{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:23:55Z","timestamp":1791829435440,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Augsburg"},{"id":[{"id":"https:\/\/ror.org\/03p14d497","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Topical imiquimod is an established non-invasive treatment for superficial basal cell carcinoma (sBCC). However, data on treatment-associated changes in tumor microvascularization remain limited. This study investigated vascular changes before and after imiquimod therapy using multimodal non-invasive imaging. Methods: In this single-center, prospective observational study, 31 basal cell carcinomas in 20 patients were examined before and 12\u201316 weeks after topical imiquimod therapy (5%, five times weekly for six weeks) using dermoscopy, dynamic optical coherence tomography (D-OCT), and line-field confocal optical coherence tomography (LC-OCT). Analyses were performed as paired before-and-after comparisons. While approved for sBCC, a small number of thin nodular and infiltrative BCCs were included exploratorily; subgroup analyses were not powered. Results: Dermoscopy showed a nominally significant shift toward smaller vessel diameter categories after therapy (ATS = 8.183, df = 1, p = 0.004). D-OCT-derived parameters (vessel density, vessel diameter, and depth of the vascular plexus) did not show nominally significant changes. LC-OCT showed nominally lower apparent intratumoral flow scores (ATS = 13.285, df = 1, p &lt; 0.001), reduced occurrence of vessel-wall-associated intraluminal structures showing a rolling-like motion pattern (86.7% before treatment versus 33.3% after treatment; ATS = 13.357; df = 1, p &lt; 0.001), and a reduction in maximum vessel diameter (ATS = 6.110, df = 1, p = 0.013). The primary LC-OCT inferential analyses were performed at the lesion level without adjustment for within-patient clustering and should therefore be interpreted as exploratory. An additional patient-cluster-adjusted paired change-score sensitivity analysis for LC-OCT maximum vessel diameter yielded a directionally consistent estimate (\u221217.81 \u00b5m; 95% CI: \u221234.40 to \u22121.23; p = 0.037). The primary exploratory endpoints were LC-OCT\u2013based apparent intratumoral flow and maximum vessel diameter; secondary endpoints included dermoscopic and D-OCT\u2013based vascular parameters. In the exploratory response-stratified analysis, the change in LC-OCT-based maximum vessel diameter did not differ significantly among the assigned response groups (Kruskal\u2013Wallis H = 3.870, df = 2, raw p = 0.144; BH-adjusted p = 0.753). Conclusions: LC-OCT detected several exploratory vascular changes between the pre-treatment examination and follow-up and may provide complementary information for the non-invasive assessment of BCC after imiquimod therapy. Given the exploratory design, limited sample size, and lack of systematic histological confirmation, these findings are hypothesis-generating and require validation in larger prospective studies.<\/jats:p>","DOI":"10.3390\/cancers18132153","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:05:38Z","timestamp":1783325138000},"page":"2153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploratory Multimodal Analysis of Vascular Changes in Basal Cell Carcinoma Before and After Topical Imiquimod Therapy Using Dermoscopy and Non-Invasive Imaging"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9908-9042","authenticated-orcid":false,"given":"Oliver","family":"Mayer","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1962-0618","authenticated-orcid":false,"given":"Hanna","family":"Wirsching","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3288-2549","authenticated-orcid":false,"given":"Sophia","family":"Schlingmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5902-4989","authenticated-orcid":false,"given":"Deborah","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2223-0591","authenticated-orcid":false,"given":"Lena","family":"Schemet","sequence":"additional","affiliation":[{"name":"Chair of Mathematical Statistics and Artificial Intelligence in Medicine, University of Augsburg, 86159 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Kaps","sequence":"additional","affiliation":[{"name":"Chair of Mathematical Statistics and Artificial Intelligence in Medicine, University of Augsburg, 86159 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-7418","authenticated-orcid":false,"given":"Julia","family":"Welzel","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-7619","authenticated-orcid":false,"given":"Sandra","family":"Schuh","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"ref_1","unstructured":"(2024). S2k-Leitlinie Basalzellkarzinom der Haut, AWMF."