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18 pages, 5297 KB  
Review
HCC in the Era of Emerging MASH: The Role of Ultrasound in Surveillance and New Sonographic Features in Diagnosis
by Antonio Giorgio, Massimo De Luca, Anna Lombardi, Emanuela Ciracì, Valeria Cosima Rollo, Antonella Di Sarno, Luca Montesarchio, Giuseppe Stella and Valentina Giorgio
Cancers 2025, 17(24), 4037; https://doi.org/10.3390/cancers17244037 - 18 Dec 2025
Viewed by 426
Abstract
Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound [...] Read more.
Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound (CEUS) has significantly improved the characterization of nodules first identified on conventional US. Yet, when CEUS is performed using sulfur hexafluoride (SonoVue)—the only contrast agent available in Western countries—assessment remains restricted to a single nodule per examination, and enhanced CT or MRI is still required for full characterization and staging. In clinical settings, such as hepatology, internal medicine, infectious diseases, and surgery, CEUS offers the advantage of immediate availability, enabling rapid characterization of suspicious nodules in cirrhotic livers and facilitating timely therapeutic decisions. Although the introduction of direct-acting antivirals (DAAs) has substantially reduced HCV-related HCC, HCC incidence is increasingly driven by metabolic dysfunction-associated steatohepatitis (MASH). Evidence on surveillance strategies for MASH patients remains limited, and current EASL guidelines recommend monitoring only patients with >F2 fibrosis. Additionally, the effectiveness of US in obese or diabetic/obese populations is under ongoing investigation; abbreviated non-contrast MRI has been proposed as an alternative surveillance tool, but its adoption would entail significant economic implications for healthcare systems. HCC arising from MASH—sometimes even without cirrhosis—exhibits different sonographic and pathological features. Instead of small, hypoechoic nodules, typically seen in HCV-related cirrhosis, clinicians increasingly encounter larger or multiple lesions, often accompanied by macrovascular invasion, limiting access to curative treatments. Furthermore, typical CEUS LI-RADS patterns are less frequently observed. This review summarizes the evolving US findings in the era of MASH-related HCC and underscores the continued importance of US as the primary imaging tool in routine clinical practice. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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15 pages, 6684 KB  
Article
High-Resolution Contrast-Enhanced Ultrasound with SRCEUS for Assessing the Intrahepatic Microvasculature and Shunts in Patients with Hereditary Haemorrhagic Teleangiectasia (Osler’s Disease)
by Irmgard Maria Sieber, Friedrich Jung and Ernst Michael Jung
Life 2025, 15(10), 1631; https://doi.org/10.3390/life15101631 - 20 Oct 2025
Viewed by 825
Abstract
The aim of this retrospective clinical pilot study is to evaluate multiparametric ultrasound liver parenchyma assessments in the diagnosis of Osler’s disease, and to detect micro-shunts using SRCEUS with quantifications at the capillary level. Material/Method: All examinations were performed by an experienced examiner [...] Read more.
The aim of this retrospective clinical pilot study is to evaluate multiparametric ultrasound liver parenchyma assessments in the diagnosis of Osler’s disease, and to detect micro-shunts using SRCEUS with quantifications at the capillary level. Material/Method: All examinations were performed by an experienced examiner with a multi-frequency probe on a high-resolution matrix ultrasound device (SC 7-1U), convex probe (Mindray A 20), and were stored digitally in the PACS system. Vascular ultrasound was performed using colour-coded Doppler ultrasound (CCDS) and ultrasound microangiography (UMA). The recent M-Ref tool was utilised for the purpose of liver tissue characterisation, encompassing the domains of shear wave elastography, fat evaluation, and viscosity. Dynamic CEUS, HiFR CEUS, and SR CEUS were performed after the intravenous bolus injection of 1–2.4 mL of ultrasound contrast agent (SonoVue®). Measurements of SR CEUS capillary changes were performed independently by PACS-stored digital cine loops up to 5 s. Results: In the context of angiomas or haemangiomas, the initial contrast enhancement of echogenic or almost echogenic foci within 25 s without late wash-out was observed in 5/10 cases. In the evaluation of microvasculature, the presence of capsule-proximal shunts in Osler’s disease was observed, resulting in the identification of increased numbers of dilated capillaries within both peripheral and central shunts. In the control group, general liver tissue changes (20 cases) were observed in instances of inflammation (3/20 cases), peripherally in 4/20 cases with micro-shunts in altered parenchyma. In the context of multiparametric ultrasound, 16 out of 30 cases exhibited elevated fibrosis values, with a maximum recorded as high as 1.7 m/s, and in 13 out of 30 cases, there was an increase in fat values up to 0.65 dB/cm/MHz, indicative of moderate steatosis. Additionally, in seven cases, there was an increase in viscosity values up to 2.7 Pa·s, suggesting reactive changes. Conclusions: Recent advancements in medical imaging technology, specifically SR CEUS contrast ultrasound imaging, have led to the development of novel diagnostic tools that facilitate the evaluation of tissue and haemodynamic changes, in addition to capillary alterations, associated with Osler’s disease. Full article
(This article belongs to the Section Cell Biology and Tissue Engineering)
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20 pages, 2681 KB  
Article
Analysing the Renal Vasculature Using Super-Resolution Ultrasound Imaging: Considerations for Clinical and Research Applications
by Amy McDermott, Nathalie Sarup Panduro, Iman Taghavi, Hans Martin Kjer, Stinne Byrholdt Søgaard, Michael Bachmann Nielsen, Jørgen Arendt Jensen and Charlotte Mehlin Sørensen
Diagnostics 2025, 15(12), 1515; https://doi.org/10.3390/diagnostics15121515 - 14 Jun 2025
Cited by 1 | Viewed by 1517
Abstract
Background: Vascular imaging is essential for clinical practice, research, and the diagnosis and management of vascular diseases. Super-resolution ultrasound (SRUS) imaging is an emerging high-resolution imaging technique with broad applications in soft tissue vascular imaging. However, the impact of biological and clinical variables [...] Read more.
