Abstract Objectives Selection of an appropriate site along the coronary artery tree is vital for measuring computed tomography fractional flow reserve (FFR CT ) in patients with coronary artery diseases (CAD). The purpose of this study was to evaluate the performance of FFR CT measured at different sites distal to the target lesion in detecting lesion-specific ischemia in patients with CAD as compared with fractional flow reserve (FFR) measured with invasive coronary angiography (ICA). Methods In this retrospective study, 52 patients suspected of having CAD were enrolled between March 2017 to December 2021. All patients underwent coronary computed tomography angiography (CCTA) and ICA together with FFR measurement within 90 days. Vessels with 30%-90% diameter stenosis as determined by ICA were referred to invasive FFR evaluation, which was performed 2–3 cm distal to the stenosis under the condition of hyperemia. For each vessel with 30–90% diameter stenosis, if only one stenosis was present, this stenosis was selected as the target lesion; if serial stenoses were present, the stenosis most distal to the vessel end was chosen as the target lesion. FFR CT was measured at four sites: 1cm, 2 cm, and 3 cm distal to the lower border of the target lesion (FFR CT -1cm, FFR CT -2cm, FFR CT -3cm), and the lowest FFR CT at the distal vessel tip (FFR CT -lowest). Pearson's correlation analysis and Bland–Altman plots were used to assess the correlation and difference between invasive FFR and FFR CT . The performances of significant obstruction stenosis (diameter stenosis ≥ 50%) at CCTA and FFR CT measured at the four different sites in diagnosing lesion-specific ischemia were evaluated by receiver-operating characteristic (ROC) curves using invasive FFR as the reference standard. The areas under ROC curves (AUCs) of CCTA, FFR CT measured at the different sites were compared by the DeLong test. Results A total of 72 coronary arteries in 52 patients were included for analysis. Twenty-five vessels (34.7%) had lesion-specific ischemia detected by invasive FFR. Good correlation was found between invasive FFR and FFR CT -2cm and FFR CT -3cm (r = 0.80, 95% CI, 0.70 to 0.87, p < 0.001; r = 0.82, 95% CI, 0.72 to 0.88, p < 0.001). Moderate correlation was found between invasive FFR and FFR CT -1cm and FFR CT -lowest (r = 0.77, 95% CI, 0.65 to 0.85, p < 0.001; r = 0.78, 95% CI, 0.67 to 0.86, p < 0.001). Bland–Altman plots revealed a mild difference between invasive FFR and the four FFR CT (invasive FFR vs. FFR CT -1cm, mean difference − 0.0158, 95% limits of agreement: -0.1475 to 0.1159; invasive FFR vs. FFR CT -2cm, mean difference 0.0001, 95% limits of agreement: -0.1222 to 0.1220; invasive FFR vs. FFR CT -3cm, mean difference 0.0117, 95% limits of agreement: -0.1085 to 0.1318; and invasive FFR vs. FFR CT -lowest, mean difference 0.0343, 95% limits of agreement: -0.1033 to 0.1720). AUCs of CCTA, FFR CT -1cm, FFR CT -2cm, FFR CT -3cm, and FFR CT -lowest in detecting lesion-specific ischemia were 0.578 (95% CI, 0.443 to 0.713), 0.768 (95% CI, 0.640 to 0.896), 0.857 (95% CI, 0.754 to 0.961), 0.856 (95% CI, 0.756 to 0.957) and 0.770 (95% CI, 0.657 to 0.882), respectively. All FFR CT had a higher AUC than CCTA (all p < 0.05), FFR CT -2cm achieved the highest AUC at 0.857. The AUCs of FFR CT -2cm and FFR CT -3cm were comparable ( p > 0.05). Conclusions FFR CT measured at 2 cm distal to the lower border of the target lesion is the optimal measurement site for identifying lesion-specific ischemia in patients with CAD.
