Search

Purpose: This study aimed to facilitate research progress in MR elastography (MRE) by providing a versatile and convenient application for MRE reconstruction, namely the MRE research tool (MRE-rTool). It can be used for a series of MRE image analyses, including phase unwrapping, arbitrary bandpass and directional filtering, noise assessment of the wave propagation image (motion SNR), and reconstruction of the elastogram in both 2D and 3D MRE acquisitions. To reinforce the versatility of MRE-rTool, the conventional method of motion SNR was modified into a new method that reflects the effects of image filtering., Methods: MRE tests of the phantom and liver were performed using different estimation algorithms for stiffness value (algebraic inversion of the differential equation [AIDE], local frequency estimation [LFE] in MRE-rTool, and multimodel direct inversion [MMDI] in clinical reconstruction) and acquiring dimensions (2D and 3D acquisitions). This study also tested the accuracy of masking low SNR regions using modified and conventional motion SNR under various mechanical vibration powers., Results: The stiffness values estimated using AIDE/LFE in MRE-rTool were comparable to that of MMDI (phantom, 3.71 ± 0.74, 3.60 ± 0.32, and 3.60 ± 0.54 kPa in AIDE, LFE, and MMDI; liver, 2.26 ± 0.31, 2.74 ± 0.16, and 2.21 ± 0.26 kPa in AIDE, LFE, and MMDI). The stiffness value in 3D acquisition was independent of the direction of the motion-encoding gradient and was more accurate than that of 2D acquisition. The masking of low SNR regions using the modified motion SNR worked better than that in the conventional motion SNR for each vibration power, especially when using a directional filter., Conclusion: The performance of MRE-rTool on test data reached the level required in clinical MRE studies. MRE-rTool has the potential to facilitate MRE research, contribute to the future development of MRE, and has been freely released online.

Fullerene whiskers (FLW)s are thin rod-like structures composed of C 60 and C 70 fullerene (FL). The shape of FLWs suggests potential toxic effects including carcinogenicity to the lung and pleura, similar to effects elicited by asbestos and multi-walled carbon nanotubes (MWCNT)s. However, no long-term carcinogenic studies of FL or FLW have been conducted. In the present study we investigated the pulmonary and pleural carcinogenicity of FL and FLW. Twelve-week-old male F344 rats were administered 0.25 or 0.5 mg FL, FLW, MWCNT-7, and MWCNT-N by intra-tracheal intra-pulmonary spraying (TIPS). Acute lung lesions and carcinogenicity were analyzed at 1 and 104 weeks after 8 doses/15 days TIPS administration. At week 1, FLW, MWCNT-7, and MWCNT-N significantly increased alveolar macrophage infiltration. Expression of Ccl2 and Ccl3, reactive oxygen species production, and cell proliferation were significantly increased by administration of MWCNT-7 and MWCNT-N but not FL or FLW. At week 104, the incidence of bronchiolo-alveolar adenoma plus adenocarcinoma was significantly increased in the MWCNT-7 and MWCNT-N groups, and the incidence of mesothelioma was significantly increased in the MWCNT-7 group. No significant induction of pulmonary or pleural tumorigenesis was observed in the FL or FLW groups. The number of 8-OHdG-positive cells in the alveolar epithelium was significantly increased in the MWCNT-7 and MWCNT-N groups but not in the FL or FLW groups. FL and FLW did not exert pulmonary or pleural carcinogenicity in our study. In addition, oxidative DNA damage was implicated in MWCNT-induced lung carcinogenesis, suggesting that it may be a useful initial marker of carcinogenicity., (© 2024. The Author(s).)

