Grantee Research Project Results

2004 Progress Report: Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure

EPA Grant Number: R829389C005
Subproject: this is subproject number 005 , established and managed by the Center Director under grant R829389
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children
Center Director: Lanphear, Bruce
Title: Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure
Investigators: Lanphear, Bruce , Ris, Douglas , Dietrich, Kim , Cecil, Kim , Hornung, Richard , Holland, Scott
Current Investigators: Cecil, Kim
Institution: Children Hospital of Cincinnati , University of Cincinnati
Current Institution: Children Hospital of Cincinnati
EPA Project Officer: Hahn, Intaek
Project Period: November 1, 2001 through October 31, 2006
Project Period Covered by this Report: November 1, 2003 through October 31, 2004
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

The objective of this research project is to examine the effects of lead exposure on brain function.

Hyphothesis1. Childhood exposure to lead disrupts neuronal circuitry, resulting in changes in brain structure and metabolism as measured by magnetic resonance (MR) methods.

Hypothesis 2. Delinquent behavior and antisocial outcomes (e.g., crime, violence, drug abuse) associated with childhood lead exposure correlate with differences in quantitative MR measures of brain structure and metabolism.

Specific Aims
We will use advanced in vivo MR methods in approximately 150 subjects from the Cincinnati Lead Study (CLS) to test these hypotheses according to the following specific aims:

Specific Aim1. We will use localized proton MR spectroscopy (MRS) to measure metabolite concentrations of N-acetyl aspartate, creatine, choline, and myo-inositol in young adults with lead exposure history to: (1) determine if metabolite concentrations are related to levels of exposure, and (2) evaluate if metabolite concentrations are related to measures of anti-social outcome.

Specific Aim 2. We will use volumetric MR imaging (MRI) to measure total brain volume and volumes of cortical gray matter, white matter, and substructures within the basal ganglia in young adults with lead exposure history to: (1) determine whether structural volumes are related to levels of exposure, and (2) evaluate if structural volumes are related to measures of antisocial outcome.

Specific Aim 3. We will compare the results of the MR measures with the cognitive, behavioral, and social assessments defined in the companion project (i.e., R829389C004) to determine the significance of individual and collective measures for assessing the brain-behavior relationships.

Pilot Study Sub-Group of the Cincinnati Lead Study

Specific Aim 4. We will use functional MRI to measure levels of brain activation during semantic language tests, working memory, and attention tests in 40 young adults with a childhood history of lead exposure. We will recruit two groups of subjects from the CLS based on average childhood blood lead levels (high group > 20 μg/dL; low group < 10 μg/dL) and subdivide each group for members at the top 75th percentile and bottom 25th percentile for behavioral events to: (1) determine correlation between brain activation and levels of lead exposure, and (2) evaluate correlation of brain activation and measures of antisocial outcome.

Progress Summary:

Participation Rate

The participation rate has been excellent. As shown in Table 1, an additional 54 subjects were enrolled in the study during Year 2. To date a total of 101 subjects have been imaged, and recruitment continues at the expected rate. This year some subjects were excluded as a result of known pregnancy; one pregnancy was found during screening of the MR examination, and one subject was excluded because of claustrophobia upon attempting to perform the examination.

Table 1. Population Enrolled in Study (06/05/03-06/22/04)

	American Indian or Alaskan Native	Asian or Pacific Islander	Black, not of Hispanic Origin	Hispanic	White, not of Hispanic Origin	Other or Unknown	TOTAL
Female	0	0	22	0	3	1	26
Male	2	0	28	0	0	0	28
Unknown	0	0	0	0	0	0	0
TOTAL	0	0	50	0	3	1	54

Future Activities:

During the next period, we will continue to enroll subjects for the imaging examinations. We anticipate imaging six to eight subjects per month.

We seek to extend the significance of the project with two tangential projects. First, we will investigate a novel approach for assessing low-level manganese exposure and brain manganese deposition in the cohort of 150 young adults enrolled in the CLS. Two proposals have been submitted to the National Institutes of Health and U.S. Department of Energy, respectively. Our aim is to develop a noninvasive MRI brain biomarker useful for assessing manganese exposure.

We also want to explore the relationship between postural sway and cerebellar structure revealed by MRI and MRS. A preliminary review of historic postural sway data and current cerebellar spectroscopy-derived metabolite levels is ongoing.

Erin Haynes, a postdoctoral trainee in the National Institute of Environmental Health Sciences (NIEHS)-funded Molecular Epidemiology for Children’s Environmental Health Training Program, will work with Drs. Kim Cecil, Kim Dietrich, Bruce Lanphear, and other scientists in the NIEHS-funded Center for Environmental Genetics to conduct the manganese study. The postural sway study also will include the aforementioned Center scientists along with Dr. Amit Bhattacharya, Professor at the University of Cincinnati Department of Environmental Health.

A publication from the preliminary analysis of this project data is forthcoming later in the calendar year.

Journal Articles:

No journal articles submitted with this report: View all 6 publications for this subproject

Supplemental Keywords:

toxicology, ADHD behavioral assessment, behavioral deficit, genetic susceptibility, pesticides, biomarkers, environmental agents, exposure, exposure assessment, hearing loss, lead, meconium, neurotoxicity, pesticide exposure, risk assessment, toxicants,, RFA, Scientific Discipline, Health, ENVIRONMENTAL MANAGEMENT, Toxicology, Health Risk Assessment, Chemistry, Risk Assessments, Children's Health, Biology, Risk Assessment, magentic resonance, behavioral assessment, lead, neurotoxicity, children, toxicity, behavioral deficits, biological markers, exposure assessment, biomarker

Relevant Websites:

http://www.healthyhomestoday.com Exit
http://www.cincinnatichildrens.org/research/project/enviro Exit

Progress and Final Reports:

Original Abstract

Main Center Abstract and Reports:

R829389 CECEHDPR - University of Cincinnati Center for the Study of Prevalent Neurotoxicants in Children

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829389C001 Neurobehavioral Effects of Prevalent Toxicants in Children
R829389C002 Validation of Meconium Markers of Fetal Neurotoxicant Exposures
R829389C003 Community-Based Research Project Identifying Residential Hazards Using Home Test Kits
R829389C004 Early Exposure to Lead and Adult Antisocial Outcome
R829389C005 Magnetic Resonance Assessment of Brain Function Altered by Lead Exposure

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.