Contrast-enhanced Ultrasound Research Articles

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.

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.

Value of Contrast-Enhanced Ultrasound in the Diagnosis of Clear Cell Renal Cell Carcinoma: A Meta-Analysis.

This meta-analysis aims to evaluate the accuracy of contrast-enhanced ultrasound (CEUS) in diagnosing clear cell renal cell carcinoma (ccRCC). Literature published in five databases was searched. Twelve studies were included. The pooled results showed sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CEUS were 79% (95% CI: 75%-83%), 84% (95% CI: 80%-88%), 4.97 (95% CI: 3.86-6.39), 0.24 (95% CI: 0.20-0.30), and 20.32 (95% CI: 13.84-29.84), respectively. The area under the summary receiver operating characteristic curve was 0.86. In conclusion, CEUS demonstrates high sensitivity and specificity in diagnosing ccRCC, showing good diagnostic accuracy.

Is Contrast-Enhanced Ultrasonography a New, Reliable Tool for Early-Graft-versus-Host Disease Diagnosis?

Acute gastrointestinal graft-versus-host disease (GI aGVHD) is a significant and life-threatening complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). Early diagnosis of GI aGVHD is crucial for improving patient outcomes, but it remains a challenge due to the condition's nonspecific symptoms and the reliance on invasive diagnostic methods, such as biopsies and endoscopic procedures. In recent years, interest in non-invasive diagnostic techniques for graft-versus-host disease has increased, with contrast-enhanced ultrasound (CEUS) being one of them. For this reason, we aimed to examine the potential of ultrasound as a non-invasive, safe, and cost-effective alternative for the early detection and monitoring of GI aGVHD in this review. Our narrative review aims to describe the use of multimodal US that includes conventional US (B-mode and Doppler US) and advanced ultrasound techniques such as CEUS and CRTE for the non-invasive diagnosis of GI GVHD. We browsed several databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search spanned 2000 to the present, focusing on articles written in English that reviewed the use of these imaging techniques in the context of GI GVHD. Following our research, we noticed that CEUS offers several advantages, including the real-time visualization of the gastrointestinal wall, assessment of blood flow, and detailed microvascular analysis-all achieved without the use of ionizing radiation. This feature makes CEUS an appealing option for repeated assessments, which are often necessary in monitoring the progression of GI aGVHD. When used in conjunction with conventional gastrointestinal ultrasound (GIUS), CEUS provides a more comprehensive view of the structural and functional changes occurring in the GI tract, potentially enhancing diagnostic accuracy and allowing for earlier intervention. In comparison to traditional diagnostic methods like tissue biopsy or CT scans, CEUS is less invasive, quicker to perform, and better tolerated by patients, especially those in fragile health following allo-SCT. Its non-invasive nature and ability to provide immediate imaging results make it a valuable tool for clinicians, particularly in settings where minimizing patient discomfort and risk is paramount. However, despite these advantages, there are still gaps in the literature regarding CEUS's full diagnostic accuracy for GI aGVHD. Further research, including larger clinical trials and comparative studies, is needed to validate CEUS's role in routine clinical practice and to establish standardized protocols for its use. Nonetheless, CEUS shows considerable potential to transform the diagnostic approach to GI aGVHD by improving early detection, reducing the need for invasive procedures, and ultimately enhancing treatment outcomes for affected patients.

Phase-change ultrasound contrast agents for proton range verification: towards an in vivo application

Objective.In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a firstin vivoproof-of-concept of this technology.Approach.First, thein vitrobiocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,in vivoultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of thein vivobiocompatibility was performed using ADV and a combination of physiology monitoring and histology.Main results.Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV.Significance.These findings underline the potential of phase-change ultrasound contrast agents forin vivoproton range verification and provide the next step towards eventual clinical applications.

