Development and Validation of a Nomogram Based on Multimodality Ultrasonography Images for Differentiating Malignant from Benign American College of Radiology Thyroid Imaging, Reporting and Data System (TI-RADS) 3-5 Thyroid Nodules.

OBJECTIVE: The aim of the work described here was to develop and validate a predictive nomogram based on combined image features of gray-scale ultrasonography (US), elastosonography (ES) and contrast-enhanced US (CEUS) to differentiate malignant from benign American College of Radiology Thyroid Imaging, Reporting and Data System (ACR TI-RADS) 3-5 thyroid nodules. METHODS: Among 2767 thyroid nodules scanned by CEUS in Xijing Hospital between April 2014 and November 2018, 669 nodules classified as ACR TI-RADS 3-5 were included, with confirmed diagnosis and ES examination. Four hundred fifty-five nodules were set as a training cohort and 214 as a validation cohort. Images were categorized as gray-scale US ACR TI-RADS 3, TI-RADS 4 and TI-RADS 5; ES patterns of ES-1 and ES-2; and CEUS patterns of either heterogeneous hypo-enhancement, concentric hypo-enhancement, homogeneous hyper-/iso-enhancement, no perfusion, hypo-enhancement with sharp margin, island-like enhancement or ring-like enhancement. On the basis of multivariate logistic regression analysis, a predictive nomogram model was developed and validated by receiver operating characteristic curve analysis. RESULTS: In the training cohort, ACR TI-RADS 4 and 5, ES-2, heterogeneous hypo-enhancement, concentric hypo-enhancement and homogeneous hyper-/iso-enhancement were selected as predictors of malignancy by univariate logistic regression analysis. A predictive nomogram (combining indices of ACR TI-RADS, ES and CEUS) indicated excellent predictive ability for differentiating malignant from benign lesions in the training cohort: area under the receiver operating characteristic curve (AUC) = 0.93, 95% confidence interval (CI): 0.90-0.95. The prediction nomogram model was determined to have a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 0.84, 0.88, 0.91 and 0.81. In the validation cohort, the AUC of the prediction nomogram model was significantly higher than those of the single modalities (p < 0.005) . The AUCs of the validation cohort were 0.93 (95% CI: 0.89-0.96) and 0.93 (95% CI: 0.89-0.97), respectively, for senior and junior radiologists. The prediction nomogram model has a sensitivity, specificity, PPV and NPV of 0.86, 0.87, 0.87 and 0.86. CONCLUSION: A predictive nomogram model combining ACR TI-RADS, ES and CEUS exhibited potential clinical utility in differentiating malignant from benign ACR TI-RADS 3-5 thyroid nodules.

Thermal/ultrasound-triggered release of liposomes loaded with Ganoderma applanatum polysaccharide from microbubbles for enhanced tumour ablation.

The effectiveness of thermal ablation for the treatment of liver tumours is limited by the risk of incomplete ablation, which can result in residual tumours. Herein, an enhancement strategy is proposed based on the controlled release of Ganoderma applanatum polysaccharide (GAP) liposome-microbubble complexes (GLMCs) via ultrasound (US)-targeted microbubble destruction (UTMD) and sublethal hyperthermic (SH) field. GLMCs were prepared by conjugating GAP liposomes onto the surface of microbubbles via biotin-avidin linkage. In vitro, UTMD promotes the cellular uptake of liposomes and leads to apoptosis of M2-like macrophages. Secretion of arginase-1 (Arg-1) and transforming growth factor-beta (TGF-ß) by M2-like macrophages decreased. In vivo, restriction of tumour volume was observed in rabbit VX2 liver tumours after treatment with GLMCs via UTMD in GLMCs + SH + US group. The expression levels of CD68 and CD163, as markers of tumour-associated macrophages (TAMs) in the GLMCs + SH + US group were reduced in liver tumour tissue. Decreased Arg-1, TGF-ß, Ki67, and CD31 factors related to tumour cell proliferation and angiogenesis was evident on histological analysis. In conclusion, thermal/US-triggered drug release from GLMCs suppressed rabbit VX2 liver tumour growth in the SH field by inhibiting TAMs, which represents a potential approach to improve the effectiveness of thermal ablation.

Comparison of contrast-enhanced ultrasound characteristics of inflammatory thyroid nodules and papillary thyroid carcinomas using a quantitative time-intensity curve: a propensity score matching analysis.

