Diffusion-tensor magnetic resonance imaging as a non-invasive assessment of extracellular matrix remodeling in lumbar paravertebral muscles of rats with sarcopenia.

BACKGROUND: Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. METHODS: Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. RESULTS: The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were - 0.71, -0.94, -0.85, and - 0.88, respectively (p < 0.05 for all). CONCLUSIONS: The fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia.

An experimental study for quantitative assessment of fatty infiltration and blood flow perfusion in quadriceps muscle of rats using IDEAL-IQ and BOLD-MRI for early diagnosis of sarcopenia.

BACKGROUND: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. METHODS: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. RESULTS: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p < 0.001), oil red O (ORO) area with PDFF (r = 0.67; p < 0.001), microvascular density (MVD) (r = -0.79; p < 0.001) and VEGF-A (r = -0.73; p < 0.001) with R2*, MuRF-1 with MRI-CSA (r = -0.82; p < 0.001). The AUC of PDFF, R2*, and T2 values used for modeling evaluation are 0.81, 0.93, and 0.98, respectively. CONCLUSION: Imaging parameters PDFF, R2*, and T2 can be used to sensitively evaluate early pathological changes in sarcopenia. The successful construction of a sarcopenia rat model can be assessed when PDFF exceeds 1.25, R2* exceeds 53.85, and T2 exceeds 33.88.

Functional magnetic resonance imaging reveals dysfunction of the paraspinal muscles in patients with chronic low back pain: a cross-sectional study.

Background: Patients with chronic low back pain (CLBP) undergo structural changes of the paraspinal muscles; however, it is unclear if functional changes also occur. This study aimed to examine the metabolic and perfusion function changes in the paraspinal muscles of patients with CLBP as indirectly reflected by blood oxygen level-dependent (BOLD) imaging and T2 mapping. Methods: All participants were consecutively enrolled at our local hospital from December 2019 to November 2020. Patients were diagnosed with CLBP in the outpatient clinic, and asymptomatic participants were considered to be those with no CLBP or other diseases. This study was not registered on a clinical trial platform. Participants underwent BOLD imaging and T2 mapping scans at the L4-S1 disc level. The effective transverse relaxation rate (R2* values) and transverse relaxation time (T2 values) of the paraspinal muscles were measured on the central plane of the L4/5 and L5/S1 intervertebral discs. Finally, the independent samples t-test was used to assess the differences in R2* and T2 values between the 2 groups, while Pearson correlation analysis was used to determine their correlation with age. Results: A total of 60 patients with CLBP and 20 asymptomatic participants were enrolled. The paraspinal muscles of the CLBP group had higher total R2* values [46.7±2.9 vs. 44.0±2.9 s-1; 95% confidence interval (CI): 1.2-4.2; P=0.001] and lower total T2 values (45.4±4.2 vs. 47.1±3.7 ms; 95% CI: -3.8 to 0.4; P=0.109) than did the asymptomatic participants. For the different muscles, R2* values for the erector spinae (ES) (L4/5: 45.5±2.6 vs. 43.0±3.0 s-1, 95% CI: 1.1-4.0, P=0.001; L5/S1: 48.5±4.9 vs. 45.9±4.2 s-1; 95% CI: 0.2-5.1; P=0.035) and the R2* values of the multifidus (MF) muscles (L4/5: 46.4±2.9 vs. 43.7±3.5 s-1, 95% CI: 1.1-4.3, P=0.001; L5/S1: 46.3±3.5 vs. 42.5±2.8 s-1, 95% CI: 2.1-5.5, P<0.001) of the CLBP group at both spinal levels were higher than those of the asymptomatic participants. In the patients with CLBP, the R2* values at the L4/5 (45.9±2.1 s-1) were lower than those at the L5/S1 (47.4±3.6 s-1; 95% CI: -2.6 to -0.4; P=0.007). The R2* values were positively correlated with age in both groups (CLBP group: r=0.501, 95% CI: 0.271-0.694, P<0.001; asymptomatic group: r=0.499, 95% CI: -0.047 to 0.771; P=0.025). Conclusions: The R2* values were higher in the paraspinal muscles of patients with CLPB and may suggest metabolic and perfusion dysfunction of the paraspinal muscles in these patients.

