Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models

Joshua R. St Clair, David Ramirez, Samantha Passman and Richard K. P. Benninger ()
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Joshua R. St Clair: University of Colorado Anschutz Medical Campus
David Ramirez: University of Colorado Anschutz Medical Campus
Samantha Passman: University of Colorado Anschutz Medical Campus
Richard K. P. Benninger: University of Colorado Anschutz Medical Campus

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-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.

Date: 2018
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DOI: 10.1038/s41467-018-03953-y

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