Project 5: Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure
Investigator: Kim M. Cecil, PhD
Project Period: 10/1/2001 through 6/30/2006
Objectives / Hypothesis
Magnetic Resonance (MR) assessment of brain function altered by lead exposure seeks to relate environmental lead exposure with alterations in brain structure, neurochemistry and function assessed with magnetic resonance imaging (MRI) and spectroscopy (MRS). The population selected for study is the Cincinnati Lead Study (CLS); a unique and ideal cohort of approximately 240 subjects with detailed histories of exposure and behavioral outcomes in lead exposed children monitored for approximately 20 years. Historical and ongoing measures of behavior (Project 4) will be integrated with this project to determine the significance of the imaging assessments. Childhood exposure to lead and specific outcomes of behavior in young adulthood will be compared, employing advanced brain imaging methodologies to test the following hypotheses:
- Childhood exposure to lead disrupts neuronal circuitry, resulting in changes in brain structure and metabolism as measured by MR.
- Delinquent behavior and anti-social outcomes (crime, violence, drug abuse, etc.) associated with childhood lead exposure correlate with differences in quantitative MR measures of brain structure and metabolism.
Structural and chemical findings should provide a neurobiological basis for improving our understanding of the in-vivo effects of lead exposure. Although the exposure level of this cohort is higher than contemporary exposures in the general community, the subjects are likely to demonstrate impaired brain function that will be relevant to inner-city, urban and lower levels of exposure. Ultimately, the development of these imaging tools in assessing environmental toxicant exposures and long-term effects could be applied to new cohorts to directly assess the impact of exposure on the developing brain.
Approach
We will utilize advanced in-vivo MR methods in approximately 150 subjects from the CLS to test these hypotheses according to the following specific aims:
- We will use localized proton MRS to measure brain metabolite concentrations of N-acetyl aspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) to determine if metabolite concentrations are related to levels of lead exposure and evaluate if metabolite concentrations are related to measures of anti-social outcome.
- We will use volumetric MRI to measure total brain volume, volumes of cortical gray matter, white matter and sub-structures within the basal ganglia to determine if structural volumes are related to levels of lead exposure and evaluate if structural volumes are related to measures of anti-social outcome.
- We will compare the results of the MR measures with the cognitive, behavioral, and social assessments defined in Project 4 to determine the significance of individual and collective measures for assessing the brain-behavior relationships.
Expected Results
MR Spectroscopy performed in a population of lead-exposed individuals may identify regions of abnormal neuronal functioning (NAA declines), demyelination (elevated choline and lipids) and disturbances of astrocytic and other glial cells (increased myo-inositol). We anticipate young adults with a history of lead exposure to demonstrate lowered neuronal marker levels (NAA), particularly in the frontal lobe. The NAA concentration is expected to correlate with a composite measure of lead exposure level and duration. Anti-social outcomes are expected to also correlate with metabolite concentrations reflecting neuronal (NAA) and glial (mI, Cho) functioning. Reduction of volumes of the frontal lobe cortex and within the basal ganglia structures is expected to be related to lead exposure and anti-social outcomes.
