ABSTRACT

INTRODUCTION The ten years since the second issue of Neurotoxicology was published have brought signifi cant advances in neuroimaging techniques. However, the potential of in vivo neuroimaging to characterize and quantify deleterious effects of neurotoxin exposure on the brain and identify mechanisms for their effects remains to be fully realized. In this chapter we focus primarily on in vivo magnetic resonance imaging (MRI) that yields several imaging formats. Conventional structural MRI images are amenable to sensitive and reliable measurements of macrostructure-the size, shape, and some aspects of tissue quality of neuroanatomical structures, such as the basal ganglia, cerebellum, and hippocampus, which are often sites of neurotoxic damage. Structural images also reveal areas where the signal intensity is higher or lower than adjacent tissue within a structure, suggesting some form of pathology. diffusion tensor imaging (DTI) enables detection of microstructural defi cits in white matter tracts, a feature of brain architecture particularly vulnerable to certain neurotoxins. Magnetic resonance spectroscopy (MRS) provides the means to assess a range of brain metabolites that can refl ect neurotoxic effects on cell bodies, axonal constituents, and glia. Functional magnetic resonance imaging (fMRI) provides a proxy measure of localized changes in blood volume during brain activity and can refl ect reorganization of functioning in response to neurotoxic damage. Other imaging techniques, such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT), have also been used to delineate physiological, gene expression, and biochemical or cellular mechanisms for neurotoxic effects. The reader is referred elsewhere, however, for studies using these techniques and particularly for emerging applications of micro-PET scanning, which provides higher resolution data but is primarily confi ned to research settings and with animal models of neurotoxicity ( 1 , 2 ). In all studies, the contribution of nonspecifi c variables, such as age, gender, poor nutrition, seizure disorder, high blood pressure, or psychopathology to observed neurotoxic pathology remains a signifi cant challenge. Several new studies have provided evidence linking a history of toxic exposure, behavioral defi cits, and macroscopic, microscopic, or functional brain compromise.