Contrast-enhanced Ultrasound Research Articles

Diagnostic Methods of Atherosclerotic Plaque and the Assessment of Its Prognostic Significance—A Narrative Review

Cardiovascular diseases (CVD) are a leading cause of death. The most notable cause of CVD is an atherosclerotic plaque. The aim of this review is to provide an overview of different diagnostic methods for atherosclerotic plaque relevant to the assessment of cardiovascular risk. The methods can be divided into invasive and non-invasive. This review focuses on non-invasive with attention paid to ultrasonography, contrast-enhanced ultrasonography, intravascular ultrasonography, and assessment of intima-media complex, coronary computed tomography angiography, and magnetic resonance. In the review, we discuss a number of Artificial Intelligence technologies that support plaque imaging.

Diagnostic Value of Contrast-Enhanced Ultrasound in Differentiating Malignant from Benign Small Renal Masses After CT/MRI.

Background: The aim of this study was to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) in characterizing small renal masses (SRMs) measuring less than 3 cm and in distinguishing between malignant and benign SRMs. Methods: A retrospective study was conducted between January 2022 and January 2023 at the Radiology Department of (Anonymized data), with a total of 43 patients assessed via CT and MRI scans, which were subsequently studied by experienced radiologists who were blinded to the pathology results. The CEUS findings were then compared with histopathological examination outcomes or follow-up imaging results. Results: The study results revealed a notably high level of diagnostic accuracy, with sensitivity at 0.875, specificity at 0.94, positive predictive value at 0.95, and negative predictive value at 0.86 for characterizing SRMs. Spearman rank correlation analysis substantiated a robust positive linear correlation between the CEUS findings and biopsy results (r = 0.972). Conclusions: These findings underscore the potential utility of CEUS as a valuable tool for discriminating between malignant and benign SRMs, carrying significant implications for clinical decision-making and leading to improved patient outcomes. However, larger validation studies are imperative to establish its role in routine clinical practice and to address potential limitations.

Inter-Reader Agreement for Contrast-Enhanced Ultrasound Liver Imaging Reporting and Data System Major Features and Final Categorization: A Subanalysis From a Prospective Multicenter Study.

Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is used to definitively diagnose hepatocellular carcinoma (HCC) in patients at risk. However, the user variability associated with CEUS LI-RADS has not been validated in North American and European patients. This study aims to evaluate the inter-reader agreements of CEUS LI-RADS features for, and final categorization of, HCC in patients at risk. This retrospective multicenter clinical study used the database of a previous prospective multinational study, evaluating the accuracy of CEUS LI-RADS for HCC diagnosis in patients at risk. All cases were first evaluated by a site physician performing/supervising the CEUS examination. Randomly selected cases were re-evaluated by a blinded central reader. Final diagnosis was confirmed with the reference standard, which was a composite of imaging tests and histology. Cohen's kappa test was used to evaluate inter-reader agreement. This study included 150 liver nodules and 58.0% (87/150) were confirmed as HCC, 4.7% (7/150) non-HCC malignancies, 22.7% (34/150) had no confirmed final diagnosis, and 14.7% (22/150) were nonmalignant. Inter-reader agreements were substantial for CEUS LI-RADS categorization (κ = 0.61; 95% confidence interval [CI]: 0.51-0.71) and major features assessment (ranged κ = 0.64-0.78), LR-5 (κ = 0.65; 95% CI: 0.52-0.77), and LR-M (κ = 0.67; 95% CI: 0.44-0.90), while for LR-1 and LR-2 categorization was almost perfect (κ = 0.85; 95% CI: 0.65-1.00). Our study reported a substantial inter-reader agreement for overall CEUS LI-RADS categorization, especially for LR-5 and LR-M, and major imaging features of HCC, further confirming CEUS LI-RADS as a valuable and reliable tool for diagnosis of HCC.

