Magnetic Resonance Spectroscopy in the Evaluation of Central Nervous System Manifestations of Systemic Lupus Erythematosus SIMONE APPENZELLER, LILIAN T. L. COSTALLAT, LI MIN LI, AND FERNANDO CENDES Introduction Neuropsychiatric (NP) systemic lupus erythematosus (SLE) is characterized by a large spectrum of physical and behavioral manifestations. One major difficulty is the ab- sence of diagnostic tools for assessing disease activity and severity of NP manifestation. The neurologic symptoms can be of new onset, chronic, or of a former or resolved nature (1). Although several studies have used different neuroimaging tools, including computed tomography, magnetic resonance imaging (MRI), and single-photon– emission computed tomography, no single technique has proven to be definitive for diagnosis of NP manifestations in persons with SLE (1). Magnetic resonance spectroscopy (MRS) permits chem- ically specific, noninvasive measurements of some com- pounds of biologic importance in living tissues. MRS was discovered in 1946, but was only first used in living ani- mal brain in 1980 (2), followed by use in human brains in several pathologies. In the human brain, phosphate energy stores, intracellular pH, lactate concentrations, and the neuronal marker N-acetylaspartate are examples of MRS- measurable variables (3). The purpose of this article is to review studies using MRS in SLE and to discuss the clinical utility of this technique in determining central nervous system (CNS) involvement in individuals with SLE. We will also discuss future applications of MRS in the evaluation and treatment of NP manifestations in patients with SLE. History The nuclear magnetic resonance (NMR) phenomenon was discovered independently in 2 laboratories in 1946 by Bloch and Purcell, which led them to receive the Nobel Prize for physics in 1952. When imaging methods using the NMR signal were first developed, the term NMR imag- ing had been applied. But because of increasing danger of nuclear energy in the 1980s and because MR techniques do not use ionizing radiation, the term nuclear was dropped in clinical use, being maintained only to describe the physical phenomenon itself (3). MRS physics Spectroscopy deals with the interaction of electromagnetic radiation with matter; therefore, because the structure of atomic nuclei have magnetic properties, they respond to strong magnetic fields. During relaxation from the excita- tion of a magnetic field, atomic nuclei emit oscillating signals at a frequency that perturbs the nuclei. These sig- nals may be detected by coils and then converted into spectra or images. The position of peaks in the spectrum is determined by its molecular characteristics. Information about their metabolites can be extracted based upon the amplitude or area under a given peak (3). Advantages of MRS There are several advantages to performing MRS in vivo. Metabolic studies of organs in their normal environment can increase understanding of the function of complex organisms and enable researchers to evaluate changes dur- ing diseases. The noninvasive nature of MRS allows re- peated measurements in order to evaluate kinetic and lon- gitudinal studies and to study human tissues that are inaccessible by invasive techniques. At the strength of the magnetic field needed for human studies in vivo, no del- eterious effect on living tissue has been noted (3). Precau- tions such as excluding magnetic objects from the magnet are the main recommendation. Disadvantages of MRS The major disadvantage of MRS is its lack of sensitivity, which depends on a wide range of factors, including the Supported by grants from the Fundac ¸a ˜ o de Amparoa ` Pes- quisa do Estado de Sa ˜ o Paulo and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. Simone Appenzeller, MD, Lilian T. L. Costallat, MD, PhD, Li Min Li, MD, PhD, Fernando Cendes, MD, PhD: State University of Campinas, Campinas, Brazil. Address correspondence to Fernando Cendes, MD, PhD, Department of Neurology, University of Campinas- UNICAMP, Cidade Universita ´ ria, Campinas SP, Brazil, CEP 13083-970. E-mail: fcendes@unicamp.br. Submitted for publication November 27, 2005; accepted in revised form March 21, 2006. Arthritis & Rheumatism (Arthritis Care & Research) Vol. 55, No. 5, October 15, 2006, pp 807– 811 DOI 10.1002/art.22228 © 2006, American College of Rheumatology REVIEW ARTICLE 807