MR offers unique tools for measuring molecular diffusion. This review focus
es on the use of diffusion-weighted MR spectroscopy (DW-MRS) to non-invasiv
ely quantitate the translational displacement of endogenous metabolites in
intact mammalian tissues. Most of the metabolites that are observed by in v
ivo MRS are predominantly located in the intracellular compartment. DW-MRS
is of fundamental interest because it enables one to probe the in situ stat
us of the intracellular space from the diffusion characteristics of the met
abolites, while at the same time providing information on the intrinsic dif
fusion properties of the metabolites themselves. Alternative techniques req
uire the introduction of exogenous probe molecules, which involves invasive
procedures, and are also unable to measure molecular diffusion in and thro
ughout intact tissues, The length scale of the process(es) probed by MR is
in the micrometer range which is of the same order as the dimensions of man
y intracellular entities. DW-MRS has been used to estimate the dimensions o
f the cellular elements that restrict intracellular metabolite diffusion in
muscle and nerve tissue. In addition, it has been shown that DW-MRS can pr
ovide novel information on the cellular response to pathophysiological chan
ges in relation to a range of disorders, including ischemia and excitotoxic
ity of the brain and cancer. Copyright (C) 2001 John Wiley & Sons, Ltd.