Diabetes & Obesity
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Friday May 13th
Room 513A-D  10:30 - 12:30 Moderators: Scott Reeder and Amita Shukla-Dave

10:30 734.   Liver Fat and Water MR T2 Values at 3T: Dependence Upon Steatosis Level 
Andrew James Gilman1, Aliya Qayyum1, Michelle Nystrom1, and Susan Moyher Noworolski1
1Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States

While T2 decay times are known to change between tissues and with disease, liver T2fat and T2water and their dependence on steatosis haven’t been reported at 3T. T2 values were calculated from multiple-echo 3T MR liver spectra in 12 NAFLD patients and 3 healthy controls. T2fat (62.9±9.8ms) was much higher than T2water(27.2±4.0ms). With increasing MRS fat fraction, T2fat tended to increase (p<0.075) while T2water significantly decreased (p<0.04). Similar correlations were observed versus the patients’ histologically determined steatosis grades. This suggests the importance of accounting for T2 when acquiring liver MRS because of its dependency upon measurement technique and disease state.

10:42 735.   In vivo detection and quantification of diet induced changes in adipose tissue composition by non linear NMR spectroscopy 
Rosa Tamara Branca1, and Warren Sloan Warren2
1Chemistry, Duke University, Durham, North Carolina, United States, 2Chemistry Department, Duke University

In vivo analysis of adipose tissue composition by NMR often requires water suppression, accurate voxel localization to avoid tissue interfaces, and the use of relatively small voxels and tedious localized shimming procedures to minimize local magnetic field inhomogeneities. In this report we show how non linear NMR spectroscopy can be used to acquire high resolution spectra of lipid depots spread over large (several cubic centimeter) volumes, without using localized shimming procedures or water suppression modules. We show how we calibrate and validate this method for samples containing known amounts of fatty acids, and how we use it in vivo to measure the total adipose tissue composition change induced by diet intervention in mice.

10:54 736.   Direct multi-tissue assessment of in vivo postprandial lipid handling in ZDF rats using localized 1H-[13C] MRS 
Richard Jonkers1, Luc van Loon2, Klaas Nicolay1, and Jeanine Prompers1
1Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, 2Department of Human Movement Sciences, Maastricht University Medical Centre+, Maastricht, Netherlands

Insulin resistance and type 2 diabetes are associated with excessive lipid accumulation in liver and muscle. In this study, we investigated in vivo lipid handling in liver and muscle tissue of pre-diabetic and diabetic ZDF rats using localized 1H-[13C] MRS after administration of 13C-labeled lipids. In liver, lipid uptake was increased in both pre-diabetic and diabetic rats compared with controls. Lipid uptake in muscle was likewise increased in diabetic rats, but in contrast it was lower in pre-diabetic rats compared with controls. Whereas lipid utilization was largely unaffected in liver, it was impaired in muscle of pre-diabetic and diabetic rats.

11:06 737.   Longitudinal hepatocellular lipid levels (IHCL) on ob/ob mice and the correlation to insulin levels 
Qiong Ye1, Carsten Friedrich Danzer2, Divya Vats1, and Markus Rudin1,3
1University and ETH Zürich, Institute for Biomedical Engineering, Zürich, 8093, Switzerland, 2Institute of Cell Biology, Zürich, Switzerland, 3Institute of Pharmacology and Toxicology, Zürich, Switzerland

Progression of hepatocellular lipid (IHCL) levels was investigated with 1H MRS on mouse of obesity model and correlated with blood plasma insulin levels. In this work, accurate quantification of IHCL was obtained with T2 correction and long TR avoiding T1 saturation. From the results, the IHCL levels were significantly higher in ob/ob mice than their age-matched ob/+ control mice at all ages studies. No increase was observed in IHCL of ob/ob mice at all the ages, though there were considerable fluctuations in the values. In contrast, IHCL values in ob/+ mice increased as a function of age. A significant correlation between IHCL and blood plasma insulin levels has been observed in ob/ob mice at the observation period.

11:18 738.   Compartmental Analysis of R2 measurements of Hepatic Lipid and Iron In Vivo using Breath-hold Multi-Echo 1H Spectroscopy (HISTO) 
Puneet Sharma1, Hiroumi D Kitajima1, Xiaodong Zhong2, Bobby Kalb3, and Diego R Martin3
1Radiology, Emory Healthcare, Atlanta, GA, United States, 2MR R&D Collaborations, Siemens Healthcare, Atlanta, GA, United States, 3Radiology, Emory University, Atlanta, GA, United States

Multi-echo T2-corrected MR spectroscopy (HISTO-MRS) is technique known to accurately measure lipid fraction in the liver. The ability for HISTO-MRS to distinguish water and lipid components, in addition to measuring individual T2, allows the concurrent estimation of hepatic iron content. This study presents in vivo data to support the findings from controlled phantoms studies, which demonstrate high positive correlation of R2water with iron, but relative insensitivity for R2fat. These observations suggest a water-compartmental dependence on hepatic iron deposition. Conversely, MRI-derived R2* showed sensitivity to hepatic lipid in addition to iron, which can obscure estimations of hepatic iron/lipid in combined disease.