The predictive value of contrast-enhanced ultrasonography combined with aspartate aminotransferase-to-lymphocyte ratio in predicting therapeutic efficacy and prognosis of post-transarterial chemoembolization in primary liver cancer

ObjectiveTo investigate the predictive value of contrast-enhanced ultrasonography (CEUS) combined with the aspartate aminotransferase-to-lymphocyte ratio (ALRI) in predicting the therapeutic efficacy and prognosis of primary liver cancer after transarterial chemoembolization (TACE). MethodsWe included 75 patients with hepatocellular carcinoma (HCC) who underwent TACE in our oncology department between January 2019 and December 2021. The patients' clinical data, preoperative ALRI, and postoperative CEUS results were analyzed. ResultsThe optimal cutoff value of ALRI for predicting residual tumor lesions using digital subtraction angiography (DSA) was 42.50. CEUS had a specificity of 0.92, sensitivity of 0.96, and area under the curve (AUC) of 0.940 for determining residual tumor lesions, while ALRI had a specificity of 0.88, sensitivity of 0.70, and AUC of 0.825. The combination of CEUS and ALRI provided a specificity of 0.92, sensitivity of 0.98, and AUC of 0.985 for determining residual tumor lesions. All patients were followed up continuously after the operation. The optimal cutoff value of ALRI for predicting residual tumor lesions in relation to 3-year survival was 41.50. In terms of 3-year survival prediction, DSA showed a specificity of 0.559, sensitivity of 0.889, and AUC of 0.724, CEUS exhibited a specificity of 0.500, sensitivity of 0.852, and AUC of 0.676, and ALRI had a specificity of 0.618, sensitivity of 0.704, and AUC of 0.611. Combined detection of CEUS and ALRI resulted in a specificity of 0.500, sensitivity of 0.889, and AUC of 0.662 for predicting 3-year survival. Patients with negative DSA results, CEUS-negative patients, and those with ALRI ≤41.5 exhibited significantly better survival outcomes compared to their positive counterparts. ConclusionCEUS combined with ALRI yields a higher predictive value in predicting residual tumor lesions and death in patients with HCC after TACE.

Value of contrast-enhanced ultrasound in differentiating granulomatous mastitis from invasive ductal carcinoma.

This study aims to analyze the imaging manifestations of granulomatous mastitis (GM) and invasive ductal carcinoma (IDC) using conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS). The objective is to investigate the clinical value of CEUS in differentiating between GM and IDC. We retrospectively enrolled 39 GM patients and 64 IDC patients between January 2020 and June 2023. All diagnoses were confirmed via core needle biopsy or surgical pathology. The characteristics of both conventional US and CEUS in these patients were analyzed to distinguish GM from IDC. Based on CEUS features, GM lesions most commonly presented as hypoechoic areas (43.6%), followed by pseudocysts (28.2%), hypoechoic nodules (15.4%), and honeycomb cysts (12.8%). The diffuse enhancement pattern was an independent characteristic for distinguishing GM from IDC, with the ROC analysis revealing an area under the curve (AUC) value of 0.794. US is the preferred initial examination for GM, and both its conventional and CEUS features can enhance diagnostic accuracy and guide clinical treatment. CEUS demonstrates high differential diagnostic value in distinguishing GM from IDC. This study categorizes GM manifestations on CEUS into four types, each corresponding to different pathological stages of GM. We identified that the diffuse enhancement pattern on CEUS is a distinctive characteristic associated with GM, aiding in its differentiation from IDC.

Encapsulated papillary carcinoma of breast: Comparative study of multimodal ultrasound manifestations and pathological features.

To investigate the conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) manifestations and the corresponding histopathological characteristics of patients diagnosed with breast encapsulated papillary carcinoma (EPC) and to explore the value of CEUS in diagnosis of EPC. The clinical, pathological, US, and CEUS features of 16 patients (17 lesions) with EPC confirmed by postoperative histopathology were retrospectively analyzed. EPC was prevalent in the postmenopausal women. The majority of conventional US images of EPC showed complex cystic and solid masses with circumscribed margins (70.6%), enhanced posterior echo (94.1%), no sonographic calcification (88.2%), rich blood flow in the solid components within lesions (70.6%) on Color Doppler flow imaging, and high resistance index of blood flow (94.1%). Moreover, CEUS showed mainly centripetal hyperenhancement of the solid components within the lesions with irregular outline, and the enhancement area of the whole masses was essentially the same as the B-mode US area. EPC typically presents as a complex cystic and solid mass. CEUS is helpful to clarify the extent of the solid component and facilitate preoperative core-needle biopsy. A comprehensive evaluation by CEUS is valuable for diagnosing EPC and combining it with clinical features are helpful to further improve the diagnosis of this rare kind of breast cancer.