Contrast-enhanced ultrasound combined with percutaneous ultrasound-guide core needle biopsies in the diagnosis of pancreatic lesions: a propensity score-matched study

ObjectiveTo compare the diagnostic performance of pancreatic lesions using percutaneous ultrasound (US)-guided core needle biopsy (CNB) with and without contrast-enhanced ultrasound (CEUS).MethodThe patients were divided into two groups, US and CEUS group, based on whether CEUS was performed prior to biopsy. Before and after propensity score matching (PSM), the CNB-relevant characteristics of the two groups, including the first puncture success rate, the number of sampling, complication rate, type of complications, and degree of abdominal pain, were compared. The accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of percutaneous US-guided CNB were compared between the groups.ResultsThis study included 277 patients (173 men and 104 women) with pancreatic lesions who underwent percutaneous CNB before PSM; 190 patients in the CEUS group, and 87 in the US group prior to CNB. After controlling for potential biases using PSM, no significant differences were observed in the complication rate, type of complications, or degree of abdominal pain between the CEUS and US groups (P > 0.05). However, significant differences were observed in the first puncture success rate and the number of sampling (P < 0.05). Importantly, before and after PSM, the CEUS group achieved a higher first-puncture success rate while obtaining a lower number of sampling (P < 0.05). Compared to the US group, the CEUS group demonstrated improved accuracy, sensitivity, specificity, PPV, and NPV of 13.1%, 14.9%, 13.4%, 2.5%, and 38.7%, respectively. Furthermore, the significant difference was observed in the AUC for diagnostic performance between the two groups when compared using DeLong’s test (P = 0.043).ConclusionsPerforming CEUS before percutaneous CNB for pancreatic lesions can help achieve better biopsy results, reduce the number of punctures samples, increase the success rate of biopsies, and avoid the need for repeat biopsies.

Effect of intrarenal pelvic pressure on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy.

To investigate the effects of intrarenal pelvic pressure (IPP) on pyelo-tubular backflow and renal cortical blood perfusion during mini-percutaneous nephrolithotomy (MPCNL). Dynamic changes in pyelo-tubular backflow and renal cortical blood perfusion were studied in six patients undergoing MPCNL using dynamic contrast-enhanced ultrasonography (CEUS) and IPP monitoring. CEUS of intrarenal pelvic perfusion revealed that renal tubules began to exhibit contrast agent reflux when IPP exceeded 34 mmHg during the MPCNL procedure. There was a positive correlation between renal tubule contrast agent reflux and IPP (P < 0.05). Intravenous CEUS of renal cortical blood flow demonstrated that both intrarenal pelvic perfusion time and IPP during MPCNL significantly affected renal cortical blood perfusion. Intrarenal pelvic perfusion time and pressure were negatively correlated with contrast agent peak intensity (PI) and area under the curve (AUC) (P < 0.05). Longer intrarenal pelvic perfusion times and higher pressures resulted in decreased renal cortical blood perfusion. This study directly confirmed through dynamic CEUS and real-time IPP monitoring that an increase in IPP above the threshold of approximately 34 mmHg during MPCNL in patients leads to reflux through the renal tubules and a significant decrease in renal cortical blood perfusion. The safe upper limit for intrarenal pelvic perfusion pressure during MPCNL is approximately 34 mmHg.

Prediction of microvascular invasion in hepatocellular carcinoma with conventional ultrasound, Sonazoid-enhanced ultrasound, and biochemical indicator: a multicenter study

