Utility of quantitative contrast-enhanced ultrasound for the prediction of lymph node metastasis in patients with papillary thyroid carcinoma.

OBJECTIVES: The aim of this study was to find the optimal parameters and cutoffs to differentiate metastatic lymph nodes (LNs) from benign LNs in the patients with papillary thyroid carcinoma (PTC) on the quantitative contrast-enhanced ultrasound (CEUS) features. METHODS: A total of 134 LNs in 105 patients with PTCs were retrospectively enrolled. All LNs were evaluated by conventional ultrasound (US) and CEUS before biopsy or surgery. The diagnostic efficacy of CEUS parameters was analyzed. RESULTS: Univariate analysis indicated that metastatic LNs more often manifested centripetal or asynchronous perfusion, hyper-enhancement, heterogeneous enhancement, ring-enhancing margins, higher PI, larger AUC, longer TTP and DT/2 than benign LNs at pre-operative CEUS (p < 0.001, for all). Multivariate analysis showed that centripetal or asynchronous perfusion (OR = 3.163; 95% CI, 1.721-5.812), hyper-enhancement(OR = 0.371; 95% CI, 0.150-0.917), DT/2 (OR = 7.408; 95% confidence interval CI, 1.496-36.673), and AUC (OR = 8.340; 95% CI, 2.677-25.984) were predictive for the presence of metastatic LNs. The sensitivity and accuracy of the quantitative CEUS were higher than qualitative CEUS (75% vs 55 % and 83.6% vs 76.1 %, respectively). CONCLUSIONS: Quantitative CEUS parameters can provide more information to distinguish metastatic from benign LNs in PTC patients; In particular, DT/2 and AUC have a higher sensitivity and accuracy in predicting the presence of metastatic LNs and reduce unnecessary sampling of benign LNs.

Combination of contrast-enhanced ultrasound and strain elastography to assess cytologically non-diagnostic thyroid nodules.

The aim of the present study was to investigate the benefits of combining contrast-enhanced ultrasound (CEUS) and strain elastography (SE) for the diagnosis of thyroid nodules with non-diagnostic fine-needle aspiration cytology (FNAC) results. Between October 2013 and March 2017, CEUS and SE were performed in 226 patients (236 thyroid nodules) with non-diagnostic FNAC results prior to thyroidectomy. The diagnostic value of CEUS, SE and their combination (CEUS+SE) in distinguishing malignant from benign thyroid nodules was evaluated, using surgical pathology as a reference. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of CEUS, SE and CEUS+SE in determining malignant thyroid nodules. Subsequently, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS, SE and CEUS + SE were calculated. The malignancy rate in patients with thyroid nodules and non-diagnostic FNAC results was 26.3% in the present study. The sensitivity, specificity, PPV, NPV, accuracy and area under the curve in predicting malignant thyroid nodules were 80.6, 85.6, 66.7, 92.5, 84.3 and 0.831%, respectively, using SE alone; 59.7, 95.9, 84.1, 86.9, 86.4 and 0.778%, respectively, using CEUS alone; and 83.9, 89.1, 73.6, 94.5, 88.1 and 0.865%, respectively, using the combination of CEUS and SE. Overall, the combination of CEUS with SE resulted in higher sensitivity, NPV and accuracy in the diagnosis of cytologically non-diagnostic thyroid nodules compared with CEUS or SE alone.

The features of contrast enhanced ultrasound and BRAF V600E in papillary thyroid carcinoma.

BACKGROUND: BRAF V600E mutation was proved to be associated with thyroid cancer. Papillary thyroid carcinoma (PTC) with positive BRAF mutation might have a more aggressive behavior. We investigated the correlation of the contrast-enhanced ultrasound (CEUS) features with BRAF 600VE in PTC. METHODS: The medical records of 1,199 patients with 1,315 nodules who underwent CEUS prior to fine needle aspiration (FNA) from January 2016 to March 2018 were retrospectively reviewed. The features of their enhancement were assessed from eight aspects: degree of enhancement, method of enhancement, homogeneity of enhancement, completeness of enhancement, boundary of the enhanced lesions, shape of the enhanced lesions, size of the enhanced lesions, and wash out period of the enhanced lesions. The patients then examined for the BRAF V600E mutation using specimens obtained from FNA. RESULTS: BRAF mutations were found in 888 of 1,315 nodules. The CEUS features were significantly different between BRAF-positive and BRAF-negative nodules. The BRAF mutation positive nodules were more often with larger size, hypo-enhancement, centripetal enhancement, inhomogeneous enhancement, complete enhancement, blurred boundary, irregular shape, and with wash out period at preoperative CEUS than those without BRAF mutations (P<0.001). However, no significant correlation was showed in Spearman's rank correlation between the CEUS features and BRAF mutation, except for degree of enhancement, method pattern of enhancement, and completeness of complete enhancement. Multivariate analysis showed that centripetal (OR: 1.465, 95% CI: 1.129-1.903) and no significant enhancement (OR: 0.790, 95% CI: 0.639-0.977) were predictive for the presence of BRAF mutations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of no significant enhancement and centripetal enhancement of CEUS for predicting BRAF mutation were 68.3%, 40.0%, 91.6%, 11.7%, and 72.4%, 35.1%, 37.8%, 70.0%, respectively. CONCLUSIONS: Our study indicated that preoperative thyroid nodule characteristics on CEUS might serve as a useful tool to BRAF mutation in PTC.

Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF165 to the ischemic myocardium.

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA3.1-human vascular endothelial growth factor 165 (pcDNA3.1-hVEGF165) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA3.1-hVEGF165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA3.1-hVEGF165 plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.

Role of Virtual Touch Tissue Quantification in Hashimoto's Thyroiditis.

We investigated the role of the virtual touch tissue quantification (VTQ) technique in diagnosing Hashimoto's thyroiditis (HT) and in distinguishing various HT-related thyroid dysfunctions. Two hundred HT patients and 100 healthy volunteers (the control group) were enrolled. The diagnostic performance of VTQ in predicting HT was calculated as the area under the receiver operating characteristic curve (AZ). The HT patients were further classified into three subgroups on the basis of serologic tests of thyroid function: hyperthyroidism, euthyroidism and hypothyroidism. Comparisons of shear wave velocity (SWV) between three subgroups were evaluated by analysis of variance. The mean SWV of the control group was significantly lower than that of the HT group (1.93 ± 0.33 m/s vs. 2.32 ± 0.49 m/s, p <0.001). Az was 0.734 with a cut-off value of 1.86 m/s for performance of SWV in distinguishing between HT and a healthy thyroid; the sensitivity and specificity were 82.5% and 50.0%, respectively. Mean SWV values in the three HT subgroups (hyperthyroidism [2.07 ± 0.37 cm/s] vs. euthyroidism [2.20 ± 0.40 cm/s] vs. hypothyroidism [2.49 ± 0.46 cm/s]) were significantly different (p <0.05). Our results suggest that VTQ is a promising technique for assessing HT and HT-related thyroid dysfunction.

Conventional US, elastography, and contrast enhanced US features of papillary thyroid microcarcinoma predict central compartment lymph node metastases.

Lymph node metastases at the time of diagnosis have a major impact on both therapeutic strategy and tumor recurrence for patients with papillary thyroid microcarcinoma (PTMC). Our objective was to evaluate the usefulness of PTMC characteristics on ultrasonography for predicting central compartment lymph node metastases (CCLNM) of PTMC. One hundred twenty seven patients who underwent surgery for PTMC were enrolled in this study. The relationship between the CCLNM and the characteristics on conventional US, elastographic, and contrast enhanced ultrasound (CEUS) were investigated. Univariate analysis indicated that PTMCs with CCLNM were more often nodule irregular shape, microcalcifications, hyperenhancing or isoenhancing parametric maps, and peak index ≥1 at preoperative US and CEUS than those without CCLNM (P< 0.01, 0.05, 0.01 and 0.05 respectively). Multivariate analysis showed that microcalcification (OR:2.378, 95% CI: 1.096-5.158) and hyperenhancement or isoenhancement (OR:2.8, 95% CI: 1.287-6.094) were predictive for the presence of CCLNM. Elastography score was not significantly different between the groups. Our study indicated that preoperative thyroid nodule characteristics on conventional US and CEUS may serve as a useful tool to predict central compartment lymph node metastases in PTMC.

[Ultrasonic scores of conventional ultrasound and ultrasound elastography in the diagnosis of thyroid nodular lesions].

OBJECTIVE: To explore the values of total ultrasonic scores of conventional ultrasound and ultrasound elastography in the diagnosis of thyroid nodular lesions. METHODS: A total of 347 thyroid nodules proved by fine-needle aspiration cytology (FNAC) and surgery underwent preoperative conventional ultrasound and ultrasound elastography. The features on gray scale, color Doppler flow imaging (CDFI) and elastograms were documented and total ultrasonic scores recorded. RESULTS: Among 347 nodules, 184 nodules were benign and 163 malignant. Significant differences of total ultrasonic scores were found between thyroid carcinoma and benign nodular lesions including the parameters of nodular shape, edge, echoes, sound attenuation, psammous calcifications, internal blood flow and ultrasound elastography score. The higher the total ultrasonic scores, the more possibility of thyroid carcinoma was. By the analysis of receiver operating characteristic curve, the sensitivity, specificity and accuracy of distinguishing thyroid carcinoma from benign nodular lesions was 84.0%, 89.6% and 84.9% if the cut-off value of total ultrasonic scores was over 4. CONCLUSION: For the differential diagnosis of benign and malignant thyroid lesions, the total ultrasonic scores of conventional ultrasound and ultrasound elastography can offer greater values.