Diagnostic value of FNA, ultrasound elastography and CEUS in thyroid carcinoma

Background: To investigate the role of fine needle aspiration cytology (FNA), sonoelastography and contrast-enhanced ultrasound (CEUS) in the diagnosis of thyroid carcinoma. Methodology: A total of 150 patients with suspected thyroid cancer admitted to our hospital from January 2019 to December 2021 were selected and divided into group A, group B and group C according to random number table, with 50 cases in each group. FNA was used in group A, ultrasound elastography was used in group B, and CEUS was used in group C. Pathological diagnosis was performed in all patients, and the diagnostic sensitivity, specificity, and accuracy were compared among the three groups. Results: The diagnostic sensitivity, specificity and accuracy of FNA in group A were 90.91%, 70.59% and 84.00%, respectively; the diagnostic sensitivity, specificity and accuracy of ultrasound elastography in group B were 94.12%, 81.25% and 90.00%, respectively; the diagnostic sensitivity, specificity and accuracy of CEUS in group C were 88.57%, 73.33% and 84.00%, respectively; the three groups were compared (P &gt; 0.05). Conclusion: All three diagnostic techniques had a relatively high sensitivity and accuracy in the diagnosis of thyroid carcinoma. Ultrasound elastography had the highest sensitivity and specificity among the three techniques, while FNA and CEUS had similar diagnostic performance. Keywords: Fine needle aspiration cytology; ultrasound elastography; contrast-enhanced ultrasound; thyroid cancer; diagnostic efficacy.

8402 The Usefulness of the Contrast-Enhanced Ultrasound (CEUS) in Preoperative Localization of Parathyroid Gland Adenomas

Abstract Disclosure: A. Żyłka: None. K. Dobruch-Sobczak: None. H. Piotrzkowska-Wróblewska: None. P. Góralski: None. J. Gałczyński: None. E. Bakuła-Zalewska: None. M. Dedecjus: None. Objectives: Preoperative localization of parathyroid gland adenomas in patients diagnosed with primary hyperparathyroidism (pHPT) is challenging process. The aim of the study was to assessed the usefulness of contrast-enhanced ultrasound (CEUS) as complimentary diagnostic modality to conventional ultrasonography for detection of hyperfunctioning parathyroid gland lesions. Methods: Between the years 2021 and 2022, 36 adult patients (33 women and 3 men, aged 37-76) diagnosed with pHPT, underwent high-resolution ultrasound (US) and CEUS of parathyroid gland adenomas, suspected after fine-needle aspiration biopsy with positive parathormone (PTH) wash-out results and/or avid in 99mTechnetium -sestamibi scintigraphy. During CEUS examination 1.5 ml of SonoVue contrast has been injected and followed by analysing of qualitative CEUS enhancement features. All patients were qualified to surgical treatment according to clinical symptoms, laboratory and imaging findings and underwent parathyroidectomy with histopathologic results confirming parathyroid gland adenomas. Analysis of the B-mode features and visual CEUS enhancement patterns was performed retrospectively. Ten CEUS qualitative parameters of lesions were assessed including: homo- or heterogenous enhancement; hyper- or hypoenhancement; distribution of contrast in wash-in phase as: centripetal, centrifugal or combined and in wash-out phase as: centrally, peripherally or combined. Then the model was extended using the results based on US B-mode imaging which involved size, echogenicity, calcifications, cystic components and vascularity patterns assessed in Color Doppler (CD) and superb microvascular imaging (SMI). Results: Histopathologic results included 36 parathyroid adenomas (in 33 women and 3 men), the medium size 18.8mm (±11.1) and volume 3.7mm3 (±8.2). In B-mode US examination the majority of lesions were assessed as hypoechoic (n=36; 100%) with dominant inhomogenous echostructure (n=20; 55.5%), mixed vascularity (n=24; 66.6%) and polar vessel observed in 14 lesions (38.8%). There were no adenomas with calcifications, cystic components were observed only in 4 nodules (11.1%). In the CEUS study, dominated qualitative features were homogenous (n=22; 61,1%) and hyperenhancement (n=27; 75%), with centripetal distribution of contrast in wash-in phase (n=24; 66,6%) and dominant centrally wash-out of the contrast (n=20; 55,5%). Conclusions: Preliminary results indicate ultrasonographic patterns characteristic for parathyroid gland adenomas in multiparametric ultrasound involved CEUS examination, which seemed to be valuable tool for localization hyperfunctional parathyroid glands. Further multicenter studies should be performed to standardize qualitative CEUS features in order to diagnose primary hyperparathyroidism preoperatively. Presentation: 6/1/2024