PurposeTo develop and validate a preoperative prediction model based on multimodal ultrasound and biochemical indicator for identifying microvascular invasion (MVI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm.MethodsFrom May 2022 to November 2023, a total of 318 patients with pathologically confirmed single HCC ≤ 5 cm from three institutions were enrolled. All of them underwent preoperative biochemical, conventional ultrasound (US), and contrast-enhanced ultrasound (CEUS) (Sonazoid, 0.6 mL, bolus injection) examinations. Univariate and multivariate logistic regression analyses on clinical information, biochemical indicator, and US imaging features were performed in the training set to seek independent predictors for MVI-positive. The models were constructed and evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis in both validation and test sets. Subgroup analyses in patients with different liver background and tumor sizes were conducted to further investigate the model’s performance.ResultsLogistic regression analyses showed that obscure tumor boundary in B-mode US, intra-tumoral artery in pulsed-wave Doppler US, complete Kupffer-phase agent clearance in Sonazoid-CEUS, and biomedical indicator PIVKA-II were independently correlated with MVI-positive. The combined model comprising all predictors showed the highest AUC, which were 0.937 and 0.893 in the validation and test sets. Good calibration and prominent net benefit were achieved in both sets. No significant difference was found in subgroup analyses.ConclusionsThe combination of biochemical indicator, conventional US, and Sonazoid-CEUS features could help preoperative MVI prediction in patients with a single HCC ≤ 5 cm.Critical relevance statementInvestigation of imaging features in conventional US, Sonazoid-CEUS, and biochemical indicators showed a significant relation with MVI-positivity in patients with a single HCC ≤ 5 cm, allowing the construction of a model for preoperative prediction of MVI status to help treatment decision making.Key PointsMVI status is important for patients with a single HCC ≤ 5 cm.The model based on conventional US, Sonazoid-CEUS and PIVKA-II performs best for MVI prediction.The combined model has potential for preoperative prediction of MVI status.Graphical

Transcranial doppler to detect high-risk PFO and predict decompression illness in divers

Abstract Background It has not yet been clearly demonstrated whether it is feasible to diagnose patent foramen ovale (PFO) using transcranial doppler (TCD) and to use it in strategies to prevent decompression illness (DCI) in self-contained breathing apparatus (SCUBA) divers. Purpose DIVER-PFO study confirmed that high-risk PFO is associated with an increased risk of DCI in SCUBA divers. In this prespecified post-hoc analysis, we aimed to prospectively evaluate the accuracy of TCD to diagnose high-risk PFO and to predict the occurrence of DCI. Methods Eighty-two consecutive divers (mean age; 41 years, male 80.5%) underwent transesophageal echocardiogram (TEE) and TCD with a saline bubble test to determine the presence of PFO and were subsequently divided into high-risk and low-risk groups by TEE findings. Divers in the high-risk PFO group included those with the following conditions: PFO with atrial septal aneurysm, hypermobility, PFO size ≥2 mm, or right to left shunt at resting state. The enrolled divers were then followed-up using a self-reported questionnaire through e-mail or telephone interview for 3 years, while they were blinded to their PFO status. The primary endpoint of the study was PFO-related DCI, comprising cases of cutaneous or neurologic DCI, DCI symptoms requiring hyperbaric chamber therapy, DCI symptoms within 30 minutes after surfacing, or unexplained death occurring within 2 weeks after diving. Results PFO was detected in 47 (57.3%) and 59 (72.0%) divers by TCD and TEE, respectively. Diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of TCD were 68.3%, 67.8%, 69.6% 85.1%, and 45.7% for the diagnosis of PFO, and 65.9%, 82.8%, 56.6%, 51.1% and 85.7% for the diagnosis of high-risk PFO, respectively. PFO-related DCI occurred in 9 divers in the PFO group (PFO vs non-PFO: 6.4 vs 0.7 incidences per 10,000 person dives; p=0.03) during a mean follow-up of 25.6 months. Integrated time-dependent Area Under the Curves for TCD and TEE to predict DCI occurrence using Cox’s proportional hazards regression model were 0.714 and 0.675, respectively. Conclusions TCD was moderately accurate to diagnose high-risk PFO in divers. However, it predicted DCI as much as TEE.Study flowIncidence of DCI in the PFO vs No PFO

Continuous transcranial ultrasound in large vessel stroke: Image guidance for high-intensity focused sonothrombolysis.