The aim of this study was to develop a vibration pad suitable for renal MR elastography (MRE). Chronic kidney disease (CKD) is a progressive condition affecting >800 million people worldwide. Renal fibrosis is a common pathological feature of CKD that causes fibrotic regions to be much stiffer than those in normal renal tissues. Therefore, MRE can be used to diagnose CKD because it can image organ stiffness. In MRE, the shear modulus is obtained from the wavelength of the shear waves. Therefore, it is highly important to propagate shear waves with sufficient vibration strength in the tissue. By using a three-dimensional (3D) printer, we created a "Flexible Pad" suitable for renal MRE. The Flexible Pad was placed under the back of the participant in the supine position and deformed in response to the participant's weight, adhering closely to the body surface. Six healthy volunteers participated in this study. Our Flexible Pad allowed for coherent shear waves (clear waves with little scattering and interference) to be efficiently transmitted to the kidney deep-lying tissues in the abdomen. The shear moduli of the kidney (n = 6) were 8.95 ± 0.84 kPa in the right kidney and 9.70 ± 0.99 kPa in the left kidney. Our results indicate that using our Flexible Pad for renal MRE can provide a more reliable measurement of renal shear modulus., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Three-dimensional (3D) magnetic resonance elastography (MRE) is more accurate than two-dimensional (2D) MRE; however, it requires long-term acquisition. This study aimed to reduce the acquisition time of abdominal 3D MRE using a new sample interval modulation (short-SLIM) approach that can acquire all three motions faster while reducing the prolongation of echo time and flow compensation. To this end, two types of phantom studies and an in vivo test of the liver in three healthy volunteers were performed to compare the performances of conventional spin-echo echo-planar (SE-EPI) MRE, conventional SLIM and short-SLIM. One phantom study measured the mean amplitude and shear modulus within the overall region of a homogeneous phantom by changing the mechanical vibration power to assess the robustness to the lowered phase-to-noise ratio in short-SLIM. The other measured the mean shear modulus in the stiff and background materials of a phantom with an embedded stiffer rod to assess the performance of short-SLIM for complex wave patterns with wave interference. The Spearman's rank correlation coefficient was used to assess similarity of elastograms in the rod-embedded phantom and liver between methods. The results of the phantom study changing the vibration power indicated that there was little difference between conventional MRE and short-SLIM. Moreover, the elastogram pattern and the mean shear modulus in the rod-embedded phantom in conventional SLIM and short-SLIM did not change for conventional MRE; the liver test also showed a small difference between the acquisition techniques. This study demonstrates that short-SLIM can provide MRE results comparable to those of conventional MRE. Short-SLIM can reduce the total acquisition time by a factor of 2.25 compared to conventional 3D MRE time, leading to an improvement in the accuracy of shear modulus estimation by suppressing the patient movements., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Carbon fibers are high aspect ratio structures with diameters on the submicron scale. Vapor grown carbon fibers are contained within multi-walled carbon tubes, with VGCF™-H commonly applied as a conductive additive in lithium-ion batteries. However, several multi-walled carbon fibers, including MWNT-7, have been reported to induce lung carcinogenicity in rats. This study investigated the carcinogenic potential of VGCF™-H fibers in F344 rats of both sexes with the vapor grown carbon fibers VGCF™-H and MWNT-7 over 2 years. The carbon fibers were administered to rats by intratracheal instillation at doses of 0, 0.016, 0.08, and 0.4 mg/kg (total doses of 0, 0.128, 0.64, and 3.2 mg/kg) once per week for eight weeks and the rats were observed for up to 2 years after the first instillation., Results: Histopathological examination showed the induction of malignant mesothelioma on the pleural cavity with dose-dependent increases observed at 0, 0.128, 0.64, and 3.2 mg/kg in rats of both sexes that were exposed to MWNT-7. On the other hand, only two cases of pleural malignant mesothelioma were observed in the VGCF™-H groups; both rats that received 3.2 mg/kg in male. The animals in the MWNT-7 groups either died or became moribund earlier than those in the VGCF™-H groups, which is thought related to the development of malignant mesothelioma. The survival rates were higher in the VGCF™-H group, and more carbon fibers were observed in the pleural lavage fluid (PLF) of the MWNT-7 groups. These results suggest that malignant mesothelioma is related to the transfer of carbon fibers into the pleural cavity., Conclusions: The intratracheal instillation of MWNT-7 clearly led to carcinogenicity in both male and female rats at all doses. The equivocal evidence for carcinogenic potential that was observed in male rats exposed to VGCF™-H was not seen in the females. The differences in the carcinogenicities of the two types of carbon fibers are thought due to differences in the number of carbon fibers reaching the pleural cavity. The results indicate that the carcinogenic activity of VGCF™-H is lower than that of MWNT-7., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In subcutaneous tumor models, changes in the tumor microenvironment can lead to differences in therapeutic treatment responses between the subcutaneous and parent tumors. Accordingly, we generated a lung carcinogenesis model that combines genetically modified mice (Tg-rasH2 mice) with two-stage chemical carcinogenesis as an alternative to the subcutaneous tumor model. In this model, Tg-rasH2 mice were treated with 1-ethyl-1-nitrosourea, followed by butylhydroxytoluene. Mice developed lung adenomas five weeks after treatment initiation. Subsequently, anti-mouse PD-1 antibody (α-mPD-1) or isotype control was administered intraperitoneally twice a week for 4 weeks. Tumor growth was examined by measuring the relative tumor area in serially sliced lung histopathological specimens. No statistically significant differences were observed in the relative lung tumor areas between treated and control groups. A second experiment then examined the antitumor efficacy of α-mPD-1 combined with gemcitabine in a mouse model. Mice were treated identically as in Experiment 1, except that the treated group received once-weekly intraperitoneal injections of 10 mg/kg gemcitabine. In contrast to Experiment 1, the combined treatment significantly reduced the relative tumor areas in the lungs. This result also resembles that of a phase III clinical trial (ORIENT-12), showing that patients with non-small-cell lung carcinoma benefited from combination treatment with gemcitabine and the anti-human PD-1 antibody sintilimab. Thus, this mouse model could be a feasible means to preclinically evaluate the antitumor efficacy of different immunotherapy and chemotherapy drug combinations., (©2022 The Japanese Society of Toxicologic Pathology.)

