Dynamic contrast enhanced ultrasound in differential diagnosis of hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND: Non-invasive differential diagnosis between hepatocellular carcinoma (HCC) and other liver cancer (i.e. cholangiocarcinoma or metastasis) is highly challenging and definitive diagnosis still relies on histological exam. The patterns of enhancement and wash-out of liver nodules can be used to stratify the risk of malignancy only in cirrhotic patients and HCC frequently shows atypical features. Dynamic contrast-enhanced ultrasound (DCEUS) with standardized software could help to overcome these obstacles, providing functional and quantitative parameters and potentially improving accuracy in the evaluation of tumor perfusion. AIM: To explore clinical evidence regarding the application of DCEUS in the differential diagnosis of liver nodules. METHODS: A comprehensive literature search of clinical studies was performed to identify the parameters of DCEUS that could relate to histological diagnosis. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: Rise time was significantly higher in HCC patients with a standardized mean difference (SMD) of 0.83 (95%CI: 0.48-1.18). Similarly, other statistically significant parameters were mean transit time local with a SMD of 0.73 (95%CI: 0.20-1.27), peak enhancement with a SMD of 0.37 (95%CI: 0.03-0.70), area wash-in area under the curve with a SMD of 0.47 (95%CI: 0.13-0.81), wash-out area under the curve with a SMD of 0.55 (95%CI: 0.21-0.89) and wash-in and wash-out area under the curve with SMD of 0.51 (95%CI: 0.17-0.85). SMD resulted not significant in fall time and wash-in rate, but the latter presented a trend towards greater values in HCC compared to intrahepatic cholangiocarcinoma. CONCLUSION: DCEUS could improve non-invasive diagnosis of HCC, leading to less liver biopsy and early treatment. This quantitative analysis needs to be applied on larger cohorts to confirm these preliminary results.

Simulation of time-intensity curve based on k-space filling in breast dynamic contrast-enhanced three-dimensional magnetic resonance imaging.

This study elucidated the effects of a three-dimensional k-space trajectory incorporating the partial Fourier (PF) technique on a time-intensity curve (TIC) in a dynamic contrast-enhanced magnetic resonance imaging of a typical malignant breast tumor using a digital phantom. Images were obtained from the Cancer Imaging Archive Open Data for Breast Cancer, and 1-min scans with high temporal resolution were analyzed. The order of the k-space trajectory was set as Linear (sequential), Low-High (centric), PF (62.5%; Z-, Y-, and both directions), and Low-High Radial. k0 (center of the k-space) timing and TIC shape were affected by the chosen k-space trajectory and implementation of the PF technique. A small TIC gradient was obtained using a Low-High Radial order. If the k-space filling method (particularly the radial method) produces a gentle TIC gradient, misinterpretation could arise during the assessment of tumor malignancy status.

Blood flow evaluation of reconstructed gastric tube in esophageal surgery using near-infrared imaging and retrospective time-intensity curve analysis.

PURPOSE: Near-infrared fluorescence imaging using indocyanine green (ICG-NIFI) can visualize a blood flow in reconstructed gastric tube; however, it depends on surgeon's visual assessment. The aim of this study was to re-analyze the ICG-NIFI data by an evaluator independent from the surgeon and feasibility of creating the time-intensity curve (TIC). METHODS: We retrospectively reviewed 97 patients who underwent esophageal surgery with gastric tube reconstruction between January 2017 and November 2022. From the stored ICG videos, fluorescence intensity was examined in the four regions of interest (ROIs), which was set around the planned anastomosis site on the elevated gastric tube. After creation the TICs using the OpenCV library, we measured the intensity starting point and time constant and assessed the correlation between the anastomotic leakage. RESULTS: Postoperative leakage occurred for 12 patients. The leakage group had significantly lack of blood flow continuity between the right and left gastroepiploic arteries (75.0% vs. 22.4%; P < 0.001) and tended to have slower ICG visualization time assessed by the surgeon's eyes (40 vs. 32 s; P = 0.066). TIC could create in 65 cases. Intensity starting point at all ROIs was faster than the surgeon's assessment. The leakage group tended to have slower intensity starting point at ROI 3 compared to those in the non-leakage group (22.5 vs. 19.0 s; P = 0.087). CONCLUSION: A TIC analysis of ICG-NIFI by an independent evaluator was able to quantify the fluorescence intensity changes that the surgeon had visually determined.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in differentiation of soft tissue sarcoma from benign lesions: a systematic review of literature.