Background: Vascular imaging is essential for clinical practice, research, and the diagnosis and management of vascular diseases. Super-resolution ultrasound (SRUS) imaging is an emerging high-resolution imaging technique with broad applications in soft tissue vascular imaging. However, the impact of biological and clinical variables on its imaging accuracy is currently unknown. This study investigates these factors in an animal model and compares SRUS with contrast-enhanced µCT. Methods: Kidney scans from 29 Zucker rats (Zucker Diabetic Fatty and Zucker Lean) were retrospectively analysed. The left kidney was imaged in vivo using SRUS during microbubble infusion, then filled with Microfil and excised for ex vivo µCT. SRUS parameters and clinical variables were analysed, and SRUS scans were co-registered with µCT to compare vascular density measurements. Results: Mean arterial blood pressure and anaesthesia time showed significant linear relationships with SRUS microbubble detection and vascular track reconstruction. The anaesthesia time was also strongly correlated with vascular density measurement. Visualisation and velocity estimations of renal arteries were limited with SRUS. Ultrasound signal attenuation had significant impacts, particularly in cortical far-field imaging. Despite differences between kidney regions, the vascular density distribution did not differ considerably between SRUS and µCT datasets for whole-kidney imaging. Conclusions: This study outlines key factors SRUS users must consider for optimal technique use. Careful region selection and control of clinical variables ensure more reliable and comparable images. Further research is necessary to translate these findings from a rat model into clinical application. Full article
(This article belongs to the Special Issue Ultrasound Imaging in Medicine in 2025)
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7 pages, 193 KB  
Brief Report
Anaphylaxis after SonoVue: A Case Report and a Literature Review
by David Longhino, Alessandro Buonomo, Maria Assunta Zocco, Maria Elena Ainora, Giorgio Esposto, Irene Mignini, Lucia Cerrito, Francesca Romana Ponziani, Antonio Gasbarrini, Eleonora Nucera and Arianna Aruanno
J. Clin. Med. 2024, 13(17), 5018; https://doi.org/10.3390/jcm13175018 - 24 Aug 2024
Cited by 1 | Viewed by 2496
Abstract
SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions [...] Read more.
SonoVue (Bracco, Milan, Italy) is a drug used in ultrasonography for the purpose of increasing the echogenicity of blood or fluids by improving the signal-to-noise ratio. Background/Objectives/Methods: We described a case of anaphylaxis due to SonoVue and performed a literature review. Results and Conclusions: We reported a case of anaphylaxis secondary to the administration of SonoVue and described all the 13 literature cases. Given its widespread use and the potentially dangerous nature of the reactions it can cause, it is advisable to know how to promptly recognize fatal reactions. Full article
(This article belongs to the Section Immunology & Rheumatology)
12 pages, 2149 KB  
Article
Performance of Intraoperative Contrast-Enhanced Ultrasound (Io-CEUS) in the Diagnosis of Primary Lung Cancer
by Martin Ignaz Schauer, Ernst Michael Jung, Hans-Stefan Hofmann, Natascha Platz Batista da Silva, Michael Akers and Michael Ried
Diagnostics 2024, 14(15), 1597; https://doi.org/10.3390/diagnostics14151597 - 24 Jul 2024
Cited by 5 | Viewed by 1776
Abstract
Background: Suspicious tumors of the lung require specific staging, intraoperative detection, and histological confirmation. We performed an intrathoracic, intraoperative contrast-enhanced ultrasound (Io-CEUS) for characterization of lung cancer. Methods: Retrospective analysis of prospectively collected data on the application of Io-CEUS in thoracic surgery for [...] Read more.