This study aimed to analyze the time-course of the physical properties of the psoas major muscle (PM) before and after exercise using magnetic resonance elastography (MRE). Muscle stiffness is one of the important properties associated with muscle function. However, there was no research on the stiffness of the PM after exercise. In this study, we investigated time-course changes of the shear modulus of the PM after exercise. Furthermore, T2 values and apparent diffusion coefficient (ADC), as the additional information associated with muscular physical properties, were also measured simultaneously. Healthy young male volunteers were recruited in this study (n = 9) and they were required to perform a hand-to-knee isometric and unilateral exercise (left side). At each time-point before and after exercise, a set of 3 types of MR scans to measure multiple physical properties of the PM [shear modulus (MRE), T2 values, and ADC] were repeatedly taken. On day 1, a single set MR scan was taken before exercise (pre-exercise MR scan), and 6 sets MR scans were taken (5.5 to 38.0 min after exercise). After about 10-min rest (46.0 to 56.0 min after exercise), 4 sets MR scans were taken (57.5 to 77.0 min after exercise). About 10-min rest was taken again (85.0-95.0 min after exercise), 4 sets MR scans were taken (96.5 to 116.0 min after exercise). On days 2 and 7, a single set MR scan (MRE, T2 value, and ADC) was taken on each experimental day. The data were analyzed as relative changes (%) of the given parameters to the pre-exercise values. The results indicated significant decreases in PM shear modulus up to about 30 min after exercise. Then, it gradually increased and showed significant increases at about 100 min after exercise compared to that before exercise. T2 values and ADC showed significant increases up to about 65 min after exercise compared to those before exercise, and then returned to the pre-exercise values. On days 2 and 7, all values showed no significant changes compared to the pre-exercise values. This study is the first to report the time-course of the physical properties of the PM after exercise., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Antibody levels decrease substantially at 6 months after the BNT162b2 vaccine. The factors influencing titer of antibodies against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among healthcare workers for coronavirus disease 2019 (COVID-19) is unclear., Methods: We conducted a 6-month longitudinal prospective study in Japanese healthcare workers in a tertiary care hospital for COVID-19. Participants in the study were tested for the presence of anti-spike protein (SP) IgG antibodies before and at 1 and 6 months after the last vaccination dose., Results: Among 1076 healthcare workers, 794 received the vaccine, and 469 entered the study. Five were infected with SARS-CoV-2 (none among COVID-19 section workers) by the end of the study and 451 participants were finally analyzed (mean age, 42.5 years; 27.3 % male; 18.8 % COVID-19 section workers). Median SP IgG index values were 0.0, 44.4, and 5.5 before and at 1 and 6 months after the last dose, respectively. Regression analysis revealed a negative correlation of SP IgG antibody levels with age (P < 0.0001), and higher levels in COVID-19 section workers (P = 0.0185) and in females (P = 0.0201)., Conclusion: In healthcare workers at a COVID-19 hospital, IgG antibody titer was substantially lower at 6 months after receipt of the last dose of the BNT162b2 vaccine compared with that 1 month after the last dose, but was better preserved among younger participants, COVID-19 section workers and females., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Background: A mounting number of studies have been documenting the carcinogenic potential of multiwalled carbon nanotubes (MWCNTs); however, only a few studies have evaluated the pulmonary carcinogenicity of MWCNTs in vivo. A 2-year inhalation study demonstrated that MWNT-7, a widely used MWCNT, was a pulmonary carcinogen in rats. In another 2-year study, rats administered MWNT-7 by intratracheal instillation at the beginning of the experimental period developed pleural mesotheliomas but not lung tumors. To obtain data more comparable with rats exposed to MWNT-7 by inhalation, we administered MWNT-7 to F344 rats by intratracheal instillation once every 4-weeks over the course of 2 years at 0, 0.125, and 0.5 mg/kg body weight, allowing lung burdens of MWNT-7 to increase over the entire experimental period, similar to the inhalation study., Results: Absolute and relative lung weights were significantly elevated in both MWNT-7-treated groups. Dose- and time-dependent toxic effects in the lung and pleura, such as inflammatory, fibrotic, and hyperplastic lesions, were found in both treated groups. The incidences of lung carcinomas, lung adenomas, and pleural mesotheliomas were significantly increased in the high-dose group compared with the control group. The pleural mesotheliomas developed mainly at the mediastinum. No MWNT-7-related neoplastic lesions were noted in the other organs. Cytological and biochemical parameters of the bronchoalveolar lavage fluid (BALF) were elevated in both treated groups. The lung burden of MWNT-7 was dose- and time-dependent, and at the terminal necropsy, the average value was 0.9 and 3.6 mg/lung in the low-dose and high-dose groups, respectively. The number of fibers in the pleural cavity was also dose- and time-dependent., Conclusions: Repeated administration of MWNT-7 by intratracheal instillation over the 2 years indicates that MWNT-7 is carcinogenic to both the lung and pleura of rats, which differs from the results of the 2 carcinogenicity tests by inhalation or intratracheal instillation., (© 2022. The Author(s).)