OBJECTIVE: To systematically review the literature assessing the role of Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) in the differentiation of soft tissue sarcomas from benign lesions. MATERIALS AND METHODS: A comprehensive literature search was performed with the following keywords: multiparametric magnetic resonance imaging, DCE-MR perfusion, soft tissue, sarcoma, and neoplasm. Original studies evaluating the role of DCE-MRI for differentiating benign soft-tissue lesions from soft-tissue sarcomas were included. RESULTS: Eighteen studies with a total of 965 imaging examinations were identified. Ten of twelve studies evaluating qualitative parameters reported improvement in discriminative power. One of the evaluated qualitative parameters was time-intensity curves (TIC), and malignant curves (TIC III, IV) were found in 74% of sarcomas versus 26.5% benign lesions. Six of seven studies that used the semiquantitative approach found it relatively beneficial. Four studies assessed quantitative parameters including Ktrans (contrast transit from the vascular compartment to the interstitial compartment), Kep (contrast return to the vascular compartment), and Ve (the volume fraction of the extracellular extravascular space) in addition to other parameters. All found Ktrans, and 3 studies found Kep to be significantly different between sarcomas and benign lesions. The values for Ve were variable. Additionally, eight studies assessed diffusion-weighted imaging (DWI), and 6 of them found it useful. CONCLUSION: Of different DCE-MRI approaches, qualitative parameters showed the best evidence in increasing the diagnostic performance of MRI. Semiquantitative and quantitative approaches seemed to improve the discriminative power of MRI, but which parameters and to what extent is still unclear and needs further investigation.

Associations between contrast-enhanced ultrasound features and WHO/ISUP grade of clear cell renal cell carcinoma: a retrospective study.

BACKGROUND: Clear cell renal cell carcinoma (CCRCC) comprises 70%-80% of RCCs. The World Health Organization/International Society of Urology Pathology (WHO/ISUP) classification is the most important prognostic factor for CCRCC. By evaluating the variations of tumor microvascular density, contrast-enhanced ultrasound (CEUS) can noninvasively predict the WHO/ISUP grade of CCRCC, and provide the appropriate treatment plan before clinical operation. METHODS: In this study, we used CEUS features to analyze 116 CCRCC cases and assess the value of correlation between each indicator and CCRCC WHO/ISUP grading. RESULTS: When compared to high-grade (WHO/ISUP grade III/IV) tumors, low-grade (WHO/ISUP grade I/II) tumors had reduced relative peak intensity (ΔPI) (P = 0.021), relative area under the curve (ΔAUC) (P = 0.019). However, the frequency of incomplete pseudocapsule (P = 0.021) was significantly higher in high-grade tumors. A cut-off value of mean diameter > 5.5 cm, ΔPI > 304 × 10-3, ΔAUC > 350 × 10-3 allowed identification of high-grade tumors with an area under the curve (AUC) of 74.6%, 71.7%, 70.7%, respectively (95% confidence interval). CONCLUSIONS: The features of CEUS are effective for differentiating high-grade tumors from low-grade tumors, thus CEUS can be considered an acceptable method for the preoperative assessment of tumor grade.

Incorporation of CEUS and SWE parameters into a multivariate logistic regression model for the differential diagnosis of benign and malignant TI-RADS 4 thyroid nodules.