Background: Suspicious tumors of the lung require specific staging, intraoperative detection, and histological confirmation. We performed an intrathoracic, intraoperative contrast-enhanced ultrasound (Io-CEUS) for characterization of lung cancer. Methods: Retrospective analysis of prospectively collected data on the application of Io-CEUS in thoracic surgery for patients with operable lung cancer. Analysis of the preoperative chest CT scan and FDG-PET/CT findings regarding criteria of malignancy. Immediately before lung resection, the intrathoracic Io-CEUS was performed with a contrast-enabled T-probe (6–9 MHz—L3-9i-D) on a high-performance ultrasound machine (Loqic E9, GE). In addition to intraoperative B-mode, color-coded Doppler sonography (CCDS), or power Doppler (macrovascularization) of the lung tumor, contrast enhancement (Io-CEUS) was used after venous application of 2.4–5 mL sulfur hexafluoride (SonoVue, Bracco, Italy) for dynamic recording of microvascularization. The primary endpoint was the characterization of operable lung cancer with Io-CEUS. Secondly, the results of Io-CEUS were compared with the preoperative staging. Results: The study included 18 patients with operable lung cancer, who received Io-CEUS during minimally invasive thoracic surgery immediately prior to lung resection. In the chest CT scan, the mean size of the lung tumors was 2.54 cm (extension of 0.7–4.5 cm). The mean SUV in the FDG-PET/CT was 7.6 (1.2–16.9). All lung cancers were detected using B-mode and power Doppler confirmed macrovascularization (100%) of the tumors. In addition, Io-CEUS showed an early wash-in with marginal and mostly simultaneous central contrast enhancement. Conclusions: The intrathoracic application of Io-CEUS demonstrated a peripheral and simultaneous central contrast enhancement in the early phase, which seems to be characteristic of lung cancer. In comparison to preoperative imaging, Io-CEUS was on par with the detection of malignancy and offers an additional tool for the intraoperative assessment of lung cancer before resection. Full article
(This article belongs to the Special Issue Current Challenges and Perspectives of Ultrasound)
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8 pages, 1123 KB  
Article
Value of Ultrasound Super-Resolution Imaging for the Assessment of Renal Microcirculation in Patients with Acute Kidney Injury: A Preliminary Study
by Xin Huang, Yao Zhang, Qing Zhou and Qing Deng
Diagnostics 2024, 14(11), 1192; https://doi.org/10.3390/diagnostics14111192 - 5 Jun 2024
Cited by 11 | Viewed by 2921
Abstract
The present study aimed to explore the clinical applicability of ultrasound super-resolution imaging (US SRI) for assessing renal microcirculation in patients with acute kidney injury (AKI). A total of 62 patients with sepsis were enrolled in the present study—38 with AKI and 24 [...] Read more.
The present study aimed to explore the clinical applicability of ultrasound super-resolution imaging (US SRI) for assessing renal microcirculation in patients with acute kidney injury (AKI). A total of 62 patients with sepsis were enrolled in the present study—38 with AKI and 24 control patients—from whom renal ultrasounds and clinical data were obtained. SonoVue contrast (1.5 mL) was administered through the elbow vein and contrast-enhanced ultrasound (CEUS) images were obtained on a Mindray Resona A20 ultrasound unit for 2 min. The renal perfusion time-intensity curve (TIC) was analyzed and, after 15 min, additional images were obtained to create a microscopic blood flow map. Microvascular density (MVD) was calculated and its correlation with serum creatinine (Scr) levels was analyzed. There were significant differences in heart rate, Scr, blood urea nitrogen, urine volume at 24 h, and glomerular filtration rate between the two groups (p < 0.01), whereas other characteristics, such as renal morphology, did not differ significantly between the AKI group and control group (p > 0.05). The time to peak and mean transit times of the renal cortex in the AKI group were prolonged compared to those in the control group (p < 0.01), while the peak intensity and area under the TIC were lower than those in the control group (p < 0.05). The MVD of the renal cortex in the AKI group was lower than that in the control group (18.46 ± 5.90% vs. 44.93 ± 11.65%; p < 0.01) and the MVD in the AKI group showed a negative correlation with Scr (R = −0.84; p < 0.01). Based on the aforementioned results, US SRI can effectively assess renal microcirculation in patients with AKI and is a noninvasive technique for the diagnosis of AKI and quantitative evaluation of renal microcirculation. Full article
(This article belongs to the Special Issue Abdominal Diseases: Diagnosis, Treatment and Management)
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23 pages, 4969 KB  
Article
The Utility of Contrast-Enhanced Ultrasound (CEUS) in Assessing the Risk of Malignancy in Thyroid Nodules
by Agnieszka Żyłka, Katarzyna Dobruch-Sobczak, Hanna Piotrzkowska-Wróblewska, Maciej Jędrzejczyk, Elwira Bakuła-Zalewska, Piotr Góralski, Jacek Gałczyński and Marek Dedecjus
Cancers 2024, 16(10), 1911; https://doi.org/10.3390/cancers16101911 - 17 May 2024
Cited by 6 | Viewed by 3058
Abstract
Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid [...] Read more.