8402 The Usefulness Of The Contrast-Enhanced Ultrasound (CEUS) In Preoperative Localization Of Parathyroid Gland Adenomas

Abstract Disclosure: A. Żyłka: None. K. Dobruch-Sobczak: None. H. Piotrzkowska-Wróblewska: None. P. Góralski: None. J. Gałczyński: None. E. Bakuła-Zalewska: None. M. Dedecjus: None. Objectives: Preoperative localization of parathyroid gland adenomas in patients diagnosed with primary hyperparathyroidism (pHPT) is challenging process. The aim of the study was to assessed the usefulness of contrast-enhanced ultrasound (CEUS) as complimentary diagnostic modality to conventional ultrasonography for detection of hyperfunctioning parathyroid gland lesions. Methods: Between the years 2021 and 2022, 36 adult patients (33 women and 3 men, aged 37-76) diagnosed with pHPT, underwent high-resolution ultrasound (US) and CEUS of parathyroid gland adenomas, suspected after fine-needle aspiration biopsy with positive parathormone (PTH) wash-out results and/or avid in 99mTechnetium -sestamibi scintigraphy. During CEUS examination 1.5 ml of SonoVue contrast has been injected and followed by analysing of qualitative CEUS enhancement features. All patients were qualified to surgical treatment according to clinical symptoms, laboratory and imaging findings and underwent parathyroidectomy with histopathologic results confirming parathyroid gland adenomas. Analysis of the B-mode features and visual CEUS enhancement patterns was performed retrospectively. Ten CEUS qualitative parameters of lesions were assessed including: homo- or heterogenous enhancement; hyper- or hypoenhancement; distribution of contrast in wash-in phase as: centripetal, centrifugal or combined and in wash-out phase as: centrally, peripherally or combined. Then the model was extended using the results based on US B-mode imaging which involved size, echogenicity, calcifications, cystic components and vascularity patterns assessed in Color Doppler (CD) and superb microvascular imaging (SMI). Results: Histopathologic results included 36 parathyroid adenomas (in 33 women and 3 men), the medium size 18.8mm (±11.1) and volume 3.7mm3 (±8.2). In B-mode US examination the majority of lesions were assessed as hypoechoic (n=36; 100%) with dominant inhomogenous echostructure (n=20; 55.5%), mixed vascularity (n=24; 66.6%) and polar vessel observed in 14 lesions (38.8%). There were no adenomas with calcifications, cystic components were observed only in 4 nodules (11.1%). In the CEUS study, dominated qualitative features were homogenous (n=22; 61,1%) and hyperenhancement (n=27; 75%), with centripetal distribution of contrast in wash-in phase (n=24; 66,6%) and dominant centrally wash-out of the contrast (n=20; 55,5%). Conclusions: Preliminary results indicate ultrasonographic patterns characteristic for parathyroid gland adenomas in multiparametric ultrasound involved CEUS examination, which seemed to be valuable tool for localization hyperfunctional parathyroid glands. Further multicenter studies should be performed to standardize qualitative CEUS features in order to diagnose primary hyperparathyroidism preoperatively. Presentation: 6/1/2024

7090 The Largest Study on Asymptomatic Primary Hyperparathyroidism (APHPT) Conducted at the Tertiary Care Riga East Clinical University Hospital (RECUH)— Three Years of Data

