Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: a computerized tomography study with history length matched cases.

Background: There have been concerns that literature described radiological feature differences between drug-sensitive pulmonary tuberculosis (DS-PTB) and multidrug-resistant (MDR)-PTB were confounded by that MDR-PTB cases tend to have a longer history. Using history length matched DS-PTB and MDR-PTB cases from a well-defined urban region in Dalian, we retrospectively analysed the CT feature differences of these paired cases with a focus on pulmonary nodular (PN) consolidation and pulmonary cavity (PC). Methods: There were 33 consecutive MDR-PTB cases [inclusive of rifampicin-resistant (RR) cases, 27 males and 6 females, mean age: 49.2 years], with 19 cases had a history of <1 month and 8 and 6 cases had a history of 1-6 and >6 months respectively. To pair the MDR-PTB cases with history length, matched 33 cases of DS-PTB patients (21 males and 12 females, mean age: 56.5 years) were included. All patients were new PTB without HIV infection. The first CT exams prior to treatment were analysed. Results: Compared with DS cases, MDR cases had a much higher prevalence of PN (75.76% vs. 45.45%) and a higher number of PN per positive case for PN (6.2 vs.1.53). For the cases >1 month history, MDR-PTB had a higher number of PC per positive case than that of DS-PTB cases (7.18 vs. 2.36). To differentiate DS-PTB from MDR-PTB, receiver operating characteristic (ROC) analysis showed a cutoff PN number of ≥3 had 48.5% sensitivity and 93.9% specificity, and a cutoff PC number of ≥4 had 39.4% sensitivity and 84.9% specificity. The lung field distribution of all lesions tended to be wider for MDR-PTB cases. MDR-PTB cases appeared to be associated with a faster progression in the absence of treatment. Conclusions: MDR-TB is likely intrinsically more invasive than DS-TB. Multiple PN and Multiple PC are promising signs for the suspicion of MDR-PTB on chest imaging.

Bi-exponential fitting excluding b=0 data improves the scan-rescan stability of liver IVIM parameter measures and particularly so for the perfusion fraction.

Background: A prerequisite to translating intravoxel incoherent motion (IVIM) imaging into meaningful clinical applications is sufficient scan-rescan reproducibility. This study aims to confirm the hypothesis that IVIM data fitting by not using b=0 images will improve the stability of liver IVIM measurement. Methods: Healthy volunteers' liver IVIM images were prospectively acquired using a 1.5-T magnet or a 3.0 T with 16 b-values. Repeatability study subjects were scanned twice during the same session, resulted in 35 paired scans for 35 subjects (11 men, mean age: 41.82 years, range: 32-60 years; 24 women, mean age: 42.67 years, range: 20-71 years). IVIM analysis was performed with full-fitting and segmented-fitting with a threshold b-value of 60 s/mm2, and fitting started from b=0 s/mm2 or from b=2 s/mm2. Reproducibility study subjects were scanned and then rescanned with an interval of 5-18 days, resulted in 20 paired scans for 11 subjects (4 men, mean age: 26.25 years, range: 25-27 years; 7 women, mean age: 25.57 years, range: 24-27 years). IVIM analysis was performed with segmented-fitting with a threshold b-value of 50 s/mm2, and fitting started from b=0 s/mm2 or from b=3 s/mm2. Results: Fitting without b=0 data generally improved the repeatability and reproducibility for both PF and Dslow, and particularly so for PF. For with b=0 data segmented fitting repeatability, PF had within-subject standard deviation of 0.019, bland-Atman 75% agreement limit of -31.52% to 28.35%, and ICC of 0.647, while these values were 0.009, -20.78% to 16.86%, and 0.837 for without b=0 analysis. Though the repeatability and reproducibility for Dfast generally also improved, they remained suboptimal. Measurement stability was better for repeatability than for reproducibility. Conclusions: Scan-rescan repeatability and reproducibility of liver IVIM parameters can be improved by fitting without b=0 data, which is particularly so for PF.

