two-dimensional thin layer chromatography with base treatment, and mass spectrometry. All candidate factors reported to be possible inducer of 9-O- acetylation, such as bitamine D binding protein, acetyl CoA transporter, or O-acetyl ganglioside synthase were not up-regulated. Tis21 which had been reported to be a 9-O-acetylation inducer was partially down-regulated in the null mutants, suggesting that Tis21 is not involved in the induction of 9-O-acetyl-GD3 and that accumulated high amount of GD3 might be the main factor for the dramatic increase of 9-O-acetyl GD3. The ability to acetylate exogenously added GD3 in the normal mouse astrocytes was examined, showing that the wild-type brain might be able to synthesize very low levels of 9-O-acetyl GD3. Increased 9-O-acetyl GD3, in addition to GM3 and GD3, may play an important role in the compensation for deleted complex gangliosides in the mutant mice.

alpha2,8-Sialyltransferase (alpha2,8S-T, GD3 synthase) has been reported to be involved in the enhanced cell proliferation of malignant tumors. Using a cloned cDNA of alpha2,8S-T, transfectant cells were established and the effects of the gene expression on the cell phenotypes were analyzed. In contrast with PC12 cells, in which we reported marked growth enhancement based on the transfection of alpha2,8S-T, Swiss3T3 cells showed no enhancement in either cell proliferation or phosphorylation of MAP kinases after the transfection of alpha2,8S-T when treated with platelet-derived growth factor. Correspondingly, the receptor for platelet-derived growth factor also showed no increased phosphorylation upon the factor stimulation. However, in the wound-healing scratching assay, the Swiss3T3 transfectant cells demonstrated increased mobility as the PC12 transfectant cells. These results suggest that the enhancing effects of alpha2,8S-T on the proliferation and mobility are differential depending on the cell types, and ganglioside-associating molecules in the individual cell types need to be investigated.