Sonothrombolysis is a potential adjunctive therapy for large vessel occlusion (LVO) stroke. Bedside ultrasound image-guided high-intensity focused ultrasound (HIFU) therapy could deliver higher energy therapeutic ultrasound to the thrombus with higher precision than what was previously accomplished in human trials. The aim is to test the feasibility of diagnostic transcranial contrast-enhanced ultrasound (CEUS) to image the occlusion site and continuously maintain the guidance image on-target for a sufficient exposure time for HIFU to be effective during LVO stroke evaluation and treatment. This prospective, single center, observational cohort study included adult patients, presenting within 6 hours of stroke symptom onset, with LVO identified on computed tomography angiography (CTA). A hand-held CEUS imaging study was initiated following CTA and lasted up to 30 minutes. The primary outcome is the proportion of patients where a guidance CEUS image of the occlusion was achieved. A CEUS image of the occluded artery was obtained in 32/35 of the included patients. The median total imaging time was 23 minutes (interquartile range 15-30). Patients undergoing thrombectomy had a lower total imaging time (17 vs. 29.5 minutes, p=.002). When imaging was successful, on-target image was maintained for only 58% (standard deviation 23.8%) of total imaging time. No complications related to CEUS were observed. This feasibility study explored the use of diagnostic transcranial CEUS for continuous imaging of occlusion sites in LVO strokes. Challenges in maintaining target image during HIFU were identified, highlighting the need for technical advances for clinical application.

Cross-institutional evaluation of deep learning and radiomics models in predicting microvascular invasion in hepatocellular carcinoma: validity, robustness, and ultrasound modality efficacy comparison

PurposeTo conduct a head-to-head comparison between deep learning (DL) and radiomics models across institutions for predicting microvascular invasion (MVI) in hepatocellular carcinoma (HCC) and to investigate the model robustness and generalizability through rigorous internal and external validation.MethodsThis retrospective study included 2304 preoperative images of 576 HCC lesions from two centers, with MVI status determined by postoperative histopathology. We developed DL and radiomics models for predicting the presence of MVI using B-mode ultrasound, contrast-enhanced ultrasound (CEUS) at the arterial, portal, and delayed phases, and a combined modality (B + CEUS). For radiomics, we constructed models with enlarged vs. original regions of interest (ROIs). A cross-validation approach was performed by training models on one center’s dataset and validating the other, and vice versa. This allowed assessment of the validity of different ultrasound modalities and the cross-center robustness of the models. The optimal model combined with alpha-fetoprotein (AFP) was also validated. The head-to-head comparison was based on the area under the receiver operating characteristic curve (AUC).ResultsThirteen DL models and 25 radiomics models using different ultrasound modalities were constructed and compared. B + CEUS was the optimal modality for both DL and radiomics models. The DL model achieved AUCs of 0.802–0.818 internally and 0.667–0.688 externally across the two centers, whereas radiomics achieved AUCs of 0.749–0.869 internally and 0.646–0.697 externally. The radiomics models showed overall improvement with enlarged ROIs (P < 0.05 for both CEUS and B + CEUS modalities). The DL models showed good cross-institutional robustness (P > 0.05 for all modalities, 1.6–2.1% differences in AUC for the optimal modality), whereas the radiomics models had relatively limited robustness across the two centers (12% drop-off in AUC for the optimal modality). Adding AFP improved the DL models (P < 0.05 externally) and well maintained the robustness, but did not benefit the radiomics model (P > 0.05).ConclusionCross-institutional validation indicated that DL demonstrated better robustness than radiomics for preoperative MVI prediction in patients with HCC, representing a promising solution to non-standardized ultrasound examination procedures.

B-Flow and Contrast-Enhanced Ultrasound (CEUS) Features of Subcutaneous Masses and Nodular Lesions in Dogs.

Subcutaneous lesions in dogs are common in clinical practice. This prospective clinical study aims to compare B-flow and CEUS for the characterization of subcutaneous lesions evaluating their usefulness to distinguish benign subcutaneous lesions from malignant ones. Dogs were enrolled and ultrasound cine-loops were achieved in B-mode, Colour Doppler, Power Doppler, B-flow and CEUS. Lesions vascularisation highlighted through B-flow and CEUS were classified into five patterns: P1, absence of contrast uptake; P2, enhancement only in the peripheral area of the lesion; P3, thin (<2 mm) and few vessels (<5/field); P4, thicker (>2 mm) and more numerous vessels (>5/field); P5 enhancement with a reticular aspect and both thick and thin bands inside. Patterns highlighted with B-flow and CEUS were compared to a histological diagnosis of subcutaneous lesions. A total of 24 dogs and 30 subcutaneous nodules were included and divided into three groups: 3 non-neoplastic, 16 benign tumours and 11 malignant tumours. There was a statistically significant difference for B-flow and CEUS to differentiate benign tumours from malignant tumours. B-flow and CEUS had an excellent agreement. B-flow and CEUS displayed similar ability to evaluate different patterns and could be helpful in the evaluation of subcutaneous nodules.

