Noninvasive imaging of pancreatic islet inflammation in type 1A diabetes patients.
Type 1A diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration of the pancreatic islets of Langerhans. A major impediment to advances in understanding, preventing, and curing T1D has been the inability to "see" the disease initiate, progress, or regress, especially during the occult phase. Here, we report the development of a noninvasive method to visualize T1D at the target organ level in patients with active insulitis. Specifically, we visualized islet inflammation, manifest by microvascular changes and monocyte/macrophage recruitment and activation, using magnetic resonance imaging of magnetic nanoparticles (MNPs). As a proof of principle for this approach, imaging of infused ferumoxtran-10 nanoparticles permitted effective visualization of the pancreas and distinction of recent-onset diabetes patients from nondiabetic controls. The observation that MNPs accumulate in the pancreas of T1D patients opens the door to exploiting this noninvasive imaging method to follow T1D progression and monitoring the ability of immunomodulatory agents to clear insulitis.
Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
Jason L
JL
Gaglia
Alexander R
AR
Guimaraes
Mukesh
M
Harisinghani
Stuart E
SE
Turvey
Richard
R
Jackson
Christophe
C
Benoist
Diane
D
Mathis
Ralph
R
Weissleder
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003911:Dextrans; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000473:pathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007515:Islets of Langerhans / Q000473:pathology*; D008264:Macrophages / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D008833:Microcirculation; D009000:Monocytes / Q000473:pathology; D055815:Young Adult
D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10