Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-03953-y
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Funding
- Juvenile Diabetes Research Foundation [5-CDA-2014-198-A-N, 1-INO-2017-435-A-N]
- NIH [R01 DK102950, R01 DK106412, U01 AI101990, T32 HL072738, F32 DK112525]
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In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and beta-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and beta-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.
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