Methylprednisolone is recommended as the front-line therapy for radiation-induced brain necrosis (RN) after radiotherapy for nasopharyngeal carcinoma. However, some patients fail to benefit from methylprednisolone or even progress. This study aimed to develop and validate a radiomic model to predict the response to methylprednisolone in RN.Sixty-six patients receiving methylprednisolone were enrolled. In total, 961 radiomic features were extracted from the pre-treatment magnetic resonance imagings of the brain. Least absolute shrinkage and selection operator regression was then applied to construct the radiomics signature. Combined with independent clinical predictors, a radiomics model was built with multivariate logistic regression analysis. Discrimination, calibration and clinical usefulness of the model were assessed. The model was internally validated using 10-fold cross-validation.The radiomics signature consisted of 16 selected features and achieved favorable discrimination performance. The radiomics model incorporating the radiomics signature and the duration between radiotherapy and RN diagnosis, yielded an AUC of 0.966 and an optimism-corrected AUC of 0.967 via 10-fold cross-validation, which also revealed good discrimination. Calibration curves showed good agreement. Decision curve analysis confirmed the clinical utility of the model.The presented radiomics model can be conveniently used to facilitate individualized prediction of the response to methylprednisolone in patients with RN.
Inactivation of the tumor suppressor p53 is critical for pathogenesis of glioma, in particular glioblastoma multiforme (GBM). MDM2, the main negative regulator of p53, binds to and forms a stable complex with p53 to regulate its activity. Hitherto, it is unclear whether the stability of the p53/MDM2 complex is affected by lncRNAs, in particular circular RNAs that are usually abundant and conserved, and frequently implicated in different oncogenic processes.RIP-seq and RIP-qPCR assays were performed to determine the most enriched lncRNAs (including circular RNAs) bound by p53, followed by bioinformatic assays to estimate the relevance of their expression with p53 signaling and gliomagenesis. Subsequently, the clinical significance of CDR1as was evaluated in the largest cohort of Chinese glioma patients from CGGA (n = 325), and its expression in human glioma tissues was further evaluated by RNA FISH and RT-qPCR, respectively. Assays combining RNA FISH with protein immunofluorescence were performed to determine co-localization of CDR1as and p53, followed by CHIRP assays to confirm RNA-protein interaction. Immunoblot assays were carried out to evaluate protein expression, p53/MDM2 interaction and p53 ubiquitination in cells in which CDR1as expression was manipulated. After AGO2 or Dicer was knocked-down to inhibit miRNA biogenesis, effects of CDR1as on p53 expression, stability and activity were determined by immunoblot, RT-qPCR and luciferase reporter assays. Meanwhile, impacts of CDR1as on DNA damage were evaluated by flow cytometric assays and immunohistochemistry. Tumorigenicity assays were performed to determine the effects of CDR1as on colony formation, cell proliferation, the cell cycle and apoptosis (in vitro), and on tumor volume/weight and survival of nude mice xenografted with GBM cells (in vivo).CDR1as is found to bind to p53 protein. CDR1as expression decreases with increasing glioma grade and it is a reliable independent predictor of overall survival in glioma, particularly in GBM. Through a mechanism independent of acting as a miRNA sponge, CDR1as stabilizes p53 protein by preventing it from ubiquitination. CDR1as directly interacts with the p53 DBD domain that is essential for MDM2 binding, thus disrupting the p53/MDM2 complex formation. Induced upon DNA damage, CDR1as may preserve p53 function and protect cells from DNA damage. Significantly, CDR1as inhibits tumor growth in vitro and in vivo, but has little impact in cells where p53 is absent or mutated.Rather than acting as a miRNA sponge, CDR1as functions as a tumor suppressor through binding directly to p53 at its DBD region to restrict MDM2 interaction. Thus, CDR1as binding disrupts the p53/MDM2 complex to prevent p53 from ubiquitination and degradation. CDR1as may also sense DNA damage signals and form a protective complex with p53 to preserve p53 function. Therefore, CDR1as depletion may play a potent role in promoting tumorigenesis through down-regulating p53 expression in glioma. Our results broaden further our understanding of the roles and mechanism of action of circular RNAs in general and CDR1as in particular, and can potentially open up novel therapeutic avenues for effective glioma treatment.
