Prediction of new cerebral ischemic lesion after carotid artery stenting: a high-resolution vessel wall MRI-based radiomics analysis.

OBJECTIVES: Carotid artery stenting (CAS) is an established treatment for local stenosis. The most common complication is new ipsilateral ischemic lesions (NIILs). This study aimed to develop models considering lesion morphological and compositional features, and radiomics to predict NIILs. MATERIALS AND METHODS: One hundred and forty-six patients who underwent brain MRI and high-resolution vessel wall MR imaging (hrVWI) before and after CAS were retrospectively recruited. Lumen and outer wall boundaries were segmented on hrVWI as well as atherosclerotic components. A traditional model was constructed with patient clinical information, and lesion morphological and compositional features. Least absolute shrinkage and selection operator algorithm was performed to determine key radiomics features for reconstructing a radiomics model. The model in predicting NIILs was trained and its performance was tested. RESULTS: Sixty-one patients were NIIL-positive and eighty-five negative. Volume percentage of intraplaque hemorrhage (IPH) and patients' clinical presentation (symptomatic/asymptomatic) were risk factors of NIILs. The traditional model considering these two features achieved an area under the curve (AUC) of 0.778 and 0.777 in the training and test cohorts, respectively. Twenty-two key radiomics features were identified and the model based on these features achieved an AUC of 0.885 and 0.801 in the two cohorts. The AUCs of the combined model considering IPH volume percentage, clinical presentation, and radiomics features were 0.893 and 0.842 in the training and test cohort respectively. CONCLUSIONS: Compared with traditional features (clinical and compositional features), the combination of traditional and radiomics features improved the power in predicting NIILs after CAS. KEY POINTS: • Volume percentage of IPH and symptomatic events were independent risk factors of new ipsilateral ischemic lesions (NIILs). • Radiomics features derived from carotid artery high-resolution vessel wall imaging had great potential in predicting NIILs after CAS. • The combination model with radiomics and traditional features further improved the diagnostic performance than traditional features alone.

Identification of high-risk carotid plaque with MRI-based radiomics and machine learning.

OBJECTIVES: We sought to build a high-risk plaque MRI-based model (HRPMM) using radiomics features and machine learning for differentiating symptomatic from asymptomatic carotid plaques. MATERIALS AND METHODS: One hundred sixty-two patients with carotid stenosis were randomly divided into training and test cohorts. Multi-contrast MRI including time of flight (TOF), T1- and T2-weighted imaging, and contrast-enhanced imaging was done. Radiological characteristics of the carotid plaques were recorded and calculated to build a traditional model. After extracting the radiomics features on these images, we constructed HRPMM with least absolute shrinkage and selection operator algorithm in the training cohort and evaluated its performance in the test cohort. A combined model was also built using both the traditional and radiomics features. The performance of all the models in the identification of high-risk carotid plaque was compared. RESULTS: Intraplaque hemorrhage and lipid-rich necrotic core were independently associated with clinical symptoms and were used to build the traditional model, which achieved an area under the curve (AUC) of 0.825 versus 0.804 in the training and test cohorts. The HRPMM and the combined model achieved an AUC of 0.988 versus 0.984 and of 0.989 versus 0.986 respectively in the two cohorts. Both the radiomics model and combined model outperformed the traditional model, whereas the combined model showed no significant difference with the HRPMM. CONCLUSIONS: Our MRI-based radiomics model can accurately distinguish symptomatic from asymptomatic carotid plaques. It is superior to the traditional model in the identification of high-risk plaques. KEY POINTS: • Carotid plaque multi-contrast MRI stores other valuable information to be further exploited by radiomics analysis. • Radiomics analysis can accurately distinguish symptomatic from asymptomatic carotid plaques. • The radiomics model is superior to the traditional model in the identification of high-risk plaques.

Comparison study between multicontrast atherosclerosis characterization (MATCH) and conventional multicontrast MRI of carotid plaque with histology validation.

