Impact of Microbubble Degradation and Flow Velocity on Subharmonic-aided Pressure Estimation (SHAPE): An Experimental Investigation.

OBJECTIVE: This study aimed to investigate the impact of microbubble degradation and flow velocity on Sub-Harmonic Aided Pressure Estimation (SHAPE), and to explore the correlation between subharmonic amplitude and pressure as a single factor. METHODS: We develop an open-loop vascular phantom platform system and utilize a commercial ultrasound machine and microbubbles for subharmonic imaging. Subharmonic amplitude was measured continuously at constant pressure and flow velocity to assess the impact of microbubble degradation. Flow velocity was varied within a range of 4-14 cm/s at constant pressure to investigate its relationship to subharmonic amplitude. Furthermore, pressure was varied within a range of 10-110 mm Hg at constant flow velocity to assess its isolated effect on subharmonic amplitude. RESULTS: Under constant pressure and flow velocity, subharmonic amplitude exhibited a continuous decrease at an average rate of 0.221 dB/min, signifying ongoing microbubble degradation during the experimental procedures. Subharmonic amplitude demonstrated a positive correlation with flow velocity, with a variation ratio of 0.423 dB/(cm/s). Under controlled conditions of microbubble degradation and flow velocity, a strong negative linear correlation was observed between pressure and subharmonic amplitude across different Mechanical Index (MI) settings (all R2 > 0.90). The sensitivity of SHAPE was determined to be 0.025 dB/mmHg at an MI of 0.04. CONCLUSION: The assessment of SHAPE sensitivity is affected by microbubble degradation and flow velocity. Excluding the aforementioned influencing factors, a strong linear negative correlation between pressure and subharmonic amplitude was still evident, albeit with a sensitivity coefficient lower than previously reported values.

Identification of novel serum protein biomarkers in the context of 3P medicine for intravenous leiomyomatosis: a data-independent acquisition mass spectrometry-based proteomics study.

Background: Intravenous leiomyomatosis (IVL) is a rare endocrine-associated tumor with unique characteristics of intravascular invasion. This study aimed to identify reliable biomarkers to supervise the development or recurrence of IVL in the context of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: A total of 60 cases were recruited to detect differentially expressed proteins (DEPs) in serum samples from IVL patients. These cases included those with recurrent IVL, non-recurrent IVL, uterine myoma, and healthy individuals without uterine myoma, with 15 cases in each category. Then, weighted gene co-expression network analysis (WGCNA), lasso-penalized Cox regression analysis (Lasso), trend clustering, and a generalized linear regression model (GLM) were utilized to screen the hub proteins involved in IVL progression. Results: First, 93 differentially expressed proteins (DEPs) were determined from 2582 recognizable proteins, with 54 proteins augmented in the IVL group, and the remaining proteins declined. These proteins were enriched in the modulation of the immune environment, mainly by activating the function of B cells. After the integrated analyses mentioned above, a model based on four proteins (A0A5C2FUE5, A0A5C2GPQ1, A0A5C2GNC7, and A0A5C2GBR3) was developed to efficiently determine the potential of IVL lesions to progress. Among these featured proteins, our results demonstrated that the risk factor A0A5C2FUE5 was associated with IVL progression (OR = 2.64). Conversely, A0A5C2GPQ1, A0A5C2GNC7, and A0A5C2GBR3 might act in a protective manner and prevent disease development (OR = 0.32, 0.60, 0.53, respectively), which was further supported by the multi-class receiver operator characteristic curve analysis. Conclusion: Four hub proteins were eventually identified based on the integrated bioinformatics analyses. This study potentiates the promising application of these novel biomarkers to predict the prognosis or progression of IVL by a 3PM approach. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00338-0.

The performance of duplex ultrasonography for the assessment of renal artery stenosis in Takayasu's arteritis patients.

