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Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):2139-44. doi: 10.1073/pnas.1424993112. Epub 2015 Feb 3.

Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients.

Author information

1
Joslin Diabetes Center, Boston, MA 02215;
2
Center for Systems Biology and Department of Radiology, Massachusetts General Hospital, Boston, MA 02114;
3
Department of Radiology, Massachusetts General Hospital, Boston, MA 02114;
4
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA, 02115.
5
Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; and Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston MA, 02115 dm@hms.harvard.edu rweissleder@mgh.harvard.edu.
6
Center for Systems Biology and Department of Radiology, Massachusetts General Hospital, Boston, MA 02114; dm@hms.harvard.edu rweissleder@mgh.harvard.edu.

Abstract

The inability to visualize the initiation and progression of type-1 diabetes (T1D) noninvasively in humans is a major research and clinical stumbling block. We describe an advanced, exportable method for imaging the pancreatic inflammation underlying T1D, based on MRI of the clinically approved magnetic nanoparticle (MNP) ferumoxytol. The MNP-MRI approach, which reflects nanoparticle uptake by macrophages in the inflamed pancreatic lesion, has been validated extensively in mouse models of T1D and in a pilot human study. The methodological advances reported here were enabled by extensive optimization of image acquisition at 3T, as well as by the development of improved MRI registration and visualization technologies. A proof-of-principle study on patients recently diagnosed with T1D versus healthy controls yielded two major findings: First, there was a clear difference in whole-pancreas nanoparticle accumulation in patients and controls; second, the patients with T1D exhibited pronounced inter- and intrapancreatic heterogeneity in signal intensity. The ability to generate noninvasive, 3D, high-resolution maps of pancreatic inflammation in autoimmune diabetes should prove invaluable in assessing disease initiation and progression and as an indicator of response to emerging therapies.

KEYWORDS:

autoimmune diabetes; insulitis; magnetic resonance imaging; nanoparticle; pancreas

PMID:
25650428
PMCID:
PMC4343112
DOI:
10.1073/pnas.1424993112
[Indexed for MEDLINE]
Free PMC Article

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