Magnetic resonance spectroscopic imaging of tumor metabolic
markers for cancer diagnosis, metabolic phenotyping, and characterization of
tumor microenvironment
Issue title: Functional Imaging of Early Markers of Disease.
Part 2
Affiliations: Memorial Sloan-Kettering Cancer Center, Departments of
Medical Physics and Radiology, 1275 York Avenue, New York, NY 10021,
USA | Magnetic Resonance Center, Yale University School of
Medicine, New Haven, CT 06520, USA | Department of Radiology, College of Physicians &
Surgeons, Columbia University, New York, NY 10032, USA | Winship Cancer Institute, Emory University, 1365C
Clifton Road, N.E., C5008, Atlanta, GA 30322, USA
Note: [] Corresponding author: Magnetic Resonance Research Center, B-804
PUH-UPMC, Department of Radiology and Bioengineering, University of Pittsburgh
Cancer Institute, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA
15213, USA. Tel.: +1 412 647 3088; Fax: +1 412 647 9800; E-mail: heq@upmc.edu
Abstract: Cancer cells display heterogeneous genetic characteristics,
depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and
poor tissue oxygenation generate a fraction of hypoxic tumor cells that have
selective advantages in metastasis and invasion and often resist chemo- and
radiation therapies. The genetic alterations acquired by tumors modify their
biochemical pathways, which results in abnormal tumor metabolism. An elevation
in glycolysis known as the "Warburg effect" and changes in lipid synthesis and
oxidation occur. Magnetic resonance spectroscopy (MRS) has been used to study
tumor metabolism in preclinical animal models and in clinical research on human
breast, brain, and prostate cancers. This technique can identify specific
genetic and metabolic changes that occur in malignant tumors. Therefore, the
metabolic markers, detectable by MRS, not only provide information on
biochemical changes but also define different metabolic tumor phenotypes. When
combined with the contrast-enhanced Magnetic Resonance Imaging (MRI), which has
a high sensitivity for cancer diagnosis, in vivo magnetic resonance
spectroscopic imaging (MRSI) improves the diagnostic specificity of malignant
human cancers and is becoming an important clinical tool for cancer management
and care. This article reviews the MRSI techniques as molecular imaging methods
to detect and quantify metabolic changes in various tumor tissue types,
especially in extracranial tumor tissues that contain high concentrations of
fat. MRI/MRSI methods have been used to characterize tumor microenvironments in
terms of blood volume and vessel permeability. Measurements of tissue
oxygenation and glycolytic rates by MRS also are described to illustrate the
capability of the MR technology in probing molecular information non-invasively
in tumor tissues and its important potential for studying molecular mechanisms
of human cancers in physiological conditions.