BACKGROUND: This study intends to analyze the hemodynamic parameters of the renal artery in patients with Takayasu's arteritis (TAK) to explore the diagnostic efficacy of duplex ultrasonography in assessing the involved renal artery in TAK patients. METHODS: One hundred fifteen TAK patients with 314 renal arteries were retrospectively analyzed, who were admitted to Peking Union Medical College Hospital between 2017 and 2022. These patients underwent both renal artery ultrasonography and angiography within a 4-week period. Specifically, the study compared seven ultrasonic parameters across groups categorized by the severity of renal artery stenosis (RAS), including noninvolvement, < 50% stenosis, 50-69% stenosis, and 70-99% stenosis. Receiver operating characteristic (ROC) curves were employed to determine the optimal threshold values for renal artery peak systolic velocity (RPSV), renal-aortic PSV ratio (RAR), and renal-interlobar PSV ratio (RIR) in order to diagnose various degrees of RAS in TAK patients. RESULTS: Statistically significant differences were observed in RAR and RIR among the four groups (all P < 0.05). However, no statistically significant differences were found in RPSV and AT between the moderate stenosis group (50-69% stenosis) and the severe stenosis group (70-99% stenosis). The discrimination of interlobar PSV (IPSV) and interlobar RI (IRI) was not significant, and IEDV did not show statistical significance among the four groups. For TAK patients, the recommended thresholds of RPSV for the diagnosis of renal artery involvement (RAI), ≥ 50% RAS, and ≥ 70% RAS were determined to be 143 cm/s, 152 cm/s, and 183 cm/s, respectively. The sensitivities, specificities, and accuracies of these thresholds were all found to be greater than 80%. Additionally, the optimal thresholds of RIR for detecting RAI, ≥ 50% RAS, and ≥ 70% RAS were determined to be 4.6, 5.6, and 6.4, respectively, with satisfactory diagnostic efficiencies. The areas under the curve (AUCs) for RPSV and RIR were calculated to be 0.908 and 0.910, respectively, for the diagnosis of ≥ 50% RAS, and 0.876 and 0.882 for the diagnosis of ≥ 70% RAS. When the aortic PSV is greater than or equal to 140 cm/s, the RAR exhibits inadequate diagnostic efficacy. Conversely, when the aortic PSV is less than 140 cm/s, a RAR value of 2.2 or higher can be employed as the diagnostic threshold for identifying RAS of 70% or greater, with a sensitivity of 84.00%, specificity of 89.93%, and an overall accuracy of 89.08%. CONCLUSION: In the present study, it has been demonstrated that RPSV and RIR possess substantial diagnostic value as ultrasonic parameters for diagnosing RAS in TAK patients. Furthermore, when assessing the diagnostic efficacy of RAR, it is crucial to consider the severity of aortic stenosis as a determining factor.

Diagnostic experience of intravenous leiomyomatosis with emphasis on conventional ultrasonography imaging: a single-center study.

Objective: Intravenous leiomyomatosis (IVL) is a rare and aggressive tumor type that has the potential to extend into the inferior vena cava (IVC) and is susceptible to be misdiagnosed and neglected. Despite its clinical significance, there is a paucity of research that has focused on the specific manifestations of IVL on ultrasonography. Therefore, this study aims to systematically analyze the specific ultrasound features of IVL and augment its diagnostic accuracy. Materials and method: Prospective inclusion was granted to patients admitted to our hospital between December 2016 and March 2021 for an IVC-occupying lesion. Multi-modal ultrasonography, encompassing gray-scale and color Doppler, was conducted. Lesions were categorized as IVL or non-IVL based on pathological or follow-up data. Two ultrasound sonographers with over 5 years of experience read and recorded ultrasound data for all lesions, which were subsequently comparatively analyzed to identify specific signs of IVL. Results: A total of 284 patients diagnosed with IVC-occupying lesions were included in the study. The lesion types comprised of IVL (n=67, 23.6%), IVC thrombus (n=135, 47.5%), tumor thrombus of renal carcinoma involving the IVC (n=35, 12.4%), tumor thrombus of liver carcinoma involving the IVC (n=24, 8.5%), leiomyosarcoma of the IVC (n=14, 4.9%), and tumor thrombus of adrenocortical adenocarcinoma (n=9, 4.1%). The presence of "sieve hole" and "multi-track" signs was observed in 20 IVL lesions under the grey-scale modality, while both signs were absent in the non-IVL group (P<0.01). The study found no statistically significant differences in the presentation of "sieve hole" and "multi-track" signs under the grey-scale and color Doppler modalities in cases of intravascular lithotripsy (IVL) (P>0.05). Using these two signs as diagnostic criteria for IVL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), miss rate, misdiagnosis rate, and accuracy were determined to be 29.9%, 100%, 100%, 82.2%, 70.1%, 0, and 83.5%, respectively (AUC ROC=0.649; 95%CI: 0.537-0.761). Conclusion: IVL exhibits distinct ultrasound presentations, including "sieve hole" and "multi-track" signs, which demonstrate high specificity and accuracy as diagnostic indicators. Furthermore, these signs are corroborated by pathological evidence and effectively distinguish IVL from other lesions occupying the IVC.