Abstract Disclosure: D. Stūrīte: None. I. Rasa: None. Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder and a leading cause of hypercalcemia in the outpatient setting. The study aimed to assess the characteristics, management and outcomes of pts with APHPT. Methods: A retrospective analysis of data from 168 pts with APHPT, evaluated at RECUH from January 2021 to November 2023 was conducted. Information obtained included medical records, laboratory data, imaging results, surgical protocols, histopathology data. Statistical analysis was performed using IBM SPSS 29.0. Results: From the 168 pts (mean age: 63.7±11.8 years), 86.3% (n=145) were females. Predominantly, 67.3% (n=113) exhibited mild hypercalcemia (2.6-3.0mmol/L), while 22.6% (n=38) had moderate hypercalcemia (3.0-3.49mmol/L), and 4.8% (n=8) -severe hypercalcemia (≥3.5mmol/L). 5.3% (n=9) had normocalcaemic PHPT. The mean preoperative maximal calcium level was 2.9±0.3mmol/L, iPTH level - 247.6±224.9pg/mL, minimal phosphorus - 1.3±6.7mmol/L and 25-OH vitamin D level - 28.3±14.7ng/mL. The mean preoperative eGFR was 90.6±28.2 ml/min/1.73m2, creatinine - 72.5±23.9μmol/L. Parathyroid adenoma sizes ranged from 0.3x0.4cm to 5.3x3.7cm. Calcium levels positively correlated with adenoma cross-sectional area (ρ=0.187, p=0.029) and maximal adenoma dimension (ρ=0.215, p=0.011). Ultrasonography convincingly detected parathyroid adenomas in 63.9% (107/168), SPECT/CT - 68.4% (52/76), 99mTc-sestamibi scintigraphy - 65.6% (61/93), 3D-CT - 70.6% (24/34), contrast-enhanced ultrasonography - 84% (21/25) and MRI in - 40% (2/5) cases. 12.5% (n=21) pts had unlocated parathyroid adenoma. 34.5% (n=58) of pts had osteoporosis, 47.6% (n=80) osteopenia, 12.5% (n=21) had a history of osteoporotic fracture, 17.3% (n=29) had gallstones and 22.0% (n=37) - kidney stones. 80.4% (n=135) of pts had thyroid nodules, 48.2% (n=81) - nontoxic goitre, 24.4% (n=31) - autoimmune thyroiditis, 41.7% (n=70) - hypertension, 10.5% (n=18) - type 2 diabetes. 18.5% (n=31) pts were found to have a diagnosis of malignancy. 61.9% (n=104) of pts underwent parathyroidectomy. Histopathology and radiologic imaging revealed single parathyroid adenoma in 95.2% (n=99), double parathyroid adenomas in 1.9% (n=2), parathyroid hyperplasia in 2.9% (n=3) and parathyroid carcinoma in 1.9% (n=2) pts. The mean maximal postoperative calcium level (n=103) was 2.4±0.1mmol/L, iPTH (n=101) - 63.5±27.7pg/mL, 25-OH vitamin D - 41.5±13.3ng/mL, and the mean minimal phosphorus (n=56) - 1.1±0.2mmol/L. Conclusions: APHPT remains frequently encountered and often showcases bone manifestations. It's crucial to consider the diverse clinical manifestations and associated conditions in patients with APHPT. Presentation: 6/2/2024

Macrophage uptake rate of Sonazoid in breast lymphosonography is highly conserved in healthy controls

