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Southwestern NMR Center for In Vivo Metabolism

Craig R. Malloy, Ph.D.
P41EB015908
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Center Overview

The Southwestern NMR Center for In Vivo Metabolism exists to develop and apply new methods for analysis of metabolic networks in intact tissues, animals and human patients. The importance of understanding abnormal metabolism in common diseases such as cancer, diabetes and heart disease has long been appreciated. Because of constraints in technology, however, much of this research has been conducted in isolated systems where clinical relevance may be uncertain. Advances in magnetic resonance technology provide a foundation for major advances towards new ways of imaging metabolism in patients. These new techniques offer the advantage of imaging biochemical pathways without radiation. The focus of this Resource is to bring these technologies to the level where clinical research is feasible. The focus is development of new MR contrast agents and pulse sequences, NMR spectroscopy at high fields, and imaging of hyperpolarized 13C.

Impact on Human Health

Many high-impact diseases such as type 2 diabetes are a consequence of disrupted metabolism. For other diseases such as cancer, ischemic heart disease, or congestive heart failure, the relation between abnormal metabolism and the progression of disease is controversial. However, in these examples there is no doubt that intermediary metabolism is altered, sometimes dramatically. Although imaging metabolism has been a long-standing goal, current methods do not capture the complexity of disease. To take just one example - cancer - key biological information such as the clinical stage, rate of growth, genetics, sensitivity to therapy, etc., cannot be monitored by current imaging methods. The Resource's goal is to build on its expertise in intermediary metabolism plus recent advances in NMR physics to capture metabolic activity in real time.

We are optimistic about these goals and the potential for applications in patients. There has been an enormous investment by the scientific community in understanding the interaction between disease and metabolism. Virtually all of this work has been performed in experimental animals, yet many concepts permeate clinical thinking. The hypermetabolic state of many cancers is familiar territory to oncologists, and hibernating myocardium is a physiological concept discussed daily by cardiologists and thoracic surgeons. Nevertheless these well-accepted conditions cannot be measured with confidence in patients because the technology is limiting. The impact of adequate technology will allow clinicians to quantify these highly relevant conditions in patients.

Resources

ResourceDescriptionSupported PlatformsSupported FormatsData TypeData Size (compressed)
tcaCALC
Southwestern NMR Center for In Vivo Metabolism
NIBIB

The tcaCALC program performs an isotopomer analysis to estimate relative pathway fluxes in biological systems at metabolic and isotopic steady state.  It is used in 13C labeling studies where biological systems (isolated cells, perfused organs or intact animals) are provided enriched substrate(s), and the labeling of intermediates detected using 13C NMR spectroscopy, mass- and tandem mass spectrometry.  The 13C spectra are collected either directly from intact tissue, such as in the case of perfusions conducted...

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tcaSIM
Southwestern NMR Center for In Vivo Metabolism
NIBIB

The tcaSIM program is a tool for use with labeling studies in intermediary metabolism - primarily those applying 13C NMR spectroscopy, but also for 14C radiolabel studies and 13C mass isotopomer analysis. The simulation has been developed to assist in the design of experiments and to help the user understand the effect of various metabolic states and substrate enrichment levels on labeling patterns.

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