Pathological Intraplaque Hemorrhage as the Gold Standard to Assess the Efficacy of Ultrasound in Predicting Vulnerable Carotid Plaque Rupture.

OBJECTIVE: To assess the clinical utility of ultrasound in predicting the risk of carotid vulnerable plaque rupture using pathological intraplaque hemorrhage as the gold standard. METHODS: A total of 118 patients who underwent endarterectomy due to symptomatic carotid artery stenosis were enrolled. Conventional ultrasound assessed the plaque thickness, area stenosis rate, echo, and surface morphology. Neovascularization were assessed by contrast-enhanced ultrasound (CEUS) and tracing intraplaque nonenhanced areas. According to neovascularization grade (0-4), plaques were classified as low-, intermediate-, and high risk. Fresh intraplaque hemorrhage within the pathology was adopted as the gold standard for diagnosing plaque rupture risk. Thus, we divided patients into ruptured risk and nonruptured risk groups to assess the value of crucial factors for plaque rupture risk using ultrasound. RESULTS: Of the 118 patients, hypertension accounted for 71.2%, hyperlipidemia 68.6%, diabetes 52.5%, and statin history 64.4%. In the rupture risk group, diabetes, smoking, and stenosis rate were significantly higher than the nonrupture risk group (P < .001); plaque thickness ≥4 mm (P > .05); and mainly hypoechoic with irregular surface morphology (P < .001), nonenhanced areas in the plaques (P < .001), and neovascularization >grade 2 (P < .001). Compared with the low-risk group, plaque rupture risk was 7.219 times higher in the medium-risk group and 18.333 times higher in the high-risk group. The kappa value of the interobserver consistency of crucial ultrasound parameters was >0.75, and the intraclass correlation coefficient was 0.919 (P < .01). CONCLUSIONS: Both conventional ultrasound and CEUS have significant clinical importance in the prediction of rupture risk in vulnerable carotid plaques, thereby enabling stroke risk stratification and the assessment of plaque rupture risk.

Double contrast-enhanced ultrasound for the preoperative gross classification of gastric cancer: a comparison with multidetector computed tomography.

PURPOSE: To compare the diagnostic performance of double contrast-enhanced ultrasound (DCEUS) and multi-detector row computed tomography (MDCT) in the gross classification of gastric cancer (GC) preoperatively. METHODS: 54 patients with histology proved GC were included in this retrospective study. The sensitivity and specificity of DCEUS and MDCT for the gross classification of GC was calculated and compared. The area under the curve (AUC) from a receiver operating characteristic curve analysis was used to evaluate the difference of the diagnostic performance between these two methods. RESULTS: There were no significant differences between DCEUS and MDCT in terms of AUC for early gastric cancer (EGC), Borrmann I, II, III and Borrmann (III + IV) (P = 0.248, 0.317, 0.717, 0.464 and 0.594, respectively). The accuracy of DCEUS in diagnosing EGC, Borrmann I, II and Borrmann (III + IV) was higher than that of MDCT (96% vs 92%; 96% vs 94%; 87% vs 80%; 83% vs 73%), while in determining Borrmann III and IV, that of DCEUS was lower than that of MDCT (72% vs 74%; 89% vs 96%). CONCLUSION: Considering the revolution in clinical decision, prognosis evaluation, safety and non-invasion aspects, DCEUS can be used as the main alternative method for Borrmann classification of GC preoperatively.

Cascade Drug Delivery through Tumor Barriers of Pancreatic Cancer via Ultrasound in Combination with Functional Microbubbles.

The abundant desmoplastic stroma and the lack of sufficient targets on pancreatic cancer cells render poor drug penetration and cellular uptake, which significantly compromise the chemotherapy efficacy. Herein, we reported a three-step cascade delivery strategy for selective delivery of paclitaxel (PTX) to achieve a targeted therapy for pancreatic cancer. cRGD and cCLT1 peptides, which could target the integrin and fibronectin, respectively, overexpressed in pancreatic cancer cells and stroma, were decorated on PTX-loaded microbubbles, resulting in the formation of dual-targeting PTX-RCMBs. In this strategy, ultrasound in combination with PTX-RCMBs first enhanced the permeability of tumor vessels via cavitation effects and simultaneously helped the generated PTX-RCNPs penetrate into the stroma. Then, the cCLT1 peptide modified on PTX-RCNPs selectively bound the fibronectin highly expressed in the stroma and later targeted the integrin (α5ß1) on the cell surface. Finally, another targeting cRGD peptide modified on PTX-RCNPs would further promote PTX uptake via targeting the integrin (αvß3) on the cell surface. This strategy significantly increased the delivery of PTX into tumor tissues. Moreover, the in vivo effective accumulation of PTX was monitored by ultrasound and fluorescence bimodal imaging. The tumor growth inhibition was investigated on subcutaneous tumor mouse models with 89.8% growth inhibition rate during 21 days of treatment, showing great potential for improving pancreatic cancer therapy.