Sequential multi-parametric MRI in assessment of the histological subtype and features in the malignant pleural mesothelioma xenografts.

Objective: It is still a challenge to find a noninvasive technique to distinguish the histological subtypes of malignant pleural mesothelioma (MPM) and characterize the development of related histological features. We investigated the potential value of multiparametric MRI in the assessment of the histological subtype and development of histologic features in the MPM xenograft model. Methods: MPM xenograft models were developed by injecting tumour cells into the right axillary space of nude mice. The T1, T2, R2*, T2*, apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) at 14 d, 28 d, and 42 d were measured and compared between the epithelial and biphasic MPM. Correlations between multiparametric MRI parameters and histologic features, including necrotic fraction (NF) and microvessel density (MVD), were analysed. Results: This study found that T2, T2* and IVIM-DWI parameters can reflect the spatial and temporal heterogeneity of MPM. Compared to the epithelial MPM, T2 and T2* were higher and ADC, D, D*, and f were lower in the biphasic MPM (P < 0.05). MRI parameters were different in different stages of epithelial and biphasic MPM. Moderate correlations were found between ADC and tumor volume and NF in the epithelial MPM, and there was a correlation between f and tumor volume and NF and MVD in the two groups. Conclusion: MRI parameters changed with tumor progression in a xenograft model of MPM. MRI parameters may provide useful biomarkers for evaluating the histological subtype and histological features development of MPM.

Lithocholic acid inhibits gallbladder cancer proliferation through interfering glutaminase-mediated glutamine metabolism.

Lithocholic acid (LCA), one of the most common metabolic products of bile acids (BAs), is originally synthesized in the liver, stored in the gallbladder, and released to the intestine, where it assists absorption of lipid-soluble nutrients. LCA has recently emerged as a powerful reagent to inhibit tumorigenesis; however, the anti-tumor activity and molecular mechanisms of LCA in gallbladder cancer (GBC) remain poorly acknowledged. Here, we analyzed serum levels of LCA in human GBC and found that LCA was significantly downregulated in these patients, and reduced LCA levels were associated with poor clinical outcomes. Treatment of xenografts with LCA impeded tumor growth. Furthermore, LCA treatment in GBC cell lines decreased glutaminase (GLS) expression, glutamine (Gln) consumption, and GSH/GSSG and NADPH/NADP+ ratios, leading to cellular ferroptosis. In contrast, GLS overexpression in tumor cells fully restored GBC proliferation and decreased ROS imbalance, thus suppressing ferroptosis. Our findings reveal that LCA functions as a tumor-suppressive factor in GBC by downregulating GLS-mediated glutamine metabolism and subsequently inducing ferroptosis. This study may offer a new therapeutic strategy tailored to improve the treatment of GBC.

Soluble ß-amyloid impaired the GABA inhibition by mediating KCC2 in early APP/PS1 mice.

Alzheimer's disease (AD) is a neurodegenerative disorder, which has become the leading cause of dementia cases globally. Synaptic failure is an early pathological feature of AD. However, the cause of synaptic failure in AD, especially the GABAergic synaptic activity remains unclear. Extensive evidence indicates that the presence of soluble amyloid-ß is an early pathological feature in AD, which triggers synaptic dysfunction and cognitive decline. Our recent study explored the relation of GABAergic transmission and soluble Aß in early APP/PS1 mice. Firstly, we found soluble Aß42 levels were significantly increased in serum, hippocampus and prefrontal cortex in 3-4 months APP/PS1 mice, which was much earlier than Aß plagues formation. In addition, we found TNF-α and BDNF expression levels were increased, while KCC2 and GABAAR expression were decreased in 3-4 months APP/PS1 hippocampus. When we treated 3-4 months APP/PS1 mice with a potent γ-secretase inhibitor, LY411575, which can reduce the soluble Aß42 levels, the TNF-α and BDNF protein levels were decreased, while KCC2 and GABAAR levels were increased. In conclusion, our study suggested soluble Aß may impaired the GABA inhibition by mediating KCC2 levels in early APP/PS1 mice. KCC2 may be served as a potential biomarker for AD.