Background: Ultrasonography is a primary method used in the evaluation of thyroid nodules, but no single feature of this method predicts malignancy with high accuracy. Therefore, this paper aims to assess the utility of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of thyroid nodules. Methods: The study group comprised 188 adult patients (155 women and 33 men) who preoperatively underwent CEUS of a thyroid nodule classified as Bethesda categories II–VI after fine-needle aspiration biopsy. During the CEUS examination, 1.5 mL of SonoVue contrast was injected intravenously, after which 15 qualitative CEUS enhancement patterns were analysed. Results: The histopathologic results comprised 65 benign thyroid nodules and 123 thyroid carcinomas. The dominant malignant CEUS features, such as hypo- and heterogeneous enhancement and slow wash-in phase, were evaluated, whereas high enhancement, ring enhancement, and a slow wash-out phase were assessed as predictors of benign lesions. Two significant combinations of B-mode and CEUS patterns were noted, namely, hypoechogenicity with heterogeneous enhancement and non-smooth margins with hypo- or iso-enhancement. Conclusions: The preliminary results indicate that CEUS is a useful tool in assessing the risk of malignancy of thyroid lesions. The combination of the qualitative enhancement parameters and B-mode sonographic features significantly increases the method’s usefulness. Full article
(This article belongs to the Section Methods and Technologies Development)
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15 pages, 2815 KB  
Article
Application of Dynamic Contrast-Enhanced Ultrasound in Evaluation the Activity of Crohn’s Disease
by Ying Wang, Li Wei, Wen-Song Ge, You-Rong Duan, Wen-Jun Ding, Xiu-Yun Lu, Yun-Lin Huang, Sheng Chen, Yi Dong and Peng Du
Diagnostics 2024, 14(7), 672; https://doi.org/10.3390/diagnostics14070672 - 22 Mar 2024
Cited by 6 | Viewed by 2722
Abstract
Background and Objective: The dynamic assessment of disease activity during the follow-up of patients with Crohn’s disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. [...] Read more.
Background and Objective: The dynamic assessment of disease activity during the follow-up of patients with Crohn’s disease (CD) remains a significant challenge. In this study, we aimed to identify the role of dynamic contrast-enhanced ultrasound (DCE-US) in the evaluation of activity of CD. Methods: In the retrospective study, patients diagnosed with CD in our hospital were included. All the diagnoses were confirmed by clinical symptoms and ileocolonoscopical results. All patients underwent intestinal ultrasound and contrast-enhanced ultrasound (CEUS) examinations within 1 week of the ileocolonoscopy examinations. Acuson Sequoia (Siemens Healthineers, Mountain View, CA, USA) and Resona R9 Elite (Mindray Medical Systems, China) with curved array and Line array transducers were used. The CEUS examination was performed with SonoVue (Bracco SpA, Milan, Italy). DCE-US analysis was performed by UltraOffice (version: 0.3-2010, Mindray Medical Systems, China) software. Two regions of interest (ROIs) were set in the anterior section of the infected bowel wall and its surrounding normal bowel wall 2 cm distant from the inflamed area. Time–intensity curves (TICs) were generated and quantitative perfusion parameters were obtained after curve fittings. The Simple Endoscopic Score for Crohn’s disease (SES-CD) was regarded as the reference standard to evaluate the activity of CD. The receiver operating characteristic curve (ROC) analyses were used to determine the diagnostic efficiency of DCE-US quantitative parameters. Results: From March 2023 to November 2023, 52 CD patients were included. According to SES-CD score, all patients were divided into active group with the SES-CD score > 5 (n = 39) and inactive group SES-CD score < 5 (n = 13). Most of the active CD patients showed bowel wall thickness (BWT) > 4.2 mm (97.4%, 38/39) or mesenteric fat hypertrophy (MFH) on intestinal ultrasound (US) scan (69.2%, 27/39). Color Doppler signal of the bowel wall mostly showed spotty or short striped blood flow signal in active CD patients (56.4%, 22/39). According to CEUS enhancement patterns, most active CD patients showed a complete hyperenhancement of the entire intestinal wall (61.5%, 24/39). The TICs of active CD showed an earlier enhancement, higher peak intensity, and faster decline. Among all CEUS quantitative parameters, amplitude-derived parameters peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in rate (WiR), wash-in perfusion index (WiPI), and wash-out rate (WoR) were significantly higher in active CD than in inactive CD (p < 0.05). The combined AUROC of intestinal ultrasound features and DCE-US quantitative perfusion parameters in the diagnosis of active CD was 0.987, with 97.4% sensitivity, 100% specificity, and 98.1% accuracy. Conclusions: DCE-US with quantitative perfusion parameters is a potential useful noninvasive imaging method to evaluate the activity of Crohn’s disease. Full article
(This article belongs to the Special Issue Research Update on Contrast-Enhanced Ultrasound)
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14 pages, 2991 KB  
Article
The Green Synthesis of Reduced Graphene Oxide Using Ellagic Acid: Improving the Contrast-Enhancing Effect of Microbubbles in Ultrasound
by Qiwei Cheng, Yuzhou Wang, Qi Zhou, Shaobo Duan, Beibei Zhang, Yaqiong Li and Lianzhong Zhang
Molecules 2023, 28(22), 7646; https://doi.org/10.3390/molecules28227646 - 17 Nov 2023
Cited by 4 | Viewed by 2716
Abstract
There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and [...] Read more.
