Diffusion tensor imaging (DTI) has proven to be an important tool for investigating white matter changes associated with many central nervous system (CNS) diseases [Sullivan and Pfefferbaum, 2003;Salat et al., 2005;Assaf and Pasternak, 2008]. Recently, a new diffusion MRI imaging method called Diffusional Kurtosis Imaging (DKI) [Jensen and Helpern, 2003;Jensen et al., 2005;Lu et al., 2006] has been developed. DKI is capable of quantifying the non-Gaussian behavior of water diffusion. Recent DKI studies have demonstrated that mean kurtosis (MK) yields useful and distinct information from that provided by conventional DTI in detecting changes in brain microstructure associated with neurological diseases. [Falangola et al., 2008;Helpern et al., 2007;Ramani et al., 2007]. However, at this point in time, no histological correlation has been performed in the few published DKI animal studies [Falangola et al., 2007, Cheung et al., 2008a;Cheung et al., 2008b] and the quantitative interpretation of DKI metrics remains to be validated. The overall goal of this project is to validate and understand what these new MRI indices of diffusion, mainly the DKI measurements of Mean Kurtosis, axial (K//) and radial (K4) kurtosis, reflect at the tissue level by investigating the relationship between these measurements and axonal and myelin damage in a model of demyelination and remyelination, the cuprizone mouse model. This goal will be achieved by comparing indices of DK metrics and conventional DTI metrics with histological markers of myelin loss, axonal damage and glial cells accumulation during the process of demyelination and remyelination that occur in the corpus callosum of the cuprizone mouse model

Public Health Relevance

The questions addressed in this proposal are whether a new Magnetic Resonance Imaging (MRI) diffusion technique, called Diffusional Kurtosis Imaging (DKI), can be accurate and suitable for quantitative evaluation of brain microstructure changes. As with any new MR technique, the validation and understanding of what the proposed MRI indices reflect at the tissue level is essential for characterizing the normal morphological aspects and the underlying pathology on a disease set. For this validation we will use the cuprizone mouse model of demyelination and remyelination. The significance of this project is to try to validate and understand what these new MRI indices of diffusion reflect at the brain morphological level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Small Research Grants (R03)
Project #
5R03EB009711-02
Application #
7871464
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Liu, Guoying
Project Start
2009-08-01
Project End
2011-10-31
Budget Start
2010-08-01
Budget End
2011-10-31
Support Year
2
Fiscal Year
2010
Total Cost
$78,210
Indirect Cost
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962