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In this study, we present a dual-modality imaging approach that integrates Ultrafast power Doppler ultrasound (UPD) with multispectral photoacoustic (PA) imaging to quantify spatiotemporal changes in tumor oxygenation and perfusion following photodynamic therapy (PDT). Our results demonstrate that PDT induces dose- and time-dependent spatial heterogenic alterations in both oxygenation and perfusion. To better interpret the spatial interplay between tumor oxygenation and vascular perfusion, we developed a Vascular Function Index (VFI), which classifies tumor subregions into four functional quadrants based on perfusion and oxygenation status at every voxel within the 3D tumor region. This framework revealed dynamic, time-dependent changes in tumor hypoxia and perfusion, with high-dose treatment groups showing a progressive increase in hypoxic and non-perfused regions, underscoring the spatiotemporal nature of PDT-induced vascular response.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Teaser<\/jats:title>\n                  <jats:p>Tumoral Blood flow and oxygenation interplay, assessed by label-free imaging, unravels heterogeneous therapy response.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.19.688289","type":"posted-content","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T18:05:22Z","timestamp":1763661922000},"source":"Crossref","is-referenced-by-count":0,"title":["Label-Free Hemodynamic Mapping via Ultrafast Power Doppler-Enhanced Photoacoustic Imaging reveals early therapy-induced functional changes in the tumor"],"prefix":"10.64898","author":[{"given":"Deeksha M","family":"Sankepalle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronak","family":"Shethia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Kruzinga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1547-1764","authenticated-orcid":false,"given":"Srivalleesha","family":"Mallidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025112213301069000_2025.11.19.688289v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2005.10.006"},{"key":"2025112213301069000_2025.11.19.688289v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81683-9"},{"key":"2025112213301069000_2025.11.19.688289v1.3","first-page":"e934116","article-title":"A Review of the Role of Hypoxia in Radioresistance in Cancer Therapy","volume":"27","year":"2021","journal-title":"Med Sci Monit"},{"key":"2025112213301069000_2025.11.19.688289v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.06.006"},{"issue":"6","key":"2025112213301069000_2025.11.19.688289v1.5","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1109\/51.544510","article-title":"Doppler ultrasound","volume":"15","year":"1996","journal-title":"IEEE Engineering in Medicine and Biology Magazine"},{"issue":"3","key":"2025112213301069000_2025.11.19.688289v1.6","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.crad.2017.10.006","article-title":"The utility of ultrasound superb microvascular imaging for evaluation of breast tumour vascularity: comparison with colour and power Doppler imaging regarding diagnostic performance","volume":"73","year":"2018","journal-title":"Clinical Radiology"},{"issue":"1","key":"2025112213301069000_2025.11.19.688289v1.7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s40644-024-00767-8","article-title":"Current trends in the characterization and monitoring of vascular response to cancer therapy","volume":"24","year":"2024","journal-title":"Cancer Imaging"},{"issue":"7","key":"2025112213301069000_2025.11.19.688289v1.8","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.7863\/ultra.16.07004","article-title":"Role of Superb Micro-Vascular Imaging in the Preoperative Evaluation of Thyroid Nodules: Comparison With Power Doppler Flow Imaging","volume":"36","year":"2017","journal-title":"Journal of Ultrasound in Medicine"},{"issue":"5","key":"2025112213301069000_2025.11.19.688289v1.9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/01617346211029542","article-title":"Ultrasonographic Detection of Vascularity of Focal Breast Lesions: Microvascular Imaging Versus Conventional Color and Power Doppler Imaging","volume":"43","year":"2021","journal-title":"Ultrasonic Imaging"},{"key":"2025112213301069000_2025.11.19.688289v1.10","doi-asserted-by":"publisher","DOI":"10.1109\/TUFFC.2018.2850811"},{"issue":"1","key":"2025112213301069000_2025.11.19.688289v1.11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jum.15079","article-title":"Superb Microvascular Imaging Compared With Power Doppler Ultrasound in Assessing Synovitis of the Knee in Juvenile Idiopathic Arthritis: A Preliminary Study","volume":"39","year":"2020","journal-title":"J Ultrasound Med"},{"key":"2025112213301069000_2025.11.19.688289v1.12","doi-asserted-by":"crossref","unstructured":"Dias, A.B. , C. 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