Radiomics analysis of lesion-specific pericoronary adipose tissue to predict major adverse cardiovascular events in coronary artery disease.

OBJECTIVE: To investigate the prognostic performance of radiomics analysis of lesion-specific pericoronary adipose tissue (PCAT) for major adverse cardiovascular events (MACE) with the guidance of CT derived fractional flow reserve (CT-FFR) in coronary artery disease (CAD). MATERIALS AND METHODS: The study retrospectively analyzed 608 CAD patients who underwent coronary CT angiography. Lesion-specific PCAT was determined by the lowest CT-FFR value and 1691 radiomic features were extracted. MACE included cardiovascular death, nonfatal myocardial infarction, unplanned revascularization and hospitalization for unstable angina. Four models were generated, incorporating traditional risk factors (clinical model), radiomics score (Rad-score, radiomics model), traditional risk factors and Rad-score (clinical radiomics model) and all together (combined model). The model performances were evaluated and compared with Harrell concordance index (C-index), area under curve (AUC) of the receiver operator characteristic. RESULTS: Lesion-specific Rad-score was associated with MACE (adjusted HR = 1.330, p = 0.009). The combined model yielded the highest C-index of 0.718, which was higher than clinical model (C-index = 0.639), radiomics model (C-index = 0.653) and clinical radiomics model (C-index = 0.698) (all p < 0.05). The clinical radiomics model had significant higher C-index than clinical model (p = 0.030). There were no significant differences in C-index between clinical or clinical radiomics model and radiomics model (p values were 0.796 and 0.147 respectively). The AUC increased from 0.674 for clinical model to 0.721 for radiomics model, 0.759 for clinical radiomics model and 0.773 for combined model. CONCLUSION: Radiomics analysis of lesion-specific PCAT is useful in predicting MACE. Combination of lesion-specific Rad-score and CT-FFR shows incremental value over traditional risk factors.

Deep learning-based coronary artery calcium score to predict coronary artery disease in type 2 diabetes mellitus.

Background: Coronary artery disease (CAD) in type 2 diabetes mellitus (T2DM) patients often presents diffuse lesions, with extensive calcification, and it is time-consuming to measure coronary artery calcium score (CACS). Objectives: To explore the predictive ability of deep learning (DL)-based CACS for obstructive CAD and hemodynamically significant CAD in T2DM. Methods: 469 T2DM patients suspected of CAD who accepted CACS scan and coronary CT angiography between January 2013 and December 2020 were enrolled. Obstructive CAD was defined as diameter stenosis ≥50%. Hemodynamically significant CAD was defined as CT-derived fractional flow reserve ≤0.8. CACS was calculated with a fully automated method based on DL algorithm. Logistic regression was applied to determine the independent predictors. The predictive performance was evaluated with area under receiver operating characteristic curve (AUC). Results: DL-CACS (adjusted odds ratio (OR): 1.005; 95% CI: 1.003-1.006; P ＜ 0.001) was significantly associated with obstructive CAD. DL-CACS (adjusted OR:1.003; 95% CI: 1.002-1.004; P ＜ 0.001) was also an independent predictor for hemodynamically significant CAD. The AUCs, sensitivities, specificities, positive predictive values and negative predictive values of DL-CACS for obstructive CAD and hemodynamically significant CAD were 0.753 (95% CI: 0.712-0.792), 75.9%, 66.5%, 74.8%, 67.8% and 0.769 (95% CI: 0.728-0.806), 80.7%, 62.1%, 59.6% and 82.3% respectively. It took 1.17 min to perform automated measurement of DL-CACS in total, which was significantly less than manual measurement of 1.73 min (P ＜ 0.001). Conclusions: DL-CACS, with less time-consuming, can accurately and effectively predict obstructive CAD and hemodynamically significant CAD in T2DM.

Lesion-specific pericoronary adipose tissue CT attenuation improves risk prediction of major adverse cardiovascular events in coronary artery disease.