Background: Considering the expanding industrial applications of carbon nanotubes (CNTs), safety assessment of these materials is far less than needed. Very few long-term in vivo studies have been carried out. This is the first 2-year in vivo study to assess the effects of double walled carbon nanotubes (DWCNTs) in the lung and pleura of rats after pulmonary exposure., Methods: Rats were divided into six groups: untreated, Vehicle, 3 DWCNT groups (0.12 mg/rat, 0.25 mg/rat and 0.5 mg/rat), and MWCNT-7 (0.5 mg/rat). The test materials were administrated by intratracheal-intrapulmonary spraying (TIPS) every other day for 15 days. Rats were observed without further treatment until sacrifice., Results: DWCNT were biopersistent in the rat lung and induced marked pulmonary inflammation with a significant increase in macrophage count and levels of the chemotactic cytokines CCL2 and CCL3. In addition, the 0.5 mg DWCNT treated rats had significantly higher pulmonary collagen deposition compared to the vehicle controls. The development of carcinomas in the lungs of rats treated with 0.5 mg DWCNT (4/24) was not quite statistically higher (p = 0.0502) than the vehicle control group (0/25), however, the overall incidence of lung tumor development, bronchiolo-alveolar adenoma and bronchiolo-alveolar carcinoma combined, in the lungs of rats treated with 0.5 mg DWCNT (7/24) was statistically higher (p < 0.05) than the vehicle control group (1/25). Notably, two of the rats treated with DWCNT, one in the 0.25 mg group and one in the 0.5 mg group, developed pleural mesotheliomas. However, both of these lesions developed in the visceral pleura, and unlike the rats administered MWCNT-7, rats administered DWCNT did not have elevated levels of HMGB1 in their pleural lavage fluids. This indicates that the mechanism by which the mesotheliomas that developed in the DWCNT treated rats is not relevant to humans., Conclusions: Our results demonstrate that the DWCNT fibers we tested are biopersistent in the rat lung and induce chronic inflammation. Rats treated with 0.5 mg DWCNT developed pleural fibrosis and lung tumors. These findings demonstrate that the possibility that at least some types of DWCNTs are fibrogenic and tumorigenic cannot be ignored., (© 2022. The Author(s).)

Musa basjoo (MB) is a species of the banana plant belonging to the genus Musa that has been used as a folk medicine. However, evidence-based biological activities and the molecular mechanism of action of MB are unknown. Thus, the aim of the present study was to examine whether the crude dried leaf extracts of MB inhibit the growth of colorectal (HT29 and HCT116) and other types (HepG2, MCF-7 and PC-3) of human cancer cell lines. Crude extracts of MB inhibited the growth of cells with IC 50 values of 136 µg/ml (acetone extract, HT29), 51 µg/ml (acetone extract, HCT116), 45 µg/ml (acetone extract, HepG2), 40 µg/ml (acetone extract, MCF-7), 29 µg/ml (acetone extract, PC-3), 175 µg/ml (methanol extract, HT29), 137 µg/ml (methanol extract, HCT116), 102 µg/ml (methanol extract, HepG2), 85 µg/ml (methanol extract, MCF-7), and 85 µg/ml (methanol extract, PC-3) in colony formation assays, and 126 µg/ml (acetone extract, HT29), 68 µg/ml (acetone extract, HCT116), 260 µg/ml (methanol extract, HT29), and 216 µg/ml (methanol extract, HCT116) in MTT assays. Thin layer chromatography analysis revealed the potential existence of aromatic compounds in the acetone extract of MB. Flow cytometric analysis indicated that the percentage of cells in G1 increased, and this was associated with a concomitant decrease of cells in the S and/or G2-M phases of the cell cycle. When colorectal cancer cells were treated with acetone extract of MB, there was a marked decrease in the levels of expression of the cyclin D1, cyclin E, cdk2 and cdk4 proteins and a marked increase in the levels of the expression of the p21 CIP1 , p27 KIP1 , and p53 proteins, but those of apoptosis-associated protein PARP did not change. There was a tendency for acetone extract of MB to inhibit xenograft tumor growth in mice. Collectively, the crude extracts of MB contain active components that exert growth inhibition of human cancer cells. This is the first systematic study of the anticancer activity of MB and may broaden insights into the possible clinical approach of specific herbal medicines., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Matsumoto et al.)