Ultrasonography and contrast-enhanced ultrasound for activity assessment in 115 patients with carotid involvement of Takayasu arteritis.

OBJECTIVES: To evaluate the efficacy of ultrasound and contrast-enhanced ultrasound (CEUS) in disease activity assessment of Takayasu arteritis (TA) with carotid involvement. METHODS: This is a cohort study of 115 patients of TA with carotid involvement. We investigated correlations between clinical data, sonographic features, and CEUS enhancement at the site most prominent lesion of each patient. Disease activity was assessed by the National Institute of Health Kerr criteria. Sonographic findings were compared with follow-up examinations. CEUS was repeated after a 3-7 months interval in 35 patients to evaluate change of CEUS enhancement after treatment. RESULTS: Extensiveness of CEUS enhancement at most prominent carotid lesions had significant correlations with disease activity by the Kerr criteria (P < .001). The specificity of extensive enhancement for indicating active disease was 95%, while sensitivity was 67%. Patients with active disease showed greater arterial wall thickness and more prominent reduction of arterial wall thickness after treatment. Most of the patients (68%) with subsided active disease after treatment featured decrease of CEUS enhancement. CONCLUSIONS: Extensiveness of enhancement by CEUS and arterial wall thickness by ultrasonography may be useful markers for initial and follow-up assessment of disease activity of TA with common carotid artery involvement.

Diagnostic value of contrast-enhanced ultrasound in intravenous leiomyomatosis: a single-center experiences.

Objective: Intravenous leiomyomatosis (IVL) is a rare disease, and few studies have focused on the diagnostic value of contrast-enhanced ultrasound (CEUS) in this condition. This study aimed to investigate the diagnostic value of CEUS in IVL and summarize the specific CEUS characteristics of IVL. Materials and Method: From December 2016 to March 2021, 93 patients admitted to our hospital with inferior vena cava (IVC) occupying lesions were prospectively enrolled and underwent detailed ultrasound multi-modality examinations, including conventional and contrast-enhanced ultrasound scans. The diagnostic value of CEUS and conventional ultrasound (CU) in IVL was compared, and the specific IVL signs were summarized. Results: Among the 93 patients with inferior vena cava mass, 67 were IVL while 26 were non-IVL. The inter-observer agreement of the two senior doctors was good, with Kappa coefficient = 0.71 (95% CI: 0.572-0.885). The area under the ROC curve of CU for IVL diagnosis was 0.652 (95% CI: 0.528-0.776), and its sensitivity, specificity, accuracy, positive predictive value, negative predictive value, missed diagnosis rate, and misdiagnosis rate were 61.1%, 69.2%, 63.4%, 83.7%, 40.9%, 38.8%, and 30.8%, respectively. The area under curve (AUC) for IVL diagnosis by CEUS was 0.807 (95% CI: 0.701-0.911), and the sensitivity, specificity, accuracy, positive predictive value, negative predictive value, missed diagnosis rate, and misdiagnosis rate were 82.0%, 84.6%, 82.8%, 93.2%, 64.7%, 15.4%, and 17.9%, respectively. In CEUS mode, "sieve hole sign" and "multi-track sign" were detected in 57 lesions, and the detected rate was higher than that of CU (https://loop.frontiersin.org/people/1014187 < 0.01). Conclusion: CEUS can better show the fine blood flow inside the IVL, which is important for IVL differential diagnosis. Moreover, CEUS can obtain more information about IVL diagnosis than CU, compensating for the shortcomings of CU in detecting more blood flow within the lesion. Thus, this technique has great significance for IVL diagnosis.