Feasibility study of early prediction of postoperative MRI findings for knee stability after anterior cruciate ligament reconstruction.

BACKGROUND: At present, the most effective and mature treatment after ACL injury and tear is ACL reconstruction, but the rehabilitation process after ACL reconstruction that is very long, so it is very important to find early MRI positive findings of knee instability. METHODS: We retrospectively collected the clinical and imaging data of 70 patients who underwent ACL reconstruction from January 2016 to December 2019; Based on clinical criteria, the patients were divided into a stable group (n = 57) and an unstable group (n = 13); We measured the MRI imaging evaluation indexes, including the position of the bone tunnel, graft status, and the anatomical factors; Statistical methods were used to compare the differences of imaging evaluation indexes between the two groups; The prediction equation was constructed and ROC curve was used to compare the prediction efficiency of independent prediction factors and prediction equation. RESULTS: There were significant differences in the abnormal position of tibial tunnel entrance, percentage of the position of tibial tunnel entrance, position of tibial tunnel exit, lateral tibial posterior slope (LTPS), width of intercondylar notch between stable knee joint group and unstable knee joint group after ACL reconstruction (P < 0.05); The position of tibial tunnel exits and the lateral tibial posterior slope (LTPS) and the sagittal obliquity of the graft were independent predictors among surgical factors and self-anatomical factors (P < 0.05); The prediction equation of postoperative knee stability was established: Logit(P) = -1.067-0.231*position of tibial tunnel exit + 0.509*lateral tibial posterior slope (LTPS)-2.105*sagittal obliquity of the graft; The prediction equation predicted that the AUC of knee instability was 0.915, the sensitivity was 84.6%, and the specificity was 91.2%. CONCLUSIONS: We found that abnormalities of the position of the exit of the bone tunnel, lateral tibial posterior slope (LTPS) and sagittal obliquity of the graft were the early MRI positive findings of knee instability after ACL reconstruction. It is helpful for clinicians to predict the stability of knee joint after ACL reconstruction.

Clinical utility of a computed tomography-based receiver operating characteristic curve model for the diagnosis of COVID-19.

BACKGROUND: The outbreak of COVID-19 poses a major and urgent threat to global public health. CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. This study aimed to retrospectively analyze abnormal lung changes following initial computed tomography (CT) among patients with coronavirus disease 2019 (COVID-19) in Yunnan, and to evaluate the effectiveness of a chest CT-based model for the diagnosis of COVID-19. METHODS: One hundred and nine patients with COVID-19 pneumonia confirmed with the positive new coronavirus nucleic acid antibody who exhibited abnormal findings on initial CT were retrospectively analyzed. Thereafter, changes in the number, distribution, shape, and density of the lesions were observed. Further, the epidemiological, clinical, and CT imaging findings (+/-) were correlated. Following univariate and multivariate logistic regression analysis, receiver operating characteristic (ROC) curves were generated for significant factors, and models were established to evaluate the diagnostic ability of CT for COVID-19. RESULTS: Our results showed significant differences between patients with COVID-19 in epidemiological history (first, second, and third generation), clinical type (moderate, severe, and critical), and abnormal CT imaging characteristics (+/-) (P<0.05). Moreover, significant differences in abnormal CT imaging characteristics, including region, extent, and focus, were observed between the first generation and the other generations (P<0.05). For the diagnosis of COVID-19, the areas under the ROC curves for logistic regression models 1, 2, and 3 were 0.8016 (95% CI: 0.6759-0.9274), 0.9132 (95% CI: 0.8571-0.9693), and 0.9758 (95% CI: 0.9466-1), respectively. CONCLUSIONS: The ROC curve regression model based on chest CT signs displayed a high diagnostic value for COVID-19.