OBJECTIVES: To determine whether lesion-specific pericoronary adipose tissue CT attenuation (PCATa) is superior to PCATa around the proximal right coronary artery (PCATa-RCA) and left anterior descending artery (PCATa-LAD) for major adverse cardiovascular events (MACE) prediction in coronary artery disease (CAD). METHODS: Six hundred and eight CAD patients who underwent coronary CTA from January 2014 to December 2018 were retrospectively included, with clinical risk factors, plaque features, lesion-specific PCATa, PCATa-RCA, and PCATa-LAD collected. MACE was defined as cardiovascular death, non-fatal myocardial infarction, unplanned revascularization, and hospitalization for unstable angina. Four models were established, encapsulating traditional factors (Model A), traditional factors and PCATa-RCA (Model B), traditional factors and PCATa-LAD (Model C), and traditional factors and lesion-specific PCATa (Model D). Prognostic performance was evaluated with C-statistic, area under receiver operator characteristic curve (AUC), and net reclassification index (NRI). RESULTS: Lesion-specific PCATa was an independent predictor for MACE (adjusted hazard ratio = 1.108, P < .001). The C-statistic increased from 0.750 for model A to 0.762 for model B (P = .078), 0.773 for model C (P = .046), and 0.791 for model D (P = .005). The AUC increased from 0.770 for model A to 0.793 for model B (P = .027), 0.793 for model C (P = .387), and 0.820 for model D (P = .019). Compared with model A, the NRIs for models B, C, and D were 0.243 (-0.323 to 0.792, P = .392), 0.428 (-0.012 to 0.835, P = .048), and 0.708 (0.152-1.016, P = .001), respectively. CONCLUSIONS: Lesion-specific PCATa improves risk prediction of MACE in CAD, which is better than PCATa-RCA and PCATa-LAD. ADVANCES IN KNOWLEDGE: Lesion-specific PCATa was superior to PCATa-RCA and PCATa-LAD for MACE prediction.

Radiomics analysis of pericoronary adipose tissue based on plain CT for preliminary screening of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a markedly increased prevalence of coronary artery disease (CAD). Radiomics features of pericoronary adipose tissue (PCAT) were correlated with inflammation, which may have potential value in the prediction of CAD. PURPOSE: To determine whether radiomics analysis of PCAT captured by plain computed tomography (CT) could predict obstructive CAD in patients with T2DM. MATERIAL AND METHODS: The study included 155 patients with T2DM with suspected CAD between January 2020 and December 2021. Volumes of right coronary artery of 10-50 mm were delineated in the plain CT to extract radiomics features and PCAT CT attenuation (PCATa). Least absolute shrinkage and selection operator was used to select the useful radiomics features to calculate the radiomics score (Rad-score). Univariate and multivariable logistic regression were applied to select independent predictors. The predictive performance was evaluated by the area under the receiver operating characteristics curve (AUC). RESULTS: Rad-score (per 0.1 increments: odds ratio [OR] = 1.297; P < 0.001), coronary artery calcium score (CACS) (OR = 1.003; P = 0.037), and sex (OR = 3.245; P = 0.026) were identified as independent predictors for obstructive CAD. Rad-score (AUC = 0.835) outperformed CACS (AUC = 0.780), sex (AUC = 0.665), and PCATa (AUC = 0.550) in predicting obstructive CAD (P = 0.017 and 0.003 for Rad-score vs. sex and PCATa, respectively); however, the improvement between Rad-score and CACS had no statistical significance (P = 0.490). CONCLUSION: Plain CT-derived Rad-score may be used as a preliminary screening tool for obstructive CAD in patients with T2DM.

Iodixanol activation of mast cells: Implications in the pathogenesis of iodixanol-induced delayed cutaneous adverse reactions.

