{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:51:56Z","timestamp":1792623116384,"version":"4.5.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>This article investigates the first use of dynamic microvascularization of liver lesions in clinical evaluation using real-time super-resolution contrast-enhanced ultrasound (SR CEUS). A retrospective analysis of SR CEUS examinations of liver lesions was performed. All examinations were conducted using an SC7-1U convex probe after the bolus injection of the ultrasound contrast agent. Digital cine loops were stored for independent evaluation. The evaluation was performed with respect to parallel measuring lines (the diameter corresponded to the capillary density) in the area of the reference lesion, liver tissue, and liver capsule using statistical analysis. In total, 65 patients (female n = 28; male n = 37; average age 57.8 \u00b1 17.2 years) were evaluated. The examined liver lesions were mostly benign masses (n = 46). Mild liver fibrosis (stage F1) was present in most cases (n = 35). The lesions examined were located at an average tissue depth of 6.07 \u00b1 2.47 cm. The highest number of lesion measurements was observed in the malignant lesion group. Significant differences in the measurements were found when comparing benign lesions with the capillary region (p &lt; 0.001) and normal liver tissue (p &lt; 0.01). The use of SR CEUS opens up new possibilities for the quantification of neovascularization, assessment of microvascular changes, and evaluation of the follow-up of intrahepatic interventions.<\/jats:p>","DOI":"10.3390\/life15070991","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T06:50:45Z","timestamp":1750402245000},"page":"991","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Super-Resolution Contrast-Enhanced Ultrasound Examination Down to the Microvasculature Enables Quantitative Analysis of Liver Lesions: First Results"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0321-5245","authenticated-orcid":false,"given":"Ulrich","family":"Kaiser","sequence":"first","affiliation":[{"name":"Medical Clinic and Polyclinic for Internal Medicine III, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Vehling-Kaiser","sequence":"additional","affiliation":[{"name":"MVZ Dr. Vehling-Kaiser GmbH, 84036 Landshut, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"K\u00fcck","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, University Medical Center G\u00f6ttingen, 37073 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Gilanschah","sequence":"additional","affiliation":[{"name":"Institute for Diagnostic Radiology and Interdisciplinary Ultrasound Center, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, Molecular Cell Biology, Brandenburg University of Technology, 01968 Senftenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst Michael","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Diagnostic Radiology and Interdisciplinary Ultrasound Center, University Hospital Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s43657-023-00122-0","article-title":"The Protocol of Ultrasonic Backscatter Measurements of Musculoskeletal Properties","volume":"4","author":"Bi","year":"2024","journal-title":"Phenomics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3233\/CH-239100","article-title":"Current aspects of multimodal ultrasound liver diagnostics using contrast-enhanced ultrasonography (CEUS), fat evaluation, fibrosis assessment, and perfusion analysis\u2014An update","volume":"83","author":"Jung","year":"2023","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.3233\/CH-249103","article-title":"Novel high-resolution contrast agent ultrasound techniques HiFR CEUS and SR CEUS in combination with shear wave elastography, fat assessment and viscosity of liver parenchymal changes and tumors","volume":"86","author":"Jung","year":"2024","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pausch, A.M., Kammerer, S., Weber, F., Herr, W., Stroszczynski, C., Holler, E., Edinger, M., Wolff, D., Weber, D., and Jung, E.M. (2021). Parametric Imaging of Contrast-Enhanced Ultrasound (CEUS) for the Evaluation of Acute Gastrointestinal Graft-Versus-Host Disease. Cells, 10.","DOI":"10.3390\/cells10051092"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hu, S., Zhang, X., Unger, M., Patties, I., Melzer, A., and Landgraf, L. (2020). Focused Ultrasound-Induced Cavitation Sensitizes Cancer Cells to Radiation Therapy and Hyperthermia. Cells, 9.","DOI":"10.3390\/cells9122595"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Landgraf, L., Kozlowski, A., Zhang, X., Fournelle, M., Becker, F.J., Tretbar, S., and Melzer, A. (2022). Focused Ultrasound Treatment of a Spheroid In Vitro Tumour Model. Cells, 11.","DOI":"10.3390\/cells11091518"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2579","DOI":"10.1016\/j.ultrasmedbio.2020.04.030","article-title":"Guidelines and Good Clinical Practice Recommendations for Contrast-Enhanced Ultrasound (CEUS) in the Liver-Update 2020 WFUMB in Cooperation with EFSUMB, AFSUMB, AIUM, and FLAUS","volume":"46","author":"Dietrich","year":"2020","journal-title":"Ultraschall Med.