This paper reviews basic methods and recent applications of length-based fiber bundle analysis of cerebral white matter using diffusion magnetic resonance imaging (dMRI). improving the methodology through more complex anatomical models and potential areas of new application for qtDTI. Keywords: Diffusion tensor imaging, White matter, Quantitative tractography, Aging INTRODUCTION Advances in diffusion Moxonidine HCl weighted imaging (DWI) technology have allowed researchers to characterize the structural integrity of white matter tissue. Diffusion tensor imaging (DTI) is an extension of DWI utilized to non-invasively examine neuronal tracts to quantitatively measure white matter integrity (1,22,34,37,46). Highly advanced DTI methods have been developed in recent years and have significantly improved the utility of diffusion tensor measurements to detect subtle Rabbit polyclonal to ISOC2 white matter changes in both healthy and diseased populations (13C14,17,39C41). One example includes the integration of quantitative tractography based on diffusion tensor imaging (qtDTI) technology that has enhanced our ability to examine specific detail about the direction and curvature Moxonidine HCl of white matter pathways using in vivo imaging (17). This method is usually highly sensitive to white matter changes within entire tracts and, therefore, may be more advantageous than methods that involve placing regions of interest on two-dimensional scalar DTI parameter maps (17). In this review, we Moxonidine HCl describe the fundamentals of the diffusion tensor model and qtDTI technology. We then Moxonidine HCl review the existing literature on length-based metrics using qtDTI, followed by a discussion of the strengths and limitations of qtDTI. Finally, a brief review of future applications is provided. DIFFUSION MR TECHNIQUES DTI Physical Basis DTI is usually a noninvasive magnetic resonance imaging (MRI) technology that measures water diffusion at each voxel in the brain. Water molecules diffuse differently along tissues depending on tissue microstructure and the presence of anatomical barriers. One simple and useful way to characterize diffusion at a location in the brain is usually along a spectrum between isotropic and anisotropic. Diffusion that is highly similar in all directions (i.e., isotropic diffusion) is typically observed in grey matter and cerebrospinal fluid. By contrast, directionally dependent diffusion (i.e., anisotropic diffusion) is usually observed in white matter due to the linear organization of the fiber tracts. Water within these tracts preferentially diffuses in one direction because physical barriers such as axonal walls and myelin restrict water movement in other directions (5,24,47,48). Neuropathological mechanisms associated with multiple conditions, including subcortical ischemia, neurodegeneration, and traumatic brain injury, cause reductions in the linear organization of white matter pathways with corresponding reductions in linear anisotropy (5,19,48,52). DTI is usually sensitive to these changes in linear anisotropy even when white matter integrity appears healthy based on structural neuroimaging methods (referenced as normal appearing white matter) (4,30), making DTI a powerful in vivo imaging method for the examination of the microstructural integrity of white matter. DTI Scalar Metrics A symmetric 33 diffusion tensor characterizes water diffusion in brain tissues. This model represents the diffusion pattern with a second-order tensor that can be decomposed into three non-negative eigenvalues and three eigenvectors that describe the magnitude and orientation of water diffusion in each voxel (Physique 1). Eigenvalues describe the shape and size of the tensor, impartial of orientation, while eigenvectors describe the orientation of the tensor, impartial of shape and size. The tensor model parameterizes the diffusion in each voxel with Moxonidine HCl an ellipsoid whose diameter in any direction estimates the diffusivity in that direction and whose major principle axis is usually oriented in the direction of maximum diffusivity The major.