08:00 |
1001.
|
Co-transplantation of
encapsulated human mesenchymal stem cells improves the
viability of human islet xenografts in a mouse model of type
I diabetes
Mangesh Kulkarni1,2, Dian Arifin1,2,
and Jeff Bulte1,2
1Institute for Cell Engineering, the Johns
Hopkins University School of Medicine, Baltimore,
Maryland, United States, 2Russell
H. Morgan Department of Radiology and Radiological
Science, Division of MR Research, Baltimore, Maryland,
United States
Transplantation of microencapsulated islets circumvents
the need for immunosuppression which is a requirement
for the clinically used Edmonton protocol. We developed
complementary strategies to improve transplant survival.
Incorporation of perfluorocarbons within the capsules
enabled in vivo monitoring using 19F MRI following
subcutaneous implantation of human islets in a mouse
model of type I diabetes mellitus. In this xenogeneic
environment, encapsulated human islet viability was
significantly improved following co-transplantation with
encapsulated human MSCs.
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08:12 |
1002. |
HP-13C-NMR
detects the alternation of LDH kinetics and redox state
induced by metabolite modulation
Lin Z. Li1,2, Stephen Kadlececk1,
Hoora Shaghaghi1, He N. Xu1,2,
Harrilla Profka1, and Rahim Rizi1
1Department of Radiology, University of
Pennsylvania, Philadelphia, Pennsylvania, United States, 2Britton
Chance Laboratory of Redox Imaging, Johnson Research
Foundation, University of Pennsylvania, Philadelphia,
Pennsylvania, United States
Abnormal enzyme activities and cellular redox state have
been observed in various medical conditions including
cancer, diabetes, neurodegenerative diseases and lung
diseases. We employed hyperpolarized 13C-pyruvate NMR to
investigate non-invasively how the enzyme kinetics (rate
constants) and cellular redox state may be modulated by
the levels of metabolites. Our results indicate a strong
coupling of the lactate dehydrogenase reaction with the
cellular redox state. Hyperpolarized 13C-pyruvate can be
a metabolic indicator of redox state for the study of
normal physiology and diseases.
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08:24 |
1003. |
Assessment of pancreatic
islets using optical projection tomography and magnetic
resonance imaging
JanakiRaman Rangarajan1,2, Ting Yin3,4,
Josephine Gilbert5, Ashwini Atre3,4,
Anna Eriksson5, Tom Dresselaers3,4,
Frederik Maes1, Ulf Ahlgren5, and
Uwe Himmelreich3,4
1ESAT/PSI - Medical Image Computing, KU
Leuven, Leuven, Belgium, 2iMinds-KU
Leuven Future Health Department, KU Leuven, Leuven,
Belgium,3Biomedical MRI unit, Department of
Imaging and Pathology, KU Leuven, Belgium, 4Molecular
Small Animal Imaging Center (MoSAIC), KU Leuven,
Belgium, 5Umeå
Centre for Molecular Medicine, Umea University, Sweden
Islet graft transplantation is an promising treatment
practice for diabetic treatment, but progressive islet
loss is a major issue, which drives the interest to
study islet location and function in vivo. MRI offers
high spatial resolution for in vivo assessment of
pancreatic islets (PI) labeled with iron-oxide
particles, but the quantification of PIs in MR is
confounded by the false positive signals. Optical
projection tomography (OPT) offers multi-spectral
assessment of PI labeled with fluorescent markers, but
only allow ex vivo measurements. Using spatial
normalization methods, we co-register the multi-modal
data of MRI and OPT, which allowed co-localization of
PIs. The. successful co-registration of pancreatic
tissue allowed cross-validation of PIs in MR images,
confirming its suitability for in vivo PI imaging. This
is an essential prerequisite for future validation of in
vivo MRI data using beta-cell targeting iron oxide based
nanoparticles
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08:36 |
1004. |
Quantification of
intragastric fat distribution using IDEAL
Dian Liu1, Jelena Curcic1,2,
Andreas Steingoetter1,2, and Sebastian
Kozerke1
1Institute for Biomedical Engineering,
University and ETH Zurich, Zurich, Switzerland, 2Division
of Gastroenterology and Hepatology, University of
Zurich, Zurich, Switzerland
The increase in nutrition-related diseases has prompted
immense efforts to understand how food systems, and in
particular lipids, are sensed, processed and digested in
the gastrointestinal (GI) tract. Accurate in vivo fat
quantification by MRI requires modeling of all relevant
chemical shift species contained in fat, and thus the
acquisition of sufficient number of echo times.