PURPOSE: To investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) quantitative analysis parameters combined with shear wave elastography (SWE) quantitative parameters in the differentiation of benign and malignant ACR TI-RADS category 4 thyroid nodules and to provide a more effective reference for clinical work. METHODS: We analyzed 187 category 4 nodules, including 132 nodules in the development cohort and 55 nodules in the validation cohort, divided the development cohort into benign and malignant groups, and analyzed the differences in all CEUS and SWE quantitative parameters between the two groups. We selected the highest AUC of the two parameters, performed binary logistic regression analysis with the ACR TI-RADS score and constructed a diagnostic model. ROC curves were applied to evaluate their diagnostic efficacy. RESULTS: 1) The diagnostic model had an AUC of 0.926, sensitivity of 87.5%, specificity of 86.8%, diagnostic threshold of 3, accuracy of 87.12%, positive predictive value of 86.15%, and negative predictive value of 88.06%. 2) The diagnostic model had an AUC of 0.890 in the validation cohort, sensitivity of 81.5%, specificity of 79.6%, and accuracy of 80.00%. CONCLUSION: The combined multiparameter construction of the nodule diagnostic model can effectively improve the diagnostic efficacy of 4 types of thyroid nodules and provide a new reference index for clinical diagnostic work.

Voxel-wise mapping of DCE-MRI time-intensity-curve profiles enables visualizing and quantifying hemodynamic heterogeneity in breast lesions.

OBJECTIVES: To propose a novel model-free data-driven approach based on the voxel-wise mapping of DCE-MRI time-intensity-curve (TIC) profiles for quantifying and visualizing hemodynamic heterogeneity and to validate its potential clinical applications. MATERIALS AND METHODS: From December 2018 to July 2022, 259 patients with 325 pathologically confirmed breast lesions who underwent breast DCE-MRI were retrospectively enrolled. Based on the manually segmented breast lesions, the TIC of each voxel within the 3D whole lesion was classified into 19 subtypes based on wash-in rate (nonenhanced, slow, medium, and fast), wash-out enhancement (persistent, plateau, and decline), and wash-out stability (steady and unsteady), and the composition ratio of these 19 subtypes for each lesion was calculated as a new feature set (type-19). The three-type TIC classification, semiquantitative parameters, and type-19 features were used to build machine learning models for identifying lesion malignancy and classifying histologic grades, proliferation status, and molecular subtypes. RESULTS: The type-19 feature-based model significantly outperformed models based on the three-type TIC method and semiquantitative parameters both in distinguishing lesion malignancy (respectively; AUC = 0.875 vs. 0.831, p = 0.01 and 0.875vs. 0.804, p = 0.03), predicting tumor proliferation status (AUC = 0.890 vs. 0.548, p = 0.006 and 0.890 vs. 0.596, p = 0.020), but not in predicting histologic grades (p = 0.820 and 0.970). CONCLUSION: In addition to conventional methods, the proposed computational approach provides a novel, model-free, data-driven approach to quantify and visualize hemodynamic heterogeneity. CLINICAL RELEVANCE STATEMENT: Voxel-wise intra-lesion mapping of TIC profiles allows for visualization of hemodynamic heterogeneity and its composition ratio for differentiation of malignant and benign breast lesions. KEY POINTS: • Voxel-wise TIC profiles were mapped, and their composition ratio was compared between various breast lesions. • The model based on the composition ratio of voxel-wise TIC profiles significantly outperformed the three-type TIC classification model and the semiquantitative parameters model in lesion malignancy differentiation and tumor proliferation status prediction in breast lesions. • This novel, data-driven approach allows the intuitive visualization and quantification of the hemodynamic heterogeneity of breast lesions.

Application of Quantitative Parameters of Contrast-Enhanced Ultrasound in Common Benign and Malignant Lesions in Pediatric Livers: A Preliminary Study.