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Attal, Z.G., Shalata, W., Soklakova, A., Tourkey, L., Shalata, S., Abu Saleh, O., Abu Salamah, F., Alatawneh, I., and Yakobson, A. (2024). Advanced and Metastatic Non-Melanoma Skin Cancer: Epidemiology, Risk Factors, Clinical Features, and Treatment Options. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071448"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Verzi, A.E., Micali, G., and Lacarrubba, F. (2021). Line-Field Confocal Optical Coherence Tomography May Enhance Monitoring of Superficial Basal Cell Carcinoma Treated with Imiquimod 5% Cream: A Pilot Study. Cancers, 13.","DOI":"10.3390\/cancers13194913"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lin, T.-L., Lee, K.-H., Karmakar, R., Mukundan, A., Sundarraj, J., Lu, C.-T., Hsieh, S.-C., and Wang, H.-C. (2025). Artificial Intelligence-Assisted Dermatologic Screening: Epidemiology and Clinical Features of Basal Cell Carcinoma, Squamous Cell Carcinoma, Seborrheic Keratosis and Actinic Keratosis. Bioengineering, 12.","DOI":"10.3390\/bioengineering12111258"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113254","DOI":"10.1016\/j.ejca.2023.113254","article-title":"European consensus-based interdisciplinary guideline for diagnosis and treatment of basal cell carcinoma-update 2023","volume":"192","author":"Peris","year":"2023","journal-title":"Eur. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102037","DOI":"10.1016\/j.esmoop.2023.102037","article-title":"Guidelines for the diagnosis and treatment of basal cell carcinoma: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology","volume":"8","author":"Queirolo","year":"2023","journal-title":"ESMO Open"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jaad.2003.11.066","article-title":"Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies","volume":"50","author":"Geisse","year":"2004","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1111\/j.1365-2133.2005.06486.x","article-title":"Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from a randomized vehicle-controlled phase III study in Europe","volume":"152","author":"Schulze","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/srt.12102","article-title":"Optical coherence tomography imaging of non-melanoma skin cancer undergoing imiquimod therapy","volume":"20","author":"Banzhaf","year":"2014","journal-title":"Ski. Res. Technol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1001\/archderm.140.12.1485","article-title":"Vascular structures in skin tumors: A dermoscopy study","volume":"140","author":"Argenziano","year":"2004","journal-title":"Arch. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/jdv.14508","article-title":"Dynamic optical coherence tomography of skin blood vessels\u2014Proposed terminology and practical guidelines","volume":"32","author":"Ulrich","year":"2018","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Markowitz, O., Schwartz, M., Minhas, S., and Siegel, D.M. (2016). Speckle-variance optical coherence tomography: A novel approach to skin cancer characterization using vascular patterns. Dermatol. Online J., 22.","DOI":"10.5070\/D3224030620"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.23.10.106007","article-title":"Line-field confocal optical coherence tomography for high-resolution noninvasive imaging of skin tumors","volume":"23","author":"Dubois","year":"2018","journal-title":"J. Biomed. Opt."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8853","DOI":"10.3390\/curroncol30100639","article-title":"Line-Field Confocal Optical Coherence Tomography for the Diagnosis of Skin Carcinomas: Real-Life Data over Three Years","volume":"30","author":"Donelli","year":"2023","journal-title":"Curr. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S1470-2045(22)00347-3","article-title":"Optical coherence tomography versus punch biopsy for diagnosis of basal cell carcinoma: A multicentre, randomised, non-inferiority trial","volume":"23","author":"Adan","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.jaad.2009.11.698","article-title":"How to diagnose nonpigmented skin tumors: A review of vascular structures seen with dermoscopy: Part I. Melanocytic skin tumors","volume":"63","author":"Zalaudek","year":"2010","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S0738-081X(02)00227-4","article-title":"Vascular patterns in skin tumors","volume":"20","author":"Kreusch","year":"2002","journal-title":"Clin. