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Introduction to Diffusion Tensor Imaging November 2010 Jennifer Campbell

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Page 1: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

November 2010

Jennifer Campbell

Page 2: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

• Molecular diffusion• Diffusion weighting in MRI• The diffusion tensor in use• Problems and solutions

Page 3: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

• Molecular diffusion• Diffusion weighting in MRI• The diffusion tensor in use• Problems and solutions

Page 4: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion MRI measures Brownian motion of water molecules

Path of diffusing water molecule

Water displacement distribution

Page 5: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion MRI measures Brownian motion of water molecules

−−•

=d

T

d

drrDrr

DrrP

τπττ

4)()(exp

)4(1),|( 0

10

30 dDr τ6; 2 >=<

Page 6: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion MRI measures Brownian motion of water molecules

Restricted diffusion: Apparent Diffusion Coefficient (ADC)

Page 7: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion MRI measures Brownian motion of water molecules

Restricted diffusion: Apparent Diffusion Coefficient (ADC)

Page 8: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion MRI measures Brownian motion of water molecules

−−•

=d

T

d

drrrrrrP

τπττ

4)((ADC))(exp

)4(ADC1),|( 0

10

30

Page 9: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tissue structures determine which directions of motion are most probable

White matter fibre bundle: oriented

structure

Water molecules prefer to travel parallel to fibre

direction

Page 10: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tissue structures determine which directions of motion are most probable

−−•

=d

T

d

drrrrrrP

τπττ

4)()(exp

)4(||1),|( 0

10

30

DD

Page 11: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

The diffusion tensor

λ1

λ3λ2

e1

Page 12: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

• Molecular diffusion• Diffusion weighting in MRI• The diffusion tensor in use• Problems and solutions

Page 13: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion weighted MR sequenceTE

G

90° 180° echo

G

Stejskal-Tanner diffusion weighted sequence: pulsed-gradient spin-echo (PGSE)

)3/(222 δδγ −∆= Gb

∆δ

bDoeSbS −=)(

Page 14: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

bDoeSbS −=)(

b

)(bS

Diffusion weighted MR sequence

Page 15: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

B0B0 + G B0

G

180° echo

B0, 180o

G

B0 + G

Gradients, phase, and motion

Page 16: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

G

180° echo

G

Gradients, phase, and motion

B0 + G B0, 180o B0 + G B0B0

Page 17: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion weighted images (DWIs)

Page 18: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

• series of DWIs: 3-6-60-100+ encoding directions• Full brain coverage: 15-20 minutes per 100 directions • b value: 1000-3000 s/mm2

• Voxel size: roughly 2mm x 2mm x 2mm isotropic voxels typically used

Acquisition parameters for diffusion weighted images (DWIs)

Page 19: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Sequence modifications: trace weighted sequence

GGx

RF

90° 180°

G

GyG G

GzG G

Page 20: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Computing the diffusion tensor

Page 21: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Computing the diffusion tensor

Page 22: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

λ1

λ3λ2

e1

Computing the diffusion tensor

Page 23: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

FA: anisotropy

index

trace of diffusion tensor

RGB plot: principal

eigenvector (e1) direction, scaled

by FA

Maps obtainable from diffusion tensor

)()()()(

23FA 2

32

31

23

22

21

2 λλλλλλλλλ

++−+−+−

=

Page 24: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

λ1

λ2∼λ3

cylindrical symmetry

Page 25: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

λ⊥, radial

λ||, axial

cylindrical symmetry

Page 26: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

• Molecular diffusion• Diffusion weighting in MRI• The diffusion tensor in use• Problems and solutions

Page 27: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

normal white matter

Page 28: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

myelin degeneration:•radial diffusivity ↑•FA ↓

Page 29: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

normal white matter

Page 30: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

axonal fragmentation:•axial diffusivity ↓•FA ↓

Page 31: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

normal white matter

Page 32: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

decreased axon density:•radial diffusivity ↑•FA ↓

Page 33: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

crossing fibres:•FA lower than for single direction

Page 34: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

degeneration of one fibre population in crossing case:•FA ↑

Page 35: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

curvature:•FA lower than for single direction

Page 36: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion tensor imaging (DTI)

splay:•FA lower than for single direction

Page 37: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

normal tissue

Diffusion tensor imaging (DTI)

Page 38: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

cellular swelling:•MD ↓

Diffusion tensor imaging (DTI)

Page 39: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Fibre tracking using diffusion MRI data

Diffusion MRI data

Water displacement profile

Fibre directions

Fibre tracts

Page 40: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tractography

What does tractography tell us?-is A connected to B?-how are A and B connected?-how confident are we in this

connection?

Applications of tractography:-visualization in 3D: localization,

education-segmentation (both white matter and

grey matter)-investigating clinically relevant

differences between pathways in different populations-neuroanatomical questions

Page 41: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tractography

Streamline integration methods:• “fibre assignment using continuous tracking”

(FACT)• Euler• RK4

Tract delineation techniques:• tract delineating ROIs (as many as desired): drawn

manually, by protocol, or based on other data• exclusion masks, stopping criteria S. Mori et al, AN 45:265-269, 1999

Page 42: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tractography: warnings

Diffusion MRI tractography results include many false positives and false negatives: priors are essential.– Tractography is good for segmentation of parts of

pathways, but segmenting the entire pathway can be challenging.