This study aims to develop and assess a new automated processing technique in MR elastography (MRE), namely coherent-wave auto-selection (CHASE). CHASE enables automatic selection of the region of interest (ROI) for stiffness measurement by extraction of the coherent wave region (CHASE ROI), and it improves the reconstruction of stiffness by a directional filter oriented along the main wave in each pixel (CHASE filtering). In this study, MRE of a phantom and of the liver of four healthy volunteers was performed. To investigate the potential of CHASE, this study assessed the CHASE according to three indices through the phantom study: 1) agreement on the ROI settings between CHASE and expert observers, 2) noise dependency, and 3) effect of the CHASE on stiffness variability within the CHASE ROI. The agreements on the ROI settings were analyzed by Cohen's kappa coefficient (κ). The noise dependency was analyzed by the mean absolute percentage errors (MAPEs) within the ROI between low (20%-80% amplitudes) and high vibration amplitudes (100% amplitude). The stiffness variability was assessed by standard deviation (SD) within the ROI. In the volunteer study, agreements on the ROI settings (or stiffness value) and stiffness variability within the CHASE ROI were assessed using κ-value (or intraclass correlation coefficient: ICC) and coefficient of variation, respectively. The results showed close agreement on the ROI settings and stiffness (κ-value: greater than 0.61 in both the phantom and volunteer studies, ICC: 0.97 in the volunteer study). The MAPEs within the CHASE ROI were much smaller than those in the whole region of the phantom (CHASE ROI vs. the whole region at 20% amplitude: 10.3% vs. 50.8%). Moreover, in both the phantom and volunteer studies, the stiffness variation within the CHASE ROI was smaller in the elastogram processed with CHASE filtering than in the unprocessed one. Our results demonstrated that the CHASE has high robustness against noise and the potential to provide ROI settings for stiffness measurement comparable to expert observers, as well as improve the reconstruction of stiffness., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Recently, intratracheal instillation has been focused on as a simple, low-cost alternative to the inhalation method. In this study, intratracheal instillation of sulfuric acid, a typical acidic compound, was performed to compare the acute toxicity of acidic compounds that could cause damage to the respiratory system between intratracheal instillation and inhalation. Sulfuric acid was administered to male rats at doses of 0.7, 2, 7, 20, and 60 mg/kg by dividing the total dose into four doses. General condition and body weight were examined up to 14 days after administration, and macropathological and histopathological examinations were performed. The half-lethal dose was then estimated. All animals administered 20 and 60 mg/kg sulfuric acid and one animal administered 2 mg/kg sulfuric acid died within 4 h after administration. No abnormalities were observed in other animals. At 20 and 60 mg/kg, multiple red foci or diffuse red areas were macroscopically observed in the lungs. In these lesions, histopathologically, clefts between the mucosal epithelium and basement membrane and necrosis of the alveolar epithelium were observed. Deaths in these groups may have resulted from lung injury. No notable changes were observed in other animals. Therefore, the half-lethal dose of sulfuric acid by intratracheal instillation was estimated as 7-20 mg/kg. The acute toxicity by intratracheal instillation was evaluated with two-fold sensitivity since the exposure at the half-lethal sulfuric acid concentration in inhalation studies was calculated as 43.2 mg/kg., Competing Interests: The authors declare no conflicts of interest., (©2021 The Japanese Society of Toxicologic Pathology.)

Background: Digital radiography (DR) is grayscale adjustable and it can be unclear whether an acquired DR image is captured with the minimum radiation dose required. It is necessary to make an image of the amount of noise when taken at a lower dose than the acquired image, without increased exposure., Objective: To examine whether an image of unacquired dose can be created from two types of dose DR images acquired using a phantom., Methods: To create an additive image from two images of different doses, the pixel value of one image is multiplied by a coefficient and added to the other. The normalized noise power spectra (NNPS) of the normal image and the additive image with the same signal-to-noise ratio (SNR) are compared. The image noise of the unacquired doses is estimated from the graph changes of the pixel values and standard deviations of two images. The error between the SNR of the image obtained by changing the dose and the estimated SNR is measured. We propose a multiplication coefficient calculation formula that theoretically adjusts the additive image to the target SNR. The SNR error of the image created based on this formula is measured., Results: The NNPS curves of the additive and normal images show a difference on the high frequency side. According to the statistics considering the preset of mAs value, there is no significant difference at 85%. The SNR estimation error is approximately 1%. The SNR error of the additive image created based on the formula is approximately 5%., Conclusion: The noise of the image of unacquired dose can be estimated, and the additive image adjusted to this value can be considered equivalent to the image taken at the actual dose.

Carbon fibers have excellent physicochemical and electrical properties. Vapor-grown carbon fibers are a type of carbon fibers that have a multi-walled carbon tube structure with a high aspect ratio. The representative vapor-grown carbon fiber, VGCF TM -H, is extremely strong and stable and has superior thermal and electrical conductivity. Because some high-aspect-ratio multi-walled carbon nanotubes (MWCNTs) have been reported to have toxic and carcinogenic effects in the lungs of rodents, we performed a 13-week lung toxicity study using VGCF TM -H in comparison with one of MWCNTs, MWNT-7, in rats. Male and female F344 rats were intratracheally administered VGCF TM -H at doses of 0.2, 0.4, and 0.8 mg/kg bw or MWNT-7 at doses of 0.4 and 0.8 mg/kg bw once a week for 8 weeks and then up to week 13 without treatment. The lung burden was equivalent in the VGCF TM -H and MWNT-7 groups; however, the lung weight had increased and the inflammatory and biochemical parameters in the broncho-alveolar lavage fluid and histopathological parameters, including inflammatory cell infiltration, alveolar type II cells proliferation, alveolar fibrosis, pleural fibrosis, lung mesothelium proliferation, and diaphragm fibrosis, were milder in the VGCF TM -H group than in the MWNT-7 group. In addition, the proliferating cell nuclear antigen (PCNA)-positive index in the visceral and pleural mesothelium was significantly higher in the MWNT-7 group than in the controls, but not in the VGCF TM -H group. Thus, the results of this study indicate that the lung and pleural toxicities of VGCF TM -H were less than those of MWNT-7., (©2021 The Japanese Society of Toxicologic Pathology.)