Spleen in viral Hepatitis-B liver fibrosis patients may have a reduced level of per unit micro-circulation: non-invasive diffusion MRI evidence with a surrogate marker.

Spleen micro-perfusion level can be evaluated by DDVD (diffusion derived vessel density): DDVD (unit: au/pixel) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the spleen signal when b is 0 or 2 (s/mm2) and ROI is 'region-of-interest'. This study investigated whether spleen DDVD is altered in patients with viral hepatitis-b (VHB) liver fibrosis. Three datasets were retrospectively analysed. Shenzhen data-1 had 25 healthy volunteers and 15 VHB liver fibrosis patients. Changsha data had 24 healthy volunteers and 31 patients with VHB liver fibrosis. Shenzhen data-2 had 67 healthy volunteers. Shenzhen data-2 were measured by reader-1. Shenzhen data-1 were measured by reader-1 and reader-2. For Changsha data, reader-1 measured all subjects, while Reader-2 measured a random selection of 10 healthy volunteers and two patients from each liver fibrosis grade (total=8). Shenzhen data-2 showed in healthy volunteers there was no age-dependent change of spleen DDVD during 20 ∼71 years old, and women had higher spleen DDVD values than those of men's (16.17±7.34 vs. 12.88±5.91, p=0.04). Changsha data by reader-1 showed patients with liver fibrosis had lower spleen DDVD values than those of healthy volunteers (median=16.24 vs. 23.54, p=0.0031). Results of reader-2 showed the same trend (median=11.64 vs. 23.33, p=0.0165). Shenzhen data-1 measured by reader-1 showed medians of spleen DDVD for patients and volunteers were 8.535 and 12.33 respectively; and those measured by reader-2 were 13.89 and 14.31 respectively. We conclude that diffusion MRI shows spleen DDVD, i.e., micro-circulation per volume tissue, is decreased in VHB liver fibrosis patients.

Usefulness of diffusion derived vessel density computed from a simplified IVIM imaging protocol: An experimental study with rat biliary duct blockage induced liver fibrosis.

OBJECTIVES: Liver vessel density can be evaluated by DDVD (diffusion derived vessel density): DDVD(b0b1) = Sb0/ROIarea0 - Sb1/ROIarea1, where Sb0 and Sb1 refer to the liver signal when b is 0 or 1 s/mm2. Sb1 and ROIarea1 may be replaced by other b-values. With a rat biliary duct ligation (BDL) model, this study assesses the usefulness of liver DDVD computed from a simplified IVIM imaging protocol using b = 25 and b = 50 to replace b = 1 s/mm2, alone and in combination with other IVIM parameters. METHODS: Male Sprague-Dawley rats were used. The rat number was 5, 5, 5, and 3 respectively, for the timepoints of 7, 14, 21, 28 days post-BDL surgery. 12 rats had partial biliary duct recanalization performed after the rats had BDL for 7 days and then again followed-up for a mean of 14 days. Liver diffusion MRIs were acquired at 3.0 T with a b-value distribution of 0, 25, 50, 75, 100, 150, 300, 700, 1000 s/mm2. DDVDmean (control rats n = 6) was the mean of DDVD(b0b25) and DDVD(b0b50). IVIM fitting started from b = 0 s/mm2 with segmented fitting and a threshold b of 50 s/mm2 (n = 5 for control rats). Three 3-D spaces were constructed using a combination of the four diffusion parameters. RESULTS: The control rats and BDL rats (n = 18) had a liver DDVDmean of 84.0 ± 26.2 and 44.7 ± 14.4 au/pixel (p < 0.001). All 3-D spaces totally separated healthy livers and all fibrotic livers (n = 30, BDL rats and recanalization rats). The mean relative distance between healthy liver cluster and fibrotic liver cluster was 0.331 for PF, Dslow, and Dfast; 0.381 for PF, Dfast, and DDVDmean; and 0.384 for PF, Dslow, and DDVDmean. CONCLUSION: A combination of PF, Dslow, and Dfast allows total separation of healthy livers and fibrotic livers and the integration of DDVD improved the separation.

