Advances in Molecular Targeted Ultrasound Contrast Agents / 中国医学科学院学报

In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.

Contrast-enhanced ultrasonography with intra-glandular contrast injection can improve the diagnostic accuracy of central compartment lymph node metastasis of thyroid cancer / 南方医科大学学报

OBJECTIVE@#To investigate the value of lymphatic contrast-enhanced ultrasound (LCEUS) with intra-glandular injection of contrast agent for diagnosis of central compartment lymph node metastasis of thyroid cancer.@*METHODS@#From November, 2020 to May, 2022, the patients suspected of having thyroid cancer and scheduled for biopsy at our center received both conventional ultrasound and LCEUS examinations of the central compartment lymph nodes before surgery. All the patients underwent surgical dissection of the lymph nodes. The perfusion features in LCEUS were classified as homogeneous enhancement, heterogeneous enhancement, regular/irregular ring, and non-enhancement. With pathological results as the gold standard, we compared the diagnostic ability of conventional ultrasound and LCEUS for identifying metastasis in the central compartment lymph nodes.@*RESULTS@#Forty-nine patients with 60 lymph nodes were included in the final analysis. Pathological examination reported metastasis in 34 of the lymph nodes, and 26 were benign lymph nodes. With ultrasound findings of heterogeneous enhancement, irregular ring and non-enhancement as the criteria for malignant lesions, LCEUS had a diagnostic sensitivity, specificity and accuracy of 97.06%, 92.31% and 95% for diagnosing metastatic lymph nodes, respectively, demonstrating its better performance than conventional ultrasound (P < 0.001). Receiver-operating characteristic curve analysis showed that LCEUS had a significantly greater area under the curve than conventional ultrasound for diagnosing metastatic lymph nodes (94.7% [0.856-0.988] vs 78.2% [0.656-0.878], P=0.003).@*CONCLUSION@#LCEUS can enhance the display and improve the diagnostic accuracy of the central compartment lymph nodes to provide important clinical evidence for making clinical decisions on treatment of thyroid cancer.

Comparison between Ultrasonography and CT in Diagnosis of Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ2=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ 2=82.26,P<0.001;χ2=114.01,P<0.001;χ2=82.26,P<0.001) and accuracy (χ2=20.27,P<0.001;χ2=15.56,P<0.001;χ2=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ2=17.01,P<0.001;χ2=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.

Application of Micro-flow Imaging in the Differentiation of Benign and Malignant Thyroid Nodules / 中国医学科学院学报

Objective To evaluate the performance of micro-flow imaging(MFI)in the differential diagnosis of benign and malignant thyroid nodules. Methods Totally 50 patients with thyroid nodules examined by conventional ultrasound,MFI,and contrast-enhanced ultrasound and confirmed by histological or cytological pathology in the First Medical Center of Chinese PLA General Hospital from May to December in 2020 were enrolled in the study.The clinical data and ultrasound images were retrospectively analyzed.A binary logistic regression model was established to evaluate the performance of the model in predicting benign and malignant thyroid nodules. Results Logistic regression showed that composition and "S-W-C" sign were independent risk factors for predicting malignant thyroid nodule.The sensitivity,specificity,and Youden index of the logistic regression model were 73.33%,80.00%,and 0.53,respectively,and the area under receiver operating characteristic curve was 0.799(95%CI=0.662-0.899). Conclusion MFI facilitates the differential diagnosis of benign and malignant thyroid nodules and has the potential to be applied in the future.

