Diffusion-Tensor Imaging for Stroke

Veronica Wallace BMB 601: Fundamentals of Magnetic Resonance1 March 2011

Saturday, 5 March 2011

Outline

✤ I. Overview of diffusion tensor imaging (DTI)

✤ II. Historical development of diffusion imaging

✤ III. Applications of DTI to stroke imaging

✤ IV. Current research, future directions

Saturday, 5 March 2011

Diffusion Imaging

✤ Diffusion: random (Brownian) motion of one form of matter through another matter, in this case, of fluid through tissue

✤ Isotropic: free diffusion (independent of orientation), usually in larger areas

✤ Anisotropic: diffusion is directional (varies with orientation), often in smaller restricted areas

✤ 2 Types of Diffusion Imaging:

✤ DWI: Diffusion Weighted Imaging

✤ Based on T1, T2 values

✤ Scalar; applies single gradient with pulse sequence

✤ DTI: Diffusion Tensor Imaging

Saturday, 5 March 2011

Diffusion Tensor Imaging

✤ Biology:

✤ Based on anisotropy of brain matter

✤ Physics:

✤ Minimum 6 gradients applied, to obtain 3 acquisitions of interest: Dx, Dy, Dz

✤ Apply 3 combination gradient pulses (3x3 matrix)

✤ Mathematics:

✤ Similarity transform orients axes to yield 3 eigenvectors (eigenvalues D1, D2, D3)

✤ Given eigenvalues, quantify anisotropy

Saturday, 5 March 2011

Orientation

✤ D = DXX DXY DXZ

DYX DYY DYZ

DZX DZY DZZ

X

Z

Y

Tract

Z’Y’

X’

Content Source: Hashemi, 2004

Eigenvalues: D1, D2, D3

Diffusion tensor becomes the diagonal terms:

DXX, DYY, DZZ

Saturday, 5 March 2011

Diffusion Tensor Imaging

✤ For DTI, we are interested in the degree of anisotropy

✤ Describes how much molecular displacements vary in space, according to relative orientation. Diffusion anisotropy is described quantitatively as:

✤ Fractional Anisotropy

✤ Relative Anisotropy

✤ Volume Ratio

Saturday, 5 March 2011

Diffusion Tensor Imaging

✤ Given eigenvalues (D1, D2, and D3) and mean diffusivity, D = (1/3)(D1+D2+D3):

✤ Fractional Anisotropy:

✤ Relative Anisotropy:

✤ Volume Ratio:

Saturday, 5 March 2011

Diffusion Tensor Imaging

✤ When D1 is much greater than D2 and D3, diffusion is ellipsoid (b)

✤ When any two eigenvalues are large, and much larger than the third, diffusion is planar (c)

✤ Anisotropy based on principle eigenvector, D1: if the 3 eigenvalues are much different from each other, diffusion is anisotropic.

✤ When D1, D2, D3 are all similar values, diffusion is isotropic, represented by a sphere (a)

Source: Reiser, 2007

Saturday, 5 March 2011

Historical Development of DTI

✤ Edwin Hahn (1950) Spin-echoes.

✤ Spin echoes are sensitive to effects of diffusion

✤ Signal reduction due to dephasing caused by translational diffusion of spins subjected to magnetic field gradients due to inhomogeneties in the magnetic field

✤ Carr and Purcell (1954) Effects of diffusion on free precession in nuclear magnetic resonance experiments.

✤ Spin echoes can be sensitized to diffusion in order to take measurements

✤ Mathematical framework measures diffusion coefficients

✤ Apply constant gradients throughout pulse sequences

Saturday, 5 March 2011

Historical Development of DTI

✤ Stejskal and Tanner (1965) Spin diffusion measurements: spin echoes in the presence of time-dependent field gradient.

✤ Introduced PGSE, Pulsed Gradient Spin Echo (replacing Carr and Purcell’s gradient pulse work)

✤ Solved Bloch-Torrey equations to show that magnitude and phase of MR signal was related to diffusivity

✤ Developed Fourier relationship for PGSE experiment between measured signal and displacement distribution, laying foundations for q-space

✤ Le Bihan (1980’s - Present)

✤ Development of diffusion MR for research and clinical practice

Saturday, 5 March 2011

Applications to Stroke Imaging

✤ Brain is the target of investigation

✤ Brain has complex diffusion (heterogeneous and compartmentalized), and therefore simple diffusion imaging techniques --such as DWI for isotropic diffusion-- are limiting

✤ Diffusion is in three dimensions (anisotropic); therefore 3D imaging is ideal

✤ Why is diffusion imaging useful for strokes, what information does it give about the nature of a patient’s stroke?

Saturday, 5 March 2011

Applications to Stroke Imaging

Source: http://bughealth.com/physical/how-can-happen-stroke.html

Source: http://www.sciencephoto.com/images/download_lo_res.html?id=771360157

-Hemorrhagic Stroke (intracerebral hemorrhage): blood vessel going to the brain bursts

-Ischemic Stroke: blood vessel is clogged by a blood clot or other mass

Brain in the area affected by stroke stops receiving oxygen and blood, nerve cells die within minutes.