Purpose To determine the role of diffusion tensor imaging (DTI) metrics as biomarkers for the therapeutic effects of mesenchymal stem cells (MSCs) in acute peripheral nerve injury. Materials and Methods Forty‐four adult rats received subepineurial microinjection of MSCs (n = 22) or phosphate buffered saline (PBS, n = 22) 1 week after the sciatic nerve trunk crush injury. Sequential fat‐suppressed T2‐weighted imaging, T2 measurement, DTI and sciatic nerve functional assessment were performed at a 3.0 Tesla MR unit over an 8‐week follow‐up, with histological assessments performed at regular intervals. The sciatic nerve function index, T2 value, and DTI metrics, including fractional anisotropy (FA), axial diffusivity, radial diffusivity (RD), and mean diffusivity values of the distal stumps of crushed nerves were measured and compared between the two groups. Results Nerves treated with MSCs showed better functional recovery and exhibited more pronounced nerve regeneration compared with nerves treated with PBS. T2 values in nerves treated with MSCs or PBS showed a similar change pattern ( P = 0.174), while FA and RD values in nerves treated with MSCs showed more rapid return (one week earlier) to baseline level than nerves treated with PBS ( P = 0.045; 0.035). Nerves treated with MSCs had higher FA and lower RD values than nerves treated with PBS during the period from 2 to 3 weeks after surgery ( P ≤ 0.0001, 0.004; P = 0.004, 0.006). Conclusion FA and RD values derived from DTI might be used as sensitive biomarkers for detecting the therapeutic effect of stem cells in acute peripheral nerve crush injuries. Level of Evidence: 2 J. Magn. Reson. Imaging 2017;45:855–862.
Transplantation of neural stem cells (NSCs) is emerging as a new therapeutic approach for stroke. Real-time imaging of transplanted NSCs is essential for successful cell delivery, safety monitoring, tracking cell fate and function, and understanding the interactions of transplanted cells with the host environment. Magnetic resonance imaging (MRI) of magnetic nanoparticle-labeled cells has been the most widely used means to track stem cells in vivo. Nevertheless, it does not allow for the reliable discrimination between live and dead cells. Reporter gene-based MRI was considered as an alternative strategy to overcome this shortcoming. In this work, a class of lentiviral vector-encoding ferritin heavy chain (FTH) and enhanced green fluorescent protein (EGFP) was constructed to deliver reporter genes into NSCs. After these transgenic NSCs were transplanted into the contralateral hemisphere of rats with acute ischemic stroke, MRI and fluorescence imaging (FLI) were performed in vivo for tracking the fate of transplanted cells over a long period of 6 wk. The results demonstrated that the FTH and EGFP can be effectively and safely delivered to NSCs via the designed lentiviral vector. The distribution and migration of grafted stem cells could be monitored by bimodal MRI and FLI. FTH can be used as a robust MRI reporter for reliable reporting of the short-term viability of cell grafts, whereas its capacity for tracking the long-term viability of stem cells remains dependent on several confounding factors such as cell death and the concomitant reactive inflammation.
