What is MRS? Magnetic resonance(MR) has developed over the years into the principal method for determining molecular structure and conformation. More recently, it has matured into a noninvasive technique that can help physicians diagnose disease. The mathematical equations first proposed by Felix Bloch in 1946 to describe the behavior of nuclei in a magnetic field have played a very important role in understanding the MR phenomena, including the concept of relaxationÑhow the nuclei return to their resting state after absorption of energy. Relaxation mechanisms and the behavior of the protons of water in vivo are the basis from which magnetic resonance images (MRI) are constructed. MRS (magnetic resonance spectroscopy) and MRI are based on the same theory and magnetic resonance phenomena. MRS produces a characteristic spectrum of a specific nucleus, such as a proton(1H) or a carbon (13C), in which the resonance frequency (chemical shift) is influenced by the surrounding environment and neighboring nuclei cause an effect (coupling) on the observed signals. This coupling can be caused by the adjacent chemical bonds of the material or through proximity (space) to other nuclei and is unique to the three-dimensional structure of the materials. On the other hand, MRI can produce an image showing outstanding anatomical detail of the subject. When the advantage of three-dimensional spatial localization is combined with chemical shift information, it is possible to show how specific molecules interact in vivo (localized MRS).

How is MRS used? Interpreting MR spectra can allow scientists to determine the absolute structure of a drug or compound of interest. Using modern multidimensional techniques, a protein chemist can determine the structures of relatively small- to medium-sized proteins. A biologist can use MRS to examine metabolic energy levels and/or intracellular acid/base concentration(pH) in cultured cells, perfused organs, or in an animal or human. MRS has long been the most important structural tool available to the organic chemist. It is rapidly gaining importance in the research of biochemists, physiologists, and other scientists in biomedically related fieldsÑespecially because the technology and techniques are now available to scientists and clinicians to perform MR imaging and localized MR spectroscopy in vivo. Such experiments can probe the fundamental mechanisms of biologic function in both normal and diseased states.

MRS at the Research Imaging Center (RIC). The types of studies performed at the RIC in the Magnetic Resonance Spectroscopy Division are quite varied. One project examines the protein structure of lung surfactant protein C. Lung surfactant, made of four proteins and several phospholipids, is responsible for the exchange of oxygen in the lungs and is therefore necessary for life. This project uses modern two-dimensional techniques to solve the structure of this biologically important protein. Another project uses recombinant DNA techniques to produce the protein, NADPH-cytochrome P-450 reductase, which has been modified to contain fluorine-labeled amino acids. 19F MRS will be used to provide the researcher information about the location of these fluorine atoms and therefore the corresponding amino acids in the enzyme. A third project involves examining the solution conformation of biological high-energy compounds, diadenosine polyphosphates. Diadenosine tetraphosphate (AP4A) is a ubiquitous component of all cells, plays a role in the response of cells to various forms of shock, is a regulatory molecule in the initiation of DNA replication, and participates in platelet functions. Because the conformation of a regulatory molecule affects its ability to bind to and cause a response in a biological effector molecule, an understanding of the conformation of AP4A is very important. Several other projects use fluorine(19F), deuterium (2D), sodium (23Na), or other nuclei, in addition to protons(1H), to probe the environment of the nucleus, to probe how it interacts with other materials, or to determine how it relaxes back to its equilibrium state. All these spectroscopic projects have counterparts in MR imaging and will hopefully help us to explain and understand the complex working of biological systems.