项目来源

美国卫生和人类服务部基金(HHS)

项目主持人

MALLOY, CRAIG R.

项目受资助机构

UT SOUTHWESTERN MEDICAL CENTER

立项年度

2021

立项时间

未公开

项目编号

5P41EB01590833

研究期限

未知 / 未知

项目级别

国家级

受资助金额

422869.00美元

学科

Biomedical Imaging; Biotechnology; Digestive Diseases; Liver Disease; Nutrition;

学科代码

未公开

基金类别

RESEARCH CENTERS

Abdomen ; Acetates ; Acetyl Coenzyme A ; Advisory Committees ; Alanine ; Animals ; Appearance ; Bicarbonates ; Biochemical ; Body Temperature ; Bolus Infusion ; Cell Nucleus ; Characteristics ; Chemical Shift Imaging ; Citric Acid Cycle ; Clinical ; Clinical Research ; Data ; Detection ; Dichloroacetate ; Dietary Intervention ; Dihydroxyacetone ; Dinitrophenols ; Disease ; Doctor of Philosophy ; Esters ; Ethanol ; Family suidae ; Fasting ; Gluconeogenesis ; Glucose ; Glutamates ; Glycolysis ; Goals ; Hour ; Human ; Image ; Injections ; Intervention ; Kidney ; Kinetics

参与者

MALLOY, CRAIG R

参与机构

NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

项目标书摘要：Project Summary/AbstractBiochemical imaging using hyperpolarized(HP)nuclei now offers the possibility of extending the inherentpower of 13C NMR to rapidly image intermediary metabolism in human patients.The recent installation of aclinical polarizer in this BTRC provides the opportunity to test and validate this technology as it moves towardsclinical research applications.The overall intent is to develop a good understanding of how to interpret 13CNMR spectra and images from the liver after injection of HP-[1-13C]pyruvate and other substrates.A generaltheme in this TR&D project is to perform conventional 2H and 13C isotopomer analysis and hyperpolarizationexams in the same tissue.With this approach,standard tracer methods are used to efficiently validate andinterpret the HP data.Aim 1 will focus on the utility of HP[1-13C]pyruvate for monitoring TCA cycle flux andpathways related to gluconeogenesis in a rat model.Pharmacological and nutritional interventions will be usedto selectively manipulate specific aspects of liver metabolism.The sensitivity of HP data to these interventionswill be tested,and critically compared to results from simultaneous 2H and 13C NMR isotopomer analysis.InAim 2 we will investigate novel probes such as HP-[2-13C]dihydroxyacetone for imaging phosphoenol pyruvate(PEP).13C labeled mono-esters of TCA cycle intermediates,developed in TR&D 1,will also be evaluated invivo.With our collaborators,we have already determined that detection of HP-[1-13C]lactate,HP-[1-13C]alanine and HP-[13C]bicarbonate from the liver is feasible in the pig.Consequently Aim 3 will test theeffects of nutritional state on gluconeogenic pathways and TCA cycle flux,using conventional methods,and atthe same time perform HP spectroscopy and imaging after injection of HP-[1-13C]pyruvate.Parallelexperiments in the same animals with an identical protocol will be performed with[U-13C]pyruvate,nothyperpolarized,to measure the fraction of exogenous pyruvate entering the malate,lactate,alanine and acetyl-CoA pools.These methods will be extended to human subjects in Aim 4 where we will monitor metabolism ofHP-[1-13C]pyruvate in the liver and evaluate the impact of simple alterations in nutritional state.The primarygoal is to implement hyperpolarization exams in the human liver and to critically evaluate the metabolicinformation resulting from these exams.

项目持续时间

33 years

项目负责机构类型

Domestic Higher Education