Effect of the size of benign thyroid degenerative nodules on ACR TI-RADS categories.

PURPOSE: Our study aimed to identify ultrasound characteristics of benign thyroid degenerative nodules and reveal the correlation between their sizes and 2017 ACR Thyroid Imaging Reporting and Data System (TI-RADS) categories. METHODS: A total of 174 thyroid degenerative nodules were divided into three groups: 0.5-1 cm group (70 nodules), 1-2 cm group (27 nodules), and > 2 cm group (77 nodules). The ultrasound appearance of each nodule was evaluated, and the ACR TI-RADS scores and levels of the nodules were also calculated and compared among the three groups. RESULTS: The ultrasound appearance of degenerative nodules of different sizes is diversified, and the 0.5-1 cm group tended to have more malignant features and higher TI-RADS scores and categories. The scatterplot of Spearman correlation showed a significant negative correlation between the nodule sizes and TI-RADS categories. CONCLUSION: The 2017 ACR TI-RADS, which recommends fine-needle aspiration according to the nodule size and category, is still useful in managing these nodules, and following the clinical recommendations of ACR TI-RADS is necessary.

Ultrasound Microbubbles Mediated Sonosensitizer and Antibody Co-delivery for Highly Efficient Synergistic Therapy on HER2-Positive Gastric Cancer.

Trastuzumab combined with chemotherapy is the first-line treatment for advanced HER2-positive gastric cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency and the drug resistance of tumor cells to the chemotherapeutic drugs. Herein, a type of ultrasound microbubble for simultaneous delivery of sonosensitizers and therapeutic antibodies to achieve targeting combination of sonodynamic therapy and antibody therapy of HER2-positive gastric cancer was constructed from pyropheophorbide-lipid followed by trastuzumab conjugation (TP MBs). In vitro and in vivo studies showed that TP MBs had good biological safety, and their in vivo delivery can be monitored by ultrasound/fluorescence bimodal imaging. With ultrasound (US) located at the tumor area, TP MBs can be converted into nanoparticles (TP NPs) in situ by US-targeted microbubble destruction; plus the enhanced permeability and retention effects and the targeting effects of trastuzumab, the enrichment of sonosensitizers and antibodies in the tumor tissue can be greatly enhanced (∼2.1 times). When combined with ultrasound, TP MBs can not only increase the uptake of sonosensitizers in HER2-positive gastric cancer NCI-N87 cells but also efficiently generate singlet oxygen to greatly increase the killing effect on cells, obviously inhibiting the tumor growth in HER2-positive gastric cancer NCI-N87 cell models with a tumor inhibition rate up to 79.3%. Overall, TP MBs combined with US provided an efficient way for co-delivery of sonosensitizers and antibodies, greatly enhancing the synergistic therapeutic effect on HER2-positive gastric cancer while effectively reducing the side effects.

A Predictive Model for Tumor Invasion of the Inferior Vena Cava Wall Using Multimodal Imaging in Patients with Renal Cell Carcinoma and Inferior Vena Cava Tumor Thrombus.

PURPOSE: Developed a preoperative prediction model based on multimodality imaging to evaluate the probability of inferior vena cava (IVC) vascular wall invasion due to tumor infiltration. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 110 patients with renal cell carcinoma (RCC) with level I-IV tumor thrombus who underwent radical nephrectomy and IVC thrombectomy between January 2014 and April 2019. The patients were categorized into two groups: 86 patients were used to establish the imaging model, and the data validation was conducted in 24 patients. We measured the imaging parameters and used logistic regression to evaluate the uni- and multivariable associations of the clinical and radiographic features of IVC resection and established an image prediction model to assess the probability of IVC vascular wall invasion. RESULTS: In all of the patients, 46.5% (40/86) had IVC vascular wall invasion. The residual IVC blood flow (OR 0.170 [0.047-0.611]; P = 0.007), maximum coronal IVC diameter in mm (OR 1.203 [1.065-1.360]; P = 0.003), and presence of bland thrombus (OR 3.216 [0.870-11.887]; P = 0.080) were independent risk factors of IVC vascular wall invasion. We predicted vascular wall invasion if the probability was >42% as calculated by: {Ln [Pre/(1 - pre)] = 0.185 × maximum cornal IVC diameter + 1.168 × bland thrombus-1.770 × residual IVC blood flow-5.857}. To predict IVC vascular wall invasion, a rate of 76/86 (88.4%) was consistent with the actual treatment, and in the validation patients, 21/26 (80.8%) was consistent with the actual treatment. CONCLUSIONS: Our model of multimodal imaging associated with IVC vascular wall invasion may be used for preoperative evaluation and prediction of the probability of partial or segmental IVC resection.

