{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:33:37Z","timestamp":1780450417619,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leiden University Medical Center"},{"name":"Health~Holland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Vein grafts (VGs) are used to bypass atherosclerotic obstructions and arteriovenous fistulas (AVFs) as vascular access for hemodialysis. Vascular remodeling governs post-interventional arterialization, but may also induce VG and AVF failure. Although the endpoint characteristics of vascular remodeling are known, the in vivo process and the role of blood flow dynamics has not been fully studied. Therefore, here we non-invasively quantify vascular remodeling and blood flow alterations over time in murine VG and AVF models. C57BL\/6J (n = 7, chow diet) and atherosclerosis-prone ApoE3*Leiden (n = 7) mice underwent VG surgery. Ultrasound imaging was performed at 3, 7, 14, 21, and 28 days post-surgery. C57BL\/6J mice (n = 8) received AVF surgery. Ultrasound imaging was performed at 7 and 14 days post-surgery. The luminal volume increased by 42% in the VGs of C57BL\/6J and 38% in the VGs of ApoE3*Leiden mice at 28 days relative to 3 days post-surgery. Longitudinally, an 82% increase in wall volume and 76% increase in outward remodeling was found in the ApoE3*Leiden mice, with a constant wall size in C57BL\/6J mice. Proximally, the pulsatility index, resistive index, and peak systolic velocity decreased longitudinally in both groups. Distally, the maximum acceleration increased with 56% in C57BL\/6J VGs. Among the AVFs, 50% showed maturation after 7 days, based on a novel flow-criterium of 23 mL\/min. Distinct flow patterns were observed at the anastomotic site and inflow artery of the AVFs relative to the control carotid arteries. Vascular remodeling can be quantified by ultra-high-frequency ultrasound imaging over time in complex animal models, via three-dimensional structural parameters and site-specific hemodynamic indices.<\/jats:p>","DOI":"10.3390\/ijms232113298","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"13298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Visualization of Murine Vascular Remodeling and Blood Flow Dynamics by Ultra-High-Frequency Ultrasound Imaging"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3463-1217","authenticated-orcid":false,"given":"Vincent Q.","family":"Sier","sequence":"first","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4556-5393","authenticated-orcid":false,"given":"Alwin","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6853-5760","authenticated-orcid":false,"given":"Paul H. A.","family":"Quax","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-9130","authenticated-orcid":false,"given":"Margreet R.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"},{"name":"Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3389\/fcvm.2018.00003","article-title":"Inflammation in Vein Graft Disease","volume":"5","author":"Quax","year":"2018","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jvs.2012.06.098","article-title":"Thirty-day vein remodeling is predictive of midterm graft patency after lower extremity bypass","volume":"57","author":"Gasper","year":"2013","journal-title":"J. Vasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6293","DOI":"10.1096\/fj.201800437R","article-title":"Relaxin receptor deficiency promotes vascular inflammation and impairs outward remodeling in arteriovenous fistulas","volume":"32","author":"Bezhaeva","year":"2018","journal-title":"FASEB J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrcardio.2016.76","article-title":"Vein graft failure: From pathophysiology to clinical outcomes","volume":"13","author":"Simons","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1161\/ATVBAHA.106.129254","article-title":"Vascular remodeling: Hemodynamic and biochemical mechanisms underlying Glagov\u2019s phenomenon","volume":"27","author":"Korshunov","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1161\/01.RES.0000036901.58329.D7","article-title":"Accelerated atherosclerosis and calcification in vein grafts: A study in APOE*3 Leiden transgenic mice","volume":"91","author":"Lardenoye","year":"2002","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.2215\/CJN.11251210","article-title":"Outcomes of arteriovenous fistula creation after the Fistula First Initiative","volume":"6","author":"Schinstock","year":"2011","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"F794","DOI":"10.1152\/ajprenal.00440.2018","article-title":"Arteriovenous conduits for hemodialysis: How to better modulate the pathophysiological vascular response to optimize vascular access durability","volume":"316","author":"Shiu","year":"2019","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/ndt\/gft068","article-title":"Arteriovenous access failure: More than just intimal hyperplasia?","volume":"28","author":"Rothuizen","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","first-page":"e53294","article-title":"A Novel Murine Model of Arteriovenous Fistula Failure: The Surgical Procedure in Detail","volume":"108","author":"Wong","year":"2016","journal-title":"J. Vis. Exp."