Relationship Between Serum Lipid Profiles and Carotid Intraplaque Neovascularization in a High-Stroke-Risk Population: A Cross-Sectional Study in China.

Background Evidence of the association between serum lipid profiles and intraplaque neovascularization (IPN) is still limited. We aimed to study the value of a novel Doppler method, superb microvascular imaging, in correlating serum lipid profiles and evidence of IPN in a population with a high risk of stroke. Methods and Results A community-based cross-sectional study was conducted in Beijing, China. Residents (aged ≥40 years) underwent questionnaire interviews, physical examinations, and laboratory testing in 2018 and 2019. Subjects with a high risk of stroke were then selected. Standard carotid ultrasound and carotid plaque superb microvascular imaging examinations were then performed on the high-stroke-risk participants. Logistic regression was used to evaluate the relationship between serum lipid profiles and carotid plaque IPN. Overall, a total of 250 individuals (mean age, 67.20±8.12 years; 66.4% men) met the study inclusion criteria. Superb microvascular imaging revealed carotid plaque IPN in 96 subjects (38.4%). Subjects with IPN were more likely to be current smokers (34.0% versus 46.9%, P=0.046), and their identified carotid plaques were much thicker (2.35±0.63 mm versus 2.75±0.80 mm, P=0.001). Serum lipids, including total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were positively associated with the presence of IPN (4.33±1.00 mmol/L versus 4.79±1.12 mmol/L, P=0.001; 2.96±0.92 mmol/L versus 3.40±1.01 mmol/L, P=0.001; 2.18±0.76 mmol/L versus 2.46±0.80 mmol/L, P=0.005, respectively), and after adjustment for other confounders, the positive relationship remained significant. Furthermore, non-high-density lipoprotein cholesterol (odds ratio, 2.62 [95% CI, 1.35-5.06]) was significantly associated with the presence of carotid plaque IPN even after adjusting for low-density lipoprotein cholesterol. Conclusions Total cholesterol, non-high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were positively associated with the presence of carotid IPN in a Chinese high-stroke-risk population. Further prospective studies should be conducted to better understand how much finding IPN adds to current stroke prediction tools.

Identification of Novel Serum Metabolic Biomarkers as Indicators in the Progression of Intravenous Leiomyomatosis: A High Performance Liquid Chromatography-Tandem Mass Spectrometry-Based Study.

BACKGROUND: Intravenous leiomyomatosis (IVL) is a rare estrogen-dependent neoplasm. However, identifiable and reliable biomarkers are still not available for clinical application, especially for the diagnosis and prognosis of the disease. METHODS: In the present study, 30 patients with IVL and 30 healthy controls were recruited. Serum samples were isolated from these participants for further high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis to study metabolomics alterations and identify differentially expressed metabolites based on orthogonal partial least-squares discriminant analysis (OPLS-DA). Subsequently, lasso regression analysis and a generalized linear regression model were applied to screen out hub metabolites associated with the progression of IVL. RESULTS: First, 16 metabolites in the positive ion mode were determined from the 240 identifiable metabolites at the superclass level, with ten metabolites upregulated in the IVL group and the remaining six metabolites downregulated. Our data further proved that four metabolites [hypoxanthine, acetylcarnitine, glycerophosphocholine, and hydrocortisone (cortisol)] were closely related to the oncogenesis of IVL. Hypoxanthine and glycerophosphocholine might function as protective factors in the development of IVL (OR = 0.19 or 0.02, respectively). Nevertheless, acetylcarnitine and hydrocortisone (cortisol), especially the former, might serve as risk indicators for the disease to promote the development or recurrence of IVL (OR = 18.16 or 2.10, respectively). The predictive accuracy of these hub metabolites was further validated by the multi-class receiver operator characteristic curve analysis (ROC) with the Scikit-learn algorithms. CONCLUSION: Four hub metabolites were finally determined via comprehensive bioinformatics analysis, and these substances could potentially serve as novel biomarkers in predicting the prognosis or progression of IVL.

