The diffusion tensor of N-acetyl aspartate (NAA), creatine and phosphocreatine (tCr), and choline (Cho) was measured at 3T using a diffusion weighted STEAM 1 H-MRS sequence in the healthy human brain in 6 distinct regions (4 white matter and 2 cortical gray matter). The Trace/3 apparent diffusion coefficient (ADC) of each metabolite was significantly greater in white matter than gray matter. The Trace/3 ADC values of tCr and Cho were found to be significantly greater than NAA in white matter, whereas all 3 metabolites had similar Trace/3 ADC in cortical gray matter. The physical property of diffusion of water molecules has shown great utility in magnetic resonance imaging for studying a multitude of neurologic disorders, and in neurodevelopment and aging. Diffusion ordered spectroscopy (DOSY) has demonstrated enormous potential in the fields of chemistry and biochemistry (1); however, the investigation of metabolite diffusion (molecules other than water) in vivo has lagged behind due to technical challenges, such as limited signal-to-noise ratio, poor spatial resolution, pulse sequence availability, significant post-processing, lengthy acquisition times, and limited brain coverage. Despite these challenges, the pursuit of metabolite diffusion in diseased tissue is worthwhile since it may yield insights into changes in the underlying intra-cellular environment with disease (2-5).In contrast, localizing changes in water diffusion to a specific compartment of the brain has been difficult and controversial. It has long been shown that reductions in water diffusion are the most sensitive indicator of early cerebral ischemia (6), and that despite the theory that this decrease is due to a water shift from extra-cellular to intra-cellular space, purely intra-cellular metabolites also show a reduction of diffusion by a similar magnitude without any compartmental shifts (4,7-12). Thus, diffusion-weighted spectroscopy can add insight into the biophysical properties of diffusion in tissue, but it remains to be tested whether or not diffusion of intra-cellular metabolites will provide evidence of neuronal/axonal abnormalities in the absence of changes in either water diffusion or other MR properties in a variety of neurologic disorders beyond ischemia.Since diffusion is known to be anisotropic in white matter, for either water or metabolites (13-15), it can only be characterized properly by measuring the full diffusion tensor, with an unavoidable time penalty. The mean diffusivity and the degree of anisotropy provide independent and unique inferences on the micro-structural integrity of the white matter tracts (16). N-acetyl aspartate (NAA) is located in the intracellular space of neurons and axons, while creatine and phosphocreatine (tCr), and choline (Cho) are located, not only in the neurons and axons, but also in the more presumably isotropic environments within astrocytes, oligodendrocytes, and meningeal cells (17). It may be hypothesized that tCr and Cho might exhibit different degrees of anisotropy as compared to NAA ...