Ultrasound protein-copolymer microbubble library engineering through poly(vinylpyrrolidone-co-acrylic acid) structure

HypothesisWhile albumin-coated microbubbles are routine contrast agents for ultrasound imaging, their short duration of contrast enhancement limits their use, yet can be improved by incorporating protein-copolymer hybrids into microbubble shells. The incorporation of N-vinyl-2-pyrrolidone and acrylic acid copolymer (P(VP–AA)) has been shown to enhance the performance of bovine serum albumin (BSA)-coated microbubbles. However, the impact of the copolymer structural properties on key microbubble characteristics (i.e., concentration, mean diameter and acoustic response) remains poorly understood. Therefore, we hypothesize that the copolymer structure affects its capacity to form micelle-like nanoaggregates, protein-copolymer hybrids, and microbubble shells, ultimately influencing the physicochemical and acoustic properties of the microbubbles. ExperimentsHere we evaluate the production and performance of BSA@P(VP–AA) microbubbles synthesized using a series of P(VP–AA) copolymers with –C8H17 and –C18H37 end groups and molecular weight cutoffs between 3.5 and 15 kDa. Both simulation and experimental data demonstrate that interactions between BSA and the copolymers significantly influence the performance of the resulting microbubbles across the library of 60 formulations. FindingsThe introduction of –C8H17 terminated copolymers into microbubble shells resulted in up to 200-fold higher concentration, 7-fold greater acoustic response, and 5-fold longer ultrasound contrast enhancement compared to plain BSA microbubbles. The enhanced acoustic performance was sustained during in vivo cardiac ultrasound imaging, without altering liver accumulation after copolymer introduction. These findings underscore how optimizing copolymer structure (specifically the terminal end group and molecular weight) can tailor the formation and performance of protein-copolymer-coated microbubbles, offering valuable insights for designing ultrasound contrast agents.

Ring-Enhancement on CEUS: Is it Useful in the Differential Diagnosis of Solid Thyroid Nodules?

To investigate the efficiency of contrast-enhanced ultrasound (CEUS) features, particularly ring-enhancement patterns, in the differential diagnosis of thyroid nodules. 302 nodules with CEUS ring-enhancement were retrospectively enrolled, including 135 benign and 167 malignant ones. The ring-enhancement patterns were classified into regular and irregular hyper- or hypo-ring enhancement. Comparative analyses of ultrasound (US) and CEUS features between benign and malignant nodules were performed. The diagnostic performances of the ring-enhancement patterns and Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) were compared in nodules with different sizes. Irregular hypo-ring enhancement was much more common in malignancies than that in benign ones, and it was an independent predictor for thyroid malignant nodules. With irregular hypo-ring enhancement as the diagnostic criteria for malignant nodules, the specificity was higher than that of C-TIRADS (85.2% vs. 75.6%, p = .037) while the AUC was comparable (0.845 vs. 0.803, p = .136) in all nodules. When the nodule size was taken into account, the specificity and AUC were both significantly higher than those of C-TIRADS (92.8% vs. 81.1%, p = .021; 0.907 vs. 0.823, p = .026) in nodules ≥10 mm, which can decrease the unnecessary FNA rate. Irregular hypo-ring enhancement was a valuable CEUS feature for the differential diagnosis of thyroid nodules, especially in nodules ≥10 mm.

A Comprehensive and Repeatable Contrast-Enhanced Ultrasound Quantification Approach for Clinical Evaluations of Tumor Blood Flow.