Value of Ultrasound-guided Core-needle Biopsy for Evaluating the Performance of Radiofrequency Ablation for Low-risk Papillary Thyroid Microcarcinoma / 中国医学科学院学报

Objective To investigate the clinical value of core-needle biopsy(CNB)for low-risk papillary thyroid microcarcinoma(PTMC)after radiofrequency ablation(RFA). Methods A total of 190 patients(including 142 females and 48 males,20-74 years old)with unifocal low-risk PTMCs[mean volume of(106.29±96.15)mm

Value of Contrast-enhanced Ultrasound in Differential Diagnosis between Cholesterol Polyp and Gallbladder Adenoma / 中国医学科学院学报

Objective To compare the performance of contrast-enhanced ultrasound(CEUS)and ultrasound(US)in the differential diagnosis between cholesterol polyps and gallbladder adenomas. Methods A total of 136 patients with gallbladder polyp lesions(GPLs)and undergoing cholecystectomy in the First Medical Center of Chinese PLA General Hospital from January 2019 to October 2020 were retrospectively analyzed.All the patients underwent US and CEUS examinations before cholecystectomy.US and CEUS images of cholesterol polyps and gallbladder adenomas were compared for the evaluation of the performance of CEUS in the diagnosis of gallbladder adenomas. Results The 136 cases of GPLs included 95 cases of cholesterol polyps and 41 cases of gallbladder adenomas.Cholesterol polyps and gallbladder adenomas showed significant differences in the maximum size of GPLs(

Correlation between Contrast-enhanced Ultrasound and Risk of Tumor Recurrence in Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To explore the association between contrast-enhanced ultrasound and risk of tumor recurrence in papillary thyroid carcinoma(PTC). Methods A total of 287 PTCs in 287 patients who underwent surgery,conventional ultrasound,and contrast-enhanced ultrasound(CEUS)were enrolled in this study.According to 2015 American Thyroid Association(ATA)Modified Initial Risk Stratification System,the patients were categorized into three groups:low risk,intermediate risk,and high risk.The CEUS patterns of PTCs were compared between different risk stratifications. Results Hypo-enhancement was presented in 57.6% of ATA low-risk PTCs,iso-enhancement in 62.3% of ATA intermediate-risk PTCs,and hyper-enhancement in 48.2% of ATA high-risk PTCs(

Value of Trans-lymphatic Contrast-enhanced Ultrasound in the Diagnosis of Cervical Lymph Node Metastasis of Thyroid Cancer / 中国医学科学院学报

Objective To explore the value of trans-lymphatic contrast-enhanced ultrasound(CEUS)in the diagnosis of cervical lymph node metastasis of thyroid cancer. Methods The patients with suspected thyroid cancer underwent conventional ultrasound and trans-lymphatic CEUS examinations before the biopsy.The differences in ultrasound and CEUS characteristics of cervical lymph nodes between the metastatic group and the non-metastatic group were compared,and pathological results were regarded as the golden standard. Results Twenty patients had thyroid cancer,including 12 cases with lymph node metastasis and 8 cases without metastasis.The diagnostic sensitivity(91.7%

Comparison of Quality of Life of Patients with Papillary Thyroid Microcarcinoma Treated by Different Modalities / 中国医学科学院学报

Objective To compare the health-related quality of life(HRQoL)of patients with papillary thyroid microcarcinoma(PTMC)treated by different modalities. Methods The PTMC patients after treatment who came to our department for follow-up from October to December in 2019 were enrolled and assigned into three groups according to treatment modalities:radiofrequency ablation(RFA)group(

Validated Nomogram Predicting Clinical Outcome after Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma / 中国医学科学院学报

Objective To establish a prediction model for the short-term efficacy of percutaneous ultrasound-guided radiofrequency ablation(RFA)in the treatment of papillary thyroid microcarcinoma(PTMC). Methods We retrospectively analyzed the preoperative and follow-up data of 159 patients with PTMC who underwent percutaneous ultrasound-guided RFA treatment in the Department of Ultrasound,the First Medical Center of Chinese PLA General Hospital from January to December in 2018.The association with 12-month tumor status(end event)was evaluated by multivariate logistic regression model.A nomogram was built to predict the risk of tumors which did not disappear completely within 12 months after RFA. Results We found that gender(

Value of Contrast-enhanced Ultrasound Parameters in Evaluating K-W Nodule Formation in Diabetic Nephropathy / 中国医学科学院学报