What is a stroke?

Saturday, 5 March 2011

Applications to Stroke Imaging

✤ Characteristics of stroke:

✤ Hemorrhagic stroke accounts for 10-40% of cases, can be difficult to diagnose

✤ Likelihood can increase with certain medications, including anticoagulants, blood pressure, coagulotherapies

✤ Risk increases with age, hypertension, drug use

✤ Major post-stroke risks: seizures, cerebral edema, growth of hematoma, rapid neurological damage

Saturday, 5 March 2011

Applications to Stroke Imaging

✤ Common Complications

✤ Inability to distinguish between ischemic and hemorrhagic stroke

✤ Inability to recognize high risk of stroke

✤ Lack of information regarding damaged areas: worsening conditions, spread of damage, causes of condition or symptoms

Saturday, 5 March 2011

Benefits of DTI

✤ Gives a more quantitative description of stroke than, for example, DWI alone

✤ Helps determine what therapy will be/is most effective

✤ Allows repeated measurements for monitoring high-risk patients

✤ Can show how diffusion is changing, help distinguish between ischemic and hemorrhagic strokes

✤ Allows noninvasive imaging into deep internal structures

Saturday, 5 March 2011

Applications to Stroke Imaging

✤ White matter and gray matter have different properties, but need information on both to determine the quality and extent of stroke

✤ White matter is anisotropic; DTI can give information on both white and gray matter

✤ Using DTI, Mukherjee at al. (2000) found that after stroke, diffusion was significantly reduced in white matter but only slightly reduced in gray matter

Saturday, 5 March 2011

DTI for Fiber Tracking (“Tractography”)

✤ DTI provides information about connectivity and organization of white matter fibers

✤ 3D images are developed based on tensors from voxels, units describing the nature of diffusion in a given volume

✤ Advantage over conventional MRI: shows fiber tract directionality, abnormalities on a more micro- scale

Source: Kubricki, et al., 2007

Saturday, 5 March 2011

DTI for Fiber Tracking

✤ The fiber is the principle eigenvector, which is then color-coded for directionality

✤ Axons facilitate movement of water molecules in the direction of their propagation (anisotropic diffusion)

✤ Allows distinction between normal and damaged areas: water molecules move parallel to normal fibers; movement is perpendicular around damaged areas

✤ Fractional anisotropy (anisotropy in a voxel) can equate to brightness

Saturday, 5 March 2011

Current Research

✤ Imaging small vessel disease: lesion topography, networks, and cognitive deficits investigated with MRI. O'Sullivan M. Cardiff University Brain Research Imaging Centre, School of Psychology, Cardiff University, UK. Stroke. 2010 Oct; 41(10 Suppl): S154-8.

✤ DTI can be used to gather more information about cognitive decline: alterations in cognition follow changes in brain structure

✤ Imaging can be employed to assess extent of damage, understand networks, understand the effects on behavior and cognitive function

✤ Provides an approach for when anisotropy diminishes due to loss of axons and myelin (loss of directionality component)

Saturday, 5 March 2011

Current Research

✤ Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia. Meinzer M, Mohammadi S, Kugel H, Schiffbauer H, Flöel A, Albers J, Kramer K, Menke R, Baumgärtner A, Knecht S, Breitenstein C, Deppe M. University of Münster, Department of Neurology, Münster, Germany. Neuroimage. 2010 Oct 15; 53 (1) 283-90.

✤ Loss of speech associated with loss of blood supply to temporal lobe and parts of hippocampus following middle cerebral artery stroke

✤ Patients’ success in language learning following stroke dependent on maintaining microstructure in and around hippocampus

Saturday, 5 March 2011

Current Research

✤ Diffusion tensor imaging of early changes in corpus callosum after acute cerebral hemisphere lesions in newborns. Righini A., et al. Neuroradiology. 2010 Nov. 52 (11) 1025-1035.

✤ DTI can be used to observe changes in corpus callosum diffusion shortly after birth

✤ Retrospective trial, with controls, on 19 infants

✤ DTI shows location and extent of axonal damage due to lesions, stroke, Wallerian degeneration

Saturday, 5 March 2011

Current Research

✤ Post-treatment with amphetamine enhances reinnervation of the ipsilateral side cortex in stroke rats. Liu HS, Shen H, Harvey BK, Castillo P, Lu H, Yang Y, Wang Y. Magnetic Resonance Imaging and Spectroscopy Section, National Institute on Drug Abuse, Baltimore, MD. Neuroimage. 2011 Feb 21.

✤ Amphetamine treatment has been shown to have neuroregeneration capabilities in certain regions of the brain

✤ Combined DTI and T2-weighted imaging

✤ Amphetamine treatment reduces volume of tissue loss, increase FA, suggesting axonal growth

Saturday, 5 March 2011