The aim of this study is to define a comprehensive and repeatable contrast-enhanced ultrasound (CEUS) imaging protocol and analysis method to quantitatively assess lesional blood flow. Easily repeatable CEUS evaluations are essential for longitudinal treatment monitoring. The quantification method described here aims to provide a structure for future clinical studies. This retrospective analysis study included liver CEUS studies in 80 patients, 40 of which contained lesions (primarily hepatocellular carcinoma, n = 28). Each patient was given at least 2 injections of a microbubble contrast agent, and 60-second continuous loops were acquired for each injection to enable evaluation of repeatability. For each bolus injection, 1.2 mL of contrast was delivered, whereas continuous, stationary scanning was performed. Automated respiratory gating and motion compensation algorithms dealt with breathing motion. Similar in size regions of interest were drawn around the lesion and liver parenchyma, and time-intensity curves (TICs) with linearized image data were generated. Four bolus transit parameters, rise time (RT), mean transit time (MTT), peak intensity (PI), and area under the curve (AUC), were extracted either directly from the actual TIC data or from a lognormal distribution curve fitted to the TIC. Interinjection repeatability for each parameter was evaluated with coefficient of variation. A 95% confidence interval was calculated for all fitted lognormal distribution curve coefficient of determination (R2) values, which serves as a data quality metric. One-sample t tests were performed between values obtained from injection pairs and between the fitted lognormal distribution curve and direct extraction from the TIC calculation methods to establish there were no significant differences between injections and measurement precision, respectively. Average interinjection coefficient of variation with both the fitted curve and direct calculation of RT and MTT was less than 21%, whereas PI and AUC were less than 40% for lesion and parenchyma regions of interest. The 95% confidence interval for the R2 value of all fitted lognormal curves was [0.95, 0.96]. The 1-sample t test for interinjection value difference showed no significant differences, indicating there was no relationship between the order of the repeated bolus injections and the resulting parameters. The 1-sample t test between the values from the fitted lognormal distribution curve and the direct extraction from the TIC calculation found no statistically significant differences (α = 0.05) for all perfusion-related parameters except lesion and parenchyma PI and lesion MTT. The scanning protocol and analysis method outlined and validated in this study provide easily repeatable quantitative evaluations of lesional blood flow with bolus transit parameters in CEUS data that were not available before. With vital features such as probe stabilization ideally performed with an articulated arm and an automated respiratory gating algorithm, we were able to achieve interinjection repeatability of blood flow parameters that are comparable or surpass levels currently established for clinical 2D CEUS scans. Similar values and interinjection repeatability were achieved between calculations from a fitted curve or directly from the data. This demonstrated not only the strength of the protocol to generate TICs with minimal noise, but also suggests that curve fitting might be avoided for a more standardized approach. Utilizing the imaging protocol and analysis method defined in this study, we aim for this methodology to potentially assist clinicians to assess true perfusion changes for treatment monitoring with CEUS in longitudinal studies.

The value of postoperative contrast-enhanced ultrasound parameters in lymph node metastasis, tumor node metastasis, and treatment response evaluation of resected hepatocellular carcinoma.

To explore the application value of postoperative contrast-enhanced ultrasound (CEUS) parameters for lymph node metastasis (LNM), tumor, node, metastasis staging, and treatment response evaluation of resected hepatocellular carcinoma (HCC). We retrospectively analyzed 100 patients with liver cancer who underwent liver CEUS at our hospital between October 2020 and October 2022. The patient's LNM, pathological staging, and therapeutic effects were recorded based on the histopathological results. CEUS parameters were analyzed and compared CEUS parameters between different lymph node metastases, pathological stages, and therapeutic effects. Twenty-three patients experienced LNM, 77 patients did not experience LNM; and the rise time (RT), peak intensity (PI), and area under the curve (AUC) of the metastatic group were significantly smaller than those of the nonmetastatic group (P < .05). 44 cases were classified into groups I to II by pathological staging, and 56 cases were classified into groups III to IV. The RT, PI, and AUC of groups III to IV were significantly lower than those of groups I-II (P < .05). Seventy-nine cases were complete necrosis, 21 cases were residual or recurrent; The RT, PI, and AUC of the residual or recurrent group were significantly lower than those of the complete necrosis group (P < .05). The receiver operating characteristic curve shows that RT, PI, and AUC have a certain value in evaluating LNM, pathological staging, and treatment response of HCC, and the combined evaluation/evaluation value of these 3 factors is relatively high. The postoperative CEUS parameters RT, PI, and AUC can be used for LNM, pathological staging evaluation, and treatment response evaluation of HCC. Moreover, the combination of the 3 parameters is feasible and valuable in evaluating LNM, tumor, node, metastasis staging, and treatment response of HCC.