PURPOSE: To compare Multicontrast ATherosclerosis Characterization (MATCH) with conventional multicontrast magnetic resonance imaging (MRI) in the characterization and quantification of carotid plaque components. MATERIALS AND METHODS: Fifty-three consecutive patients underwent carotid plaque 3.0T MRI including conventional multicontrast sequences and MATCH, with 13 of them having carotid endarterectomy for histology validation. The detection of major plaque components including lipid-rich necrotic core (LRNC), loose matrix (LM), intraplaque hemorrhage (IPH), and calcification (CA) and measurement of lumen area, outer wall area, normalized wall index (NWI), and plaque components areas were compared between the two protocols. RESULTS: Plaque analysis and comparison were done on 298 matched cross-sectional MRI. MATCH detected significantly more calcifications than conventional consequences (P < 0.01). The difference in detection of IPH (P = 0.07) and LRNC (P = 0.10) approached significance. There was no significant difference in demonstration of LM (P =0.52). A larger area of IPH and CA was measured on MATCH (P < 0.01). The difference nearly reached significance between the two protocols in measuring lumen area (P = 0.09) and outer wall area (P = 0.08). No significant difference was found when measuring the mean area of LRNC (P = 0.15) and LM (P = 0.14) and NWI (P = 0.38). By using receiver operating characteristic curve (ROC) analysis, the accuracy of MATCH and conventional protocols did not differ significantly in the detection of IPH (P = 0.15), LRNC (P = 0.61), LM (P = 0.48), and CA (P = 0.11) when histology served as a reference. CONCLUSION: MATCH was comparable if not superior to conventional protocol in identification and quantification of major carotid plaque components. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:764-770.

LncRNA HCG18 facilitates melanoma progression by modulating miR-324-5p/CDK16 axis.

OBJECTIVE: LncRNA HCG18 has been reported to act as a tumor promoter in gastric cancer, hepatocellular carcinoma and nasopharyngeal carcinoma. However, the role of HCG18 in melanoma is still not clear. In this study, we detected the expression and molecular function of HCG18 in melanoma. METHODS: The expression of HCG18 in melanoma cell lines and 50 pairs of melanoma and corresponding non-cancer tissues was detected by RT-qPCR. The relationship between HCG18 and clinicopathology was analyzed. We used HCG18 overexpressing melanoma cell lines A375 and M14, and si-HCG18 to knock down HCG18 expression. CCK-8, clone formation, Transwell assay and FCM were used to explore the effect of HCG18 knockdown on cell proliferation, migration, invasion and apoptosis in melanoma cells. Bioinformatics software was used to predict the downstream miRNA regulated by HCG18, and the downstream target genes regulated by miR-324-5p. Dual-luciferase reporter assay and RNA pull-down assay were used to verify whether miR-324-5p was related to the predicted sequence of HCG18. RESULTS: HCG18 was highly expressed in melanoma tissues and cells. Besides, we found that HCG18 was closely correlated with thickness, TNM stage and metastasis. Functional experiments discovered that HCG18 knockdown restrained cell proliferation, migration and invasion, while promoted cell apoptosis in melanoma cells. HCG18 was confirmed to be a sponge of miR-324-5p, and CDK16 might be a downstream gene of miR-324-5p. HCG18 was found to reverse the effect of miR-324-5p by upregulating CDK16 expression in melanoma cell proliferation, apoptosis, migration and invasion in vitro. CONCLUSION: This study indicated that HCG18 played an essential role in the pathogenesis of melanoma and suggested that HCG18 might be a potential target for the treatment and diagnosis of melanoma.

WDR5 promotes the proliferation of lung adenocarcinoma by inducing SOX9 expression.

Aim: WDR5 is a coactivator of transcription factor which promotes the progression of several cancer types, but its function in lung adenocarcinoma (AC) is unknown. Materials & methods: We detected WDR5 expression in lung AC with quantitative real-time polymerase chain reaction and immunohistochemistry. Results: WDR5 was significantly overexpressed in ACs compared with normal lung tissues. Moreover, WDR5 was an independent prognostic biomarker of lung AC. With clinical analyzation and in vitro experiments, we proved that SOX9 was a downstream effector of WDR5 in promoting A549 proliferation, and that SOX9 was also an unfavorable prognostic biomarker of lung AC. Conclusion: WDR5 and SOX9 are both prognostic biomarkers predicting poor outcome of lung AC. WDR5 could promote proliferation of lung AC by elevating SOX9 expression.

Circumferential degree of carotid calcification is associated with new ischemic brain lesions after carotid artery stenting.