There is an urgent need to realize precise clinical ultrasound with ultrasound contrast agents that provide high echo intensity and mechanical index tolerance. Graphene derivatives possess exceptional characteristics, exhibiting great potential in fabricating ideal ultrasound contrast agents. Herein, we reported a facile and green approach to synthesizing reduced graphene oxide with ellagic acid (rGO-EA). To investigate the application of a graphene derivative in ultrasound contrast agents, rGO-EA was dispersed in saline solution and mixed with SonoVue (SV) to fabricate SV@rGO-EA microbubbles. To determine the properties of the product, analyses were performed, including ultraviolet–visible spectroscopy (UV–vis), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), X-ray photoelectron spectrum (XPS), X-ray diffraction analysis (XRD) and zeta potential analysis. Additionally, cell viability measurements and a hemolysis assay were conducted for a biosafety evaluation. SV@rGO-EA microbubbles were scanned at various mechanical index values to obtain the B-mode and contrast-enhanced ultrasound (CEUS) mode images in vitro. SV@rGO-EA microbubbles were administered to SD rats, and their livers and kidneys were imaged in CEUS and B-mode. The absorption of rGO-EA resulted in an enhanced echo intensity and mechanical index tolerance of SV@rGO-EA, surpassing the performance of SV microbubbles both in vitro and in vivo. This work exhibited the application potential of graphene derivatives in the field of ultrasound precision medicine. Full article
(This article belongs to the Topic Chemistry of 2D Materials)
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12 pages, 3438 KB  
Article
Comparison of Ultrasound Contrast between H2O2-Responsive Nanoparticles and Microbubble Contrast According to Muscle Injury in Rat Models
by Da-Sol Kim, Nanhee Song, Dongwon Lee and Gi-Wook Kim
Diagnostics 2023, 13(21), 3320; https://doi.org/10.3390/diagnostics13213320 - 26 Oct 2023
Cited by 1 | Viewed by 2167
Abstract
Ultrasound contrast agents are clinically used for diagnosis of internal organs, but ultrasound contrast agents are rarely applied clinically in musculoskeletal disorders. Our study aims to comparatively analyze the differences between ultrasonographic images through peri-injury injection of the clinically used microbubble and researched [...] Read more.
Ultrasound contrast agents are clinically used for diagnosis of internal organs, but ultrasound contrast agents are rarely applied clinically in musculoskeletal disorders. Our study aims to comparatively analyze the differences between ultrasonographic images through peri-injury injection of the clinically used microbubble and researched nanoparticle contrast agents in various muscular injury models. To compare contrast-enhanced images in different muscle injury models, we prepared groups of rats with sham, laceration, punch, contusion, and toxin injection injuries. We measured H2O2 levels using the Amplex Red assay by extracting tissue from the damaged area. As comparative contrast agents, SonoVue®, a commercially available microbubble contrast agent, and poly(vanillinoxalte) (PVO) nanoparticles, which are H2O2-responsive nanoparticles, were used. The difference in contrast between the two contrast agents was recorded as an ultrasound movie, and J-image software 1.53p was used to quantify and analyze the maximum and minimum echogenicity values of the images after contrast enhancement. In the Amplex red assay for the highest H2O2 level in each muscle injury model, the maximum level showed 24 h after the modeling. In the sham rats, PVO injection showed no increased echogenicity except at the needle insertion site, but SonoVue® injection showed increased echo signal throughout the injected muscle immediately after injection. One day after the preparation of the lesion, PVO and SonoVue® were injected into the lesion site and ultrasound was performed on the lesion site. After the injection of PVO nanoparticles, contrast enhancement was observed at the lesion site immediately. SonoVue® injections, on the other hand, showed a widespread pattern of echo signals and an increase in echo retention only at the lesion site over time, but this was not clear. There were statistically significant differences between the highest and lowest echogenicity in PVO and SonoVue® contrast-enhanced images in all models. Contrast enhancement lasted more than 3 h in the PVO injection, but disappeared within 3 h in the SonoVue® injection. PVO nanoparticles showed the possibility of physiologic contrast by CO2 generated by conjugation with H2O2 generated by muscle injuries, and SonoVue® injection observed the possibility of microbubble contrast as a contrast agent with a pooling effect that lasts longer on the lesion. Further research is needed to investigate the use of various ultrasound contrast agents, including nanoparticles, in musculoskeletal disorders, as well as the potential for further utilities of microbubble contrast agents. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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8 pages, 1514 KB  
Case Report
Usefulness of Contrast-Enhanced Endoscopic Ultrasound (CH-EUS) to Guide the Treatment Choice in Superficial Rectal Lesions: A Case Series
by Giulia Gibiino, Monica Sbrancia, Cecilia Binda, Chiara Coluccio, Stefano Fabbri, Paolo Giuffrida, Graziana Gallo, Luca Saragoni, Roberta Maselli, Alessandro Repici and Carlo Fabbri
Diagnostics 2023, 13(13), 2267; https://doi.org/10.3390/diagnostics13132267 - 4 Jul 2023
Cited by 5 | Viewed by 2350
Abstract
Introduction: Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in [...] Read more.