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(

Current Situation and Advances in Diagnosing Triple-negative Breast Cancer Using Ultrasound / 中国医学科学院学报

Triple-negative breast cancer is a complex type of breast cancer,the most common malignant tumor in women.Since the early image features of triple-negative breast cancer appear benign tumor with rapid growth,this cancer has progressed into the middle and late stages once diagnosed,which leads to high mortality.Therefore,the diagnosis of triple-negative breast cancer has always been a clinical difficulty.This article summarizes the role of ultrasound in the diagnosis and treatment of triple-negative breast cancer.The extracted multi-mode ultrasound features will facilitate the early detection of this cancer and improve the prognosis of these patients.

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study / 中华医学杂志(英文版)

BACKGROUND@#The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.@*METHODS@#Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.@*RESULTS@#The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).@*CONCLUSIONS@#The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.

A Thyroid Ultrasound Image-based Artificial Intelligence Model for Diagnosis of Central Compartment Lymph Node Metastasis in Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To establish an artificial intelligence model based on B-mode thyroid ultrasound images to predict central compartment lymph node metastasis(CLNM)in patients with papillary thyroid carcinoma(PTC). Methods We retrieved the clinical manifestations and ultrasound images of the tumors in 309 patients with surgical histologically confirmed PTC and treated in the First Medical Center of PLA General Hospital from January to December in 2018.The datasets were split into the training set and the test set.We established a deep learning-based computer-aided model for the diagnosis of CLNM in patients with PTC and then evaluated the diagnosis performance of this model with the test set. Result The accuracy,sensitivity,specificity,and area under receiver operating characteristic curve of our model for predicting CLNM were 80%,76%,83%,and 0.794,respectively. Conclusion Deep learning-based radiomics can be applied in predicting CLNM in patients with PTC and provide a basis for therapeutic regimen selection in clinical practice.

Quantitative Evaluation of Sciatic Nerve Crush Injury with Conventional Ultrasound Combined with Shear-wave Elastography in Rabbit Models / 中国医学科学院学报

To explore the value of conventional ultrasound combined with shear-wave elastography in the quantitative evaluation of sciatic nerve crush injury in rabbit models. Forty healthy male New Zealand white rabbits were randomly divided into four groups (=10 in each group):three crush injury (CI) groups (2,4,and 8 weeks after crush) and control group (without injury). The thickness and stiffness of the crushed sciatic nerves and denervated triceps surae muscles were measured at different time points and compared with histopathologic parameters. Inter-reader variability was assessed with intraclass correlation coefficients. Compared with the control group,the inner diameters of the sciatic nerves significantly increased in the 2-week CI group [(1.65±0.34) mm (0.97±0.15) mm,=0.00] but recovered to the nearly normal level in the 8-week CI group [(1.12±0.18) mm (0.97±0.15) mm,=0.06];however,compared with control group [(8.75±1.02)kPa],the elastic modulus of the nerves increased significantly in all the CI groups [2-week:(14.77±2.53) kPa;4-week:(19.12±3.46) kPa;and 8-week:(28.39±5.26) kPa;all =0.00];pathologically,massive hyperplasia of collagen fibers were found in the nerve tissues. The thickness of denervated triceps surae muscle decreased gradually,and the elastic modulus decreased 2 weeks after injury but increased gradually in the following 6 weeks;pathologically,massive hyperplasia of collagen fibers and adipocytes infiltration were visible,along with decreased muscle wet-weight ratio and muscle fiber cross-sectional area. The inter-reader agreements were good. Conventional ultrasound combined with shear-wave elastography is feasible for the quantitative evaluation of the morphological and mechanical properties of crushed nerves and denervated muscles.