Subcutaneous microbubble administration in connection with contrast enhanced ultrasound (CEUS) imaging is showing promise as a noninvasive and sensitive way to detect tumor draining sentinel lymph nodes (SLNs) in patients with breast cancer. Moreover, there is potential to harness the results from these approaches to directly estimate cancer burden, since some microbubble formulas, such as the Sonazoid used in this study, are rapidly phagocytosed by macrophages, and the macrophage concentration in a lymph node is inversely related to the cancer burden. This work presents a mathematical model that can approximate a rate constant governing macrophage uptake of Sonazoid,ki, given dynamic CEUS Sonazoid imaging data. Twelve healthy women were injected with 1.0 ml of Sonazoid in an upper-outer quadrant of one of their breasts and SLNs were imaged in each patient immediately after injection, and then at 0.25, 0.5, 1, 2, 4, 6, and 24 h after injection. The mathematical model developed was fit to the dynamic CEUS data from each subject resulting in a mean ± sd of 0.006 ± 0.005 h-1and 0.4 ± 0.1 h-1for relative lymphatic flow (EFl) andki, respectively. Furthermore, the roughly 25% sd of thekimeasurement was similar to the sd that would be expected from realistic noise simulations for a stable 0.4 h-1value ofki, suggesting that macrophage concentration is highly consistent among cancer-free SLNs. These results, along with the significantly smaller variance inkimeasurement observed compared to relative lymphatic flow suggest thatkimay be a more precise and promising approach of estimating macrophage abundance, and inversely cancer burden. Future studies comparing tumor-free to tumor-bearing nodes are planned to verify this hypothesis.

Analysis and prediction of ablation zone absorption in papillary thyroid microcarcinoma undergoing microwave ablation.

This study aims to investigate the factors that influence the absorption of the ablation zone in patients with papillary thyroid microcarcinoma (PTMC) following microwave ablation (MWA) and construct a nomogram for predicting the absorption of the ablation zone. Data from 150 patients with 187 PTMCs who received MWA between April 2020 and April 2023 were analyzed. PTMCs were randomly divided into training and validation sets in a 7:3 ratio. Univariable and multivariable analyses of Cox regression were utilized to identify the independent variables associated with the absorption of the ablation zone in PTMC post-MWA, and a nomogram was established. The discrimination and calibration performance of the nomogram was assessed using the time-dependent receiver operating characteristic curves and calibration curves. At 12 months post-MWA, a 53% proportion of complete disappearance of the ablation zone was observed. Energy delivered per milliliter of volume measured in contrast-enhanced ultrasound (CEUS) mode immediately post-MWA (Edv) and the CEUS margin at 1-month post-WMA were identified as independently correlated with the ablation zone absorption post-MWA (P = 0.001, P < 0.001 respectively). A nomogram incorporating these two factors was constructed. The areas under the receiver operating characteristic curve were all above 0.78 in the training and validation sets. Edv and the CEUS margin at 1-month post-MWA were found to be significantly associated with complete absorption of the ablation zone in PTMC patients following MWA. The established nomogram can assist practitioners in formulating more appropriate ablation strategies and provide a clinical basis for explaining the recovery status to patients.

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.

Sonographic characteristics of thyroid nodules with a Halo

ObjectiveTo investigate the sonographic characteristics of thyroid nodules with a halo, explore the value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration (FNA) in identifying nodules with a halo, and predict the risk of metastasis by analyzing the pathological features of the halo.MethodsA retrospective analysis was conducted on 185 postoperative cases of thyroid nodules accompanied by halos between January 2019 and December 2022. After describing the ultrasound characteristics of the thyroid nodules and their halos, all patients were divided into three groups, the first group (group I = CEUS only) of patients underwent CEUS, the second group (group II = CEUS + FNA) underwent FNA based on the first group, and the third group (group III = FNA only) underwent FNA directly. The CEUS and FNA results were graded using the Chinese Thyroid Imaging Report and Data System (C-TIRADS) and Bethesda Reporting System for Thyroid Cytopathology, respectively. Those graded below C-TIRADS 4b or Bethesda IV were defined as benign, and the results of FNA were referenced when the two methods were combined. The surgical pathology results were used as the gold standard. We plotted working curves to compare the diagnostic efficacy of CEUS and FNA alone and in combination in the diagnosis of thyroid nodules with halos. The pathological features of the halo were analyzed and the number of patients with cervical lymph node metastases was recorded.ResultsOne hundred and sixty patients met the requirements. Benign nodules were mainly characterized by a thin (0.75 ± 0.31 mm) and uniform halo with good integrity, while malignant nodules had a thicker (1.48 ± 0.51 mm) halo with uneven and irregular margins (P < 0.05). The sensitivity and specificity were highest when the cutoff value was 1.09 mm, with 76.08% and 84.29%, respectively. The halos of benign nodules were mostly hyper- or iso-enhanced, whereas the halos of malignant nodules were predominantly hypo-enhanced (P < 0.05). The areas under the curve (AUCs) for CEUS, FNA, and CEUS + FNA were 0.751(95% CI = 0.642–0.841), 0.863(95% CI = 0.767–0.929), and 0.918(95% CI = 0.834–0.967), respectively. Cervical lymph node metastasis occurred in only 13 (11.5%) malignant nodes with halos. The primary pathological components of the halo around malignant nodules were almost reactive hyperplastic fibrous tissue.ConclusionThe halo surrounding malignant thyroid nodules is thicker, with uneven and irregular margins, and shows hypo-enhancement on CEUS. Combining CEUS with FNA improves the diagnostic efficacy of thyroid nodules with halos. The reactive hyperplastic fibrous halo may be one of the reasons why malignant nodules are less likely to metastasize.