Diffusion-weighted MRI of the liver: challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion.

Diffusion-weighted imaging (DWI) is sensitive to the mobility of water molecule at cellular and macromolecular level, much smaller than the spatial resolution of the images. It is commonly based on single shot echo-planar imaging sequence with the addition of motion-probing gradient pulses and fat suppression. DWI is increasingly incorporated into routine body magnetic resonance imaging protocols. However, the liver is particularly affected by physiological motions such as respiration; the left liver is also affected by cardiac motion artifacts and susceptibility artefact due to contents in the stomach. Intravoxel incoherent motion (IVIM) DWI data analysis requires high-quality data acquisition using multiple b-values and confidence in the measurements at low b-values. This article reviews the technical developments of DWI and its applications in the liver. Challenges and some solutions for the quantification of apparent diffusion coefficient and intravoxel incoherent motion are discussed. Currently, acquisition protocols vary between research groups; patient preparation and data post-processing are not standardized. Increased standardization, both in data acquisition and in image analysis, is imperative so to allow generation of reliable DW-MRI biomarker measures that are broadly applicable.

Interleukin 17A Derived from γδ T Cell Induces Demyelination of the Brain in Angiostrongylus cantonensis Infection.

Angiostrongylus cantonensis infection is a typical cause of eosinophilic encephalitis (EM), which has been reported to induce serious damage in the central nervous system. Both parasite and host factors contribute to the onset of EM, but the related immune-inflammation pathogenesis remains poorly characterised. An A. cantonensis infection model was generated through the infection of mice by gavage. Transmission electron microscopy and immunohistochemistry were used to assess the pathologic changes in the brain. The mRNA expression of inflammatory factors was tested using qRT-PCR. A combination of flow cytometry and western blotting was used to evaluate the alteration of leukocytes and related cytokines. A critical role of IL-17 was found by injecting IL-17A monoclonal antibody into naïve and A. cantonensis-infected mice. A. cantonensis larvae altered the immune homeostasis in the brain, leading to the destruction of myelin sheaths and activation of microglia and macrophage. During this process, IL-17A accumulation was observed, and IL-17RA was expressed in oligodendrocytes and microglia during the infection. Notably, γδ T cell was the major origin of IL-17A production induced by the parasite. After an IL-17A-neutralising antibody was applied, alterations in myelination and the state of the microglia/macrophage were discovered; the neurobehavioural scores of the mice also improved. Our study reveals one unrecognised impact of the γδ T cells in parasitic encephalopathy and emphasises that blocking IL-17A signalling can attenuate microglia and macrophage activation, thus reducing CNS demyelination and ameliorating the neurobehavioural deficit in A. cantonensis-infected mice.

Age and gender dependence of liver diffusion parameters and the possibility that intravoxel incoherent motion modeling of the perfusion component is constrained by the diffusion component.

The aim of this study was to establish reference values for middle-aged subjects and to investigate the age and gender dependence of liver diffusion MRI parameters. The IVIM type of liver diffusion scan was based on a single-shot spin-echo-type echo-planar sequence using a 1.5 T magnet with 16 b-values. Diffusion-derived vessel density (DDVD)(b0b2) or DDVD(b0b10) was the signal difference between b = 0 and b = 2 (or b = 10) s/mm2 images after removing visible vessels. IVIM analysis was performed with full fitting and segmented fitting, and with a threshold b-value of 60 or 200 s/mm2 , and fitting started from b = 2 s/mm2 . Thirty-one men (age range: 25-71 years) and 26 men (age: 22-69 years) had DDVD and IVIM analysis, respectively, while 37 women (age: 20-71 years) and 36 women (age: 20-71 years) had DDVD and IVIM analysis, respectively. DDVD results showed a significant age-related reduction for women. IVIM results for full fitting showed excellent agreement with those for segmented fitting using a threshold b of 60 s/mm2 , but this was less good for results with a threshold b of 200 s/mm2 . As age increased, female subjects' Dslow measure showed a significant reduction, while their PF and Dfast measures showed a significant increase. For the age group of 40-55 years, DDVD(b0b2), DDVD(b0b10), Dslow , PF and Dfast were 12.26 ± 3.90 au/pixel, 16.95 ± 5.45 au/pixel, 1.072 ± 0.067 (10-3 mm2 /s), 0.141 ± 0.025 and 61.0 ± 14.0 (10-3 mm2 /s) for men, and 13.35 ± 3.6 au/pixel, 17.20 ± 3.62 au/pixel, 1.069 ± 0.074 (10-3 mm2 /s), 0.119 ± 0.014 and 57.1 ± 13.2 (10-3 mm2 /s) for women, respectively. DDVD measure of this study suggest that aging is associated with a reduction in liver perfusion. There is a possibility that a lower Dslow measure is associated with artificially higher PF and Dfast measures, and that IVIM modeling of the perfusion component is constrained by the diffusion component.