Renal medullary perfusion differs from that in renal cortex in patients with sepsis associated acute kidney injury and correlates with renal function prognosis: A prospective cohort study.

Renal perfusion status remains poorly studied at the bedside during sepsis associated acute kidney injury (AKI). The aim of the study is to examine renal cortical and medullary perfusion using renal contrast enhanced ultrasound (CEUS) in septic patients. In this single-center, prospective longitudinal study, septic patients were enrolled. Renal ultrasonography was performed within 24 hours of ICU admission (D1), then repeated at D3, D5 and D7. Each measurement consisted of three destruction replenishment sequences that were recorded for delayed analysis with dedicated software (Vuebox). Renal cortex and medulla perfusion were quantified by measuring time to peak (TTP). Receiver operating characteristic (ROC) analysis was used to evaluate 28-day renal prognosis. The study included 149 septic patients, including 70 non-AKI patients and 79 AKI patients. Both renal cortical and medullary TTP was longer in the AKI group than in the non-AKI group. The difference of TTP between renal cortex and medulla in AKI group was higher than that in the non-AKI group (p = 0.000). Medullary TTP on day 3 had the best performance in predicting the prognosis of 28-day renal function (AUC 0.673, 95% confidence interval 0.528-0.818, p = 0.024), and its cut-off value was 45 s with a sensitivity 52.2% and a specificity of 82.1%. Cortical TTP on day 3 also had the performance in predicting the prognosis of 28-day renal function (AUC 0.657, 95% confidence interval 0.514-0.800, p = 0.039), and its cut-off value was 33 s with a sensitivity 78.3% and a specificity of 55.0%. Renal medullary perfusion alterations differ from those in cortex, with the medulla is worse. Simultaneous and dynamic assessment of cortical and medullary microcirculatory flow alterations necessary. TTP on day 3, especially medullary TTP, seems to be a relatively stable and useful indicator, which correlates with 28-day renal function prognosis in septic patients. Early correction of renal cortical and medullary perfusion alterations reduces the incidence of adverse renal events.

Enhanced Diagnostic Imaging: Arrival-Time Parametric Imaging in Contrast-Enhanced Ultrasound for Multi-Organ Assessment

Enhanced Diagnostic Imaging: Arrival-Time Parametric Imaging in Contrast-Enhanced Ultrasound for Multi-Organ Assessment

Exploring the potential therapeutic benefits of 7-methoxy coumarin for neuropathy pain: an in vivo, in vitro, and in silico approach.

7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods. Vincristine (0.1mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitrostudies on phospholipase inhibition by 7-MC showed an IC50 of 27.08µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin. The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.

Detecting bubbles via FDR and FNR based on calibrated p-values

Detecting bubbles in asset prices is still an open question that has attracted considerable attention in recent years. This paper improves the bubble detection and dating approaches developed in recent years by Phillips and co-authors, proposing to assess the plausibility of its outcomes via the false discovery rate (FDR) and the false non-discovery rate (FNR) based on calibrated p-values. Calibrating p-values of unit root tests, applied sequentially to detect bubbles, allows recovery of their super-uniformity property, which is crucial for a valid implementation of the inferential procedure. The paper also develops original self-calibrated versions of both FDR and FNR for the specific problem of bubble testing. Calibrated p-values are implemented in an online false discovery-based approach which monitors bubbles in real time. The effectiveness of the proposed methods is investigated via a simulation study and an empirical application.

