{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:46:09Z","timestamp":1790419569767,"version":"4.1.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T00:00:00Z","timestamp":1592956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This is an exploratory study using a novel imaging modality, quantitative ultrashort time-to-echo, contrast enhanced (QUTE-CE) magnetic resonance imaging to evaluate the permeability of the blood\u2013brain barrier in a rat model of type 2 diabetes with the presumption that small vessel disease is a contributing factor to neuropathology in diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The BBZDR\/Wor rat, a model of type 2 diabetes, and age-matched controls were studied for changes in blood\u2013brain barrier permeability. QUTE-CE, a quantitative vascular biomarker, generated angiographic images with over 500,000 voxels that were registered to a 3D MRI rat brain atlas providing site-specific information on blood\u2013brain barrier permeability in 173 different brain areas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this model of diabetes, without the support of insulin treatment, there was global capillary pathology with over 84% of the brain showing a significant increase in blood\u2013brain barrier permeability over wild-type controls. Areas of the cerebellum and midbrain dopaminergic system were not significantly affected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Small vessel disease as assessed by permeability in the blood\u2013brain barrier in type 2 diabetes is pervasive and includes much of the brain. The increase in blood\u2013brain barrier permeability is a likely contributing factor to diabetic encephalopathy and dementia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-020-02428-3","type":"journal-article","created":{"date-parts":[[2020,6,24]],"date-time":"2020-06-24T07:02:54Z","timestamp":1592982174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Evaluating blood\u2013brain barrier permeability in a rat model of type 2 diabetes"],"prefix":"10.1186","volume":"18","author":[{"given":"Ju","family":"Qiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Lawson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kilian F. G.","family":"Rentrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9744-5214","authenticated-orcid":false,"given":"Craig F.","family":"Ferris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,24]]},"reference":[{"key":"2428_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/s1262-3636(07)70298-7","author":"F Pasquier","year":"2006","unstructured":"Pasquier F, Boulogne A, Leys D, Fontaine P. Diabetes mellitus and dementia. Diabetes Metab. 2006. https:\/\/doi.org\/10.1016\/s1262-3636(07)70298-7.","journal-title":"Diabetes Metab"},{"key":"2428_CR2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2008.00987.x","author":"CL Allen","year":"2009","unstructured":"Allen CL, Bayraktutan U. Antioxidants attenuate hyperglycaemia-mediated brain endothelial cell dysfunction and blood-brain barrier hyperpermeability. Diabetes Obes Metab. 2009. https:\/\/doi.org\/10.1111\/j.1463-1326.2008.00987.x.","journal-title":"Diabetes Obes Metab"},{"key":"2428_CR3","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-017-9752-7","author":"M Bogush","year":"2017","unstructured":"Bogush M, Heldt NA, Persidsky Y. Blood brain barrier injury in diabetes: unrecognized effects on brain and cognition. J Neuroimmune Pharmacol. 2017. https:\/\/doi.org\/10.1007\/s11481-017-9752-7.","journal-title":"J Neuroimmune Pharmacol"},{"key":"2428_CR4","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.74.1.70","author":"JM Starr","year":"2003","unstructured":"Starr JM, Wardlaw J, Ferguson K, MacLullich A, Deary IJ, Marshall I. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2003. https:\/\/doi.org\/10.1136\/jnnp.74.1.70.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2428_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.10.034","author":"R Raja","year":"2018","unstructured":"Raja R, Rosenberg GA, Caprihan A. MRI measurements of Blood\u2013Brain Barrier function in dementia: a review of recent studies. Neuropharmacology. 2018. https:\/\/doi.org\/10.1016\/j.neuropharm.2017.10.034.","journal-title":"Neuropharmacology"},{"key":"2428_CR6","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.25426","author":"CA Gharagouzloo","year":"2015","unstructured":"Gharagouzloo CA, McMahon PN, Sridhar S. Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences. Magn Reson Med. 2015. https:\/\/doi.org\/10.1002\/mrm.25426.","journal-title":"Magn Reson Med"},{"key":"2428_CR7","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.45.3.292","author":"RS Tirabassi","year":"2004","unstructured":"Tirabassi RS, Flanagan JF, Wu T, Kislauskis EH, Birckbichler PJ, Guberski DL. The BBZDR\/Wor rat model for investigating the complications of type 2 diabetes mellitus. ILAR J. 2004. https:\/\/doi.org\/10.1093\/ilar.45.3.292.","journal-title":"ILAR J"},{"key":"2428_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.09.003","author":"CA Gharagouzloo","year":"2017","unstructured":"Gharagouzloo CA, Timms L, Qiao J, Fang Z, Nneji J, Pandya A, Kulkarni P, van de Ven AL, Ferris C, Sridhar S. Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function. NeuroImage. 2017. https:\/\/doi.org\/10.1016\/j.neuroimage.2017.09.003.","journal-title":"NeuroImage"},{"key":"2428_CR9","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-007-0712-0","author":"J Bremerich","year":"2007","unstructured":"Bremerich J, Bilecen D, Reimer P. MR angiography with blood pool contrast agents. Eur Radiol. 2007. https:\/\/doi.org\/10.1007\/s00330-007-0712-0.","journal-title":"Eur Radiol"},{"key":"2428_CR10","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000230","author":"AM Muehe","year":"2016","unstructured":"Muehe AM, Feng D, von Eyben R, Luna-Fineman S, Link MP, Muthig T, Huddleston AE, Neuwelt EA, Daldrup-Link HE. Safety report of ferumoxytol for magnetic resonance imaging in children and young adults. Invest Radiol. 2016. https:\/\/doi.org\/10.1097\/RLI.0000000000000230.","journal-title":"Invest Radiol"},{"key":"2428_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0189622","author":"WMT Kuwabara","year":"2017","unstructured":"Kuwabara WMT, Panveloski-Costa AC, Yokota CNF, Pereira JNB, Filho JM, Torres RP, Hirabara SM, Curi R, Alba-Loureiro TC. Comparison of Goto-Kakizaki rats and high fat diet-induced obese rats: are they reliable models to study type 2 diabetes mellitus? PLoS ONE. 2017. https:\/\/doi.org\/10.1371\/journal.pone.0189622.","journal-title":"PLoS ONE"},{"key":"2428_CR12","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.114.007538","author":"G Ding","year":"2015","unstructured":"Ding G, Yan T, Chen J, Chopp M, Li L, Li Q, Cui C, Ning R, Jiang Q. Persistent cerebrovascular damage after stroke in type two diabetic rats measured by magnetic resonance imaging. Stroke. 2015. https:\/\/doi.org\/10.1161\/STROKEAHA.114.007538.","journal-title":"Stroke"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-020-02428-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-020-02428-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-020-02428-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T19:50:24Z","timestamp":1624477824000},"score":1,"resource":{"primary":{"URL":"https:\/\/translational-medicine.biomedcentral.com\/articles\/10.1186\/s12967-020-02428-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,24]]},"references-count":12,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["2428"],"URL":"https:\/\/doi.org\/10.1186\/s12967-020-02428-3","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-16970\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-16970\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.24439\/v1","asserted-by":"object"}]},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,24]]},"assertion":[{"value":"8 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable to humans. All animal experiments were conducted in accordance with the Northeastern University Division of Laboratory Animal Medicine and Institutional Animal Care and Use Committee.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"CFF has a financial interest in Animal Imaging Research, the company that makes the RF electronics and holders for animal imaging.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"256"}}