Objective of this work was to validate and implement
hierarchical IDEAL for measuring intragastric fat
distribution of lipid emulsions. Using a 6-point IDEAL
approach, intragastric distribution and emptying of fat
in emulsions could be assessed within a single breath
hold.
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08:48 |
1005.
|
Pyruvate dehydrogenase
activation normalises carbohydrate metabolism and diastolic
function in the diabetic heart
Lydia Le Page1, Oliver Rider2,
Andrew Lewis2, Lucia Giles1, Vicky
Ball1, Latt Mansor1, Lisa Heather1,
and Damian Tyler1
1Department of Physiology, Anatomy and
Genetics, University of Oxford, Oxford, United Kingdom, 2Oxford
Centre for Clinical Magnetic Resonance Research, Oxford,
United Kingdom
Diabetics have reduced systemic glucose metabolism,
partly due to reduced pyruvate dehydrogenase (PDH) flux,
which leads to high blood glucose levels.
Dichloroacetate (DCA) stimulates PDH and this study
investigated its in
vivo effect
on the diabetic heart and liver. Four weeks of DCA
treatment in diabetic rats normalised blood glucose
levels, restored cardiac PDH flux and elevated hepatic
PDH flux compared to controls. Diastolic dysfunction,
observed in the diabetic heart, was not present in
diabetic rats treated with DCA. We conclude that PDH
modulation may be a suitable treatment for the metabolic
and functional abnormalities seen in the diabetic heart.
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09:00 |
1006. |
A Numerical Model of
Manganese Distribution in Pancreatic Tissue from meMRI
measurements
-
permission withheld
Ekkehard Küstermann1, Anke Meyer2,
Katharina Stolz2, Wolfgang Dreher1,
and Kathrin Maedler2
1AG "in-vivo-MR", FB2, Universität Bremen,
Bremen, Bremen, Germany, 2Center
for Biomolecular Interactions Bremen, Universität
Bremen, Bremen, Germany
Diabetes research and therapy will benefit from
non-invasive methods of analyzing pancreatic beta-cell
mass (BCM) and activity. Manganese mediated MR imaging
is a very potent tool for non-invasive measurements of
pancreatic activity. The Mn-induced signal time course
of pancreatic tissue is analyzed with a mathematical
model consisting of three sequentially ordered
compartments: a source and two pancreatic compartments.
The pancreatic MR-signal can be modeled by (i) a small
compartment with similar signal changes as in the liver
and (ii) a larger compartment characterized by a much
slower signal change.
|
09:12 |
1007.
|
Assessment of Diabetic
Skeletal Muscle Metabolism Using Hyperpolarized 13C MR
Spectroscopy
Jae Mo Park1, Sonal Josan1, Ralph
Hurd2, James Graham3, Peter Havel3,
David Bendahan4, Dirk Mayer5,
Daniel Spielman1, and Thomas Jue6
1Radiology, Stanford University, Stanford,
CA, United States, 2GE
Healthcare, Menlo Park, CA, United States, 3Molecular
Bioscience, UC Davis, Davis, CA, United States, 4Centre
de Resonance Magnetique Biologique et Medicale,
Marseille, France, 5Diagnostic
Radiology and Nuclear Medicine, University of Maryland,
MD, United States, 6Biochemistry,
UC Davis, Davis, CA, United States
We performed in vivo experiments to assess the oxidative
pathway contribution in the type 2 diabete mellitus
(T2DM) model using hyperpolarized [1-13C]lactate and
[2-13C]pyruvate. The metabolism of hyperpolarized
[1-13C]lactate in the muscle was different in T2DM as
compared to control rats, in particular with respect to
PDH activity. The restoration of PDH activity with
dichloroacetate in the T2DM rat suggests a
non-negligible contribution of oxidative metabolism
impairment in diabetes and a potential role for PDH
activation to restore glucose homeostasis.