We aimed to investigate the diagnostic utility of quantitative parameters of contrast-enhanced ultrasound (CEUS) for benign and malignant liver lesions in pediatric patients. This was a single-center retrospective analysis of children with liver lesions who underwent CEUS at our hospital between July 2019 and February 2023. The CEUS perfusion patterns for all lesions were qualitatively analyzed using histopathology, contrast-enhanced magnetic resonance imaging, contrast-enhanced computed tomography, or long-term clinical follow-up as reference standards. The CEUS images were quantitatively analyzed using SonoLiver® software (TomTec Imaging Systems, Munich, Germany) to obtain data regarding quantitative parameters and dynamic vascular pattern (DVP) parametric images, including rise time (RT), time to peak (TTP), mean transit time (mTT), and maximum intensity (IMAX). Statistical analysis was carried out using Student's t-test and receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic value of quantitative parameters. A total of 53 pediatric cases were included in this study, and 88.57% (31/35) of malignant lesions exhibited hyper-enhancement with rapid washout patterns; the same proportion of DVP parametric images exhibited washout patterns. Conversely, 94.44% (17/18) of benign lesions showed hyper-enhancement with slow washout patterns, and the same proportion of DVP parametric images showed no-washout patterns. RT, TTP, and mTT were significantly shorter in the malignant group than in the benign group (p < 0.05), while IMAX showed no significant difference (p > 0.05). ROC analysis indicated that mTT < 113.34 had the highest diagnostic value, with an area under the curve of 0.82. CEUS quantitative analysis had an accuracy of 98.11%, while qualitative analysis had an accuracy of 92.45%, with no statistically significant difference (p > 0.05). Quantitative analysis of CEUS provides valuable assistance in differentiating benign and malignant liver lesions in children. Among all quantitative parameters, mTT holds promise as a potentially valuable tool for identifying liver tumors.

Dynamic contrast enhanced ultrasound in gastrointestinal diseases: A current trend or an indispensable tool?

Contrast enhanced ultrasound (CEUS) has been widely implemented in clinical practice because of the enormous quantity of information it provides, along with its low cost, reproducibility, minimal invasiveness, and safety of the second-generation ultrasound contrast agents. To overcome the limitation of CEUS given by the subjective evaluation of the contrast enhancement behaviour, quantitative analysis of contrast kinetics with generation of time-intensity curves has been introduced in recent years. The quantification of perfusion parameters [named as dynamic-CEUS (D-CEUS)] has several applications in gastrointestinal neoplastic and inflammatory disorders. However, the limited availability of large studies and the heterogeneity of the technologies employed have precluded the standardisation of D-CEUS, which potentially represents a valuable tool for clinical practice in management of gastrointestinal diseases. In this article, we reviewed the evidence exploring the application of D-CEUS in gastrointestinal diseases, with a special focus on liver, pancreas, and inflammatory bowel diseases.

Domain knowledge-guided adversarial adaptive fusion of hybrid breast ultrasound data.

Contrast-enhanced ultrasound (CEUS), which provides more detailed microvascular information about the tumor, is always taken by radiologists in clinic diagnosis along with B-mode ultrasound (B-mode US). However, automatically analyzing breast CEUS is challenging due to the difference between the CEUS video and the natural video, e.g., sports or action videos, where the CEUS video has no positional displacements. Additionally, most existing methods rarely use the Time Intensity Curve (TIC) information of CEUS and non-imaging clinical (NIC) data. To address these issues, we propose a novel breast cancer diagnosis framework that learns the complementarity and correlation across hybrid modal data, including CEUS, B-mode US, and NIC data, by an adversarial adaptive fusion method. Furthermore, to fully exploit the CEUS information, the proposed method, inspired by the clinical processing of radiologists, first extracts the TIC parameters of CEUS. Then, we select a clip from CEUS using a frame screening strategy and finally get spatio-temporal features from these clips through a critical frame attention network. To our knowledge, this is the first AI system to use TIC parameters, NIC data, and ultrasound imaging in diagnoses. We have validated our method on a dataset collected from 554 patients. The experimental results demonstrate the excellent performance of the proposed method. The result shows that our method can achieve an accuracy of 87.73%, which is higher than that of uni-modal approaches by nearly 5%.