Background: Multi-walled carbon nanotubes can be divided into two general subtypes: tangled and straight. MWCNT-N (60 nm in diameter) and MWCNT-7 (80-90 nm in diameter) are straight-type MWCNTs, and similarly to asbestos, both are carcinogenic to the lung and pleura when administered to rats via the airway. Injection of straight-type MWCNTs into the peritoneal cavity also induces the development of mesothelioma, however, injection of tangled-type MWCNTs into the peritoneal cavity does not induce carcinogenesis. To investigate these effects in the lung we conducted a 2-year comparative study of the potential carcinogenicities of a straight-type MWCNT, MWCNT-A (approximately 150 nm in diameter), and a tangled-type MWCNT, MWCNT-B (7.4 nm in diameter) after administration into the rat lung. Crocidolite asbestos was used as the reference material, and rats administered vehicle were used as the controls. Test materials were administered by intra-Tracheal Intra-Pulmonary Spraying (TIPS) once a week over a 7 week period (8 administrations from day 1 to day 50), followed by a 2-year observation period without further treatment. Rats were administered total doses of 0.5 or 1.0 mg MWCNT-A and MWCNT-B or 1.0 mg asbestos., Results: There was no difference in survival between any of the groups. The rats administered MWCNT-A or asbestos did not have a significant increase in bronchiolo-alveolar hyperplasia or tumors in the lung. However, the rats administered MWCNT-B did have significantly elevated incidences of bronchiolo-alveolar hyperplasia and tumors in the lung: the incidence of bronchiolo-alveolar hyperplasia was 0/20, 6/20, and 9/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively, and the incidence of adenoma and adenocarcinoma combined was 1/19, 5/20, and 7/20 in the vehicle, 0.5 mg MWCNT-B, and 1.0 mg MWCNT-B groups, respectively. Malignant pleural mesothelioma was not induced in any of the groups., Conclusions: The results of this initial study indicate that tangled-type MWCNT-B is carcinogenic to the rat lung when administered via the airway, and that straight-type MWCNT-A did not have higher carcinogenic potential in the rat lung than tangled-type MWCNT-B.

The purpose of this study was to determine an optimal condition (vibration frequency and image filtering) for stiffness estimation with high accuracy and stiffness measurement with high repeatability in magnetic resonance elastography (MRE) of the supraspinatus muscle. Nine healthy volunteers underwent two MRE exams separated by at least a 30 min break, on the same day. MRE acquisitions were performed with a gradient-echo type multi-echo MR sequence at 75, 100, and 125 Hz pneumatic vibration. Wave images were processed by a bandpass filter or filter combining bandpass and directional filters (bandpass-directional filter). An observer specified the region of interest (ROI) on clear wave propagation in the supraspinatus muscle, within which the observer measured the stiffness. This study assessed wave image quality according to two indices, as a substitute for the assessment of the accuracy of the stiffness estimation. One is the size of the clear wave propagation area (ROI size used to measure the stiffness) and the other is the qualitative stiffness resolution score in that area. These measurements made by the observer were repeated twice at least one month apart after each MRE exam. This study assessed the intra-examiner and observer repeatability of the stiffness value, ROI size and resolution score in each combination of vibration frequency and image filter. Repeatability of the data was analyzed using the intraclass correlation coefficient (ICC) and 95% limits-of-agreement (LOA) in Bland-Altman analysis. The analyses on intra-examiner and observer repeatability of stiffness indicated that the ICC and 95% LOA were not varied greatly depending on vibration frequency and image filter (intra-examiner repeatability, ICC range, 0.79 to 0.88; 95% LOA range, ±23.95 to ±32.42%, intra-observer repeatability, ICC range, 0.98 to 1.00; 95% LOA range, ±5.10 to ±10.99%). In the analyses on intra-examiner repeatability of ROI size, ICCs were rather low (ranging from: 0.03 to 0.69) while 95% LOA was large in all the combinations of vibration frequency and image filter (ranging from: ±62.66 to ±83.33%). In the analyses on intra-observer repeatability of ROI size, ICCs were sufficiently high in the total combination of vibration frequency and image filter (ranging from 0.80 to 0.87) while the 95% LOAs were better (lower) in the bandpass-directional filter than the bandpass filter (bandpass directional filter vs. bandpass filter, ±28.81 vs. ±54.83% at 75 Hz; ±25.63 vs. ±37.83% at 100 Hz; ±34.51 vs. ±43.36% at 125 Hz). In the analyses on intra-examiner and observer repeatability of resolution score, the mean difference (bias) between the two exams (or observations) was significantly low and there was almost no difference across all the combinations of vibration frequency and image filter (range of bias: -0.11-0.11 and -0.17-0.00, respectively). Additionally, effects of vibration frequency and image filter on wave image quality (ROI size and resolution score) were assessed separately in each exam. Both mean ROI size and resolution score in the bandpass-directional filter were larger than those in the bandpass