BACKGROUND: The relationship between plaque calcification and new ischemic brain lesions after carotid artery stenting (CAS) remains controversial. The purpose of this study was to determine if the circumferential degree of carotid calcification is associated with new ischemic brain lesions on diffusion-weighted imaging (DWI) after CAS. METHODS: A total of 96 patients with carotid stenosis of ≥50% who underwent CAS were enrolled in the study. All patients underwent preoperative carotid computed tomography (CT), and preoperative and postoperative brain MRI. The brain MRI sequences included T1WI, T2WI, T2-fluid-attenuated inversion recovery (FLAIR), and DWI. The location, circumferential degree, volume, percentage volume, maximum density, mean density, Agatston score of carotid calcification, and total plaque volume were assessed and compared between patients with and without new ischemic brain lesions after CAS. Univariate and multivariate analyses were performed to evaluate predictors of new ischemic brain lesions. RESULTS: All of the 96 patients (67.8±6.8 years of age, 83.3% men) were included in the analysis. New ischemic brain lesions on DWI were observed in 40 patients (41.7%). Patients with new ischemic brain lesions after CAS had a larger circumferential degree of calcification than those without new ischemic brain lesions (P<0.001). There was only a possible trend toward significance for the percentage volume of calcification between the two groups with and without new brain ischemic lesions (P=0.07). No significant differences were found regarding the location (P=0.18), volume (P=0.37), maximum density (P=0.44), mean density (P=0.39), Agatston score (P=0.28), and total plaque volume (P=0.33) of carotid calcification between the DWI+ and DWI- groups. In the multivariate analysis, an increased risk of new ischemic brain lesions was observed in patients with a high score for the circumferential degree of calcification [score 3; odds ratio (OR): 10.7, P<0.001; score 4, OR: 11.7, P=0.038]. CONCLUSIONS: The circumferential degree of carotid calcification was associated with new ischemic brain lesions after CAS. CAS should be avoided if possible for carotid stenosis with large circumferential calcified plaques.

Associations between carotid intraplaque hemorrhage and new ipsilateral ischemic lesions after carotid artery stenting: a quantitative study with conventional multi-contrast MRI.

The risk of cerebral embolism after CAS in patients with carotid IPH is still controversial. This study was to further investigate the relationship between IPH and new ipsilateral ischemic lesion (NIIL) after CAS, and to perform a volumetric analysis of IPH for predicting the risk of NIIL following CAS. One hundred and seventeen patients with carotid stenosis undergoing CAS were prospectively enrolled. Preprocedural multi-contrast carotid MRI was performed. NIIL was evaluated by brain DWI before and after CAS. IPH volume, wall volume at the plaque (WVplaque) and relative IPH volume were calculated. Associations between IPH and postprocedural NIIL were studied. NIILs were shown in 52 patients. IPH were identified in 53 patients. NIILs were found more frequently in IPH-positive (33/53, 62.3%) than in IPH-negative patients (19/64, 29.7%, p < 0.001). There was no significant difference of WVplaque between NIIL-positive and NIIL-negative patients (1166.6 ± 432.0 mm3 vs 1124.6 ± 410.4 mm3, p = 0.592). The IPH volume from NIIL-positive group was significantly larger than that of NIIL-negative group (252.8 ± 264.9 mm3 vs 59.3 ± 131.1 mm3, p < 0.001), with also higher relative IPH volume (20.4 ± 19.1% vs 5.7 ± 12.2%, p < 0.001). ROC curve showed that 183.45 mm3 of the IPH volume was the most reliable cutoff value for predicting NIIL with a specificity of 92.3% and a positive predictive value of 86.1%. Larger IPH volume is associated with increased risk of NIIL after CAS procedure. Quantification of IPH volume may be useful for predicting cerebral ischemic events after CAS.

Heat shock protein-guided dual-mode CT/MR imaging of orthotopic hepatocellular carcinoma tumor.

The development of an ultrasensitive nanoprobe is regarded as one of the most promising strategies for the precise diagnosis of tumors. Herein, tanespimycin (17-AAG)-modified polyethylenimine-based gold nanoparticles (AuNPs) co-labeled with a gadolinium (Gd) nanoprobe are constructed for targeted dual-mode computed tomography (CT)/magnetic resonance (MR) imaging. The specific binding of tanespimycin to the N-terminal of heat shock protein 90 (HSP90) endows the modified nanoprobes (NPs) with the ability to up-regulate HSP90 tumor cells and to display excellent X-ray attenuation intensity and T1 MR imaging performance in an orthotopic hepatocellular carcinoma tumor model. Such an ultrasensitive nanoprobe holds enormous promise for highly efficient tumor diagnosis and dual-mode CT/T1 positive MR imaging. This study develops a novel strategy to prepare a multifunctional nanoprobe via polyethylenimine nanotechnology. Using this strategy, various dual-mode or multimode nanoprobes for diagnosing different cancers may be designed.