Introduction: Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in the locoregional staging of rectal cancer, although this technique has a tendency toward the over-estimation of the loco-regional (T) staging. However, there are still few data on contrast-enhanced endoscopic ultrasound (CH-EUS), especially if this ancillary technique may increase the accuracy for predicting invasive nodules among large rectal lesions. Material and Methods: Consecutive large (≥20 mm) superficial rectal lesions with high-definition endoscopy, characterized by focal areas suggestive for invasive cancer/2B type according to JNET classification, were considered for additional standardized evaluation via CH-EUS with Sonovue ©. Results: From 2020 to 2023, we evaluated 12 consecutive superficial rectal lesions with sizes ranging from 20 to 180 mm. This evaluation provided additional elements to support the therapeutic decision made. Lesions were treated with surgical (3/12) or endoscopic treatment (9/12) according to their morphology and CH-EUS evaluation. Conclusion: Contrast-enhanced endoscopic ultrasound can provide an additional evaluation for large and difficult-to-classify rectal lesions. In our experience, CH-EUS staging corresponded to the final pathological stages in 9/12 (75%) lesions, improving the distinction between T1 and T2 lesions. Larger prospective studies and randomized trials should be conducted to support and standardize this approach. Full article
(This article belongs to the Special Issue Innovation in Gastrointestinal Endoscopy)
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22 pages, 5545 KB  
Article
The Assessment of Calcium and Bleomycin Cytotoxic Efficiency in Relation to Cavitation Dosimetry
by Martynas Maciulevičius, Renaldas Raišutis, Baltramiejus Jakštys, Linas Svilainis, Andrius Chaziachmetovas and Saulius Šatkauskas
Pharmaceutics 2023, 15(5), 1463; https://doi.org/10.3390/pharmaceutics15051463 - 11 May 2023
Cited by 5 | Viewed by 2403
Abstract
Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca2+ delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extensive evidence that a 5 mM concentration of [...] Read more.
Microbubble (MB)- and ultrasound (US)-facilitated intracellular Ca2+ delivery, known as sonoporation (SP), is a promising anticancer treatment modality, since it allows a spatio-temporally controllable and side-effect-free alternative to conventional chemotherapy. The current study provides extensive evidence that a 5 mM concentration of Ca2+ in combination with US alone or US and Sonovue MBs can be an alternative to the conventional 20 nM concentration of the anticancer drug bleomycin (BLM). Ca2+ application together with SP induces a similar level of death in Chinese hamster ovary cells to the combination of BLM and SP but does not cause systemic toxicity, as is inherent to conventional anticancer drugs. In addition, Ca2+ delivery via SP alters three vital characteristics essential for viable cells: membrane permeability, metabolic activity and proliferation ability. Most importantly, Ca2+ delivery via SP elicits sudden cell death—occurring within 15 min—which remains similar during 24–72 h and 6 d periods. The extensive study of US waves side-scattered by MBs led to the quantification of the cavitation dose (CD) separately for subharmonics, ultraharmonics, harmonics and broadband noise (up to 4 MHz). The CD was suitable for the prognostication of the cytotoxic efficiency of both anticancer agents, Ca2+ and BLM, as was indicated by an overall high (R2 ≥ 0.8) correlation (22 pairs in total). These extensive analytical data imply that a broad range of frequencies are applicable for the feedback-loop control of the process of US-mediated Ca2+ or BLM delivery, successively leading to the eventual standardization of the protocols for the sonotransfer of anticancer agents as well as the establishment of a universal cavitation dosimetry model. Full article
(This article belongs to the Special Issue Ultrasound-Mediated Drug Delivery)
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15 pages, 2091 KB  
Article
Contrast-Enhanced Ultrasound in Distinguishing between Malignant and Benign Peripheral Pulmonary Consolidations: The Debated Utility of the Contrast Enhancement Arrival Time
by Carla Maria Irene Quarato, Beatrice Feragalli, Donato Lacedonia, Gaetano Rea, Giulia Scioscia, Evaristo Maiello, Concetta Di Micco, Cristina Borelli, Antonio Mirijello, Paolo Graziano, Lucia Dimitri, Rosanna Villani and Marco Sperandeo
Diagnostics 2023, 13(4), 666; https://doi.org/10.3390/diagnostics13040666 - 10 Feb 2023
Cited by 16 | Viewed by 3007
Abstract
Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and [...] Read more.