Construction of vulnerable plaque prediction model based on multimodal vascular ultrasound parameters and clinical risk factors

The rupture of vulnerable plaque (VP) are significant pathogenic factors leading to cardiovascular and cerebrovascular diseases. This study aims to construct a vulnerable plaque prediction model (VPPM) by combining multimodal vascular ultrasound parameters and clinical risk factors, and to validate it. A total of 196 atherosclerotic patients who underwent carotid endarterectomy (CEA) from January 2017 to December 2023 were collected and divided into a modeling group (n = 137) and a validation group (n = 59). Clinical information including: hypertension, diabetes, smoking history, and body mass index (BMI) was included in the analysis. All patients underwent carotid ultrasound and contrast-enhanced ultrasound (CEUS) examination after admission, with main ultrasound parameters including thickness, echogenicity types, stenosis degree, and CEUS neovascularization grading of plaques. Independent risk factors for VP in CEA patients were screened through binary Logistic regression analysis, and a prediction model was established along with a nomogram. The calibration curve, receiver-operating characteristic curve (ROC), and decision curve analysis (DCA) were employed to assess the calibration, diagnostic efficacy, and clinical utility of the VPPM model. There were no significant statistical differences in multimodal vascular ultrasound parameters and clinical risk factors between the modeling and validation groups (P > 0.05). Binary Logistic regression analysis identified plaque thickness, echo type, CEUS neovascularization grading, BMI, and smoking history as 5 variables entering the prediction model. The VPPM model showed good diagnostic efficacy, with an area under the ROC curve of 0.959 (95% CI 0.915–0.999). Using the nomogram with a VPPM risk assessment score of 135.42 as the diagnostic cutoff value in the modeling group, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and Youden index were 88.1%, 94.1%, 14.98, 0.126, and 82.2%, respectively. In the DCA curve, the VPPM model curve was significantly better than two extreme lines, indicating good clinical utility. The VPPM model constructed by integrating multimodal ultrasound parameters and clinical key risk factors has high diagnostic efficacy and is expected to be an auxiliary tool for clinical diagnosis of vulnerable plaques.

Right-to-left-shunts in patients scheduled for neurosurgical intervention in semi-sitting position – a literature review based on two case scenarios

BackgroundNeurosurgery performed in the semi-sitting position provides advantages for certain procedures. However, this approach is associated with potential complications, particularly venous air embolism. Due to typically negative venous pressure at the wound site, air can be drawn into the veins. This risk is especially high in patients presenting with an intra- or extracardiac right-to-left-shunt. Transoesophageal echocardiography can be used to detect a patent foramen ovale or other possible pulmonary-systemic shunt before placing the patient in the sitting position.Case presentationIn this report, we present two young patients undergoing scheduled microsurgical vestibular schwannoma removal in a semi-sitting position who were diagnosed with congenital heart defects during routine perioperative assessment to detect possible intracardiac right-to-left shunts, using pre- and intraoperative transesophageal echocardiography (TEE) and additionally conducting an agitated saline bubble study under Valsalva manoeuvre. Patient A was diagnosed with a persistent left superior vena cava and Patient B with an unroofed coronary sinus (UCS). These findings confronted the anesthesiological and surgical teams with difficult individual decisions regarding further perioperative management.ConclusionsPerioperative transesophageal echocardiography is a diagnostic tool to both detect intraoperative position-related air embolisms and to rule out intracardiac right-to-left shunts, e.g. a patent foramen ovale, in order to decide for or against a (semi-)sitting position. Depending on the surgical circumstances a semi-sitting positioning of patients presenting with an intracardiac right-to-left-shunt, e.g. a PFO, can be feasible in individual cases if there is an implemented therapeutic algorithm to immediately terminate significant venous air entry. However, since certain other intra- or extracardiac right-to-left-shunts, such as here presented PLSVC or UCS, are rare, there is no definitive way of estimating the amount of entered air through detected shunts or anomalous vessels. Therefore, it is recommended to avoid a (semi-)sitting position in favour of a lateral or prone position for a patient undergoing intracranial surgery, once the perioperative TEE shows air bubbles in the left atrium or ventricle whose origins cannot be defined solely through TEE for certain in order to ensure patient safety by minimizing the risk of intraoperative paradoxical air embolisms.