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Moran, C.M., and Thomson, A.J.W. (2020). Preclinical Ultrasound Imaging\u2014A Review of Techniques and Imaging Applications. Front. Phys., 8.","DOI":"10.3389\/fphy.2020.00124"},{"key":"ref_12","first-page":"2060","article-title":"The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic renal failure","volume":"10","author":"Petersen","year":"1995","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1161\/01.STR.0000032103.59213.BC","article-title":"Arterial remodeling of the common carotid artery after aortic valve replacement in patients with aortic stenosis","volume":"33","author":"Irace","year":"2002","journal-title":"Stroke"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1177\/0003319718776122","article-title":"The Growing Field of Imaging of Atherosclerosis in Peripheral Arteries","volume":"70","author":"Cattaneo","year":"2019","journal-title":"Angiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.atherosclerosis.2012.05.023","article-title":"Plaque characteristics and arterial remodeling in coronary and peripheral arterial systems","volume":"223","author":"Matsuo","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"319","DOI":"10.3400\/avd.ra.19-00070","article-title":"Updates on Ultrasonography Imaging in Abdominal Aortic Aneurysm","volume":"12","author":"Iwakoshi","year":"2019","journal-title":"Ann. Vasc. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejvs.2018.09.020","article-title":"Editor\u2019s Choice\u2014European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms","volume":"57","author":"Wanhainen","year":"2019","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Sier, V.Q., van der Vorst, J.R., Quax, P.H.A., de Vries, M.R., Zonoobi, E., Vahrmeijer, A.L., Dekkers, I.A., de Geus-Oei, L.F., Smits, A.M., and Cai, W. (2021). Endoglin\/CD105-Based Imaging of Cancer and Cardiovascular Diseases: A Systematic Review. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22094804"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/S0002-8703(05)80190-5","article-title":"Assessment of normal and atherosclerotic arterial wall thickness with an intravascular ultrasound imaging catheter","volume":"119","author":"Mallery","year":"1990","journal-title":"Am. Heart J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"784980","DOI":"10.3389\/fcvm.2021.784980","article-title":"Interfering in the ALK1 Pathway Results in Macrophage-Driven Outward Remodeling of Murine Vein Grafts","volume":"8","author":"Sier","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"H1875","DOI":"10.1152\/ajpheart.00872.2009","article-title":"Time course of carotid artery growth and remodeling in response to altered pulsatility","volume":"299","author":"Eberth","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.avsg.2021.09.056","article-title":"A New Doppler-Derived Parameter to Quantify Internal Carotid Artery Stenosis: Maximal Systolic Acceleration","volume":"81","author":"Brouwers","year":"2022","journal-title":"Ann. Vasc. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/sj.ki.5000112","article-title":"New intrarenal echo-Doppler velocimetric indices for the diagnosis of renal artery stenosis","volume":"69","author":"Bardelli","year":"2006","journal-title":"Kidney Int."},{"key":"ref_24","first-page":"391","article-title":"A comparison of the Doppler-derived maximal systolic acceleration versus the ankle-brachial pressure index or detecting and quantifying peripheral arterial occlusive disease in diabetic patients","volume":"51","author":"Bastiaansen","year":"2010","journal-title":"J. Cardiovasc. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.jvs.2019.01.088","article-title":"Using maximal systolic acceleration to diagnose and assess the severity of peripheral artery disease in a flow model study","volume":"71","author":"Brouwers","year":"2020","journal-title":"J. Vasc. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1525-139X.2005.18320.x","article-title":"Is there a place for duplex screening of the brachial artery in the maturation of arteriovenous fistulas?","volume":"18","author":"Lomonte","year":"2005","journal-title":"Semin. Dial."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/sj.ki.5001747","article-title":"Why don\u2019t fistulas mature?","volume":"70","author":"Dixon","year":"2006","journal-title":"Kidney Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1161\/01.STR.32.4.836","article-title":"Comparison of carotid arterial resistive indices with intima-media thickness as sonographic markers of atherosclerosis","volume":"32","author":"Frauchiger","year":"2001","journal-title":"Stroke"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"126","DOI":"10.3171\/2013.8.JNS13931","article-title":"Middle cerebral artery pulsatility index and cognitive improvement after carotid endarterectomy for symptomatic stenosis","volume":"120","author":"Heyer","year":"2014","journal-title":"J. Neurosurg."