Background: This study aims to compare the contrast-enhanced ultrasound (CEUS) characteristics of inflammatory thyroid nodules with those of papillary thyroid carcinomas using time-intensity curve (TIC) analysis. Methods: This was a retrospective cohort study. Among the thyroid nodules in 2161 patients who underwent CEUS from July 2014 to April 2018, 44 nodules in 44 patients ultimately diagnosed as inflammatory nodules and 44 nodules in 44 patients confirmed as papillary carcinomas (enrolled from July 2016 to April 2018) were included after propensity score matching analysis (1:1). The average diameters of lesions in the inflammatory and malignant groups (n=44 each) were 0.92±0.34 cm and 0.89±0.42 cm, respectively. CEUS patterns were evaluated and classified into four types, namely concentric hypo-enhancement, heterogeneous hypo-enhancement, hypo-enhancement with a sharp margin, and homogeneous hyper/iso-enhancement. The measured TIC parameters included peak intensity (PI), rise time (RT), time to peak (TTP), maximum slope rate of the ascending curve (AS), and maximum slope rate of the descending curve (DS). The CEUS patterns and TIC parameters were compared between the inflammatory nodules and papillary carcinomas. Results: The heterogeneous hypo-enhancement CEUS pattern was predominantly present in the inflammatory nodules. The concentric hypo-enhancement pattern was identified as a valuable predictive pattern for papillary carcinomas. For the TIC, inflammatory nodules had a lower PI [55.42 (45.41, 76.91) vs. 84.43 (74.93, 90.92)] [median (interquartile range)] and a smaller AS [22.39 (13.37, 29.93) vs. 29.54 (19.37, 44.77)], compared with papillary carcinomas (P<0.05). Conclusions: CEUS patterns with TIC parameters could provide effective and quantitative information for characterizing microvascular perfusion of inflammatory thyroid nodules and papillary carcinomas.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

Differential diagnosis of thyroid nodules through a combination of multiple ultrasonography techniques: A decision-tree model.

The present study aimed to establish a decision tree (DT) model by combining the parameters of conventional gray-scale ultrasonography (US), elastosonography (ES), color Doppler US (CDUS) and contrast-enhanced US (CEUS) for the differential diagnosis of thyroid nodules. A single-center, retrospective study of 321 thyroid nodules was conducted. For 222 nodules, parameters of conventional gray-scale US, CDUS, ES and CEUS were evaluated using univariate logistic regression. Factors for with P<0.10 were further assessed using multivariate logistic regression. Significant factors (P<0.05) were used to establish a DT. The diagnostic accuracy of this DT was then evaluated by its application to the other 99 nodules. After univariate logistic analysis, factors including gender, number of nodules and diffuse disease were excluded, due to P>0.10. The results of multivariate logistic analysis determined that the following factors were required for the DT: Extent of blood flow determined by CDUS (P=0.002), area ratio determined by ES (P=0.033), peak phase patterns determined by CEUS (P<0.001) and micro-calcification determined by conventional gray-scale US (P=0.015). When compared to the pathological or cytological results of 99 nodules, the resulting DT had a sensitivity of 98.6%, specificity of 80.1%, positive predictive value of 93.5% and negative predictive value of 95.5%. These results suggested that a DT combining conventional gray-scale US, ES, CDUS and CEUS may be helpful for differentiating between types of thyroid nodules.

Evaluation of characteristics of thyroid nodules on contrast-enhanced ultrasonography: a retrospective analysis of 252 cases.

AIM: This study investigated the enhancement patterns observed on contrast-enhanced ultrasound (CEUS) images for differentiating thyroid nodules. MATERIAL AND METHODS: A retrospective review was conducted of CEUS cine loops of 252 nodules by two independent readers. Seven categories of enhancement patterns were identified: concentric hypoenhancement; heterogeneous hypoenhancement; hypoenhancement with sharp margin; homogeneous hyper/isoenhancement; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. Associations between these patterns and the confirmed pathological/cytological outcomes (178 malignant, 74 benign) were analyzed and the sensitivity, specificity and positive predictive values (PPVs) determined. The agreement of the readers' assessments was evaluated by Kappa value. RESULTS: For malignant nodules, the predominant 3 patterns were: concentric hypoenhancement, heterogeneous hypoenhancement and homogeneous hyper/isoenhancement. For each of these, the diagnostic specificity was above 87% and the PPV more than 85%. Combining these patterns for malignancy the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 96.1% (98.9%), 71.6% (71.6%), and 89.1% (89.3%), respectively. For benign nodules, the predominant 4 patterns were: hypoenhancement with sharp margin; hyper/isoenhancement with ring-like vascularity; island-like enhancement; and no perfusion. The specificity for each was above 98% and the PPV more than 70%. Combining these patterns for benignity, the rates of sensitivity, specificity and PPV for reader 1 (reader 2) were 71.6% (71.6%), 96.1% (98.9%) and 88.3% (96.3%), respectively. The inter-reviewers agreement for classifying enhancement patterns was excellent (κ = 0.84, 95% CI: 0.79-0.89). CONCLUSIONS: Enhancement patterns of thyroid nodules on CEUS investigation, enable differentiation between malignant and benign lesions with good diagnostic sensitivity, specificity and PPV.