Short-term Outcome of T1bN0M0 Papillary Thyroid Cancer after Ultrasonography-guided Radiofrequency Ablation / 中国医学科学院学报

Objective To investigate the short-term outcome of T1bN0M0 papillary thyroid cancer after ultrasonography-guided radiofrequency ablation(RFA). Methods Eighty-nine patients with T1bN0M0 papillary thyroid cancer who were treated with ultrasonography-guided RFA in our center from April 2014 to January 2019 were retrospectively analyzed.Trans-isthmus approach and moving shot technique were used during the RFA procedure.Ultrasonography and contrast-enhanced ultrasonography were performed before ablation,and immediately,1,3,6 and 12 months after ablation and then every 6 months thereafter. Results RFA was performed in 89 cases of papillary thyroid cancer,and no major complications were observed during the RFA.The mean follow-up was(18.8±7.3)months.The ablation zones decreased gradually during follow-up,and 38 ablation zones(42.7%)completely disappeared.The volume reduction rate was(99.2±2.3)% 30 months after ablation.During follow-up,2 patients(2.2%)developed tumor recurrence and 1 patient(1.1%)developed cervical lymph node metastasis. Conclusion Ultrasonography-guided RFA may be a safe and effective method for patients with T1bN0M0 papillary thyroid cancer.

Comparison of Elasticity Imaging and Virtual Touch Tissue Imaging and Quantification in the Diagnosis of Thyroid Nodules / 中国医学科学院学报

Objective To compare the values of elasticity imaging(EI)and Virtual Touch tissue imaging and quantification(VTIQ)in diagnosing thyroid nodules and explore the factors influencing the accuracy of these two techniques.Methods Totally 62 patients who were planned to receive surgery for thyroid nodules underwent conventional ultrasound,EI,and VTIQ examinations.EI patterns were scored according to the degree and distribution of strain,the strain of nodule and surrounding normal reference tissue were measured,and then strain index was calculated.Shear wave velocity in nodules were obtained under VTIQ mode.Results The nodules were malignant in 40 patients and benign in 22 patients.When the strain score of 3 was regarded as malignant,the diagnostic sensitivity,specificity,and accuracy of EI in detecting thyroid nodules were 90.00%,31.82%,and 69.32%,respectively.Receiver operating characteristic curve results showed that the area under curves of EI-SI and VTIQ methods for diagnosing thyroid nodules was 77.8%(95%:0.64-0.91)(=0.000)and 74.3%(95%:0.62-0.87)(=0.002),respectively.Thyroid nodules' characteristics location(=0.04)and size(=0.02)were correlated with the diagnostic accuracy of EI.The accuracy of SI and VTIQ were not affected by thyroid nodules' characteristics(>0.05).Conclusions The diagnostic accuracy of EI for thyroid nodules is related to nodules' characteristics.EI combined with semi-quantitative SI and quantitative VTIQ can effectively improve the diagnostic capability for thyroid nodules.

Correlation between Ultrasound-guided Fine-needle Aspiration Combined with BRAF Detection and Invasive Pathological Features of Papillary Thyroid Cancer / 中国医学科学院学报

To analyze the potential associations of ultrasound-guided fine-needle aspiration(FNA),BRAF gene mutation detection,and the combination of these two techniques with the clinicopathological features of papillary thyroid cancer(PTC). Methods Patients with PTC confirmed by surgery from April 2016 to July 2017 were included in this study.The relationship between clinicopathological features and BRAF mutation,FNA results,and the combination of them were explored. Results The sensitivity of FNA was 86.3%(227/263)and the mutation rate of BRAF was 85.9%(226/263)in 263 patients with PTC.The mutation rate of papillary thyroid microcarcinoma(PTMC)was 91.1%(153/168)and that of non-PTMC was 76.8%(73/95).A total of 225 patients underwent lymph node dissection.The lymph node metastasis rate was 35.6%(80/225),and it was 23.8%(34/143)in PTMC,56.1%(46/82)in non-PTMC;in addition,9.9%(26/263)of PTC patients had extracapsular invasion.BRAF mutation rate was higher in patients with the following features:aged over 45 years(=0.043);the tumor was FNA diagnosed as malignant or suspected malignant(=0.011);the tumor had a maximum diameter of ≤1 cm(=0.001);and the primary tumor was in stage T(=0.039);however,there was no significant difference in BRAF mutation rate among patients with different sex,capsule invasion,or lymph node metastasis.The diagnostic sensitivity of FNA was not statistically different under different clinical and pathological characteristics.The clinicopathologic features of FNA and BRAF double-positive patients were not significantly different from those of other patients. Conclusion FNA-confirmed malignancy,BRAF gene mutation,and their double-positive results are not correlated with the invasive pathological features of PTC,and thus their roles in guiding an extended operation(or not)are limited.