filter. Among the data in the bandpass-directional filter, mean ROI size was larger at 75 and 100 Hz, and mean resolution score was larger at 100 and 125 Hz. Taking into consideration with the results of repeatability and wave image quality, the present results suggest that optimal vibration frequency and image filter for MRE of the supraspinatus muscles is 100 Hz and bandpass-directional filter, respectively., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: In this study, in order to investigate the usefulness of intratracheal instillation in assessing the pulmonary toxicity of nanomaterials, intratracheal instillation of nickel oxide-nanoparticles (NiO-NP) was performed., Methods: In this study, rats were administered test materials by intratracheal instillation at five different research institutions in order to assess the validity of using intratracheal instillation for hazard identification of nanomaterials. Eight-week-old male SD rats were administered NiO-NP dispersed in deionized water by a single intratracheal instillation at doses of 0 (vehicle control), 0.2, 0.67, and 2 mg/kg BW. Three days after instillation, histopathological examination of the lungs was performed., Results: NiO-NP was distributed in the vicinity of hilus of the lung and in the alveoli around the bronchioles. Histopathological changes such as degeneration/necrosis of macrophages, inflammation, and proliferation of type II pneumocyte in the lung were observed, and their severity corresponded with increasing dose. The histopathological observations of pulmonary toxicity were almost similar at each institution., Conclusion: The similarity of the histopathological changes observed by five independent groups indicates that intratracheal instillation can be a useful screening method to detect the pulmonary toxicity of nanomaterials., (© 2020 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Intratracheal instillation is the introduction of a substance directly into the trachea. Intratracheal instillation has been used to investigate the lung toxicity of several chemicals and requires the suspension or dissolution of test material in a vehicle for even dispersal throughout the lung. Importantly, the toxicities of vehicles used in intratracheal instillation studies are generally considered to be insignificant. Hence, evaluating the influence of different vehicles on the lung due to intratracheal instillation is crucial. We examined the toxic effects of pure water, saline, phosphate buffered saline (PBS), 0.5% Kolliphor ® P188 (KP188), 0.1% Tween 20 in saline, and 1.0% BSA in PBS. These vehicles were administered to male Crl:CD(SD) rats by a single intratracheal instillation. On day 3, broncho-alveolar lavage fluid (BALF) from the right lung was collected and processed for cell counting and biochemical analysis, while the left lung was used for histopathological examination. Accumulation of alveolar macrophages was observed in all vehicle-treated groups but was minimal in the group administered saline, somewhat higher in the groups administered pure water, PBS, 0.1% Tween 20, and 1% BSA, and notably higher in the group administered 0.5% KP188. The results from BALF analysis indicated that intratracheal instillation of 0.5% KP188 also induced alveolar damage. Additionally, administering pure water did not appear to cause tissue damage. Eosinophil infiltration in the interstitial regions was histopathologically observed. Altogether, the results of this study are helpful for the selection of appropriate vehicles for use in intratracheal instillation studies., Competing Interests: The authors have no conflict of interest., (©2020 The Japanese Society of Toxicologic Pathology.)

Some radiologic patient positioning techniques that can be used for X-ray examinations can be difficult to apply. One method involves using ultra-low-dose X-ray images to confirm positioning. These positioning images are typically discarded and not used for diagnosis. The purpose of this study was to improve the signal-to-noise ratio (SNR) in diagnostic imaging by including these ultra-low-dose positioning images rather than discarding them. To add two images together, we devised a method in which one image is multiplied by the coefficient calculated from its SNR before the addition. The images were dichotomized into a high SNR group and a low SNR group. The images in the high SNR group and the low SNR group were summed. When doing so, the images of the low SNR group were multiplied. There was one maximum SNR point while the SNR was being changed. The maximum SNR of the synthesized images was equal to the value of the square root of the sum of the squares of the two images. The multiplication coefficient, in the case of the maximum SNR, was near 1 when an image agreed with the Poisson distribution; when it did not, it was far from 1. The difference between the calculated values of the hypothetical measurement of the multiplication coefficient was small. In this study, we showed that improving SNR of a diagnostic image could be achieved by adding a positioning image. The multiplication coefficient in the case of the SNR maximum of a synthesized image is calculable. The measurement of a Wiener spectrum is needed for noise evaluation. There can be problems where there is motion after a positioning image is exposed.

