The findings of this study suggest that lead has an effect on brain metabolites as detected by MRS in vivo. More specifically, we have found statistically significant reduced levels of brain metabolites in gray but not white matter in lead-exposed individuals. These results imply that MRS is able to detect metabolic abnormalities in individuals with lead poisoning.
ABSTRACT. Objective. The effects of elevated blood lead levels on the development of children have been examined only in the context of behavioral and neuropsychological evaluations. No studies have examined the effects of lead on brain metabolism in vivo or on structural and/or functional correlates of brain function in children. In the human brain, magnetic resonance spectroscopy (MRS) provides a noninvasive, risk-free method to monitor the biochemistry of acute and chronic stages of disease. The purpose of this study was to examine in vivo the use of MRS for the evaluation of the neurotoxic effects of lead on the nervous system, by detection of brain metabolism, especially N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss.Methodology. Two male cousins who live in the same household and share the same socioeconomic background and home environment were studied. The subject, a 10-year-old boy, had elevated blood lead levels. His cousin, a 9-year-old boy, was not exposed to lead. Both underwent a comprehensive neuropsychological evaluation and both were evaluated using the magnetic resonance imaging (MRI) and MRS at the University of Pennsylvania Medical Center. High-resolution MRI and MRS were performed using a 3-in surface coil. Localized proton spectra were obtained from contiguous 6 ؋ 6 ؋ 10-mm voxels using one-dimensional phase encoding, with a 2000-millisecond repetition time and a 31-millisecond echo time.Results. Neuropsychological evaluation demonstrated areas of impairment in the lead-exposed child, including difficulties in academic skills of reading, writing, and arithmetic, as well as deficient linguistic skills and attentional mechanism. By contrast, studies of the cousin, who was not exposed to lead, showed overall neuropsychological functioning within normal limits. Although both children had a normal MRI examination of the brain, studies of the lead-exposed boy showed a significant alteration in brain metabolites, with a reduction in the N-acetylaspartate:creatine ratio for both gray and white matter on the MRS examination, compared with his cousin.Conclusions. The present study is a first attempt to determine in vivo metabolic differences in the brain of a child exposed to lead compared with a healthy control subject. This is a unique case because these children were matched on a number of variables usually regarded as confounders in behavioral lead studies, and therefore can be regarded as matched controls. The present study demonstrates that MRS is a feasible, noninvasive technique for in vivo examination of the brains of children exposed to lead. We were able to obtain high-quality spectra from voxels as small as 0.36 cm at 1.5T. The spatial resolution used in the present study is sufficient to obtain spectra from voxels almost exclusively composed of gray matter. The one-dimensional phase-encoding approach used presents the advantage of obtaining several spectra simultaneously in a relatively short time. The present study has allowed us to examine the ...
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