Insulin dependent type 1 diabetes (IDDM) is characterized by an autoimmune process leading to the destruction of beta-cells in genetically susceptible individuals (1-3). This process is believed to be caused by mononuclear cells infiltrating the pancreas (4) and it has been suggested that such destruction progresses at a linear rate from an initial trigger to the final appearance of symptoms (5). The histopathological hallmark of the disease is the Iymphocytic infiltration of the pancreas (insulitis) which begins long time before the onset of the disease, persists for many years and progressively decreases after diabetes onset as the beta-cell mass declines (6). Histological examination of pancreas of diabetic patients died soon after diagnosis showed the presence of “insulitis” in about 50% of cases (4, 7). This insulitis is the expression of an autoimmune process that is triggered and maintained by a multitude of factors. An important factor appears to be a genetic predisposition such as HLA DR3/DQB1* 0201, DR4/DQB1* 0302 and other minor genes (IDDM-2, IDDM-4, IDDM-5, IDDM-8, IDDM-12)(8) in connection with as yet unknown environmental factors (eg, viruses). Autoantibodies, such as islet cell cytoplasmic antibodies (ICA), insulin autoantibodies (IAA), and/or autoantibodies to the GABA-synthesizing enzyme glutamic acid carboxylase (GAD) and thyrosin phosphatase (IA2) are already detectable in the prediabetic phase (9). Although it is not yet possible to precisely predict the time of clinical manifestation several clinical trial are currently performed in pre-diabetic subjects, with different therapeutic approaches aiming to reverse or modify the insulitis process and prevent clinical manifestation.

After clinical diagnosis of IDDM, approximately 5% of patients undergo spontaneous clinical remission during the first year of disease, although a wider percentage may experience a partial clinical remission with a functioning residual beta-cell function. This finding has encouraged to begin clinical trials with several adjuvant immunotherapies to improve the rate of clinical remission at time of diabetes onset (10). Unfortunately no more than 20% of patients benefits of such treatments and very little is known about factors that may determine clinical remission. Patients with an active on-going pancreatic inflammation may have higher chances to benefit from immunotherapy (11-12). It therefore emerges that the possibility to quantify, directly or indirectly, the severity of pancreatic insulitis, could be useful for understanding the relationship between the autoimmune phenomena and the progression towards disease onset, and to select and follow-up patients gaining benefit from adjuvant immunotherapy in the pre-diabetic phase and at time of clinical onset. Despite the clinical relevance of studying the insulitis process in vivo no major progresses have been done in the last two decades. The reasons are related to three main aspects: 1) the islets of Langerhans represent only 2-3% of pancreatic tissue spread into the pancreas and insulitis is a chronic asymptomatic process; 2) the pancreas is not easily accessible by biopsy thus excluding histological approaches; 3) due to the small size of islets and the cronicity of insulitis, conventional CT, NMR and ultrasound tecniques have an extremely low sensitivity in imaging insulitis.