Dynamic changes in chest CT findings of patients with coronavirus disease 2019 (COVID-19) in different disease stages: a multicenter study.

BACKGROUND: To investigate the dynamic changes in high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19) patients with different severities in different disease stages. METHODS: We retrospectively collected the clinical and imaging data of 96 patients in Yunnan Province, China, who were diagnosed with COVID-19 between January 22 and March 15, 2020. Based on disease severity, the COVID-19 patients were classified into four types: mild (n=15), moderate (n=59), severe (n=19), and critical (n=3). Based on hospital stay and number of computed tomography (CT) scans, the clinical/disease course was divided into four stages, including stage 1 (days 0-4), stage 2 (days 5-9), stage 3 (days 10-14), and stage 4 (days 15-19). The HRCT findings, CT value, and lesion volume were analyzed for each stage and compared among the four stages of COVID-19 patients. RESULTS: CT findings were negative over the four stages for all mild COVID-19 patients. More lesions were found in the peripheral lung fields than in peripheral + central fields (P<0.05), and the number of negative patients in stage 4 were more than those in stages 1-3 (P<0.05). The left and right lower lobe were the most frequently affected lobes (P<0.05). In moderate patients, round ground glass opacities (GGOs) decreased from stage 1 to stage 4; partial consolidation peaked in stage 2 and then decreased in stages 3-4; fibrous stripes and subpleural lines increased from stage 1 and peaked in stage 4. Partial consolidation and consolidation were more common in severe patients than in moderate patients over the disease course (P<0.05). Critical patients showed significant partial consolidation and consolidation; The CT value, lesion volume and lesion volume percentage significantly decreased from stages 1-2 to stage 4 (all P<0.05). CONCLUSIONS: The dynamic changes in lung HRCT images are clinically related to the disease course of COVID-19.

Comparison of initial high-resolution computed tomography (HRCT) features of coronavirus disease 2019 (COVID-19) pneumonia and other viral pneumonias.

BACKGROUND: Multicenter retrospective comparison of the first high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19) and other viral pneumonias. METHODS: We retrospectively collected clinical and imaging data from 262 cases of confirmed viral pneumonia in 20 hospitals in Yunnan Province, China, from March 1, 2015 to March 15, 2020. According to the virus responsible for the pneumonia, the pneumonias were divided into non-COVID-19 (141 cases) and COVID-19 (121 cases). The non-COVID-19 pneumonias comprised cytomegalovirus (CMV) (31 cases), influenza A virus (82 cases), and influenza B virus (20 cases). The differences in the basic clinical characteristics, lesion distribution, location and imaging signs among the four viral pneumonias were analyzed and compared. RESULTS: Fever and cough were the most common clinical symptoms of the four viral pneumonias. Compared with the COVID-19 patients, the non-COVID-19 patients had higher proportions of fatigue, sore throat, expectorant and chest tightness (all P<0.000). In addition, in the CMV pneumonia patients, the proportions of acquired immunodeficiency syndrome (AIDS) and leukopenia were high (all PP<0.000). Comparison of the imaging findings of the four viral pneumonias showed that the pulmonary lesions of COVID-19 were more likely to occur in the peripheral and lower lobes of both lungs, whereas those of CMV pneumonia were diffusely distributed. Compared with the non-COVID-19 pneumonias, COVID-19 pneumonia was more likely to present as ground-glass opacity, intralobular interstitial thickening, vascular thickening and halo sign (all PP<0.05). In addition, in the early stage of COVID-19, extensive consolidation, fibrous stripes, subpleural lines, crazy-paving pattern, tree-in-bud, mediastinal lymphadenectasis, pleural thickening and pleural effusion were rare (all PP<0.05). CONCLUSIONS: The HRCT findings of COVID-19 pneumonia and other viral pneumonias overlapped significantly, but many important differential imaging features could still be observed.

CT-based radiomics combined with signs: a valuable tool to help radiologist discriminate COVID-19 and influenza pneumonia.

