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Objectives: To establish superb microvascular imaging (SMI) based thyroid imaging reporting and data system (SMI TI-RADS) for risk stratification of malignancy in thyroid nodules. Methods: In total, 471 patients, comprising 643 thyroid nodules, who received conventional ultrasound (US), SMI, and a final diagnosis were extensively analyzed. A qualitative assessment of US features of the nodules was performed followed by univariable and multivariable logistic regression analyses, leading to the construction of the SMI TI-RADS, which was further verified using internal and external validation cohorts. Results: Among the stand-alone US, predictive factors were the shape and margins of the nodules, echogenicity and echogenic foci, vascularity, extrathyroidal extension, ring-SMI patterns, penetrating vascularity, flow-signal enlarged, and vascularity area ratio. SMI TI-RADS depicted an enhanced area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.92, 0.96; p < 0.001 relative to other stratification systems), a 79% biopsy yield of malignancy (BYM, 189/240 nodules), and a 21% unnecessary biopsy rate (UBR, 51/240 nodules). In the verification cohorts, we demonstrated AUCs, malignancy biopsy yields, and unnecessary biopsy rates of 0.88 (95% CI: 0.83, 0.94), 79% (59/75 nodules), and 21% (16/75 nodules) for the internal cohort, respectively, and 0.91 (95% CI: 0.85, 0.96), 72% (31/43 nodules), and 28% (12/43 nodules) for the external cohort, respectively. Conclusion: SMI TI-RADS was found to be superior in diagnostic sensitivity, specificity, and efficiency than existing TI-RADSs, showing better stratification of the malignancy risk, and thus decreasing the rate of unnecessary needle biopsy. Critical relevance statement: To develop an imaging and data system based on conventional US and SMI features for stratifying the malignancy risk in thyroid nodules. Key Points: SMI features could improve thyroid nodule risk stratification. SMI TI-RADS showed superior diagnostic efficiency and accuracy for biopsy guidance. SMI TI-RADS can provide better guidance for clinical diagnosis and treatment of thyroid nodules. [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and safety of sulfur hexafluoride microbubbles on ultrasound-guided high-intensity focused ultrasound (HIFU) ablation of uterine fibroids. Methods: Studies that compared HIFU-microbubble combination with HIFU-only in patients with uterine fibroids were searched from inception to April 2022. The standardized mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI) for different outcome parameters was calculated. Results: Seven studies were included, with a total of 901 patients (519 in the combination group and 382 in the HIFU-only group). The energy consumption for treating 1 cm3 of the lesion in the combination group was less than that in the HIFU-only group [SMD = − 2.19, 95%CI (− 3.81, − 0.57), p = 0.008]. The use of microbubbles was associated with shortening the duration of the treatment and sonication [SMD = − 2.60, 95%CI (− 4.09, − 1.10), p = 0.0007; SMD = − 2.11, 95%CI (− 3.30, − 0.92), p = 0.0005]. The rates of significant greyscale changes during HIFU were greater in the combination group, as well as the increase of non-perfused volume ratio [RR = 1.26, 95%CI (1.04, 1.54), p = 0.02; SMD = 0.32, 95%CI (0.03, 0.61), p = 0.03]. The average sonication durations to reach significant greyscale changes and for ablating 1 cm3 of the fibroid lesion were shorter in the combination group [SMD = − 1.24, 95%CI (− 2.02, − 0.45), p = 0.002; SMD = − 0.22, 95%CI (− 0.42, − 0.02), p = 0.03]. The two groups had similar post-HIFU adverse effects, while the combination group had fewer intraprocedural adverse events like abdominal pain, sacrum pain, and leg pain. Conclusions: Sulfur hexafluoride microbubbles can be safely used to enhance and accelerate the ablation effects of HIFU in the treatment of uterine fibroids. Clinical relevance statement: The combination of HIFU with sulfur hexafluoride microbubbles offers a promising non-invasive treatment option for patients with uterine fibroids. Key Points: • Sulfur hexafluoride microbubbles combined with ultrasound-guided high-intensity focused ultrasound (USgHIFU) has potential advantages in the treatment of uterine fibroids. • Sulfur hexafluoride microbubbles not only enhance the effects of USgHIFU treatment for uterine fibroids but also shorten its duration. • Sulfur hexafluoride microbubbles do not increase the incidence of USgHIFU-related adverse events in the treatment of uterine fibroids. [ABSTRACT FROM AUTHOR]