Iodinated contrast media (ICM) is widely used in radiological examination and interventional therapy. In the commonly used ICM, iodixanol is considered to be the safer one. However, compared with other ICMs, it has a higher incidence of delayed cutaneous adverse reactions. The underlying mechanisms are unclear. In this study, mice with positive allergic reactions were selected based on the mouse clinical allergy symptom score and skin and blood samples taken 1, 6, 24, 48, and 72 h after ICMs (6 g iodine/kg) injection for histological and blood analyses. ICMs-induced pseudo-allergic reactions were investigated through in vivo intravital vascular imaging and passive cutaneous anaphylaxis (PCA) not mediated by IgE and through, calcium imaging degranulation of mast cells (MCs), and western blot assays in vitro. Results shows iodixanol-induced systemic anaphylaxis caused severe extravasation of plasma proteins and degranulation of skin MCs, and increased levels of plasma histamine, cytokines and inflammatory chemokines. Mechanistically, iodixanol increases degranulation of MCs and promotes the synthesis of inflammatory factors by activating PLC-γ and PI3K-related pathways. Trigonelline inhibit iodixanol-induced MC-related pseudo-allergic reactions in vitro and in vivo. These results suggest that mice in the iodixanol group had a higher incidence of delayed cutaneous reactions, characterized by cytokine release over time and delayed cutaneous MC degranulation. Iodixanol's delayed cutaneous adverse reactions may be due to a delayed phase of MC-related pseudo-allergic reactions. Trigonelline revealed anti-allergic activity in iodixanol-induced MC-related pseudo-allergic reactions.

Diagnostic performance of deep learning-based vascular extraction and stenosis detection technique for coronary artery disease.

OBJECTIVE: To investigate the diagnostic performance of deep learning (DL)-based vascular extraction and stenosis detection technology in assessing coronary artery disease (CAD). METHODS: The diagnostic performance of DL technology was evaluated by retrospective analysis of coronary computed tomography angiography in 124 suspected CAD patients, using invasive coronary angiography as reference standard. Lumen diameter stenosis ≥50% was considered obstructive, and the diagnostic performances were evaluated at per-patient, per-vessel and per-segment levels. The diagnostic performances between DL model and reader model were compared by the areas under the receiver operating characteristics curves (AUCs). RESULTS: In patient-based analysis, AUC of 0.78 was obtained by DL model to detect obstructive CAD [sensitivity of 94%, specificity of 63%, positive predictive value of 94%, and negative predictive value of 59%], While AUC by reader model was 0.74 (sensitivity of 97%, specificity of 50%, positive predictive value of 93%, negative predictive value of 73%). In vessel-based analysis, the AUCs of DL model and reader model were 0.87 and 0.89 respectively. In segment-based analysis, the AUCs of 0.84 and 0.89 were obtained by DL model and reader model respectively. It took 0.47 min to analyze all segments per patient by DL model, which is significantly less than reader model (29.65 min) (p < 0.001). CONCLUSION: The DL technology can accurately and effectively identify obstructive CAD, with less time-consuming, and it could be a reliable diagnostic tool to detect CAD. ADVANCES IN KNOWLEDGE: The DL technology has valuable prospect with the diagnostic ability to detect CAD.

Bone marrow adipose amount influences vertebral bone strength.

Association of bone marrow adipose and microstructure with bone strength in osteoporotic rats using MR Dixon analysis and micro-CT was evaluated. A total of 40 female Sprague-Dawley rats (6-month-old) were divided randomly into sham-operated (SHAM, n=20) group and ovariectomized (OVX, n=20) group. Fat fraction (FF) was measured by two-point Dixon method with MR imaging at the baseline, 4th, 8th and 12th week, respectively. After sacrifice by anesthesia, the fifth lumbar vertebrae bone was sampled for micro-CT scanning. The biomechanical analysis was also performed. FF in osteoporotic rats significantly increases with time, which correlates with bone microstructure parameters. Compared with biomechanical test, FF showed negative correlation with break stress and elastic modulus. It also suggested that loss of bone mass was accompanied with the increase of adipose tissue content in vertebrae bone marrow. The impairment of bone strength leads to the risk of brittle fracture. In conclusion, the bone marrow adipose amount obtained by MR Dixon and microstructure by micro-CT correlates to bone strength in osteoporotic rats.

