Metabolic brain imaging by magnetic resonance

Novel magnetic resonance methods have been developed to noninvasively measure biochemical compounds in the human brain as guided by magnetic resonance imaging. Together, these methods are referred to as magnetic resonance spectroscopy (MRS) and can be divided into three major categories: single voxel MRS, magnetic resonance spectroscopic imaging and dynamic MRS, which is a novel adaption of the first method. The techniques and range of biochemical compounds that can be measured safely and serially are advancing rapidly, with many technical developments. MRS methods, when applied to the human brain, have an important diagnostic role, help monitor and guide therapeutic interventions and provide a tool to investigate the mechanisms of neuropsychiatric disease processes, normal brain development and neuropharmacology in vivo. Rapid advances in the application of magnetic resonance techniques to neurobiological investigations have occurred over the last 30 years. In vivo magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging (MRSI) have been used to interrogate the living brain for prognostic and diagnostic markers in neurological disorders, as well as define changes that occur during normal development. The safety and noninvasiveness of MR methods make them particularly well suited to investigations in children. Significant advances have been made in both the acquisition and interpretation of the data. Presently, magnetic resonance methods allow the investigation of neuroanatomy through magnetic resonance imaging (MRI), cerebral function in response to physiological stimuli (functional MRI [fMRI]), and cerebral metabolism through multinuclear MRS. Magnetic resonance provides the only methods whereby information on neuroanatomy, cerebral metabolism and brain function can be obtained noninvasively using a single instrumentation system. Early studies using anatomical MRI in infants and children have enabled characterization of many disorders of brain development and pathological conditions [1]. Application of quantitative, image analysis methods has identified anatomical changes in many cortical and subcortical regions that occur with normal development through early adulthood [2,3]. Several investigations using fMRI have been conducted to study changes that occur with visual [4], language, reading [5,6] and memory [7] function during development. fMRI has permitted the identification of anomalies in brain function that occur in many neurological and cognitive disorders, such as epilepsy [8] and dyslexia [5,9]. MRS has been particularly useful in both diagnosing and following the progression of many neurogenetic and neurodegenerative disorders, particularly those with onset in childhood. MRS is diagnostic in disorders such as Canavan’s disease, glycine encephalopathy and creatine deficiency syndromes. MRS studies have demonstrated early metabolic changes in many neurological disorders prior to alterations in MRI. Several MRS investigations have identified characteristic changes in metabolites in neurological disorders such as stroke, tumors and multiple sclerosis. This review will discuss the methods for obtaining metabolic measurements in vivo by MRS that can be combined with any of these MR methods. Obtaining a metabolic biopsy in vivo by single-voxel MRS A number of nuclei that are present on biological molecules have physical properties which allow them to be observed in vivo using MR. When placed in an external magnetic field, the absorption and emission of electromagnetic radiation of nuclei that possess a magnetic moment can be observed. The electromagnetic radiation is typically in the radiofrequency range of 10–800 MHz. These nuclei can be divided into two broad classes: those that require the addition of exogenous label and those that do not. The most common nuclei used are phosphorus ( 31 P) and proton ( 1 H), which generate spectra that are dominated by resonances from endogenous metabolites. The proton signal from water is