By Andra Pascale

Overview

ConceptsDiffusion Weighted ImagingDiffusion TensorMeasured coefficients

ApplicationsBrain white matter studiesSpecific disordersBrain connectivity

Diffusion

Diffusion is a net transport of molecules from a region of higher concentration to one of lower concentration by random molecular motion

TensorsTensors are geometrical entities introduced to extend the notion of scalars, vectors, and matrices

0th-order tensor is a scalarA 1st -order tensor is a vector represented in coordinates

as a 1-dimensional array of componentse1 = (1,0,0)

A 2nd -order tensor can be represented as a square matrix

Diffusion Weighted Imaging

DTI is the next generation of DWI

Diffusion weighted imaging non-invasively looks at the restriction of random Brownian motion of tissue water and provides clues about the microenvironment in which the water molecules are dispersing

Why? Because disease can change the diffusion properties of the underlying tissue

Diffusion coefficient MRI - a homogeneous magnetic field,DWI - homogeneity is varied linearly by a pulsed field gradientProtons begin to precess at different rates => dispersion of the phase and signal lossAnother gradient pulse is applied in the same direction but withopposite magnitude to rephase the spinsProtons have moved during the time interval between the pulses =>the signal measured by the MRI machine is reduced

Diffusion coefficient D : computed from the signal attenuation of a MRI voxel

○ S0 signal intensity without the diffusion weighting○ S signal with the gradient○ γ gyromagnetic ratio○ G strength of the gradient pulse○ δ duration of the pulse○ Δ time between the two pulses

ADC

When other factors such as cell membranes interfere with the free diffusion, we are measuring an "apparent diffusion coefficient" or ADC

The ADC in anisotropic tissue varies depending on the direction in which it is measured

DTI

Diffusion is a 3D processThe objective is to use diffusion anisotropy to analyze the direction of the axons and the diffusion properties A 2nd order tensor is used to model 3D anisotropy

=> Diffusion Tensor Imaging

How does it work?

Diffusion in an anisotropic medium causes a group of water molecules to move out from a central point, and gradually reach the surface of an ellipsoid

The ellipsoid formalism functions also as a mathematical method of organizing tensor data

The ellipsoid tensor

MRI Voxel measurements from at least 6 directions -> calculated tensor ellipsoid -> voxel propertiesLongest axis

main eigenvector of the tensor matrix -> direction of the axonmain eigenvalue indicating axial diffusivity

FA – fractional anisotropy

Other measures of diffusion

Radial diffusivity - an assessment of the degree of restriction due to membranes and other effects

○ (λ2 + λ3)/2Sensitive measure of degenerative pathology in some neurological conditions

Total diffusivity – trace of the matrix

Mean diffusivity○ (λ1 + λ2 + λ3)/3.

Summary DTI

Describes the diffusion along each direction and interactions between the directions of the brain fibersProvides important information about tissue connectivityFrom DTI data other indices can be calculated

FA – fractional anisotropyADC – apparent diffusion coefficientTraceW – trace weighted

Applications

Mainly used to study the white matter in the brainWhite matter is one of the two components of the central nervous system and consists mostly of myelinated axonsMyelin is a white, insulating sheath on the axon, composed of fatty materials, protein, and water

Meylin

Increases the speed of impulse transmissionEssential for the proper functioning of the nervous systemDamaged meylin is the cause of many neurodegenerative autoimmune diseases

Neuropsychiatric Disorders

Based on geometry and the degree of anisotropy loss, white matter tract pathology, such as dislocation, swelling, infiltration, and disruption, can be documentedCross-sectional sizes of these pathways yield a quantitative measure of connectivity between different brain regions

Assessment of white matter loss

FA maps from a patient with mesiotemporal sclerosis which is a common cause of epilepsy

Demyelinating vs dysmyelinating disorders

Diffusional anisotropy is present in dysmyelinating disorders such as Pelizaeus-Merzbacher diseaseIt may be lost in demyelinating disease such as Krabbe disease or Alexander diseaseBoth disorders appear similar on conventional MRI => DTI can make the distinction between them

Epilepsy

Increased diffusivity and decreased anisotropy caused by the loss of structural organization and expansion of the extracellular fluid spaceThese changes in DTI may also extend

to areas of the brain that appear morphologically normal on conventional MRIs

Brain ischemia

Distinction between old and new strokes

Helps to differentiate early stroke from other focal brain processes mimicking stroke on conventional MRI

Changes in anisotropy can be detected several months after the stroke

Traumatic brain injury

Investigation of the specific fiber tracts affectedAbility to monitor the degeneration process following injuryLater decreases in ADC indicates cytotoxic edema which plays a major role in brain swelling

Alzheimer’s disease

DTI studies conducted in the early stages of the disease have revealed significant connectivity disruptions within the white matter fiber tracts

=> tracking progressive changes in Alzheimer’s disease

Possible future use to evaluate changes in response to treatment

Schizophrenia

Several DTI reports of decreased diffusion anisotropy in the white matter

Loss of orientation and organization of fiber tracts has been detected in the whole white matter

Further research may change the way we see this disorder

Tractography

Tracking a fiber along its whole length measures deficits in white matter, such as in agingIncreasingly accurate

High potential cognitive neuroscience and neurobiology

Tractography

Brain tracts are not identifiable by direct exam, CT, or MRI scans => scarcity of their description in neuroanatomy atlases and the consequent poor understanding of their functions

Summary

DTI enables research in areas that previously relied largely upon postmortem studiesStudies the white matter and connectivity in the brainDiagnostic and follow up checking for many disorders that appear normal on conventional MRI techniques

References“Diffusion Tensor Imaging and Its Application to Neuropsychiatric Disorders” ,Marek Kubicki, MD et al.,HARVARD REV PSYCHIATRY 2002;10:324–336“Diffusion Tensor Imaging: Concepts and Applications”,Denis Le Bihan, MD, PhD et al., JOURNAL OF MAGNETIC RESONANCE IMAGING 13:534–546 (2001)© 2001“Diffusion Tensor Imaging: Techniques and Clinical Applications”,X. J. Zhou , Proceedings of the 26th Annual International Conference of the IEEE EMBS San Francisco, CA, USA •September 1-5, 2004 http://emedicine.medscape.com/article/345561-overviewwww.usa.siemens.com/medicalhttp://en.wikipedia.org/wiki/Tractographyhttp://www.technologyreview.com/article/16473/http://www.rsierra.com/DA/node7.htmlhttp://en.wikipedia.org/wiki/Diffusionhttp://www.nlm.nih.gov/medlineplus/ency/article/002261.htm