The present study aimed to develop vibration techniques for magnetic resonance (MR) elastography (MRE) of the psoas major muscle (PM). Seven healthy volunteers were included. MRE was performed with motion-encoding gradient (MEG)-less multi-echo MRE sequence, which allows clinicians to perform MRE using conventional MR imaging. In order to transmit mechanical vibration of the pneumatic type to the PM, a long narrow vibration pad was designed using a 3D printer, and the optimum vibration techniques were verified. The vibration pad was placed under the lower back, with the volunteers in the supine position. The results indicated that the PM vibrated well through the transmitted vibration from the lumbar spine, which suggests that the placement of a narrow vibration pad under the supine body, along the lumbar spine, allows the vibration of the PM. The shear modulus of the PM (n = 7) was 1.23 ± 0.09 kPa (mean ± SEM) on the right side and 1.22 ± 0.15 kPa on the left side, with no significant difference (t-test, P > 0.05). Increased stiffness of the muscle due to continuous local contraction may be an important cause of non-specific low back pain (LBP). The present vibration techniques for MRE of the PM provide a quantitative diagnostic tool for changes in muscle stiffness associated with non-specific LBP., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Potassium octatitanate fibers (K 2 O•8TiO 2 , POT fibers) are used as an asbestos substitute. Their physical characteristics suggest that respirable POT fibers are likely to be carcinogenic in the lung and pleura. However, previous 2-year inhalation studies reported that respired POT fibers had little or no carcinogenic potential. In the present study ten-week old male F344 rats were left untreated or were administered vehicle, 0.25 or 0.5 mg rutile-type nano TiO 2 (r-nTiO 2 ), 0.25 or 0.5 mg POT fibers, or 0.5 mg MWCNT-7 by intra-tracheal intra-pulmonary spraying (TIPS), and then observed for 2 years., Results: There were no differences between the r-nTiO 2 and control groups. The incidence of bronchiolo-alveolar cell hyperplasia was significantly increased in the groups treated with 0.50 mg POT and 0.50 mg MWCNT-7. The overall incidence of lung tumors, however, was not increased in either the POT or MWCNT-7 treated groups. Notably, the carcinomas that developed in the POT and MWCNT-7 treated rats were accompanied by proliferative fibrous connective tissue while the carcinomas that developed in the untreated rats and the r-nTiO 2 treated rats were not (carcinomas did not develop in the vehicle control rats). In addition, the carcinoma that developed in the rat treated with 0.25 mg POT was a squamous cell carcinoma, a tumor that develops spontaneously in about 1 per 1700 rats. The incidence of mesothelial cell hyperplasia was 4/17, 7/16, and 10/14 and the incidence of malignant mesothelioma was 3/17, 1/16, and 2/14 in the 0.25 mg POT, 0.5 mg POT, and MWCNT-7 treated groups, respectively. Neither mesothelial cell hyperplasia nor mesothelioma developed in control rats or the rats treated with r-nTiO 2 . Since the incidence of spontaneously occurring malignant mesothelioma in rats is extremely low, approximately 1 per 1000 animals (Japan Bioassay Research Center [JBRC] historical control data), the development of multiple malignant mesotheliomas in the POT and MWCNT-7 treated groups was biologically significant., Conclusion: The incidence of pleural mesotheliomas in male F344 rats administered POT fibers and MWCNT-7 was significantly higher than the JBRC historical control data, indicating that the incidence of pleural mesothelioma in the groups administered POT fibers and MWCNT-7 fibers via the airway using TIPS was biologically significant. The incidence of type II epithelial cell hyperplasia and the histology of the carcinomas that developed in the POT treated rats also indicates that respirable POT fibers are highly likely to be carcinogenic in the lungs of male F344 rats.

Multi-walled carbon nanotube-7 (MWCNT-7) fibers are biopersistent and have a structure similar to asbestos. MWCNT-7 has been shown to induce malignant mesothelioma when administered by intrascrotal or intraperitoneal injection in rats and mice, and an inhalation study demonstrated that rats exposed to respirable MWCNT-7 developed lung tumors. MWCNT-N, which is similar to MWCNT-7, was shown to induce both lung tumors and malignant mesothelioma in rats when administered by trans-tracheal intrapulmonary spraying (TIPS). The present study was performed to investigate the carcinogenicity of MWCNT-7 when administered by the TIPS method. Ten-week-old male F344/Crj rats were divided into 3 groups and administered 0.5 mL vehicle, 0.250 μg/mL MWCNT-7 or 0.250 μg/mL crocidolite once a week for 12 weeks (total doses of 1.5 mg/rat) and then observed for up to 104 weeks. Rats in the MWCNT-7 group began to die from pathologies associated with the development of malignant mesothelioma 35 weeks after the final TIPS administration. Overall, the incidence of malignant mesothelioma in the MWCNT-7 group was significantly higher than in the vehicle or crocidolite groups., (© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)