Effects of helical centerline stent vs. straight stent placement on blood flow velocity.

As an approach to maintain patency in femoropopliteal stenting, a helical stent configuration was proposed, which showed improved patency in clinical trials. However, the effects of helical stent placement on the flow have not been quantitatively analyzed. The purpose of this study was to estimate flow velocities to quantify the influence of helical stent placement. Helical and straight stents were implanted in three healthy pigs, and the flow velocities were estimated using the time-intensity curve (TIC) in the angiography images. The angiographic images indicated thinning of the leading edge of the contrast medium through the helically deformed artery, which was not observed in the straight stent. The slower rise of the TIC peak in the helical stent indicated faster travel of this thinner edge. Arterial expansion due to stenting was observed in all cases, and the expansion rate varied according to location. All cases of helical stent implantation showed that velocity was maintained (55.0%-71.3% velocity retention), unlike for straight stent implantation (43.0%-68.0% velocity retention); however, no significant difference was observed.

Towards quantitative digital subtraction perfusion angiography: An animal study.

BACKGROUND: X-ray digital subtraction angiography (DSA) is the imaging modality for peri-procedural guidance and treatment evaluation in (neuro-) vascular interventions. Perfusion image construction from DSA, as a means of quantitatively depicting cerebral hemodynamics, has been shown feasible. However, the quantitative property of perfusion DSA has not been well studied. PURPOSE: To comparatively study the independence of deconvolution-based perfusion DSA with respect to varying injection protocols, as well as its sensitivity to alterations in brain conditions. METHODS: We developed a deconvolution-based algorithm to compute perfusion parametric images from DSA, including cerebral blood volume (CBV D S A $_{DSA}$ ), cerebral blood flow (CBF D S A $_{DSA}$ ), time to maximum (Tmax), and mean transit time (MTT D S A $_{DSA}$ ) and applied it to DSA sequences obtained from two swine models. We also extracted the time intensity curve (TIC)-derived parameters, that is, area under the curve (AUC), peak concentration of the curve, and the time to peak (TTP) from these sequences. Deconvolution-based parameters were quantitatively compared to TIC-derived parameters in terms of consistency upon variations in injection profile and time resolution of DSA, as well as sensitivity to alterations of cerebral condition. RESULTS: Comparing to TIC-derived parameters, the standard deviation (SD) of deconvolution-based parameters (normalized with respect to the mean) are two to five times smaller, indicating that they are more consistent across different injection protocols and time resolutions. Upon ischemic stroke induced in a swine model, the sensitivities of deconvolution-based parameters are equal to, if not higher than, those of TIC-derived parameters. CONCLUSIONS: In comparison to TIC-derived parameters, deconvolution-based perfusion imaging in DSA shows significantly higher quantitative reliability against variations in injection protocols across different time resolutions, and is sensitive to alterations in cerebral hemodynamics. The quantitative nature of perfusion angiography may allow for objective treatment assessment in neurovascular interventions.

Automated motion artifact correction for dynamic contrast-enhanced fluorescence imaging during open orthopedic surgery.

Indocyanine green (ICG)-based dynamic contrast-enhanced fluorescence imaging (DCE-FI) can objectively assess bone perfusion intraoperatively. However, it is susceptible to motion artifacts due to patient's involuntary respiration during the 4.5-minute DCE-FI data acquisition. An automated motion correction approach based on mutual information (MI) frameby-frame was developed to overcome this problem. In this approach, MIs were calculated between the reference and the adjacent frame translated and the maximal MI corresponded to the optimal translation. The images obtained from eighteen amputation cases were utilized to validate the approach and the results show that this correction can significantly reduce the motion artifacts and can improve the accuracy of bone perfusion assessment.

Efficacy of Contrast-Enhanced Endoscopic Ultrasonography for the Differentiation of Non-Hodgkin's Lymphoma: A Single-Center Retrospective Cohort Study.