-Eur. J. Ultrasound"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1148\/radiol.2019191086","article-title":"Diagnostic Accuracy of CEUS LI-RADS for the Characterization of Liver Nodules 20 mm or Smaller in Patients at Risk for Hepatocellular Carcinoma","volume":"294","author":"Huang","year":"2020","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1055\/a-1198-4874","article-title":"Contrast-Enhanced Ultrasound Algorithms (CEUS-LIRADS\/ESCULAP) for the Noninvasive Diagnosis of Hepatocellular Carcinoma\u2014A Prospective Multicenter DEGUM Study","volume":"42","author":"Schellhaas","year":"2021","journal-title":"Ultraschall Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7614","DOI":"10.1007\/s00330-021-07872-3","article-title":"Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS\u00ae\/ESCULAP) in hepatic nodules in cirrhotic patients\u2014A prospective multicenter study","volume":"31","author":"Strobel","year":"2021","journal-title":"Eur. Radiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3233\/CH-231740","article-title":"Washout appearance of hepatocellular carcinomas using standardized contrast-enhanced ultrasound (CEUS) including an extended late phase observation\u2014Real-world data from the prospective multicentre DEGUM study","volume":"84","author":"Jesper","year":"2023","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_12","first-page":"952","article-title":"[Contrast-enhanced ultrasound (CEUS) for characterisation of focal liver lesions]","volume":"62","author":"Kallenbach","year":"2024","journal-title":"Z. Fur Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.ultrasmedbio.2006.05.031","article-title":"The safety of Sonovue in abdominal applications: Retrospective analysis of 23188 investigations","volume":"32","author":"Piscaglia","year":"2006","journal-title":"Ultrasound Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.7863\/ultra.15.11075","article-title":"Safety of Sulfur Hexafluoride Microbubbles in Sonography of Abdominal and Superficial Organs: Retrospective Analysis of 30,222 Cases","volume":"36","author":"Tang","year":"2017","journal-title":"J. Ultrasound Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1225654","DOI":"10.3389\/fcvm.2023.1225654","article-title":"Safety of Lumason\u00ae (SonoVue\u00ae) in special populations and critically ill patients","volume":"10","author":"Filippone","year":"2023","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3233\/CH-209202","article-title":"Contrast enhanced ultrasound (CEUS) with parametric imaging and time intensity curve analysis (TIC) for evaluation of the success of prostate arterial embolization (PAE) in cases of prostate hyperplasia","volume":"76","author":"Jung","year":"2020","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00117-021-00891-7","article-title":"Contrast-enhanced ultrasound perfusion imaging of organs","volume":"61","author":"Jung","year":"2021","journal-title":"Radiologe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3233\/CH-151966","article-title":"Contrast-enhanced ultrasound with perfusion analysis for the identification of malignant and benign tumours of the thyroid gland","volume":"63","author":"Wendl","year":"2015","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1109\/TUFFC.2017.2778941","article-title":"Improved Super-Resolution Ultrasound Microvessel Imaging with Spatiotemporal Nonlocal Means Filtering and Bipartite Graph-Based Microbubble Tracking","volume":"65","author":"Song","year":"2018","journal-title":"IEEE Trans. Ultrason. Ferroelectr. Freq. Control."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nature16066","article-title":"Ultrafast ultrasound localization microscopy for deep super-resolution vascular imaging","volume":"527","author":"Errico","year":"2015","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.ultrasmedbio.2019.11.013","article-title":"Super-resolution Ultrasound Imaging","volume":"46","author":"Couture","year":"2020","journal-title":"Ultrasound Med. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huang, C., Zhang, W., Gong, P., Lok, U.W., Tang, S., Yin, T., Zhang, X., Zhu, L., Sang, M., and Song, P. (2021). Super-resolution ultrasound localization microscopy based on a high frame-rate clinical ultrasound scanner: An in-human feasibility study. Phys. Med. Biol., 66.","DOI":"10.1088\/1361-6560\/abef45"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1055\/s-0043-119353","article-title":"Percutaneous Treatment of Malignant Liver Lesions: Evaluation of Success Using Contrast- Enhanced Ultrasound (CEUS) and Perfusion Software","volume":"39","author":"Wiesinger","year":"2018","journal-title":"Ultraschall Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5192","DOI":"10.1016\/j.csda.2006.05.024","article-title":"A studentized permutation test for the non-parametric Behrens\u2013Fisher problem","volume":"51","author":"Neubert","year":"2007","journal-title":"Comput. Stat. Data Anal."},{"key":"ref_25","unstructured":"Team RDC (2023). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing. Available online: https:\/\/www.r-project.org\/."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.21105\/joss.03167","article-title":"Visualizations with statistical details: The \u2018ggstatsplot\u2019 approach","volume":"6","author":"Patil","year":"2021","journal-title":"J. Open Source Softw."