11:30 739.   Differences in insulin sensitivity and adipose tissue distribution in obese subjects – is there a benign form of adiposity? 
Jürgen Machann1, Norbert Stefan2, Nina Schwenzer1, Fabian Springer1, Hans-Ulrich Häring2, Claus Claussen3, Andreas Fritsche2, and Fritz Schick1
1Section on Experimental Radiology, University Hospital Tübingen, Tübingen, Germany, 2Department of Internal Medicine IV, University Hospital Tübingen, Tübingen, Germany, 3Department for Diagnostic and Interventional Radiology, University Hospital Tübingen, Tübingen, Germany

Obesity is defined by a body mass index (BMI) > 30 kg/m². However, recent data show that obese subjects with comparable BMI may strongly differ in metabolic parameters as insulin sensitivity. This study presents cross-sectional data from 144 obese volunteers separated by the median of insulin sensitivity. Adipose tissue compartments – as determined by T1-weighted whole-body MRI – and ectopic lipids in liver and skeletal muscle are compared. Insulin resistant obese subjects are characterized by higher VAT, hepatic lipids and IMCL in tibialis anterior whereas insulin sensitive subjects have more adipose tissue in lower extremities. These results indicate a kind of “benign adiposity”.

11:42 740.   Reversal of type 2 diabetes is associated with decrease in pancreas and liver fat  -permission withheld
Kieren G Hollingsworth1, Ee Lin Lim1, Benjamin S Aribisala1, Mei Jun Chen1, John C Mathers2, and Roy Taylor1
1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom, 2Institute of Human Nutrition, Newcastle University, Newcastle upon Tyne, Tyne and Wear, United Kingdom

Type 2 diabetes is regarded as a chronic progressive condition, but is clearly reversible following bariatric surgery. We hypothesised that the reversal was due to calorie restriction rather than the effect of surgery on gut hormones, as is widely supposed. Eleven subjects with type 2 diabetes followed a very low calorie diet for 8 weeks. MR measurements demonstrated that a 75% fall in liver fat was accompanied by an decrease in hepatic insulin resistance and a 20% fall in pancreas fat was accompanied by an increase in peak insulin secretion rate to normal levels. Type 2 diabetes is reversible.

11:54 741.   Model for manganese dynamic contrast-enhanced MRI of passive and glucose-stimulated active pancreatic β-cell function 
Anita Himansu Dhyani1, Xiaobing Fan1, Lara Leoni1, and Brian B Roman1
1Radiology, University of Chicago, Chicago, IL, United States

Pancreatic microvasculature alterations may be a biomarker for diabetes. A model of dynamic manganese enhanced MRI was developed to monitor pancreatic beta cell function and vasculature modifications by passive/glucose-stimulated kinetics in normal/diabetic mice. Passive Mn uptake in the pancreas over time was fit by an empirical mathematical model; active Mn uptake was evaluated by calculating the angle between the linear slope pre- and post-glucose injection. Beta cell loss and alteration in vasculature in the diabetic pancreatic tail was indicated by a decreased uptake rate compared to normal. This imaging technique is a potential methodology for assessing diabetes progression or therapy.

12:06 742.   Validation of Imaging Biomarkers of Steatosis in ob/ob Mice with Multiple SPIO Injections 
Catherine D. G. Hines1, Ian Rowland2, Calista Roen1, Diego Hernando1, Debra Horng2, Huanzhou Yu3, Jean Brittain4, and Scott B Reeder1
1Radiology, University of Wisconsin-Madison, Madison, WI, United States, 2Medical Physics, University of Wisconsin-Madison, Madison, WI, United States, 3Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, 4Global Applied Science Laboratory, GE Healthcare, Waukesha, WI, United States

Iron overload often occurs concurrently in chronic liver disease patients, confounding accurate liver fat quantification. Recent work has demonstrated the importance of T2* corrections for quantifying liver fat, using quantitative MRI imaging and spectroscopic methods. Consequently, this work validates the requirement for T2* corrections for fat quantification in an animal model of steatosis with increasing iron overload. In vivo results show this method is robust to increasing iron over a range of fat-fractions, T2* correction is necessary in the presence and absence of iron, and that MRI fat quantification is predictive of amount of stored triglycerides.

12:18 743.   Quantitative pancreatic β cell MRI using manganese-enhanced Look-Locker imaging and two-site water exchange analysis 
Patrick F Antkowiak1, Moriel Vandsburger2, and Frederick H Epstein2
1University of Virginia, Charlottesville, Virginia, United States, 2University of Virginia

Pancreatic beta cells release insulin to maintain blood glucose homeostasis, but in diabetes mellitus, functional beta cell mass decreases. Currently there is no ideal method to monitor beta cell function and mass noninvasively, which would be useful for monitoring diabetic disease progression or therapeutic response. Here we developed a two-compartment model of pancreatic T1 relaxation after injection of MnCl and used it to probe model parameters that may indicate β cell mass and function. We applied this model to normal, pharmacologically-treated, and diabetic mice and found that model parameters reflect both beta cell function and mass.