The speed, non-ionizing nature of MRI, and lack of need for contrast agent make this technique well suited for longitudinal scanning in pediatric populations

The speed, non-ionizing nature of MRI, and lack of need for contrast agent make this technique well suited for longitudinal scanning in pediatric populations. Alogliptin Benzoate This study is subject to several limitations. interrogating tissue microstructure and composition. RESULTS Within 100 days of diabetes onset, individuals with T1D had a smaller pancreas (median volume 28.6 mL) than control participants (median volume 48.4 mL; 0.001), including when normalized by individual weight ( 0.001). Longitudinal measurements of pancreas volume increased in control participants over the year, consistent with adolescent growth, but pancreas volume declined over the first year after T1D diagnosis Alogliptin Benzoate ( 0.001). In multiple autoantibodyCpositive individuals, the pancreas volume was significantly larger than that of the T1D cohort (= 0.017) but smaller than that of the control cohort (= 0.04). Diffusion-weighted MRI showed that individuals with recent-onset T1D had a higher apparent diffusion coefficient (= 0.012), suggesting a loss of cellular structural integrity, with heterogeneous pancreatic distribution. CONCLUSIONS These results indicate that pancreas volume is decreased in stages 1, 2, and 3 of T1D and decreases during the first year after diabetes onset and that this loss of pancreatic volume is accompanied by microstructural changes. Introduction Reduced pancreas size has been noted in individuals with long-standing type 1 diabetes (T1D) (1C3). Because pancreatic islets comprise only 1C2% of the pancreatic mass, the reason for the smaller pancreas in T1D is not known, but changes in the exocrine pancreas are implicated. More recently, studies in adults with recent-onset T1D have demonstrated reduced pancreatic volume within the first year after diagnosis (4,5). The development of T1D is currently thought to progress from autoimmunity as reflected by islet autoantibodies (stage 1), through dysglycemia (stage 2), and ultimately clinical manifestation of diabetes Alogliptin Benzoate (stage 3) (6). Surprisingly, one autopsy study found that pancreas weight was less in individuals without diabetes (= 8) expressing autoantibodies that portend the development of T1D (7). These studies raise the possibility that pancreas volume declines early in the course of T1D progression or that individuals who develop T1D may have a smaller pancreas prior to the onset of stage 3 T1D. A number of cross-sectional studies have examined pancreas volume as a function of T1D duration with conflicting results (1,8C11). These cross-sectional studies are hampered by the fact that pancreas volume is a function of age (12,13) and that large interindividual differences exist in the volume of the pancreas (14). Longitudinal studies of pancreas volume in children or adolescents with T1D have not been performed to determine how the pancreas changes during normal adolescence or in the early stages of T1D. MRI has a number of advantages for assessing the pancreas. Unlike computed tomography (CT), MRI does not use ionizing radiation, enabling longitudinal MRI measurements to be made in children and adolescents at frequent intervals with no known risk. Additionally, a meta-analysis comparing TSLPR studies using MRI and CT to interrogate the pancreas in diabetes demonstrated a larger difference in pancreas volume when using Alogliptin Benzoate MRI as well as lower study heterogeneity in studies using MRI than those performing CT (9). In addition to excellent soft tissue contrast, MRI can quantitatively assess other aspects of pancreas structure and composition. These quantitative MRI techniques include diffusion-weighted MRI (DW-MRI), which measures the diffusion of water in tissue and has been used in studies of both pancreatic cancer (15) and pancreatitis (16). Another quantitative MRI technique maps the transverse relaxation time (T2), which may reflect tissue edema and has previously been shown to be elevated in the NOD mouse model of T1D (17). A third quantitative technique is magnetization transfer (MT) MRI, which measures the size of the macromolecular pool in tissue and has been shown to correlate with fibrosis (17). A final MRI technique of interest is a ratio of the pancreas Alogliptin Benzoate to the spleen signal on a T1-weighted image, which has previously been shown to reflect exocrine dysfunction in chronic pancreatitis.