Multifunctional Magnetic Mesoporous Silica Nanoagents for in vivo Enzyme-Responsive Drug Delivery and MR Imaging.

In this study, we report novel multifunctional nanoagents for in vivo enzyme-responsive anticancer drug delivery and magnetic resonance imaging (MRI), based on mesoporous silica coated iron oxide nanoparticles (Fe3O4@MSNs). The anticancer drug, DOX, was encapsulated in the porous cavities with a MMP-2 enzyme responsive peptide being covalently linked to the nanoparticles surface. The in vitro experiment results indicated that the enzyme responsive nanoagents own high specificity for controlled drug release in the cell line with high MMP-2 expression. Furthermore, the targeted delivery of the nanoagents to the tumor site purpose has been successfully achieved through magnet-guided nanocarrier accumulation by utilizing the magnetic properties of the Fe3O4 nanocores, which resulted in efficient inhibition of the tumor growth. Additionally, these novel nanoagents can also be used as MRI agent for the real-time diagnosis the tumor treatment process of living animals. Taking the advantages of high specificity, controllable drug release and real-time MRI imaging, we believe these multifunctional nanoagents could also be used as a general platform for the design of stimulus-responsive multifunctional nanomaterials for the aim of accurate diagnosis and efficient treatment of other diseases.

Enhanced radiation damage caused by iodinated contrast agents during CT examination.

OBJECTIVE: To access the effect of iodinate contrast agent (ICA) on DNA double-stand breaks (DSBs) in human peripheral blood lymphocytes during computed tomography (CT) examinations. MATERIALS AND METHODS: This present study was approved by the institutional ethics committee; written informed patient consent was obtained from 70 patients. A total of 48 patients underwent computed tomography urography (CTU), in which only one time CT scanning was examined after injecting ICA, and 22 patients received unenhanced whole abdominal CT, among them 10 patients were selected to get ICA injection immediately after irradiation. Blood samples were taken from all patients prior to and immediately after CT scan, as well as 8min after the injection of ICA. The lymphocytes in these blood samples were separated by using density-gradient centrifugation, fixed and immunostained with γH2AX antibody. The average number of phosphorylated histone H2AX (γH2AX) foci per lymphocyte was counted under a fluorescence microscopy. Differences in the number of γH2AX-foci were statistically analyzed using independent sample t test and one way ANOVA. RESULT: The three patient groups had no significant differences in the baseline foci numbers(P>0.05). The γH2AX-focus levels increased in both groups after CT scan. Patients who underwent CTU examinations had a greater DSBs level (mean±standard error of mean, 0.945±0.184 foci per cell) than those who received unenhanced whole abdominal CT scan (mean±standard error of mean, 0.700±0.112 foci per cell), increasing by about 37.9%; The ICA injected before CT scan itself had an effect on the DSBs, which increased DSBs level by approximately 90.3% (0.059±0.018vs 0.031±0.025, P<0.05), but no significant difference was found if added after irradiation, increasing DSBs level only by 3.2% approximately (0.711±0.091vs 0.689±0.108, P=0.499). CONCLUSION: The iodinated contrast agent itself can lead to an increase in the level of DSBs as assessed with γH2AX foci formation, and the application of ICA can amplify DNA damage induced by diagnostic x-ray procedures such as whole abdominal CT.

Albumin-Mediated Biomineralization of Paramagnetic NIR Ag2S QDs for Tiny Tumor Bimodal Targeted Imaging in Vivo.