BACKGROUND: Contrast-enhanced endoscopic ultrasound (CE-EUS) is a promising diagnostic modality for differentiating malignant and benign lymph nodes. This study aimed to evaluate the diagnostic capability of CE-EUS in differentiating indolent non-Hodgkin's lymphoma (NHL) from aggressive NHL. METHODS: Patients who underwent CE-EUS and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for lymphadenopathy and were diagnosed with NHL were included in this study. Echo features on B-mode endoscopic ultrasound (EUS) and vascular and enhancement patterns on CE-EUS were qualitatively evaluated. The enhancement intensity of the lymphadenopathy on CE-EUS over 60 s was also quantitatively evaluated using time-intensity curve (TIC) analysis. RESULTS: A total of 62 patients who were diagnosed with NHL were enrolled in this study. Regarding qualitative evaluation using B-mode EUS, there were no significant differences in the echo features between aggressive NHL and indolent NHL. With regard to qualitative evaluation using CE-EUS, aggressive NHL showed a heterogeneous enhancement pattern that is significantly more frequent than indolent NHL (95% confidence interval: 0.57 to 0.79, p = 0.0089). When heterogeneous enhancement was defined as aggressive NHL, the sensitivity, specificity, and accuracy of the qualitative evaluation when using CE-EUS were 61%, 72%, and 66%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions was significantly higher in aggressive NHL than in indolent NHL (p < 0.0001). The sensitivity, specificity, and accuracy of CE-EUS in differentiating indolent NHL from aggressive NHL improved to 94%, 69%, and 82%, respectively, when combined with qualitative and quantitative evaluations. CONCLUSIONS: CE-EUS before EUS-FNA for mediastinal or abdominal lymphadenopathy may be useful for improving the diagnostic capability of differentiating between indolent NHL and aggressive NHL (clinical trial registration number: UMIN000047907).

Characteristic of Apparent Diffusion Coefficient and Time Intensity Curve Analysis of Dynamic Contrast Enhanced MRI in Osteosarcoma Histopathologic Subtypes.

Background: According to WHO criteria, osteosarcoma (OS) consists of various histopathological subtypes. Thus, contrast-enhanced MRI is a very useful modality in the diagnosis and evaluation of osteosarcoma. Magnetic resonance imaging with dynamic contrast enhancement (DCE-MRI) studies was used to determine the apparent diffusion coefficient (ADC) value and the slope of the time-intensity curve (TIC). This study aimed to determine the correlation between ADC and TIC analysis using %Slope and maximum enhancement (ME) of histopathological osteosarcoma subtypes. Methods: This was a retrospective study with observational analysis on OS patients. The obtained data were 43 samples. Moreover, the interpretation was conducted by placing three regions of interest (ROI) in determining ADC value. It was observed by two radiologist observers with more than 10 years of experience. In this case, as many as six obtained ROIs were averaged. The inter-observer agreement was evaluated by Kappa test. TIC curve was analyzed and slope value was obtained afterward. Through SPSS 21 software, the data was analyzed. Results: The mean of ADC values of OS was (1.031x10-3±0.31mm2/s), where the highest value was found in chondroblastic subtype (1.470 x10-3±0.31mm2/s). However, the mean of TIC %slope of OS was (45.3%/s), where the highest result was found in the osteoblastic subtype (70.8%/s) followed by small cell subtype (60.8%/s) and the mean of ME of OS was 100.55% with the highest values was in osteoblastic subtype 172.72% followed by chondroblastic subtype (144.92%). This study found a significant correlation between the mean of ADC value and the OS histopathologic results as well as the correlation between the mean of ADC value and ME. Conclusion: The various types of osteosarcoma have a characteristic of radiological appearances which may similar to some bone tumor entities. The analysis of ADC values and TIC curves using % slope and ME of osteosarcoma subtypes can improve the accuracy of diagnosis as well as the monitoring of the treatment response and the disease progression.

The findings on the CEUS of diffuse large B cell lymphoma in abdomen: A case report and literature review.