Background. Limited studies and observations conducted on a too small number of patients prevent determining the actual clinical utility of pulmonary contrast-enhanced ultrasound (CEUS). The aim of the present study was to examine the efficacy of contrast enhancement (CE) arrival time (AT) and other dynamic CEUS findings for differentiating between malignant and benign peripheral lung lesions. Methods. 317 inpatients and outpatients (215 men, 102 women; mean age: 52 years) with peripheral pulmonary lesions were included in the study and underwent pulmonary CEUS. Patients were examined in a sitting position after receiving an intravenous injection of 4.8 mL of sulfur hexafluoride microbubbles stabilized by a phospholipid shell as ultrasound contrast agent (SonoVue—Bracco; Milan, Italy). Each lesion was observed for at least 5 min in real-time and the following temporal characteristics of enhancement were detected: the arrival time (AT) of microbubbles in the target lesion; the enhancement pattern; the wash-out time (WOT) of microbubbles. Results were then compared in light of the definitive diagnosis of community acquired pneumonia (CAP) or malignancies, which was not known at the time of CEUS examination. All malignant cases were diagnosed by histological results, while pneumonia was diagnosed on the basis of clinical and radiological follow-up, laboratory findings and, in some cases, histology. Results. CE AT has not been shown to differ between benign and malignant peripheral pulmonary lesions. The overall diagnostic accuracy and sensibility of a CE AT cut-off value < 10 s in discriminating benign lesions were low (diagnostic accuracy: 47.6%; sensibility: 5.3%). Poor results were also obtained in the sub-analysis of small (mean diameter < 3 cm) and large (mean diameter > 3 cm) lesions. No differences were recorded in the type of CE pattern showed between benign and malignant peripheral pulmonary lesions. In benign lesions we observed a higher frequency of delayed CE wash-out time (WOT) > 300 s. Anyhow, a CE WOT cut-off value > 300 s showed low diagnostic accuracy (53.6%) and sensibility (16.5%) in discriminating between pneumonias and malignancies. Similar results were also obtained in the sub-analysis by lesion size. Squamous cell carcinomas showed a more delayed CE AT compared to other histopathology subtypes. However, such a difference was statistically significant with undifferentiated lung carcinomas. Conclusions. Due to an overlap of CEUS timings and patterns, dynamic CEUS parameters cannot effectively differentiate between benign and malignant peripheral pulmonary lesions. Chest CT remains the gold standard for lesion characterization and the eventual identification of other pneumonic non-subpleural localizations. Furthermore, in the case of malignancy, a chest CT is always needed for staging purposes. Full article
(This article belongs to the Special Issue Advances in Chest Imaging Diagnostics)
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15 pages, 1987 KB  
Article
Prediction of Pathological Grades of Pancreatic Neuroendocrine Tumors Based on Dynamic Contrast-Enhanced Ultrasound Quantitative Analysis
by Dao-Hui Yang, Juan Cheng, Xiao-Fan Tian, Qi Zhang, Ling-Yun Yu, Yi-Jie Qiu, Xiu-Yun Lu, Wen-Hui Lou, Yi Dong and Wen-Ping Wang
Diagnostics 2023, 13(2), 238; https://doi.org/10.3390/diagnostics13020238 - 9 Jan 2023
Cited by 10 | Viewed by 3141
Abstract
Objective: To investigate whether the dynamic contrast-enhanced ultrasound (DCE-US) analysis and quantitative parameters could be helpful for predicting histopathologic grades of pancreatic neuroendocrine tumors (pNETs). Methods: This retrospective study conducted a comprehensive review of the CEUS database between March 2017 and November 2021 [...] Read more.