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1590\/abd1806-4841.20153452","article-title":"Vascular structures in dermoscopy","volume":"90","author":"Ayhan","year":"2015","journal-title":"Bras. Dermatol."},{"key":"ref_19","unstructured":"Holmes, J. (2024, June 02). VivoSight Dx Instructions for Use. Available online: https:\/\/us.vivosight.com\/support-service\/."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1364\/OE.3.000219","article-title":"In vivo video rate optical coherence tomography","volume":"3","author":"Rollins","year":"1998","journal-title":"Opt. Express"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.mvr.2016.05.004","article-title":"Validation of Dynamic optical coherence tomography for non-invasive, in vivo microcirculation imaging of the skin","volume":"107","author":"Themstrup","year":"2016","journal-title":"Microvasc. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Mayer, O., Wirsching, H., Schlingmann, S., Welzel, J., and Schuh, S. (2025). 3D Segmentation and Visualization of Skin Vasculature Using Line-Field Confocal Optical Coherence Tomography. Appl. Sci., 15.","DOI":"10.3390\/app15010159"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: The leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1080\/10739680802350104","article-title":"Neutrophil adhesion and activation under flow","volume":"16","author":"Zarbock","year":"2009","journal-title":"Microcirculation"},{"key":"ref_25","first-page":"708","article-title":"Imiquimod as an antiangiogenic agent","volume":"4","author":"Li","year":"2005","journal-title":"J. Drugs Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s00262-025-03943-2","article-title":"Normalization of tumor vasculature by imiquimod: Proposal for a new anticancer therapeutic indication for a TLR7 agonist","volume":"74","author":"Magdalena","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/j.1365-4632.2004.02318.x","article-title":"Imiquimod is a strong inhibitor of tumor cell-induced angiogenesis","volume":"44","author":"Majewski","year":"2005","journal-title":"Int. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1046\/j.1523-1747.2003.12521.x","article-title":"Topically applied imiquimod inhibits vascular tumor growth in vivo","volume":"121","author":"Sidbury","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1046\/j.0366-077X.2003.05630.x","article-title":"Imiquimod in basal cell carcinoma: How does it work?","volume":"149","author":"Dummer","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_30","first-page":"1403","article-title":"Letter: Changes in dermoscopic features in superficial basal cell carcinomas treated with imiquimod","volume":"33","author":"Micantonio","year":"2007","journal-title":"Dermatol. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1111\/bjd.12749","article-title":"Applicability of dermoscopy for evaluation of patients\u2019 response to nonablative therapies for the treatment of superficial basal cell carcinoma","volume":"170","author":"Apalla","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Szalai, K., T\u00f3th, K., H\u00e1rsing, J., Gy\u00f6ngy, M., and Holl\u00f3, P. (2026). High-Frequency Ultrasound Assessment of Basal Cell Carcinoma: Correlations Between Histopathological Subtype, Vascularity, and Age\/Sex Distribution. Cancers, 18.","DOI":"10.3390\/cancers18020274"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wortsman, X. (2024). Ultrasound in Skin Cancer: Why, How, and When to Use It?. Cancers, 16.","DOI":"10.3390\/cancers16193301"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Popescu, C., Iliescu, C.A., Truica, A.M., Popa, L.G., Porosnicu, A.L., Tudose, I., Boeru, C., and Popescu, M.N. (2026). From Ultrasound to Histopathology: Agreement Analysis and Depth Correction Model for Basal Cell Carcinoma Using a Portable 20 MHz High-Frequency Ultrasound Device. Diagnostics, 16.","DOI":"10.3390\/diagnostics16070978"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:25:26Z","timestamp":1783326326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,4]]},"references-count":34,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cancers18132153"],"URL":"https:\/\/doi.org\/10.3390\/cancers18132153","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,4]]}}}