Background: PET-CT is the first choice for the imaging diagnosis of intraperitoneal lymphomas. Contrast-enhanced ultrasound (CEUS) is rare in the diagnosis of intraperitoneal nodal lymphoma. Case summary: A 62-year-old man was admitted for examination with "right upper abdominal pain". Ultrasound was used to refer to the masses in the hilar region, spleen, and anterior sacral region respectively. The masses were all hypoechoic, and blood flow signals could be detected by CDFI. Laboratory tests of CA125 were within normal limits. CEUS examination was performed on the three masses respectively. The three masses showed different perfusion patterns. Thickened vessels appeared around the mass in the hilar region, a peripheral centrally directed perfusion pattern was observed in the splenic mass, and blood supply vessels appeared in the center of the presacral mass with a significant filling defect. They all showed a contrast pattern with rapid clearance and hypoenhancement compared with the surrounding areas. Ultrasound guided needle biopsy revealed non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, non-germinal center origin. After biopsy, the patient was treated with R-CHOP regimen for chemotherapy, and the tumor disappeared by routine ultrasound review after 5 cycles of chemotherapy. Conclusion: To the best of our knowledge, this report is the first to describe the findings of CEUS in intraperitoneal nodal lymphoma. CEUS has various manifestations in intraperitoneal nodal lymphoma. Future studies are still needed to explore the diagnostic features of CEUS in intraperitoneal nodal lymphoma.

Characterization of the interaction of nanobubble ultrasound contrast agents with human blood components.

Nanoscale ultrasound contrast agents, or nanobubbles, are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in cancer. These sub-micron particles are approximately 10x smaller than clinically available microbubbles. This allows them to effectively traverse compromised physiological barriers and circulate for extended periods of time. While various aspects of nanobubble behavior have been previously examined, their behavior in human whole blood has not yet been explored. Accordingly, herein we examined, for the first time, the short and long-term effects of blood components on nanobubble acoustic response. We observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline (PBS), plasma, or red blood cell solutions (RBCs). Specifically, after introducing nanobubbles to fresh human whole blood, signal enhancement, or the magnitude of nonlinear ultrasound signal, gradually increased by 22.8 ± 13.1% throughout our experiment, with peak intensity reached within 145 s. In contrast, nanobubbles in PBS had a stable signal with negligible change in intensity (-1.7 ± 3.2%) over 8 min. Under the same conditions, microbubbles made with the same lipid formulation showed a -56.8 ± 6.1% decrease in enhancement in whole blood. Subsequent confocal, fluorescent, and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs, suggesting that direct interactions, or hitchhiking, of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed effects. This phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery, where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.

Application value of contrast-enhanced ultrasonography in the treatment of uterine fibroids by high-intensity focused ultrasound ablation: A retrospective study.

PURPOSE: To determine efficacy and safety of contrast-enhanced ultrasonography (CEUS) in high-intensity focused ultrasound (HIFU) ablation of uterine fibroids (UFs). METHODS: We retrospectively reviewed women undergoing HIFU ablation for UFs between June 2018 and January 2020. Before and after HIFU, patients underwent CEUS and magnetic resonance imaging (MRI) examinations. The relationship between CEUS features and ablation rate was analyzed. The time-intensity curves on CEUS were measured before and after HIFU ablation, and compared with those obtained using MRI. Adverse reactions were recorded. RESULTS: A total of 64 patients were included. The immediate HIFU ablation rate significantly differed between low-, iso-, and high-enhancement UFs (87.2% ± 1.6%, 83.3% ± 2.1%, and 72.9% ± 3.1%, respectively; p < 0.05). On CEUS, the peak time of the time-intensity curve was significantly longer after treatment than before treatment (32.2 ± 9.7 and 26.7 ± 9.4 s, respectively; p < 0.05). Peak intensity was significantly lower after treatment than before treatment (13.7 ± 7.5 and 30.9 ± 11.2 dB, respectively; p < 0.05). All measurements were comparable between CEUS and MRI. The most common peri- and post-procedure adverse reaction was pain, which was temporary. CONCLUSION: CEUS could dynamically and safely evaluate the immediate effects of the HIFU ablation of UFs.