Bimodal imaging has captured increasing interests due to its complementary characteristics of two kinds of imaging modalities. Among the various dual-modal imaging techniques, MR/fluorescence imaging has been widely studied owing to its high 3D resolution and sensitivity. There is, however, still a strong demand to construct biocompatible MR/fluorescence contrast agents with near-infrared (NIR) fluorescent emissions and high relaxivities. In this study, BSA-DTPA(Gd) derived from bovine serum albumin (BSA) as a novel kind of biotemplate is employed for biomineralization of paramagnetic NIR Ag2S quantum dots (denoted as Ag2S@BSA-DTPA(Gd) pQDs). This synthetic strategy is found to be bioinspired, environmentally benign, and straightforward. The obtained Ag2S@BSA-DTPA(Gd) pQDs have fine sizes (ca. 6 nm) and good colloidal stability. They exhibit unabated NIR fluorescent emission (ca. 790 nm) as well as high longitudinal relaxivity (r1 = 12.6 mM(-1) s(-1)) compared to that of commercial Magnevist (r1 = 3.13 mM(-1) s(-1)). In vivo tumor-bearing MR and fluorescence imaging both demonstrate that Ag2S@BSA-DTPA(Gd) pQDs have pronounced tiny tumor targeting capability. In vitro and in vivo toxicity study show Ag2S@BSA-DTPA(Gd) pQDs are biocompatible. Also, biodistribution analysis indicates they can be cleared from body mainly via liver metabolism. This protein-mediated biomineralized Ag2S@BSA-DTPA(Gd) pQDs presents great potential as a novel bimodal imaging contrast agent for tiny tumor diagnosis.

Paramagnetic albumin decorated CuInS2/ZnS QDs for CD133+ glioma bimodal MR/fluorescence targeted imaging.

Glioma stem cells (GSCs) are considered the key to the occurrence, development, invasion, recurrence and sensitivity to treatment of brain tumors. Precise molecular imaging of GSCs by means of probes in vivo has therefore become a premise of solving the above problems. Herein, a sensitive, specific, accurate and biocompatible molecular nanoprobe is reported with MR/fluorescence imaging modalities for CD133+ glioma tumor bimodal targeted imaging. Cd-free high quality CuInS2/ZnS core/shell quantum dots (QDs) were synthesized for fluorescence imaging; DTPA-coupled BSA with Gd3+ chelation (BSA-DTPAGd) were prepared and used both for phase transfer of hydrophobic CuInS2/ZnS QDs and MR imaging modality. The resulting hydrophilic paramagnetic QDs (pQDs) were then linked with anti-CD133 monoclonal antibody, pQDs-CD133mAb denoting the framework of the entire molecular probe, for tumor targeting. The obtained pQDs-CD133mAb has a proper size (ca. 45 nm) and good colloidal stability. It exhibits a high quality fluorescent emission (ca. 630 nm) together with high longitudinal relaxivity (r1 = 15.2 mM-1 s-1) compared with that of commercial Magnevist (r1 = 3.12 mM-1 s-1). Dual modal imaging in vitro and in vivo shows potent tumor enhancement with administration of pQDs-CD133mAb. A biodistribution study indicates hepatobiliary and renal processing of pQDs-CD133mAb with no obvious toxicity. It could be therefore concluded, with a dual-modal imaging and targeting strategy, pQDs-CD133mAb presents a great potential as an alternative for accurate diagnosis of glioma.

Lack of association of common polymorphisms in MUC1 gene with H. pylori infection and non-cardia gastric cancer risk in a Chinese population.

Several lines of evidence support the notion that MUC1 is often aberrantly expressed in gastric cancer, and it is a ligand for Helicobacter pylori. Genetic variation in MUC1 gene may confer susceptibility to H. pylori infection and gastric cancer. We assessed the association of common polymorphisms in MUC1 gene with H. pylori infection and non-cardia gastric cancer using an LD-based tag SNP approach in north-western Chinese Han population. A total of four SNPs were successfully genotyped among 288 patients with non-cardia gastric cancer and 281 age- and sex-matched controls. None of the tested SNPs was associated with H. pylori infection. SNP rs9426886 was associated with a decreased risk of non-cardia gastric cancer, but lost significance after adjustment for multiple testing. Overall, our data indicated that common genetic variations in MUC1 gene might not make a major contribution to the risk of H. pylori infection and non-cardia gastric cancer in our studied population.