Abstract Objectives Whether a stenosis can cause hemodynamic lesion-specific ischemia is critical for the treatment decision in patients with coronary artery disease (CAD). Based on coronary computed tomography angiography (CCTA), CT fractional flow reserve (FFR CT ) can be used to assess lesion-specific ischemia. The selection of an appropriate site along the coronary artery tree is vital for measuring FFR CT . However the optimal site to measure FFR CT for a target stenosis remains to be adequately determined. The purpose of this study was to determine the optimal site to measure FFR CT for a target lesion in detecting lesion-specific ischemia in CAD patients by evaluating the performance of FFR CT measured at different sites distal to the target lesion in detecting lesion-specific ischemia with FFR measured with invasive coronary angiography (ICA) as reference standard. Methods In this single-center retrospective cohort study, a total of 401 patients suspected of having CAD underwent invasive ICA and FFR between March 2017 and December 2021 were identified. 52 patients having both CCTA and invasive FFR within 90 days were enrolled. Patients with vessels 30%-90% diameter stenosis as determined by ICA were referred to invasive FFR evaluation, which was performed 2–3 cm distal to the stenosis under the condition of hyperemia. For each vessel with 30%–90% diameter stenosis, if only one stenosis was present, this stenosis was selected as the target lesion; if serial stenoses were present, the stenosis most distal to the vessel end was chosen as the target lesion. FFR CT was measured at four sites: 1 cm, 2 cm, and 3 cm distal to the lower border of the target lesion (FFR CT -1 cm, FFR CT -2 cm, FFR CT -3 cm), and the lowest FFR CT at the distal vessel tip (FFR CT -lowest). The normality of quantitative data was assessed using the Shapiro–Wilk test. Pearson's correlation analysis and Bland–Altman plots were used for assessing the correlation and difference between invasive FFR and FFR CT . Correlation coefficients derived from Chi-suqare test were used to assess the correlation between invasive FFR and the cominbaiton of FFR CT measred at four sites. The performances of significant obstruction stenosis (diameter stenosis ≥ 50%) at CCTA and FFR CT measured at the four sites and their combinations in diagnosing lesion-specific ischemia were evaluated by receiver-operating characteristic (ROC) curves using invasive FFR as the reference standard. The areas under ROC curves (AUCs) of CCTA and FFR CT were compared by the DeLong test. Results A total of 72 coronary arteries in 52 patients were included for analysis. Twenty-five vessels (34.7%) had lesion-specific ischemia detected by invasive FFR and 47 vesseles (65.3%) had no lesion-spefifice ischemia. Good correlation was found between invasive FFR and FFR CT -2 cm and FFR CT -3 cm ( r = 0.80, 95% CI, 0.70 to 0.87, p < 0.001; r = 0.82, 95% CI, 0.72 to 0.88, p < 0.001). Moderate correlation was found between invasive FFR and FFR CT -1 cm and FFR CT -lowest ( r = 0.77, 95% CI, 0.65 to 0.85, p < 0.001; r = 0.78, 95% CI, 0.67 to 0.86, p < 0.001). FFR CT -1 cm + FFR CT -2 cm, FFR CT -2 cm + FFR CT -3 cm, FFR CT -3 cm + FFR CT -lowest, FFR CT -1 cm + FFR CT -2 cm + FFR CT -3 cm, and FFR CT -2 cm + FFR CT -3 cm + FFR CT -lowest were correatled with invasive FFR ( r = 0.722; 0.722; 0.701; 0.722; and 0.722, respectively; p < 0.001 for all). Bland–Altman plots revealed a mild difference between invasive FFR and the four FFR CT (invasive FFR vs. FFR CT -1 cm, mean difference -0.0158, 95% limits of agreement: -0.1475 to 0.1159; invasive FFR vs. FFR CT -2 cm, mean difference 0.0001, 95% limits of agreement: -0.1222 to 0.1220; invasive FFR vs. FFR CT -3 cm, mean difference 0.0117, 95% limits of agreement: -0.1085 to 0.1318; and invasive FFR vs. FFR CT -lowest, mean difference 0.0343, 95% limits of agreement: -0.1033 to 0.1720). AUCs of CCTA, FFR CT -1 cm, FFR CT -2 cm, FFR CT -3 cm, and FFR CT -lowest in detecting lesion-specific ischemia were 0.578, 0.768, 0.857, 0.856 and 0.770, respectively. All FFR CT had a higher AUC than CCTA (all p < 0.05), FFR CT -2 cm achieved the highest AUC at 0.857. The AUCs of FFR CT -2 cm and FFR CT -3 cm were comparable ( p > 0.05). The AUCs were similar between FFR CT -1 cm + FFR CT -2 cm, FFR CT -3 cm + FFR CT -lowest and FFR CT -2 cm alone (AUC = 0.857, 0.857, 0.857, respectively; p > 0.05 for all). The AUCs of FFR CT -2 cm + FFR CT -3 cm, FFR CT -1 cm + FFR CT -2 cm + FFR CT -3 cm, FFR CT -and 2 cm + FFR CT -3 cm + FFR CT -lowest (0.871, 0.871, 0.872, respectively) were slightly higher than that of FFR CT -2 cm alone (0.857), but without significnacne differences ( p > 0.05 for all). Conclusions FFR CT measured at 2 cm distal to the lower border of the target lesion is the optimal measurement site for identifying lesion-specific ischemia in patients with CAD.