Preoperative Tumor Staging of Gastric Cancer: Comparison of Double Contrast-Enhanced Ultrasound and Multidetector Computed Tomography.

OBJECTIVES: The purpose of this study was to compare the sensitivity and specificity of double contrast-enhanced ultrasound (CEUS) and multidetector computed tomography (MDCT) in the preoperative tumor staging of gastric cancer (GC) to stratify patients for suitable treatment. METHODS: Fifty-four patients with GC proved by histologic findings were included. The sensitivity and specificity of double CEUS and MDCT for tumor staging were calculated and compared. The differences between these methods were evaluated by using the area under the curve (AUC) from a receiver operating characteristic curve analysis. RESULTS: There were no significant differences in AUC values for T1 and T2 stages between double CEUS and MDCT (P = .190 and .256, respectively). However, the sensitivity of double CEUS in the detection of the T1 stage was higher than that of MDCT (88% versus 75%). The AUC values of MDCT for T3 and T4 stages were 0.833 and 0.905, which were both significantly higher than those of double CEUS (0.759 and 0.696; P < .05). The sensitivities of double CEUS and MDCT for the T3 stage were both 89%, but the accuracy and specificity of double CEUS were lower than those of MDCT (76% versus 83% and 63% versus 78%). The specificities of double CEUS and MDCT for the T4 stage were both 98%, but the accuracy and sensitivity of double CEUS were lower than those of MDCT (85% versus 94% and 42% versus 83%). CONCLUSIONS: Multidetector CT is superior to double CEUS for T3 and T4 GC, and double CEUS may be regarded as an important complementary method to MDCT.

Usefulness of Contrast-Enhanced Ultrasound in Differentiating Inflammatory Bowel Disease From Colon Cancer.

To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of inflammatory bowel disease (IBD) and colon cancer, we enrolled 51 patients with thickened bowel walls (13 with IBD and 38 with colon cancer). Ultrasound and CEUS were performed and both qualitative and quantitative features were analyzed. The intestinal wall stratification was preserved in 63.6% of the IBD group but in only 2.6% of the colon cancer group (p <0.01). On CEUS, disordered enhancement and heterogeneous enhancement were shown in only 9.1% and 0%, respectively, of the IBD group while in 94.7% and 78.9%, respectively, of the colon cancer group (p <0.01). For quantitative analysis, compared to IBD, colon cancer showed later enhancement and slower wash-out with less speed to reach peak intensity (p <0.05). In conclusion, CEUS may prove useful for the differential diagnosis of IBD and colon cancer, but more studies are required.

Differential diagnosis of gastric cancer and gastritis: the role of contrast-enhanced ultrasound (CEUS).

OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. METHODS: From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. RESULTS: Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) (p < 0.001). Blurred, angular, or spiculated serosa margin and increased echogenicity in perigastric fat appeared only in cancer (10/58, 17.2%), and all of them proved to be pathologic T3 or T4 stage. On CEUS, gastric cancer usually manifested as diffused enhancement without comb-teeth-like vessels (parallel curvilinear structures representing arterial branching within the gastric wall) (56/58, 96.6%), while these vessels presented in most gastritis (19/24, 79.2%, p < 0.001). For quantitative analysis, the malignant lesions showed later and lower enhancement (p < 0.001), and they also had slower speed to reach the peak intensity (p < 0.001). On CEUS, the absence of comb-teeth-like vessel is most reliable for diagnosing malignancy, and the sensitivity, specificity, and accuracy were 96.5%, 79.2%, and 91.5%, respectively. CONCLUSIONS: Our results demonstrated the usefulness and accuracy of US and CEUS in differential diagnosis of gastric cancer and gastritis. CEUS has the potential to make the diagnosis more accurate.

Can ultrasound be used to differentiate tubular adenomas of breast from fibroadenomas or carcinoma?