Perfusion Patterns of Peripheral Pulmonary Metastasis Using Contrast-Enhanced Ultrasound (CEUS) and Their Correlation with Immunohistochemically Detected Vascularization Pattern.

Description of the perfusion of pulmonary metastasis by contrast-enhanced ultrasound (CEUS) and their correlation with vascularization patterns represented by immunohistochemical CD34 endothelial staining. The data of 54 patients with histologic proven peripheral pulmonary metastasis, investigated between 2004 and 2023 by CEUS. These CEUS parameters were evaluated: time to enhancement (TE), categorized as early pulmonary-arterial (PA) or delayed bronchial-arterial (BA) patterns; extent of enhancement (EE), either marked or reduced; homogeneity of enhancement (HE), homogeneous or inhomogeneous; and decrease of enhancement (DE), rapid washout (<120 s) or late washout (≥120 s). Additionally, tissue samples in 45 cases (83.3%) were stained with CD34 antibody for immunohistochemical analysis. In total, 4 lesions (7.4 %) exhibited PA enhancement, and 50 lesions (92.6%) demonstrated BA enhancement. Furthermore, 37 lesions (68.5%) showed marked enhancement, while 17 lesions (31.5%) exhibited reduced enhancement. The enhancement was homogeneous in 28 lesions (51.86%) and inhomogeneous in 26 lesions (48.14%). Additionally, 53 lesions (98.1%) displayed a rapid washout. A chaotic vascular pattern indicative of a bronchial arterial blood supply was identified in all cases (45/45, 100%), including all 4 lesions with PA enhancement. Pulmonary metastases in CEUS predominantly reveal bronchial arterial enhancement and a rapid washout. Regarding EE and HE, pulmonary metastases show heterogeneous perfusion patterns. A PA enhancement in CEUS does not exclude BA neoangiogenesis.

Clinical utility of bedside Contrast-Enhanced Ultrasound (CEUS) in the diagnosis of pneumonia in elderly patients: Comparison with clinical, -radiological and ultrasound diagnosis.