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Buschmann, E.E., Li, L., Brix, M., Zietzer, A., Hillmeister, P., Busjahn, A., Bramlage, P., and Buschmann, I. (2018). A novel computer-aided diagnostic approach for detecting peripheral arterial disease in patients with diabetes. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199374"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hennerici, M.G., and Meairs, S.P. (2001). Flow patterns and arterial wall dynamics. Cerebrovascular Ultrasound: Theory, Practice and Future Developments, Cambridge University Press.","DOI":"10.1017\/CBO9780511759079"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/ehjci\/jey103","article-title":"Focus on echovascular imaging assessment of arterial disease: Complement to the ESC guidelines (PARTIM 1) in collaboration with the Working Group on Aorta and Peripheral Vascular Diseases","volume":"19","author":"Sprynger","year":"2018","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1161\/01.ATV.0000160548.78317.29","article-title":"Mechanisms, pathophysiology, and therapy of arterial stiffness","volume":"25","author":"Zieman","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16657","DOI":"10.1364\/OE.15.016657","article-title":"Ex vivo Characterization of Atherosclerosis using Intravascular Photoacoustic Imaging","volume":"15","author":"Sethuraman","year":"2007","journal-title":"Opt. Express"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1161\/ATVBAHA.117.310296","article-title":"Carotid Artery Remodeling Is Segment Specific: An In Vivo Study by Vessel Wall Magnetic Resonance Imaging","volume":"38","author":"Watase","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1148\/radiology.204.2.9240517","article-title":"Common carotid artery: Variability of Doppler US velocity measurements","volume":"204","author":"Meyer","year":"1997","journal-title":"Radiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1148\/radiology.214.2.r00fe25387","article-title":"Variability of Doppler US measurements along the common carotid artery: Effects on estimates of internal carotid arterial stenosis in patients with angiographically proved disease","volume":"214","author":"Lee","year":"2000","journal-title":"Radiology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/2191-219X-2-44","article-title":"Anaesthesia and physiological monitoring during in vivo imaging of laboratory rodents: Considerations on experimental outcomes and animal welfare","volume":"2","author":"Tremoleda","year":"2012","journal-title":"EJNMMI Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ultrasmedbio.2006.11.002","article-title":"Effects of isoflurane on coronary blood flow velocity in young, old and ApoE\u2212\/\u2212 mice measured by Doppler ultrasound","volume":"33","author":"Hartley","year":"2007","journal-title":"Ultrasound Med. Biol."},{"key":"ref_40","first-page":"e59013","article-title":"Ultrasound Imaging of the Thoracic and Abdominal Aorta in Mice to Determine Aneurysm Dimensions","volume":"145","author":"Sawada","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_41","unstructured":"(2020). AIUM Practice Parameter for the Performance of Vascular Ultrasound Examinations for Postoperative Assessment of Hemodialysis Access. J. Ultrasound Med., 39, E39\u2013E48."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/s40477-014-0113-6","article-title":"Color Doppler ultrasound and arteriovenous fistulas for hemodialysis","volume":"17","author":"Zamboli","year":"2014","journal-title":"J. Ultrasound"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.jvs.2013.02.242","article-title":"Vascular remodeling and intimal hyperplasia in a novel murine model of arteriovenous fistula failure","volume":"59","author":"Wong","year":"2014","journal-title":"J. Vasc. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30439","DOI":"10.1038\/srep30439","article-title":"Liposomal prednisolone inhibits vascular inflammation and enhances venous outward remodeling in a murine arteriovenous fistula model","volume":"6","author":"Wong","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10269","DOI":"10.1038\/s41598-017-10108-4","article-title":"Deficiency of TLR4 homologue RP105 aggravates outward remodeling in a murine model of arteriovenous fistula failure","volume":"7","author":"Bezhaeva","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_46","first-page":"604821","article-title":"P300\/CBP Associated Factor (PCAF) Deficiency Enhances Diet-Induced Atherosclerosis in ApoE3*Leiden Mice via Systemic Inhibition of Regulatory T Cells","volume":"7","author":"Peters","year":"2020","journal-title":"Front. Cardiovasc. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:07:09Z","timestamp":1760144829000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":46,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232113298"],"URL":"https:\/\/doi.org\/10.3390\/ijms232113298","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]}}}