Breast tubular adenomas are rare benign breast tumors and detailed descriptions of their sonographic appearance are necessary for differential diagnosis from fibroadenomas or breast cancers. This study investigated twenty-one histology-proved tubular adenomas in 17 patients and also included 48 fibroadenomas in 35 patients as a control group. There was no significant difference between the two groups with clinical presentation, which was age, tumor location, tumor number (p>0.05). Statistic analysis showed three significant factors in the differential diagnosis of tubular adenomas and fibroadenomas, including macro-lobulation (p=0.01), "tiny branch like" patterns (p=0.001) and vascularity (p=0.02). Other ultrasonographic features such as echogenicity, border, uniformity of echotexture, posterior acoustic enhancement, lateral wall shadowing were of no clinical significance (p>0.05). Calcifications were seen in three tubular adenomas which were different from those of carcinomas. Although tubular adenomas have some typical characteristics on sonography, surgery and core needle biopsy are still needed for complex cases to exclude progress to malignancy.

High-intensity focused ultrasound treatment of late-stage pancreatic body carcinoma: optimal tumor depth for safe ablation.

Objective criteria are currently not available for assessing the extent of ablation by high-intensity focused ultrasound (HIFU). A retrospective review was conducted in Chinese patients with late-stage pancreatic body carcinoma treated with 1 h/d intermittent HIFU at a single center. Clinical and procedure-related characteristics were examined in relation to tumor posterior depth. Clinically, tumor ablation was negatively correlated with posterior tumor depth, with a 1-cm increase in depth decreasing ablation by 30.7%. At a computed tomography (CT)-determined 7-cm posterior tumor depth (considered the critical value for the procedure), ablation sensitivity and specificity were 77.8% and 72.7%, respectively. Tumor ablation >30% in patients with a CT-determined posterior tumor depth ≤7 cm was 9.333 times better than that in patients with a CT-determined posterior tumor depth >7 cm. Adverse effects did not affect the efficacy of HIFU. Tumors with posterior depths <7 cm may effectively be treated with HIFU-induced ablation with minimal adverse events.

[Ultrasound guided ablation therapy of hepatic colorectal metastases: initial experience of real time virtual sonography navigation system].

OBJECTIVE: To evaluate the feasibility, accuracy and efficacy of the real time virtual sonography navigation and planning system in radio frequency ablation (RFA) of hepatic colorectal metastases. METHODS: Seventeen hepatic colorectal metastases lesions in 12 patients diagnosed pathologically or clinically in Peking University Third Hospital from Oct. 2011 to Apr. 2013 were enrolled, and all the lesions were diagnosed by CT/MRI but invisible in B-mode ultrasound. The patients included 9 males and 3 females, who were 45-82 years old, with an average age of (64.6±19.2) years. Before RFA, the puncture ablation plan of each lesion was made in the planning system, and during RFA the lesion and the 5 mm ablative margin around were ablated according to the puncture ablation plan. After the image fusion between the ultrasound and CT/MRI, the navigation system could decide the location and boundary of the hepatic colorectal metastases in the ultrasound image. Navigation assisted contrast-enhanced ultrasound (CEUS) was employed right after ablation to decide whether the area of the ablative zone had covered the whole tumor. Additional puncture was applied if the ablative zone had not completely covered the tumor. All the patients received CT/MRI one month after ablation to decide whether the carcinoma had been completely ablated. RESULTS: The image fusion was successfully applied in all the 17 hepatic colorectal metastases, and on average, 12 min (8-21 min) was spent in the image fusion. One tumor (1/17, 14.3%) received extra one puncture after navigation assisted CEUS. No severe complications and death occurred in all the 12 patients. Complete ablation of the 17 lesions were observed through CT or MRI scan one month after RFA, showing that all the 17 lesions had been completely ablated. CONCLUSION: The real time virtual sonography navigation system had high detection rate for invisible focal liver lesions in B-mode ultrasound. Navigation assisted CEUS could decide whether the area of the ablative zone had covered the whole tumor. Ultrasound CT or MRI navigation and planning system is safe, feasible and accurate in assisting ablation of hepatic colorectal metastases lesions with satisfactory clinical efficacy.

Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

A preclinical in vivo investigation of high-intensity focused ultrasound combined with radiotherapy.

This study aims to perform an in vivo investigation evaluating the injury to the pancreas and adjacent tissue of swine resulting with high-intensity focused ultrasound (HIFU) combined with radiotherapy (RT). The protocol was approved by the animal ethics committee at the Peking University First Hospital. A total of 12 domestic swine were divided into four groups: control, HIFU only, RT only and HIFU + RT. The injury to the pancreas, adjacent tissue and tissue within the acoustic path of the HIFU beam was assessed based on gross and histologic findings. For the targeted region of the pancreas, the score of the combined group was higher than that of the HIFU group and there was significant difference. For the acoustic path tissue, there was no significant difference except between the control group and the other groups. HIFU combined with RT increased the injury to the targeted pancreas, without increased injury to tissue outside of the targeted region.