},{"key":"ref_27","unstructured":"Arnholt, A.T., and Evans, B. (2025, April 20). BSDA: Basic Statistics and Data Analysis. Available online: https:\/\/cran.r-project.org\/web\/packages\/BSDA\/index.html."},{"key":"ref_28","unstructured":"Christensen, R.H.B. (2025, April 20). Ordinal: Regression Models for Ordinal Data. Available online: https:\/\/cran.r-project.org\/web\/packages\/ordinal\/index.html."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"772","DOI":"10.21105\/joss.00772","article-title":"ggeffects: Tidy Data Frames of Marginal Effects from Regression Models","volume":"3","year":"2018","journal-title":"J. Open Source Softw."},{"key":"ref_30","unstructured":"Heinze, G., Ploner, M., Jiricka, L., and Steiner, G. (2025, April 20). logistf: Firth\u2019s Bias-Reduced Logistic Regression. Available online: https:\/\/cran.r-project.org\/web\/packages\/logistf\/index.html."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e48","DOI":"10.1055\/a-0641-0076","article-title":"EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version)","volume":"38","author":"Dietrich","year":"2017","journal-title":"Ultraschall Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S113","DOI":"10.3233\/CH-248109","article-title":"Improved diagnostic confidence using Super Resolution CEUS imaging in testicular lesions","volume":"88","author":"Apfelbeck","year":"2024","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3233\/CH-189417","article-title":"Influence of limited examination conditions on contrast-enhanced sonography for characterising liver lesions","volume":"71","author":"Putz","year":"2019","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_34","first-page":"18","article-title":"Focal nodular hyperplasia and hepatocellular adenoma","volume":"55","year":"2015","journal-title":"Radiologist"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1080\/00365520601021765","article-title":"Analysis of neuroendocrine tumour metastases in the liver using contrast enhanced ultrasonography","volume":"42","author":"Andre","year":"2007","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_36","first-page":"1099","article-title":"Contrast sonography for the characterization of liver tumors: Practical aspects","volume":"53","author":"Jenssen","year":"2015","journal-title":"Z Gastroenterol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Eusebi, L., Masino, F., Bertolotto, M., Montatore, M., Sortino, G., Pitoni, L., Santarelli, S., Galosi, A.B., and Guglielmi, G. (2025). Contrast-enhanced ultrasound in the evaluation and management of solid renal lesions based on EFSUMB guidelines. J. Med. Ultrason.","DOI":"10.1007\/s10396-025-01546-z"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1055\/a-2157-2587","article-title":"EFSUMB Technical Review\u2014Update 2023: Dynamic Contrast-Enhanced Ultrasound (DCE-CEUS) for the Quantification of Tumor Perfusion","volume":"45","author":"Dietrich","year":"2024","journal-title":"Ultraschall Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e232369","DOI":"10.1148\/radiol.232369","article-title":"Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024","volume":"311","author":"Lyshchik","year":"2024","journal-title":"Radiology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3779","DOI":"10.1007\/s00261-020-02573-9","article-title":"Contrast-enhanced ultrasound imaging of the liver: A review of the clinical evidence for SonoVue and Sonazoid","volume":"45","author":"Barr","year":"2020","journal-title":"Abdom. Radiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"357","DOI":"10.3233\/CH-179112","article-title":"Efficiency of contrast enhanced ultrasound for immediate assessment of ablation status after intraoperative radiofrequency ablation of hepatic malignancies","volume":"66","author":"Beyer","year":"2017","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"479","DOI":"10.15403\/jgld-4997","article-title":"Color Mapping using Ultrasound System-integrated Perfusion Software for Evaluation of Focal Liver Lesions: A Possible First Step for More Independent Reading","volume":"32","author":"Dropco","year":"2023","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_43","first-page":"82","article-title":"Liver cysts: Ultrasound and diagnostics","volume":"5","author":"Radu","year":"2024","journal-title":"Swiss Gastroenterol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ingangi, V., De Chiara, A., Ferrara, G., Gallo, M., Catapano, A., Fazioli, F., Di Carluccio, G., Peranzoni, E., Marigo, I., and Carriero, M.V. (2024). Emerging Treatments Targeting the Tumor Microenvironment for Advanced Chondrosarcoma. Cells, 13.","DOI":"10.3390\/cells13110977"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Apelt, K., Bijkerk, R., Lebrin, F., and Rabelink, T.J. (2021). Imaging the Renal Microcirculation in Cell Therapy. Cells, 10.","DOI":"10.3390\/cells10051087"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/7\/991\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:55:38Z","timestamp":1760032538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/7\/991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":45,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["life15070991"],"URL":"https:\/\/doi.org\/10.3390\/life15070991","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]}}}