[2-13C]pyruvate experiment suggests that ketogenesis is
more active rather than the oxidative phosphorylation in
diabetic muscle metabolism after dichloroacetate
infusion.
|
09:24 |
1008. |
Variation in Skeletal
Muscle and Liver Glycogen Concentration During Normal Daily
Eating in Type 2 Diabetes
Fiona Elizabeth Smith1, Mavin Macauley1,
Peter Thelwall1, and Roy Taylor1
1Institute of Cellular Medicine, Newcastle
University, Newcastle upon Tyne, United Kingdom
Skeletal muscle plays a major role in glucose
homeostasis in normal health. Approximately 30% of meal
carbohydrate is stored as muscle glycogen after the
first meal of the day and rises after subsequent meals.
Liver stores approximately 20% of meal carbohydrate in
healthy subjects. Glycogen depots behave as a dynamic
buffer allowing rapid storage of osmotically active
glucose. However, the effectiveness of this diurnal
mechanism has not been previously studied in Type 2
diabetes. The study aim was to quantify changes in
skeletal muscle and liver glycogen concentration during
normal eating in Type 2 Diabetes comparing this to
healthy subjects.
|
09:36 |
1009.
|
Differentiation of Brown
Adipose Tissue using Manganese Enhanced MRI
Hussein Srour1, Anna Ulyanova1,
and kai Hsiang chuang1
1Singapore Bioimaging Consortium, Singapore,
Singapore
Manganese-enhanced MRI (MEMRI) is a useful method for
measuring calcium-dependent cellular activity due to
accumulation of Mn2+ in cells via voltage-gated calcium
channels. We investigated the feasibility of MEMRI as a
method to detect BAT activation in mice induced by cold
exposure. We show for the first time that MEMRI can
differentiate between BAT and WAT tissue in mice.
|
09:48 |
1010.
|
Non Invasive Quantification
of Ectopic Fat Content: flexibility with bariatric surgery
induced weight loss
Inès ABDESSELAM1,2, Bénédicte GABORIT2,3,
Frank KOBER1, Alexis JACQUIER4,
Olivier EMUNGANIA5, Marie-Christine ALESSI2,
Monique BERNARD1, and Anne DUTOUR2,3
1Faculté de médecine, Aix-Marseille
University, CRMBM, CNRS7339, Marseille, France, 2Faculté
de médecine, Aix-Marseille University, NORT,
Inserm1062/Inra1260, Marseille, France, 3Endocrinology,
Metabolic diseases and nutrition, CHU Nord, Marseille,
France, 4Radiology,
CHU TImone, Marseille, France, 5Gastroenterology,
CHU Nord, Marseille, France
Bariatric surgery (BS) reduce, after 6 months,
epicardial fat deposition but doesn't induce any change
in myocardial triglyceride content. The aim of this
study was to investigate the impact of BS on pancreatic
fat content, to determine whether we can reduce
myocardial triglyceride content two years after BS and
whether decreased level of triglyceride content 6 months
after BS could be maintained 2 years later. For that
purpose, we used 1H-MRS. Our study provides compelling
evidences that pancreatic fat increase with type 2
diabetes and could be decreased with BS. Finally, we
show that this decrease is maintained overtime.
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