Advanced Imaging Research Center

Diagnosis and treatment of patients with complex diseases such as cancer will require detailed understanding of processes at a molecular level in order to tailor therapy. We have recently established a research program with neuroscientists, neurosurgeons and cancer specialists to better understand metabolism in human brain tumors. In these studies
¹³C-labeled glucose is metabolized to lactate, GABA, glutamate and other products, providing highly specific information about active metabolic pathways in the tumors. The presence of spin-coupled multiplets in glutamate, for example, proves active flux in mitochondrial pathways for energy production.


Endowed Title	Richard A. Lange Chair in Cardiology
Academic Title	Professor
Primary Appointment	Advanced Imaging Research Center
Secondary Appointment	Internal Medicine - Cardiology
School	Graduate School of Biomedical Sciences
Degree Program	Biomedical Engineering Molecular Biophysics Radiological Sciences

Craig R. Malloy, M.D.

Research Overview
My major interest is the role of metabolism in disease. The details of individual reactions in the key biochemical pathways - glycolysis, the pentose phosphate pathway, the citric acid cycle and others - are well-understood. However the integration of these pathways in vivo is poorly understood because of the intricate interconnections and feedback loops in the control of metabolism. Classical radiotracer studies for investigation of metabolism have two major limitations. First, the information that can be obtained is very limited. Consequently, these methods are optimal for studies of individual enzymes and isolated organelles in a test tube where conditions are highly controlled. However these methods are inadequate for probing metabolism in intact animals and especially in humans with disease. The second limitation is that the use of radiotracers constrains many potential applications in clinical research.

Initially much of my work in collaboration with Dr. Dean Sherry was to develop ¹³C,
¹H and ²H NMR methods for analysis of metabolism in relatively simple preparations such as isolated tissues. Methods for data analysis were worked out, and somewhat surprisingly, these techniques have translated quite well to in vivo applications in mice, rats and humans.

Recently the Advanced Imaging Research Center has acquired equipment to help move these concepts into two new research opportunities. In collaboration with Dr. Matthew Merritt, we are extending the metabolic analysis, developed over the years, to analysis of biochemical pathways with hyperpolarized ¹³C. This technology allows ¹³C imaging of specific metabolic pathways, offering the potential of using stable isotopes to acquire detailed metabolic information in patients. This technology has been demonstrated in human patients by the research group at UC San Francisco. The second direction is to use a high field instrument, 7T, to acquire ¹³C, ¹H and ³¹P NMR studies in humans. Although there are technical challenges in working at high fields, we have confirmed that spectacular ¹H spectra can be obtained, and new ¹³C and ³¹P studies in patients will become available in 2011.

Contact email: craig.malloy@utsouthwestern.edu

Research Interests

Cardiovascular radiology

MR methods for the analysis of cardiac metabolism and function

Intermediary metabolism.