PTC: The correlation between sonographic characteristics of ultrasound and metastasis of cervical lymph node / 中国医学装备

Objective: To analyze the correlation between sonographic characteristics of ultrasound and metastasis of cervical lymph node of papillary thyroid carcinoma (PTC). Methods: 498 patients with PTC who once received radical operation of thyroid cancer and cervical lymph node dissection were divided into metastasis group (n=163) and non-metastasis group (n=335) according to results post pathology. Gender, age, the number of lesion, maximum diameter, aspect ratio, margin, whether contacted with tunica, border, halo of ultrasound, whether existed hypoecho in interior, whether the echo was uniform, whether existed difference about some characteristics of calcification and blood flow between the two groups were compared and analyzed. The correlation of characteristics and cervical lymphatic metastasis was analyzed by using single factor analysis, and the malignancy phenomenon of ultrasonogram that was closely relevant with cervical lymph node metastasis of patients with PTC were screened out by using Logistic regression. Results: As the results of single factor analysis, there were a certain correlation between series of factors, such as gender, age, the number of lesion, maximum diameter, margin, whether contacted with tunica, blood flow and whether contained tiny calcification, and cervical lymph node metastasis, and these correlations were significant (x2=33.094, x2=126.566, x2=127.961, x2=145.087, x2=53.757, x2=6.807, P<0.05). The results of Logistic regression indicated that these factors, included multi- lesions, maximum diameter more than 10.0mm, irregular margin, contacted with tunica of thyroid and abundant blood flow, were closely correlative with the malignancy phenomenon of ultrasonogram of cervical lymphatic metastasis of patients with PTC, and their correlation coefficient were significant (OR=3.103, OR=3.595, OR=2.822, OR=6.317, OR=2.078, P<0.05). Conclusion: The characteristics of ultrasonogram contributes to increase the detectable rate of ultrasound for cervical lymph node metastasis of patients with PTC, and it can provide reference for clinical decision.

Ultrasound-guided Radiofrequency Ablation for Cervical Lymph Nodes Metastasis from Papillary Thyroid Carcinoma / 中国医学科学院学报

Objective To assess the effectiveness and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for nonsurgical treatment of metastatic lymph nodes (LNs) in the neck from papillary thyroid carcinoma (PTC). Methods Totally 45 PTC patients who had been treated with total thyroidectomy and radioiodine therapy were enrolled in this retrospective study. A total of 71 metastatic LNs in the neck from PTC were confirmed by percutaneous biopsy. Follow-up consisted of conventional ultrasound,contrast-enhanced ultrasound,and thyroglobulin (Tg) measurement 1,3 and 6 months after RFA and then every 6 months. Results All 45 patients were successfully treated,without immediate or later major complications occurred. During the follow-up [(23±5) months;range:12-30 months)],there was no evidence of recurrence at ablated sites. The mean volume reduction ratio (VRR) was significantly reduced during the follow-up. Significant differences in the VRR were found between every two follow-up visits (P<0.001). Furthermore,46 metastatic LNs (64.8%) completely disappeared and 25 metastatic lymph nodes (35.2%) remained as small scar-like lesions at the last follow-up visit. After RFA,mean serum Tg level decreased from (11.3±6.3)ng/ml (range:0.8-19.4 ng/ml) to (1.3±0.9)ng/ml (range:0.2-3.9 ng/ml) at the last follow-up visit (P<0.001). Conclusion Ultrasound-guided percutaneous RFA is a safe and effective therapy for patients with cervical LNs metastasis from PTC.