In order to provide clinical references for the RFA procedure and to study the pivotal factors affecting the recovery time of radiofrequency ablation (RFA) in patients with papillary thyroid microcarcinoma (PTMC), 176 patients with low-risk intrathyroidal PTMC were included in this research. We randomly divided the whole cohort into training and test groups at a ratio of 7:3. The two-sample t-test was used to detect differences between the two groups. Least absolute shrinkage and selection operator (LASSO) regression was used to select the best predictor variables for predicting the status of RFA zone. Multiple test methods were used to ensure the scientific nature and accuracy of the Cox proportional hazards model. We tested the performance for the parameters and revealed the best cut-off value of each variable by the ROC curve and log-rank tests. The results showed patients aged above 49 years old, with RFA energy above 2800 J, the average diameter of the original tumour above 0.6 cm, or the average diameter of ablation zone at 1 month after RFA above 1.1 cm are risk factors for RFA zone delayed healing. [ABSTRACT FROM AUTHOR]

Mitochondria-targeted sonodynamic therapy (SDT) is a promising strategy to inhibit tumor growth and activate the anti-tumor immune responses. Identifying the mechanisms underlying mitochondria-targeted SDT, further optimizing its efficacy, and developing novel sonosensitizer carriers with good biocompatibility pose major challenges to the clinical practice of SDT. In this study, we investigated the mechanisms of mitochondria-targeted SDT and demonstrated that it suppressed the mitochondrial electron transport chain (ETC) in pancreatic cancer cells through RNA-sequencing analysis. Based on these findings, we constructed the functional lipid droplets (LDs) (CPI-613/IR780@LDs), which combined mitochondria-targeted SDT with the tricarboxylic acid (TCA) cycle inhibitor CPI-613. CPI-613/IR780@LDs synergistically inhibited the TCA cycle and the ETC of mitochondrial aerobic respiration to reduce oxygen consumption and increase reactive oxygen species (ROS) generation at the tumor site, thus enhancing the efficacy of SDT in hypoxic pancreatic cancer. Moreover, the combination of mitochondria-targeted SDT and anti-PD-1 antibody exhibited excellent tumor inhibition and activated anti-tumor immune responses by increasing tumor-infiltrating CD8+ T cells and reducing regulatory T cells, synergistically arresting the growth of both primary and metastatic pancreatic tumors. Meanwhile, lipid droplets are cell-derived biological carriers with natural mitochondrial targeting ability and can achieve efficient hydrophobic drug loading through active phagocytosis. Therefore, the functional lipid droplet-based SDT combined with anti-PD-1 antibody holds great potential in the clinical treatment of hypoxic pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: To validate and facilitate ultrasound examinations on rheumatoid arthritis (RA) disease activity measurements in routine clinical practice. Methods: A systematic review and network meta-analysis (NMA) of ultrasound examinations on joints and its correlation with clinical RA disease activity was performed. PubMed, Embase and Cochrane library were searched for literatures published up to May 01st 2021. Bayesian random-effect NMA was conducted to pool the correlations of ultrasonographic assessment scores with composite RA disease activity measurements. Results: Fifteen studies evaluating twelve different existing ultrasonographic measurements on joints evaluation for RA disease activity scoring were included in this NMA. For comparisons with clinical disease activity index and simplified disease activity index, synovitis gray scale ultrasound 7 joints (GSUS7) demonstrated modest correlation of 0.30[− 0.74, 1.23] and 0.46[− 0.45, 1.15] respectively, followed by synovitis power Doppler ultrasound 7 joints (PDUS7) (0.25[− 0.57, 1.14], 0.31[− 0.46, 1.24]) and power Doppler ultrasound 12 joints (PDUS12) (0.23[− 1.36, 0.83], 0.25[− 1.18, 0.88]). As for disease activity score using 28 joint counts, PDUS12 showed the biggest correlation of 0.53[− 0.09, 1.11], followed by ultrasound 7 joints (US7) (0.50[0.06, 0.93]), PDUS7 (0.49[− 0.24, 1.12]), power Doppler ultrasound 6 joints (PDUS6) (0.42[− 0.29, 1.21]), synovitis PDUS7 (0.47[− 0.09, 1.27]) and synovitis GSUS7 (0.40[0.01, 0.86]). Conclusion: Comparative validity was observed on fewer joints ultrasonic evaluation for RA disease activity measurements, such as synovitis GSUS7 and synovitis PDUS7. Ultrasonographic measurements can be complementary for clinical RA disease activity measures with clinical efficiency, and technical guidelines were in need for clinical routine practice. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify the applicability of an ultrasound-guided attenuation parameter (UGAP) for the noninvasive assessment of hepatic steatosis in clinical practice and to compare its correlation with B-mode ultrasound (US). From May to July 2021, 63 subjects with different body mass index (BMI) grades were included in the prospective study. All of them performed UGAP measurements, under different breathing manipulations, positions, diet statuses, and operators. After that, the UGAP values were compared with the visual grades of hepatic steatosis on B-mode US using a 4-point scale method. The intraclass correlation (ICC) of the UGAP values between the two radiologists was 0.862 (p < 0.001), and the ICCs of the UGAP values on the same day and different days by radiologist A were 0.899 (p < 0.001) and 0.910 (p < 0.001), respectively. There were no significant differences in UGAP values under different breathing manipulations (p > 0.05), positions (p > 0.05), or diet statuses (p = 0.300). The UGAP values in the fasting (supine position, segment V, 1) condition among the lean (BMI < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2) and obese groups (BMI ≥ 28 kg/m2) were 0.60 ± 0.12, 0.66 ± 0.14, and 0.71 ± 0.11 dB/cm/MHz, respectively, with a significant difference (p = 0.006). The correlation coefficients (Rho) between the UGAP values and the visual grades of hepatic steatosis by the two reviewers were 0.845 (p < 0.001) and 0.850 (p < 0.001), corresponding to a strong relationship. Steatosis grades by reviewer 1 (p = 0.036) and reviewer 2 (p = 0.003) were significant factors determining the UGAP values according to the multivariate linear regression analysis. UGAP demonstrated excellent intraobserver and interobserver reproducibility in the assessment of hepatic steatosis. UGAP may be a promising tool in clinical practice to predict hepatic steatosis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the diagnostic performance of novel ultrasound technology normalized local variance (NLV) and the standard deviation of NLV (NLV-SD) using different ROIs for hepatic steatosis in patients with metabolic-associated fatty liver disease (MAFLD) and to identify the factors that influence the NLV value and NLV-SD value, using pathology results as the gold standard. Methods: We prospectively enrolled 34 consecutive patients with suspected MAFLD who underwent percutaneous liver biopsy for evaluation of hepatic steatosis from June 2020 to December 2020. All patients underwent ultrasound and NLV examinations. NLV values and NLV-SD values were measured using different ROIs just before the liver biopsy procedure. Results: The distribution of hepatic steatosis grade on histopathology was 4/19/6/5 for none (< 5%)/ mild (5–33%)/ moderate (> 33–66%)/ and severe steatosis (> 66%), respectively. The NLV value with 50-mm-diameter ROI and NLV-SD value with 50-mm-diameter ROI showed a significant negative correlation with hepatic steatosis (spearman correlation coefficient: − 0.449, p = 0.008; − 0.471, p = 0.005). The AUROC of NLV (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.875, 0.735, and 0.583, respectively. The AUROC of NLV-SD (50 mm) for the detection of mild, moderate, and severe hepatic steatosis was 0.900, 0.745, and 0.603, respectively. NLV (50 mm) values and NLV-SD (50 mm) values between two readers showed excellent repeatability and the intraclass correlation coefficient (ICC) was 0.930 (p < 0.001) and 0.899 (p < 0.001). Hepatic steatosis was the only determinant factor for NLV value and NLV-SD value (p = 0.012, p = 0.038). Conclusion: The NLV (50 mm) and NLV-SD (50 mm) provided good diagnostic performance in detecting the varying degrees of hepatic steatosis with great reproducibility. This study showed that the degree of steatosis was the only significant factor affecting the NLV value and NLV-SD value. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) has become an established modality in various clinical indications for liver diseases. SonoVue®, a pure blood pure agent, and Sonazoid®, which exhibits an additional Kupffer phase, are contrast agents approved for liver imaging. This review discusses and compares the current clinical evidence for these two ultrasound contrast agents in the characterization and detection of focal liver lesions in the non-cirrhotic and cirrhotic liver, as well as for the use in interventional procedures such as liver biopsy guidance, and local ablation treatment monitoring. Reference is made to clinical studies which evaluated the accuracy of CEUS using a standard of reference, its safety, or to comparative studies of these two agents. [ABSTRACT FROM AUTHOR]

