{"paper_id":"2312ca4d-09e4-4add-99ba-e3383a9fe7e3","body_text":"Multimodal Imaging Evaluation of Hypoxic Bone Marrow Microenvironment and Type H Vascular Injury in Diabetes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Multimodal Imaging Evaluation of Hypoxic Bone Marrow Microenvironment and Type H Vascular Injury in Diabetes Haoran Lei, Kejun Wang, Liang Li, Changsheng Liu, Yunfei Zha This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7779699/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Type 1 diabetes mellitus (T1DM) can lead to severe diabetic osteopathy, largely driven by alterations in the bone marrow hypoxic microenvironment and damage to type H vessels. This study employed multimodal imaging—including DCE-MRI, Micro-CT, and USPIO-enhanced MRI—to enable early in vivo assessment of hypoxic changes and type H vessel impairment in a T1DM rabbit model. Experiments involved 20 rabbits with alloxan-induced T1DM and controls, evaluated four months post-modeling. Imaging revealed significant differences in bone marrow microcirculatory perfusion and vascular permeability in T1DM rabbits, along with elevated USPIO uptake and regional heterogeneity that correlated with type H vessel distribution. Accompanying pathological changes were confirmed via immunofluorescence, qPCR, and transmission electron microscopy, supporting the role of the AGEs/ROS-HIF-1α-VEGF pathway in these microvascular lesions. Our findings offer visual and quantitative imaging evidence to inform future clinical strategies targeting type H vessel hypoxia in diabetic osteopathy. Health sciences/Diseases Health sciences/Endocrinology Health sciences/Medical research Type 1 diabetes mellitus Bone microenvironment Type H vessels HIF-1α Multimodal imaging Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Feb, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 11 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviewers agreed at journal 01 Dec, 2025 Reviews received at journal 28 Nov, 2025 Reviewers agreed at journal 20 Nov, 2025 Reviewers invited by journal 27 Oct, 2025 Editor invited by journal 08 Oct, 2025 Editor assigned by journal 06 Oct, 2025 Submission checks completed at journal 06 Oct, 2025 First submitted to journal 04 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Reports\",\"twitterHandle\":\"\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"stoa\",\"reportingPortfolio\":\"Scientific Reports\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Type 1 diabetes mellitus, Bone microenvironment, Type H vessels, HIF-1α, Multimodal imaging\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7779699/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7779699/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003eType 1 diabetes mellitus (T1DM) can lead to severe diabetic osteopathy, largely driven by alterations in the bone marrow hypoxic microenvironment and damage to type H vessels. This study employed multimodal imaging\\u0026mdash;including DCE-MRI, Micro-CT, and USPIO-enhanced MRI\\u0026mdash;to enable early in vivo assessment of hypoxic changes and type H vessel impairment in a T1DM rabbit model. Experiments involved 20 rabbits with alloxan-induced T1DM and controls, evaluated four months post-modeling. Imaging revealed significant differences in bone marrow microcirculatory perfusion and vascular permeability in T1DM rabbits, along with elevated USPIO uptake and regional heterogeneity that correlated with type H vessel distribution. Accompanying pathological changes were confirmed via immunofluorescence, qPCR, and transmission electron microscopy, supporting the role of the AGEs/ROS-HIF-1α-VEGF pathway in these microvascular lesions. 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