BACKGROUND: In this COVID-19 pandemic, the differential diagnosis of viral pneumonia is still challenging. We aimed to assess the classification performance of computed tomography (CT)-based CT signs and radiomics features for discriminating COVID-19 and influenza pneumonia. METHODS: A total of 154 patients with confirmed viral pneumonia (COVID-19: 89 cases, influenza pneumonia: 65 cases) were collected retrospectively in this study. Pneumonia signs and radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models. The predictive performance of the radiomics model, CT sign model, the combined model was constructed based on the whole dataset and internally invalidated by using 1000-times bootstrap. Diagnostic performance of the models was assessed via receiver operating characteristic (ROC) analysis. RESULTS: The combined models consisted of 4 significant CT signs and 7 selected features and demonstrated better discrimination performance between COVID-19 and influenza pneumonia than the single radiomics model. For the radiomics model, the area under the ROC curve (AUC) was 0.888 (sensitivity, 86.5%; specificity, 78.4%; accuracy, 83.1%), and the AUC was 0.906 (sensitivity, 86.5%; specificity, 81.5%; accuracy, 84.4%) in the CT signs model. After combining CT signs and radiomics features, AUC of the combined model was 0.959 (sensitivity, 89.9%; specificity, 90.7%; accuracy, 90.3%). CONCLUSIONS: CT-based radiomics combined with signs might be a potential method for distinguishing COVID-19 and influenza pneumonia with satisfactory performance.

Dynamic analysis of pulmonary computed tomography (CT) characteristics in cured coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: To retrospectively analyze the pulmonary computed tomography (CT) characteristics and dynamic changes in the lungs of cured coronavirus disease 2019 (COVID-19) patients at discharge and reexamination. METHODS: A total of 155 cured COVID-19 patients admitted to designated hospitals in Yunnan Province, China, from February 1, 2020, to March 20, 2020, were included. All patients underwent pulmonary CT at discharge and at 2 weeks after discharge (during reexamination at hospital). A retrospective analysis was performed using these two pulmonary CT scans of the cured patients to observe changes in the number, distribution, morphology, and density of lesions. RESULTS: At discharge, the lung CT images of 15 cured patients showed no obvious lesions, while those of the remaining 140 patients showed different degrees of residual lesions. Patients with moderate disease mostly had multiple pulmonary lesions, mainly in the lower lobes of both lungs. At reexamination, the lung lesions in the patients with moderate disease had significantly improved (P<0.05), and the lung lesions in the patients with severe disease had partially improved, especially in patients with multi-lobe involvement (χ 2 =3.956, P<0.05). At reexamination, the lung lesions of patients with severe disease did not show significant changes (P>0.05). CONCLUSIONS: The pulmonary CT manifestations of cured COVID-19 patients had certain characteristics and variation patterns, providing a reference for the clinical evaluation of treatment efficacy and prognosis of patients.

Attenuated NER expressions of XPF and XPC associated with smoking are involved in the recurrence of bladder cancer.

The varied NER genes and smoking are two important risk factors of bladder cancer, but the mechanism of the NER protein and smoking in cancer progression, however, remains unclear. In this report, we compared the expressions of NER genes in 79 bladder cancer tissues with or without any recurrence by real-time PCR and then analyzed the varied NER genes by immunochemistry in 219 bladder cancer tissue samples. Based on the clinical data, we analyzed the clinical value of varied NER genes and smoking in 219 bladder cancers by the Kaplan-Meier method and Cox proportional hazards regression. We found the expressions of the NER gene XPF and XPC were significantly lower in bladder cancer tissues with a recurrence compared with those without a recurrence at mRNA level. Also, the patients with the XPF and XPC defect had a statistically significant lower median recurrence-free survival time than those without the XPF and XPC defect, and smoking can make this difference more remarkable. Our results suggest that XPF and XPC expression may be a potential predictive factor for bladder cancer, and smoking can not only influence the recurrence of bladder cancer as a single factor but also aggravate the results of the XPF defect and XPC defect.