Objectives: Portal vein thrombosis (PVT) is a common complication of liver cirrhosis. However, differentiation of thrombosis and tumor-in-vein (TIV) may be challenging. Contrast-enhanced ultrasound (CEUS) is an excellent method for detection of vascularization and could help in the distinction. We performed a systematic review and meta-analysis for evaluating the diagnostic value of CEUS in differentiating between PVT and TIV in hepatocellular carcinoma (HCC) patients.Methods: PubMed, Embase, Cochrane Library, and Web of Science were searched up to the 5th of May 2019. The study quality was assessed by QUADAS-2 tool. Pooled sensitivity and specificity were calculated by the bivariate random effect model and hierarchical summary receiver-operating characteristic (SROC) curve was plotted.Results: Seven studies including 425 participants were analyzed after screening 986 articles searched from databases. The pooled sensitivity and specificity of CEUS in diagnosing TIV were 0.94 (95%CI, 0.89-0.97) and 0.99 (95%CI, 0.80-1.00), respectively. The area under the curve (AUC) of SROC curve was 0.97 (95%CI, 0.95-0.98). The pooled sensitivity and AUC were consistent across all the subgroups of different subject numbers, country, study design, CEUS contrast agents, and diagnostic criteria.Conclusions: CEUS is highly efficient in differentiating TIV from PVT and is an alternative or a substitute for CT and/or MRI.Trial Registration: PROSPERO registration number: CRD42019138847 KEY POINTS: • Characterization of portal vein thrombosis (PVT) vs tumor-in-vein (TIV) is critical for HCC staging. • CEUS has an excellent safety profile, provides a real-time analysis without any loss in accuracy compared with CT and MRI. • This meta-analysis demonstrates that contrast-enhanced ultrasound (CEUS) is a suitable method for the detection of PVT and distinction with TIV. [ABSTRACT FROM AUTHOR]

As nanomedicine-based clinical strategies have continued to develop, the possibility of combining chemotherapy and singlet oxygen-dependent photodynamic therapy (PDT) to treat pancreatic cancer (PaC) has emerged as a viable therapeutic modality. The efficacy of such an approach, however, is likely to be constrained by the mechanisms of drug release and tumor oxygen levels. In the present study, we developed an Fe(III)-complexed porous coordination network (PCN) which we then used to encapsulate PTX (PCN-Fe(III)-PTX) nanoparticles (NPs) in order to treat PaC via a combination of chemotherapy and PDT. The resultant NPs were able to release drug in response to both laser irradiation and pH changes to promote drug accumulation within tumors. Furthermore, through a Fe(III)-based Fenton-like reaction these NPs were able to convert H2O2 in the tumor site to O2, thereby regulating local hypoxic conditions and enhancing the efficacy of PDT approaches. Also these NPs were suitable for use as a T1-MRI weighted contrast agent, making them viable for monitoring therapeutic efficacy upon treatment. Our results in both cell line and animal models of PaC suggest that these NPs represent an ideal agent for mediating effective MRI-guided chemotherapy-PDT, giving them great promise for the clinical treatment of PaC. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate the effectiveness of contrast-enhanced ultrasound (CEUS) in predicting early nephropathy in cynomolgus macaques with spontaneous type 2 diabetes mellitus (T2DM). Methods: Six cynomolgus macaques with spontaneous T2DM and six normal cynomolgus macaques (Group 1) were included in this study. The time–intensity curve was used to obtain parameters such as peak values, red blood volume (RBV), red blood flow (RBF), time to peak (TTP), and mean transit time (MTT). Biopsy renal tissue samples were assessed histopathologically. Six cynomolgus macaques with spontaneous T2DM were subgrouped into T2DM without nephropathy group (Group 2) and T2DM with nephropathy group (Group 3) based on histopathological findings. Results: Peak value had the largest area under the curve comparing with RBF, RBV, TTP, MTT. The sensitivity and specificity of peak value with cut-off value of 38.65 dB for the diagnosis of DN were 98.3% and 83%, respectively. Peak value, RBV, and RBF in Group 3 was significantly decreased compared with Group 1 and Group 2 (P = 0.000, x2 = 23.99; P = 0.003, x2 = 9.14; P = 0.02, x2 = 5.14). Conclusions: The perfusion parameter of peak value in CEUS might be useful in predicting early diabetic nephropathy in spontaneous T2DM cynomolgus macaques. [ABSTRACT FROM AUTHOR]

Intracranial atherosclerotic stenosis (ICAS) is one of the most common causes of ischemic stroke (IS), especially in recurrent patients. Several studies have demonstrated an intimate association between the genetic mutation of the KALRN gene and IS. The main aim of this study was to clarify the relationship between three single nucleotide polymorphisms (SNPs) of KALRN and ICAS in a northern Chinese population and further explore the underlining mechanism. The relationship between each SNP and ICAS and the related components were examined in five models (co-dominant, dominant, recessive, heterozygous, and additive). Multivariate logistic regression models were applied and adjusted for 10,000 permutation tests. Haplotype regression analysis was performed to determine the associations between haplotypes and the severity of ICAS. qRT-PCR was used to confirm the mRNA level of Kalirin. SNP rs6438833 of the Kalirin gene in the additive model was associated with ICAS (OR = 1.642, 95%CI: 1.129-2.388, PDom = 0.048). After performing 10,000 permutations, the result showed a trend toward statistical significance (Pper = 0.048). Haplotypes of the KALRN gene were not significantly associated with ICAS (global significance, p = 0.090). qRT-PCR showed that the expression of KALRN 9 in IS patients was almost threefold the control group (p < 0.0005). SNPs of the KALRN gene are associated with ICAS in the northern Chinese population. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: ANGPTL8 is a circulatory hormone secreted from liver and adipose tissue that promotes pancreatic beta cell proliferation and interferes with triacylglycerol metabolism in mice. The clinical significance of its effects on inducing beta cell proliferation is limited because it causes severe hypertriacylglycerolaemia. Methods: We employed ultrasound-targeted microbubble destruction (UTMD) to deliver human ANGPTL8 gene plasmids to the pancreas, liver and skeletal muscle of normal adult rats. Results: Human ANGPTL8 was consistently detected in the circulation 1 month after UTMD. ANGPTL8 gene delivery promoted the proliferation of adult and aged beta cells, expanded the beta cell mass, improved glucose tolerance and increased the fasting blood insulin level after UTMD treatment without causing severe hypertriacylglycerolaemia. ANGPTL8 gene therapy significantly alleviated but did not totally reverse STZ-induced diabetes in a rat model. Conclusions/interpretation: ANGPTL8 induced adult and aged beta cell regeneration in a rat model. [ABSTRACT FROM AUTHOR]

Objectives: To examine the value of CEUS as a non-invasive tool in detecting lateral neck metastasis (LNM) and the enhancement patterns of malignant lymph nodes (LN) for thyroid cancer patients. Methods: Eighty-two consecutive patients, who underwent both preoperative non-enhanced US and CEUS examinations, were retrospectively reviewed. All patients underwent lateral neck dissection (LND). Enhancement patterns of 102 collected LNs matching to CEUS findings were analyzed. Results: CEUS detected LNM in 53 of 65 patients, showing a higher sensitivity and accuracy than that of conventional US ( p = 0.109 and p = 0.154, respectively). Thirteen patients' surgical procedures were altered by CEUS findings, including nine true positive and four false positive cases. Five patients' surgical procedures were altered by conventional US findings, including two true positive and three false positive cases. Heterogeneous enhancement, perfusion defects, microcalcification, and centripetal/hybrid enhancement were all specific criteria for malignant LNs in univariate analysis. In multivariate analysis, only heterogeneous enhancement and centripetal/hybrid enhancement were significantly related to LN metastasis ( p = 0.000 and p = 0.037, respectively). Conclusions: CEUS may be a potential tool to facilitate conventional US in detecting LNM. Heterogeneous enhancement and centripetal/hybrid enhancement are useful criteria to distinguish between malignant and benign LNs. Key Points: • CEUS findings facilitated conventional US in detecting LNM. • Heterogeneous, centripetal/hybrid enhancement, microcalcification and perfusion defects were specific criteria of malignant LNs. • Heterogeneous and centripetal/hybrid enhancement were significantly related to LN metastasis in multivariate analysis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of the angiogenesis inhibitor Endostar on carotid plaque neovascularization in patients with non-small cell lung cancer (NSCLC) using contrast-enhanced ultrasound (CEUS). Ninety-one patients who had NSCLC with soft carotid plaques were selected for treatment either with the NP regimen (vinorelbine + cisplatin) (43 patients) or with the ENP regimen (Endostar + NP) (48 patients). Plaque thickness and neovascularization of the plaque were assessed before and at 1 month after treatment using CEUS. Enhanced intensity (EI) of CEUS was used for quantification of plaque neovascularization. There was no significant changes in any group in thickness of plaque between recruitment and 1 month after treatment (P > 0.05 for all). There was no significant change in the EI of plaque in the controls or NP groups at 1 month after treatment (P > 0.05), while EI in the ENP group was significantly reduced at 1 month after treatment (P < 0.01) and significantly lower than that in the controls or NP group at 1 month after treatment (P < 0.001 both). This study indicates that carotid soft plaque neovascularization in patients with NSCLC can be reduced by anti-angiogenesis treatment. [ABSTRACT FROM AUTHOR]