Parotid tumours (PTs) have a variety of pathological types, and the surgical procedures differ depending on the tumour type. However, accurate diagnosis of PTs from the current preoperative examinations is unsatisfactory.This retrospective study was approved by the Ethics Committee of our hospital, and the requirement for informed consent was waived. A total of 73 patients with PTs, including 55 benign and 18 malignant tumours confirmed by surgical pathology, were enrolled. All patients underwent diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), susceptibility-weighted imaging (SWI), T2-weighted imaging (T2WI), and T1-weighted imaging (T1WI). The signal uniformity and capsule on T2WI, apparent diffusion coefficient (ADC) derived from DWI, semi-quantitative parameter time-intensity curve (TIC) pattern, and quantitative parameters including transfer constant (Ktrans), extravascular extracellular volume fraction (Ve), wash-out constant (Kep) calculated from DCE-MRI, and intratumoural susceptibility signal (ITSS) obtained from SWI were assessed and compared between benign and malignant PTs. Logistic regression analysis was used to select the predictive parameters for the classification of benign and malignant parotid gland tumours, and receiver operating characteristic (ROC) curve analysis was used to evaluate their diagnostic performance.Malignant PTs tended to exhibit a type C TIC pattern, whereas benign tumours tended to be type A and B (p < 0.001). Benign PTs had less ITSS than malignant tumours (p < 0.001). Multivariate analyses showed that ADC, Ve, and ITSS were predictors of tumour classification. ROC analysis showed that the area under the curve (AUC) of ADC, Ve, ITSS, and ADC combined with Ve were 0.623, 0.615, 0.826, and 0.782, respectively, in differentiating between malignant and benign PTs. When ITSS was added, the AUCs of ADC, Ve, and ADC combined with Ve increased to 0.882, 0.848, and 0.930, respectively.SWI offers incremental diagnostic value to DWI and DCE-MRI in the characterisation of parotid gland tumours.
Introduction: Recent studies employing functional imaging methodology have revealed reference brain regions of urinary tract function, namely, the midbrain periaqueductal gray matter, thalamus, and cingulate and prefrontal cortices. The orthotopic ileal neobladder is a desirable method for urinary diversion after radical cystectomy, but its supraspinal control remains unknown. We aimed to evaluate brain activity while maintaining urinary urgency and voluntary urinary control in male subjects with ileal orthotopic neobladders by performing functional MRI (fMRI) during a block design experiment. Materials and Methods: Patients were recruited at the Sun Yat-sen Memorial Hospital of the Sun Yat-sen University from October 2017 to May 2019. Two tasks were performed during fMRI scanning: (1) repeated infusion and withdrawal of sterile saline solution into and out of the neobladder to simulate urgency; and (2) repeated contraction of the pelvic floor muscle with a full neobladder to induce inhibition of micturition since the subjects were asked not to urinate. The obtained data were visualized and statistically analyzed. Results: Sixteen subjects were recruited in the study, and data were obtained from 10 subjects: mean age 60.1 years, average postoperative time 20.2 months, and daytime continence rate 100%. The parahippocampus, frontal lobe, vermis, and anterior cingulate cortex were activated with large bladder volumes, and the thalamus and caudate nucleus were deactivated during voluntary urinary control. Conclusion: A complex supraspinal program is involved during ileal orthotopic neobladder control, which is significantly different from that with normal bladders, in which the original intestine visceral volume sensation is preserved.
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