to measure the clinical impact of contrast-enhanced ultrasound (CEUS) in the diagnosis of -community-acquired pneumonia (CAP), compared to clinical, radiological and ultrasound diagnosis. 84 patients (47/37 males/females, mean age:78,57±11,7 Y) with clinical suspicion of pneumonia and with ultrasound findings of peripheral lung lesions, were investigated with CEUS for a better characterization. Final diagnosis of 65 cap was obtained with complete disappearance of symptoms and pulmonary nodule(s); 19 neoplasms: 16 patients performed histologically with bronchoscopy; 3 refused (non-invasive diagnosis with basal CT-scan and positron emission tomography (PET) with fluorodeoxyglucose (FDG)). Sensitivity, specificity, overall diagnostic accuracy (ODA) (and corresponding AUROC) of clinical-data (CD), chest X-ray(CXR), Lung-ultrasound(LUS), CEUS were calculated with SPSS 26.0 software. Final diagnosis: 65 CAP, and 19 chest cancers. 9/65 (13%) patients died, of these 7/9 with older age and heart disease as comorbidity. CD: True-Positive (TP):23, True-negative (TN): 17; False-Positive (FP):2; False-negative (FN):42 (sens:35,4% spec:89,5% ODA10%: PPV:92%, NPV:28,8%) (AUROC±SEauc:0,46±0,076); CXR: TP: 36, TN:14; FP:5, FN:29; (sens: 55,4%; spec: 73,7%; ODA: 32%; PPV:87,5%, NPV:32,66%) (AUROC±SEauc:0,645±0,068). US: TP:59; TN: 14; FP:5, FN:6 (sens: 90,8%, spec: 73,7%, ODA: 84,9%, PPV:92,2%, NPV:70%) (AUROC±SEauc:0,9417±0,024); CEUS: TP: 63; TN: 19; FP:0; FN:2 (sens: 96,9%; spec: 100% ODA: 97,5%; PPV: 100%, NPV:90,5%) (AUROC±SEauc:0,98±0,01). Clinical-data and chest X-RAYS are insufficient to obtain a correct diagnosis of CAP in elderly population; US demonstrated a good accuracy to establish CAP, but with a relatively low specificity; in these cases, CEUS is able to give a correct characterization, allowing you to save the need for a chest contrast-enhanced-CT (CECT).

The treatment response evaluation through the combination of contrast-enhanced ultrasound and squamous cell carcinoma antigen in cervical cancer.

The evaluation of the treatment response after concurrent chemotherapy and radiotherapy (CCRT) for locally advanced cervical cancer is closely related to the formulation of treatment strategies. Magnetic resonance imaging (MRI) is a recommended method for efficacy evaluation; however, a unified consensus has not yet been reached on its use, and it has its limitations. This study aimed to evaluate the diagnostic value of a combination of contrast-enhanced ultrasound (CEUS) parameters and the squamous cell carcinoma antigen (SCC-Ag) to establish another efficient and feasible examination method. The data of 94 patients with cervical cancer who underwent transvaginal contrast-enhanced ultrasound (TV-CEUS) from October 2020 to March 2023 were retrospectively collected. Based on the inclusion and exclusion criteria, 70 patients diagnosed with cervical squamous cell carcinoma (SCC) who underwent CCRT were selected for inclusion in the study. The patients were divided into the residual disease (RD) group (comprising 26 patients) and the complete response (CR) group (comprising 44 patients) according to the diagnostic standard. Data on the grayscale echogenicity, color Doppler flow imaging (CDFI), CEUS parameters, and the SCC-Ag of all the patients were collected by two experienced radiologists. Inter-observer reliability was assessed using the intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) curves were created based on the non-parametric U-test or t-test results for the two groups. Delong's test was used to compare the area under the curve (AUC) between different ROC curves. A subgroup analysis was conducted based on the patient's age, tumor diameter, and disease stage. The ICCs between the two observers ranged from 0.915 and 0.947. Hypervascular hyper-enhancement in the arterial phase, hypo-enhancement in the venous phase, and the SCC-Ag differed significantly between the RD and CR groups (P<0.05). The AUC of the ROC curve combining these indicators was 0.890 [95% confidence interval (CI): 0.792-0.989], which was higher than the AUC of any indicator alone (P<0.05). The subgroup analysis showed that the AUCs of the patients aged ≥53 and <53 years were 0.922 (95% CI: 0.816-1.00) and 0.896 (95% CI: 0.782-1.00), respectively, those of the patients with stage II, III, and IV were 0.881 (95% CI: 0.732-1.00), 0.955 (95% CI: 0.894-1.00), and 1.000 (95% CI: 1.00-1.00), respectively, and those of the patients with a tumor diameter ≤10 mm, 10 mm < tumor diameter (post) <20 mm, and tumor diameter (post) ≥20 mm were 0.976 (95% CI: 0.910-1.00), 0.883 (95% CI: 0.763-1.00), and 1.00 (95% CI: 1.00-1.00) respectively. Transvaginal ultrasound (TVUS), TV-CEUS, and the SCC-Ag can be used in combination to evaluate the patient response to CCRT in locally advanced cervical SCC. This integrated approach enhanced the accuracy of the diagnosis of residual lesions and may be helpful in treatment plan optimization.