– Characterizing unknown new anatomy is much more difficult than studying known anatomy.

– Tractography does not distinguish between afferent and efferent pathways, or between mono- and multisynaptic connections.

Page 43: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tractography incorporating uncertainty

MamayyezSiahkal et al. 2009

Page 44: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Applications• basic human neuroanatomy• structure and function• understanding disease• understanding therapies• nonhuman primates; other animal

studies

Page 45: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

• stroke• MS• cancer• trauma• dyslexia• epilepsy• schizophrenia

Applications

• ALS• dementia• CJD• surgical planning• surgical outcome• blindsight• depression

• neuroanatomy• development• aging

Page 46: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Introduction to Diffusion Tensor Imaging

• Molecular diffusion• Diffusion weighting in MRI• The diffusion tensor in use• Problems and solutions

Page 47: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Diffusion weighted signal intensity: high value in directions perpendicular to fibres

Diffusion weighted signal profile

Page 48: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Probability of water displacement orientation distribution function (ODF)

Diffusion tensor model

Page 49: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

High Angular Resolution Diffusion Imaging (HARDI)

q-ball imaging

Page 50: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

QBI DTI

High Angular Resolution Diffusion Imaging (HARDI)

Page 51: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Why use high angular resolution diffusion MRI?• Reduce false positive and false negative tractography results due to

crossings• In voxels where fibres cross, single fibre approaches can yield:

– ambiguous fibre direction– incorrect fibre direction– only one fibre direction

(that of fascicle with largest volume fraction) • Examples of such regions:

– basis pontis, subcortical white matter, superior longitudinal fasciculus, acoustic radiations, projection from subgenual white matter to amygdala, optic chiasm, caudate nucleus, corpus callosum, cortical spinal tract, cingulate bundle.

Page 52: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Crossing fibre reconstruction approaches

• multi-tensor approaches (Alexander et al., Parker et al., others)

• multi ball and stick (Behrens et al.)

• Composite hindered and restricted model of diffusion (CHARMED) (Assaf et al.)

• diffusion spectrum imaging (DSI) (Wedeen et al.)

• q-ball imaging (QBI) (Tuch et al.)

• spherical deconvolution (Tournier et al., Anderson, others)

• other variants

Page 53: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

DTI vs. HARDI :Tractography in phantom

single fibre multi-fibreCampbell et al. ISBI 2006.

Page 54: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Tractography: false negatives

Lateral connections?

Page 55: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Signal to noise ratio (SNR); spatial resolution

(b=3000 s/mm2)(b=1000 s/mm2)

Page 56: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Jumping from tract system to tract system

Effects of limited spatial resolution

Page 57: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Jumping from tract system to tract system

Effects of limited spatial resolution

Page 58: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Heidemann et al. 2010.

Signal to noise ratio (SNR); spatial resolution

Higher field strength (7T)

Page 59: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

• diffusion MRI acquisitions generally use fast imaging techniques which can create artifacts such as magnetic susceptibility-induced distortion

• these artifacts confound registration with standard structural scans

Magnetic susceptibility induced distortion

Page 60: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Magnetic susceptibility induced distortion

Heidemann et al. 2010.

segmented readout

Page 61: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Eddy-current induced distortion

• eddy currents are induced by the rapidly changing magnetic field gradients required for diffusion sensitization

• these eddy currents induce magnetic fields which distort the image.

artifacts: shifting, sheering, stretching, compression, signal loss

Page 62: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

TE

G G

90° 180° echo

G

180°

G

Twice refocused balanced echo (TRBE)

Eddy-current induced distortion

Page 63: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Suggested review articles• Susumu Mori et al. Principles of diffusion tensor imaging and its

application to basic neuroscience research. Neuron 51, 527-539, 2006.

• Basser et al. Diffusion-tensor MRI: theory, experimental design and data analysis – a technical review. NMR in Biomedicine 15, 456-467, 2002.

• Mori et al. Fiber tracking: principles and strategies - a technical review. NMR in Biomedicine 15, 468-480, 2002.

• Johansen-Berg et al. Just pretty pictures? What diffusion tractography can add in clinical neuroscience. Curr Opin Neurol 19, 379-385, 2006.

Page 64: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Software packages

• mincdiffusion (BIC)• mincDTI (Andrew Janke - BIC)• FSL (FMRIB, Oxford)• DTI Studio (Johns Hopkins)• Camino (Manchester/London)• CINCH (Stanford)• Mrtrix (Brain Research Institute, Melbourne)• more …

Page 65: Introduction to Diffusion Tensor Imaging · Introduction to Diffusion Tensor Imaging • Molecular diffusion • Diffusion weighting in MRI • The diffusion tensor in use • Problems

Acknowledgements

G. Bruce PikeKaleem SiddiqiIlana LeppertPeter SavadjievParya Mamayyez Siahkal Steven FreyIves LevesqueLuis Concha

Nikola StikovClarisse MarkEva Alonso OrtizHalleh GhaderiMike FerreiraSilvain BeriaultChristine Tardif