Analysis of the efficacy of differential diagnosis of atypical adenomyosis and uterine fibroids through contrast-enhanced ultrasound by decision tree model / 中华超声影像学杂志

Objective:To evaluate the effectiveness of contrast-enhanced ultrasound in the differential diagnosis of atypical adenomyosis and fibroids using a decision tree model.Methods:The data of cases with difficulty in differentiating atypical adenomyosis from fibroids on conventional ultrasound examination at Shengjing Hospital of China Medical University from April 2021 to April 2022 were selected and analyzed. Ninety-five patients with contrast-enhanced ultrasound examination were finally selected, including 64 patients in the pathologically confirmed adenomyosis group and 31 patients in the fibroids group. The data from the qualitative analysis and the quantitative analysis of the time-intensity curve (TIC) curve were collected separately, including the temporal variability of contrast entry into the lesion, i.e.the difference between the time when the contrast agent started to enter the lesion and the time when the contrast agent finally filled the lesion completely. Indicators were first screened for inclusion in the decision tree model by univariate and multifactorial analyses, and decision tree models based on qualitative analysis indicators, and qualitative and TIC-based analyses were developed to further assess the diagnostic efficacy of both models.Results:Through the univariate analysis, it showed that the qualitative analysis indicators of lesion onset enhancement pattern, enhancement intensity, intra-lesion contrast distribution, and post-contrast lesion border were of statistical significance (all P<0.05) between the two groups. The differences in contrast arrive time (AT), contrast time to peak (TTP), |ΔAT|, and |ΔTTP| in the TIC curve analysis indexes were statistically significant between the two groups (all P<0.05). The difference in lesion temporal phase variability was statistically significant between the two groups ( P<0.05). After further screening by multifactorial analysis, the accuracy and misdiagnosis rates were 87.40% and (17.90±3.90)% in the qualitative analysis-based decision tree model respectively, and 90.50% and (21.10±4.20) % in the qualitative and TIC curve-based analysis decision tree model respectively. The ROC curves were plotted according to the two groups of models, and the areas under the curves were 0.915 and 0.931 respectively. Conclusions:A decision tree model based on ultrasonographic image analysis has diagnostic value for the differential diagnosis of atypical adenomyosis and uterine fibroids.

Changes in vascular supply pattern associated with growth of nonfunctioning pituitary adenomas.

Background: The vascular supply to nonfunctioning pituitary adenomas (NFPAs) differs compared with that of the anterior lobe of the normal pituitary gland. In this study, we aimed to identify feeding arteries and flow dynamics using 3.0 T magnetic resonance imaging (MRI) in NFPAs. Methods: We divided 77 cases of NFPA into three groups according to the time-intensity curve (TIC) pattern by dynamic MRI. We also investigated the presence of feeder arteries as a flow void signal on T2-weighted imaging (T2WI). Results: According to the TIC, 39 cases demonstrated an ascending pattern, 10 cases demonstrated a descending pattern, and 28 cases demonstrated a monophasic pattern. Tumor size in the ascending group was larger compared with the descending group (P = 0.0036). Flow void signals were identified in 51 of 77 cases (66.2%) on T2WI. Tumor size was larger in tumors with a flow void signal compared with those without (P < 0.0001). Flow void signals were more frequently observed in the group of ascending pattern compared with the group of monophasic and descending pattern (P = 0.032 and P = 0.003, respectively). Particularly on the caudal side, the difference between the ascending group and the monophasic and descending groups was remarkable (P = 0.0035 and P < 0.0001, respectively). Conclusion: We successfully evaluated the blood supply pattern by the TIC analysis and identified flow voids using 3.0 T MRI. Blood supply pattern was significantly associated with NFPA size. These results suggested that NFPA hemodynamics changes during tumor growth.