Objective: To investigate whether the dynamic contrast-enhanced ultrasound (DCE-US) analysis and quantitative parameters could be helpful for predicting histopathologic grades of pancreatic neuroendocrine tumors (pNETs). Methods: This retrospective study conducted a comprehensive review of the CEUS database between March 2017 and November 2021 in Zhongshan Hospital, Fudan University. Ultrasound examinations were performed by an ACUSON Sequioa unit equipped with a 3.5 MHz 6C−1 convex array transducer, and an ACUSON OXANA2 unit equipped with a 3.5 MHz 5C−1 convex array transducer. SonoVue® (Bracco Inc., Milan, Italy) was used for all CEUS examinations. Time intensity curves (TICs) and quantitative parameters of DCE-US were created by Vuebox® software (Bracco, Italy). Inclusion criteria were: patients with histopathologically proved pNETs, patients who underwent pancreatic B-mode ultrasounds (BMUS) and CEUS scans one week before surgery or biopsy and had DCE-US imaging documented for more than 2 min, patients with solid or predominantly solid lesions and patients with definite diagnosis of histopathological grades of pNETs. Based on their prognosis, patients were categorized into two groups: pNETs G1/G2 group and pNETs G3/pNECs group. Results: A total of 42 patients who underwent surgery (n = 38) or biopsy (n = 4) and had histopathologically confirmed pNETs were included. According to the WHO 2019 criteria, all pNETs were classified into grade 1 (G1, n = 10), grade 2 (G2, n = 21), or grade 3 (G3)/pancreatic neuroendocrine carcinomas (pNECs) (n = 11), based on the Ki−67 proliferation index and the mitotic activity. The majority of the TICs (27/31) of pNETs G1/G2 were above or equal to those of pancreatic parenchyma in the arterial phase, but most (7/11) pNETs G3/pNECs had TICs below those of pancreatic parenchyma from arterial phase to late phase (p < 0.05). Among all the CEUS quantitative parameters of DCE-US, values of relative rise time (rPE), relative mean transit time (rmTT) and relative area under the curve (rAUC) were significantly higher in pNETs G1/G2 group than those in pNETs G3/pNECs group (p < 0.05). Taking an rPE below 1.09 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [58.70% to 99.80%], 67.64% [48.61% to 83.32%] and 85.78% [74.14% to 97.42%], respectively. Taking rAUC below 0.855 as the optimal cut-off value, the sensitivity, specificity and accuracy for prediction of pNETs G3/pNECs from G1/G2 were 90.91% [66.26% to 99.53%], 83.87% [67.37% to 92.91%] and 94.72% [88.30% to 100.00%], respectively. Conclusions: Dynamic contrast-enhanced ultrasound analysis might be helpful for predicting the pathological grades of pNETs. Among all quantitative parameters, rPE, rmTT and rAUC are potentially useful parameters for predicting G3/pNECs with aggressive behavior. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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15 pages, 4883 KB  
Article
Contrast-Enhanced Ultrasonography with Arrival Time Parametric Imaging as a Non-Invasive Diagnostic Tool for Liver Cirrhosis
by Raluca Lupușoru, Ioan Sporea, Iulia Rațiu, Diana Lungeanu, Alina Popescu, Mirela Dănilă, Ruxandra Mare, Luciana Marc, Andrada Lascău, Tudor Voicu Moga, Felix Bende, Ana-Maria Ghiuchici and Roxana Șirli
Diagnostics 2022, 12(12), 3013; https://doi.org/10.3390/diagnostics12123013 - 1 Dec 2022
Cited by 5 | Viewed by 2342
Abstract
Liver biopsy is the gold standard method for staging liver fibrosis, but it is an invasive procedure that is associated with some complications. There are also non-invasive techniques for assessing liver fibrosis, such as elastography and biological tests, but these techniques can fail [...] Read more.
Liver biopsy is the gold standard method for staging liver fibrosis, but it is an invasive procedure that is associated with some complications. There are also non-invasive techniques for assessing liver fibrosis, such as elastography and biological tests, but these techniques can fail in detection or generate false measurements depending on the subject’s condition. This study aimed to determine whether liver fibrosis can be evaluated using contrast-enhanced ultrasonography with arrival time parametric imaging using the ultrasound machine’s parametric image software, the method being called (CEUS-PAT). CEUS-PAT was performed on each subject using SonoVue as a contrast agent, and images showing liver parenchyma and the right kidney on a single screen were used for analysis in parametric imaging, which was performed using the proprietary software of the ultrasound system. The ratio between the kidney and liver arrival times was calculated. The study included 64 predominantly male (56.3%) subjects, 37 cirrhotic patients, and 27 healthy volunteers, with a mean age of 58.98 ± 8.90 years. Significant differences were found between the liver cirrhosis and healthy groups regarding CEUS-PAT, 0.83 ± 0.09 vs. 0.49 ± 0.11, p < 0.0001. The correlation between CEUS-PAT and VCTE was r = 0.81. The optimal cut-off value for detecting liver cirrhosis was >0.7, with an AUC of 0.98, p < 0.001, Se = 89.19%, Sp = 100%, PPV = 100%, and NPV = 87.1%. We demonstrate that CEUS-PAT achieves excellent performance in diagnosing liver cirrhosis and is a fast method for diagnosing liver cirrhosis that can even be applied in situations where the use of other methods is excluded. Full article
(This article belongs to the Special Issue Imaging of Hepatitis)
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