A Comprehensive Analysis of the Downregulation of miRNA-1827 and Its Prognostic Significance by Targeting SPTBN2 and BCL2L1 in Ovarian Cancer.

Background: Previous studies demonstrated that miRNA-1827 could repress various cancers on proliferation, angiogenesis, and metastasis. However, little attention has been paid to its role in ovarian cancer as a novel biomarker or intervention target, especially its clinical significance and underlying regulatory network. Methods: A meta-analysis of six microarrays was adopted here to determine the expression trend of miRNA-1827, and was further validated by gene expression profile data and cellular experiments. We explored the functional annotations through enrichment analysis for the differentially expressed genes targeted by miRNA-1827. Subsequently, we identified two hub genes, SPTBN2 and BCL2L1, based on interaction analysis using two online archive tools, miRWALK (it consolidates the resources of 12 miRNA-focused servers) and Gene Expression Profiling Interactive Analysis (GEPIA). Finally, we validated their characteristics and clinical significance in ovarian cancer. Results: The comprehensive meta-analysis revealed that miRNA-1827 was markedly downregulated in clinical and cellular specimens. Transfection of the miRNA-1827 mimic could significantly inhibit cellular proliferation. Concerning its target genes, they were involved in diverse biological processes related to tumorigenesis, such as cell proliferation, migration, and the apoptosis signaling pathway. Moreover, interaction analysis proved that two hub genes, SPTBN2 and BCL2L1, were highly associated with poor prognosis in ovarian cancer. Conclusion: These integrated bioinformatic analyses indicated that miRNA-1827 was dramatically downregulated in ovarian cancer as a tumor suppressor. The upregulation of its downstream modulators, SPTBN2 and BCL2L1, was associated with an unfavorable prognosis. Thus, the present study has identified miRNA-1827 as a potential intervention target for ovarian cancer based on our bioinformatic analysis processes.

Impact of different conditions of breath-holding on the results of renal artery Doppler sonography: A pilot study.

PURPOSE: To investigate the impact of different breath-holding conditions on the results of renal artery Doppler ultrasonography (RADS). METHODS: In 45 healthy volunteers, we performed RADS examination during breath-holding while breathing naturally and after a deep inspiration. We measured and compared peak systolic flow velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) of the right (RRA) and left (LRA) renal artery, and PSV, EDV, RI, acceleration time and acceleration index (AI) of the right and left interlobar arteries. RESULTS: The RRA and LRA PSV were, respectively, 76 ± 13 cm/s and 77 ± 15 cm/s under natural breathing and 93 ± 18 cm/s and 89 ± 24 cm/s after deep inspiration (P ≤ .001). The RRA and LRA EDV were also greater at deep inspiration (P < .001 and P = .019, respectively). There was no significant difference in RRA or LRA RI. The PSV, RI, and AI of the right and left interlobar arteries were greater after deep inspiration (P ≤ .001), without difference in AI. CONCLUSION: Breath-holding conditions may influence Doppler measurements of renal artery flow velocity and should be reported and taken into account.

Contrast-enhanced ultrasound for evaluating arteritis activity in Takayasu arteritis patients.