Collagen deposition in the liver is strongly and positively associated with T1rho elongation while fat deposition is associated with T1rho shortening: an experimental study of methionine and choline-deficient (MCD) diet rat model.

BACKGROUND: A number of questions concerning the histological mechanism of elongated T1rho in liver fibrosis remain unanswered. Using a rat model of non-alcoholic fatty liver disease (NAFLD) induced with methionine and choline-deficient (MCD) diet, the primary aim of this study is to clarify whether collagen deposition per se causes liver T1rho elongation. METHODS: There were 45 rats in the NAFLD model group and 8 rats in the control group. NAFLD model rats were fed MCD diet for 1, 2, 4, 6, 8, or 10 weeks, respectively. At the endpoint, the rats had in vivo MRI at 3.0 T and followed by histology. For T1rho data acquisition, a rotary echo spin-lock pulse was implemented in a three-dimensional fast field echo sequence with frequency selective fat suppression. The spin-lock frequency was set to 500 Hz, and the spin-lock times of 5, 10, 40, and 50 ms were used. Liver specimens were processed with hematoxylin-eosin staining for steatosis and inflammation evaluation, and Masson's trichrome staining for collagen visualization. The semiquantitative histopathological evaluation was based on NASH Clinical Research Network criteria. Histomorphometric analysis calculated percentages of fat and collagen accumulations in the livers. RESULTS: A strong (r=0.82) and significant (P<0.0001) positive correlation between liver collagen content and liver T1rho was observed. Rats with no or minimal inflammation could have very long T1rho value. Among experimental rats without a positive fibrosis grading, five rats did not have an inflammation score (i.e., had minimal inflammation or no inflammation) while four had a positive inflammation score; the difference in liver T1rho between these two types of rats was minimal. Eight control rat livers and 15 stage-1 fibrosis rat livers were separated by liver T1rho completely. When four subgroups of experiment rats were selected where the liver collagen had a very narrow range within these subgroups, all these four subgroups showed a trend of negative correlation between liver fat and liver T1rho. CONCLUSIONS: Collagen deposition in the live strongly contributes to liver T1rho elongation, while fat deposition contributes to T1rho shortening. In a well-controlled experimental setting, T1rho measure alone allows separation of healthy livers and stage-1 liver fibrosis in the MCD rat liver model.

Carbon Quantum Dots: In vitro and in vivo Studies on Biocompatibility and Biointeractions for Optical Imaging.

BACKGROUND: Understanding the biocompatibility and biointeractions of nano-carbon quantum dots (nano-CQDs) in vitro and in vivo is important for assessing their potential risk to human health. In the previous research, the physical properties of CQDs synthesized by the laser ablation in liquid (LAL) method were analyzed in detail; however, possible bioapplications were not considered. MATERIALS AND METHODS: CQDs were prepared by LAL and characterized by atomic force microscopy, fluorescence lifetime, absorption spectrum, Fourier-transform infrared spectroscopy, and dynamic light scattering. Their biocompatibility was evaluated in vitro using assays for cytotoxicity, apoptosis, and biodistribution and in vivo using immunotoxicity and the relative expression of genes. Cells were measured in vitro using fluorescence-lifetime imaging microscopy to analyze the biointeractions between CQDs and intracellular proteins. RESULTS: There were no significant differences in biocompatibility between the CQDs and the negative control. The intracellular interactions had no impact on the optical imaging of CQDs upon intake by cells. Optical imaging of zebrafish showed the green fluorescence was well dispersed. CONCLUSION: We have demonstrated that the CQDs have an excellent biocompatibility and can be used as efficient optical nanoprobes for cell tracking and biomedical labeling except for L929 and PC-3M cells.

