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. 2018 May 1;9:1742. doi: 10.1038/s41467-018-03953-y

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — Summary by which CEUS measurement of the pancreatic blood-flow dynamics can be used to predict diabetes onset and immunotherapy efficacy. (Top) In an animal that is not progressing to diabetes, there is no change in the reperfusion rate or the amplitude over time, consistent with normal islet microvasculature organization. (Bottom) In an animal that is in pre-diabetes and/or progressing to overt disease, consecutive CEUS scans will show an increase in reperfusion rate, and potentially a decrease in reperfusion amplitude. This change is associated with a decrease in the islet vascular coverage, yet an increase in diameter of the remaining vessels. Thus we suggest that changes in the reperfusion rate (increases) indicate likely progression to diabetes. Furthermore, a defined threshold may also identify an “abnormal” reperfusion measurement to indicate the likely progression to diabetes, dispensing with “scan 1”