INTRODUCTION: Contrast-enhanced ultrasound (CEUS) was recently used to evaluate vascularization within the carotid artery wall, and this process of vascularization was correlated with arteritis activity. We aimed to use CEUS to evaluate disease activity in Takayasu arteritis (TAK) patients. METHOD: We used CEUS to analyze 28 consecutive TAK patients. Disease activity was assessed according to the NIH criteria. We measured CEUS grades and assessed the correlation between contrast features and disease activity. RESULTS: Higher erythrocyte sedimentation rates (ESRs) were found (35 ± 28.7 vs. 13 ± 7.4 mm/h, p < 0.01), and CEUS carotid wall enhancement was more frequently (100% vs. 36.6%, p < 0.01) seen in TAK patients in the active phase than in those in the inactive phase. With increasing CEUS grades, both the artery wall thickness and ESR increased, and patients were more likely to be in the active phase (0 in grade 0, 42.9% in grade 1, and 75% in grade 2). Receiver operating characteristic (ROC) curve analysis showed that CEUS had an area under the ROC curve (AUC) of 0.872 (95% CI 0.785-0.959, p < 0.01), demonstrating good diagnostic accuracy. CONCLUSIONS: Higher CEUS grades reliably identify patients with active TAK.Key Points• No CEUS vascularization is obviously relative with the inactive disease of TAK patients.• Obvious CEUS vascularization is obviously relative with the active disease of TAK patients.

Assessment of Carotid Intraplaque Neovascularization Using Superb Microvascular Imaging in High Risk of Stroke Individuals: Results From a Community-Based Study.

Background: Improved stroke risk stratification may improve stroke prevention. We aimed to study the value of a novel Doppler method, superb microvascular imaging (SMI), in correlating plaque thickness and evidence of intra-plaque neovascularization with a history stroke and TIA involving any cerebrovascular territory among community residents considered at high stroke risk. Methods: We selected residents aged at least 40 years from the Donghuashi community in China who had at least three stroke risk factors (including a history of stroke or TIA) and carotid plaque thickness of at least 1.5 mm (but without heavy calcification) and no history of carotid endarterectomy or stenting. In this cross-sectional study, each subject underwent carotid plaque examination with standard ultrasound and SMI. SMI evidence of plaque neovascularization was categorized as none or mild (Grade 1) or moderate or marked (Grade 2) and correlated with past history of stroke or TIA. Results: A total of 131 individuals (mean age 69 ± 8 years, 63% male) met the study inclusion criteria. SMI revealed no or mild neovascularization in 74 subjects (56.5%) and moderate or marked neovascularization in 57 subjects (43.5%). Subjects with moderate or marked neovascularization were more likely to have a history of any territory stroke or TIA, 43.9 vs. 17.6% (P = 0.001). Multivariate logistic regression analyses showed a thicker plaque (odds ratio: 2.272, 95% CI: 1.351-3.822, P = 0.002) and a history of stroke or TIA (odds ratio: 4.017, 95% CI: 1.719-9.387, P = 0.001) significantly correlated with evidence of moderate to marked intra-plaque neovascularization. Conclusions: Moderate to marked intraplaque neovascularization detected by SMI was more likely in subjects with a history of any territory stroke or TIA or thicker plaque. This indicates a potential new role of SMI in stratifying future risk of stroke or other arterial disease complications.

Ultrasound appearance of intravenous leiomyomatosis: A case report.

RATIONALE: Intravenous leiomyomatosis (IVL) is a rare benign smooth muscle tumor that can develop from the pelvic or uterine veins and spread into the central veins and heart. Here, we report a case of recurrent IVL in a 48-year-old woman. To the best of our knowledge, this is the first case report of IVL that describes the characteristic ultrasound features of the tumor, including the rainbow sign. PATIENT CONCERNS: A 48-year-old woman developed a solid-cystic lesion in the inferior vena cava (IVC) 3 years after undergoing a right heart tumor resection and 5 years after undergoing hysterectomy. DIAGNOSES: Physical examination was unremarkable. However, ultrasonography showed a solid-cystic lesion in the IVC, and a diagnosis of IVL was made. INTERVENTIONS: The patient underwent complete surgical removal of the tumor by a multidisciplinary team. The tumor was resected successfully. OUTCOMES: Pathological examination confirmed that the IVC tumor thrombus was consistent with IVL. During follow-up, there were no signs of local or distant recurrence. LESSONS: The preoperative diagnosis of IVL is difficult, and the tumor is usually misdiagnosed as a thrombus or right atrial myxoma. A thorough understanding of the characteristic imaging features of IVL is essential for an accurate preoperative diagnosis. The lesion in our patient showed multiple tracts, a honeycomb appearance, and vividly colorful blood flow that resembled a rainbow, which we termed the rainbow sign.