In vivo immunotoxicity of Gd2 O3 :Eu3+ nanoparticles and the associated molecular mechanism.

The in vivo toxicity of Gd2 O3 :Eu3+ nanoparticles (NPs) used as dual-modal nanoprobes for molecular imaging has not been studied, and the corresponding molecular mechanism of immunotoxicity remains unknown. In this study, we investigated the cytotoxicity, in vitro apoptosis, and in vivo immunotoxicity of Gd2 O3 :Eu3+ NPs. The NPs showed little immunotoxicity to BALB/c mice. We explored the possible role of the phosphoinositide 3-kinase (PI3K) signaling pathway and found that reactive oxygen species could act as secondary messengers in cellular signaling, inhibiting PI3K expression in the liver. The immune suppression caused by PI3K inhibition helped the mice adapt to stress. The immunotoxicities caused by Gd2 O3 :Eu3+ and gadodiamide, a commonly used contrast agent, were not significantly different, and the mice were able to tolerate the immunotoxicity caused Gd2 O3 :Eu3+ NPs in vitro and in vivo experiments. The results suggest that Gd2 O3 :Eu3+ NPs are sufficiently biocompatible to be used safely in preclinical applications and show promise as bio-imaging agents. Moreover, the in vivo molecular mechanism of immunotoxicity caused by the Gd2 O3 :Eu3+ NPs provides a platform for further research on the immunotoxicity of nano-sized biomaterials.

Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. RESULTS: TSIIA+AB facilitated OL proliferation and significantly increased both myelin sheath thickness and the population of small-diameter axons. In addition, TSIIA treatment inhibited the expression of inflammation-related factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, inducible nitric oxide synthase [iNOS]) rather than inhibiting eosinophil infiltration in brain. TSIIA also decreased microglial activation and shifted their phenotype from M1 to M2. CONCLUSIONS: Taken together, these results provide evidence that TSIIA combined with AB may be an effective treatment for demyelination caused by A. cantonensis infection and other demyelinating diseases.

IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. METHODS: In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. RESULTS: Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. CONCLUSION: IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.

MagA increases MRI sensitivity and attenuates peroxidation-based damage to the bone-marrow haematopoietic microenvironment caused by iron overload.

Early evaluation of iron overload (IO) and prompt iron-chelation therapy reduce the haematopoietic damage wrought by IO-induced reactive oxygen species (ROS). We examined whether MagA could simultaneously increase the sensitivity of magnetic resonance imaging (MRI) for iron measurement and attenuate oxidative damage to the haematopoietic microenvironment. After generation of a transgenic (Tg) mouse model, MRI, transmission electron microscopy and cytotoxicity assays were used to assess various parameters in mesenchymal stem cells (MSCs). Transverse relaxation rate (R2*) of MagA-expressing MSCs in the presence of iron supplement was higher compared with that of control cells. Besides, R2* value of liver from IO magA Tg mice was higher than that of wild type mice. Moreover, MagA contributed to reduce the cytotoxicity of iron against MSCs, reduce expression of p-p38 mitogen-activated protein kinase and ferritin, and reduce inhibition of the osteogenic differentiation caused by IO. These data support the use of magA as a reporter gene for cell tracking with MRI and indicate exciting new possibilities for use of MagA in the attenuation of injury due to oxidative stress caused by exogenous iron.

Corrigendum to "Inhibiting Interleukin 17 Can Ameliorate the Demyelination Caused by A. cantonensis via iNOS Inhibition".

[This corrects the article DOI: 10.1155/2017/3513651.].