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Risultati finali
A DMI scanning protocol will be made for application in the liver at 7T. DMI sensitivity and homogeneity tests will first be performed in phantoms. Then a DMI protocol will be setup for in vivo applications, including a safety assessment. Finally the DMI protocol will be tested in vivo in volunteers at natural abundance. At this stage, no deuterated compounds will be used.
IRB approval for DMI with administration of deuterium-labeled compounds in healthy volunteers (si apre in una nuova finestra)IRB approval will be obtained for DMI with administration of deuterium-labeled compounds in healthy volunteers. N=5 healthy volunteers will be orally dosed with deuterated glucose for the measurement of glycogen synthesis in the liver. N=5 healthy volunteers will be orally dosed with heavy water for the measurement of de novo lipogenesis in the liver.
Analysis of DMI data in diabetes patients (si apre in una nuova finestra)DMI measurements of hepatic glycogen synthesis and de novo lipogenesis in type 2 diabetes patients will be analyzed. Effect-sizes between patients and controls (D2.2) will be calculated. Findings will be correlated to clinical parameters of glucose tolerance and insulin resistance and the degree of liver steatosis as determined by conventional hydrogen MRI and MRS.
IRB approval for DMI with administration of deuterium-labeled compounds in diabetes patients (si apre in una nuova finestra)IRB approval will be obtained for DMI with administration of deuterium-labeled compounds in type 2 diabetes patients. N=5 type 2 diabetes patients will be orally dosed with deuterated glucose for the measurement of glycogen synthesis in the liver. N=5 type 2 diabetes patients will be orally dosed with heavy water for the measurement of de novo lipogenesis in the liver.
Analysis of DMI data in healthy volunteers (si apre in una nuova finestra)DMI measurements of hepatic glycogen synthesis and de novo lipogenesis in healthy volunteers will be analyzed. Spatially resolved hepatic glycogen synthesis fluxes will be determined, which will be compared with literature values obtained with 13C-MRS after infusion of [1-13C]-glucose. The fraction of de novo synthesized lipids in the liver lipid pool will be compared with literature values from invasive measurements in liver biopsies.
A deuterium metabolic imaging (DMI) setup will be constructed for body applications at 7T. This encompasses the construction of a deuterium RF body coil to generate a B1 field at the deuterium frequency, the construction of deuterium receive arrays with integrated dipole hydrogen transceivers for sensitive deuterium signal detection and conventional proton MRI, respectively, and adaptation and installation of a 1T RF amplifier for 7T DMI usability.
A logo and website will be launched in M3. The website will be using the MetaScan platform to gain exposure for the BodyDMI project. It will function as gateway for stakeholders (patients, industry partners, scientist) and provide information on the project and its results.
Pubblicazioni
Autori:
Robin A. Graaf, Arjan D. Hendriks, Dennis W.J. Klomp, Chathura Kumaragamage, Dimitri Welting, Catalina S. Arteaga de Castro, Peter B. Brown, Scott McIntyre, Terence W. Nixon, Jeanine J. Prompers, Henk M. De Feyter
Pubblicato in:
NMR in Biomedicine, Numero 33/3, 2020, ISSN 0952-3480
Editore:
John Wiley & Sons Inc.
DOI:
10.1002/nbm.4235
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