Dave Frank & Maggie Mahan DIFFUSION MRI PI Dr. Kwan-Jin Jung TA Priti Albal Dave Frank & Maggie Mahan 12 July 2012

Outline Phantom Analysis Human Analysis Orientation Direction b-value Tensor vs HARDI models Human Analysis Motion correction in DWI fMRI paradigm & ROI mask creation Tracking Activation patterns Crossing Limitations

Disclaimer During this presentation we will use the words “tracts” and “fibers” These refer to the trace of the principal diffusion directions We do not presume to know the physiological constructs these may or may not reflect of which we do not assume to know the relevance to biological tracts or physiological constructs these ….

Phantom Analysis

PHANTOM Model for extra-cellular restricted diffusion Made of interdigitating polyester yarns 1 leg = 25 bundles 1 bundle = 8800, 10 mm fibers -the phantom is a model for extra-cellular restricted diffusion -1 crossing phantom consisting of 2 bundles of 25 x 400 interdigitating polyester yarns equivalent to 180,000 fibers with a circular diameter of ~10m. -Phantom cross-section is slightly elliptical with crossing angle approx 65 degrees -1 tubular phantom length ~ 125 mm -Solution: demineralized water, 0.5 g/l NaN3, 4 g/l NaCl -explain how you will use the term phantom

DTI, b800, Direction Comparison 6 Directions 50 Directions Tracts 216 Mean FA 0.546 Tracts 376 Mean FA 0.445 All tracts Center ROI Bottom left leg ROI Tracts 58 Mean FA 0.556 Tracts 214 Mean FA 0.453 -The tensor analysis assumes that there is a single ellipsoid in each imaging voxel a single diffusion direction—as if all of the tracts traveling through a voxel traveled in exactly the same direction -all tracking parameters constant for comparisons -[V6, 2b=0, b=800, 50slices, TR=10s, TE=100ms] -[V50, 6b=0, b=800, 50slices, TR=10s, TE=100ms] -Parameters: Fiber threshold = 0.2 Step size (mm) = 1.198 Length constraint (mm): min = 30, max = 500 Max angle = 80 Smoothing = 0 Random direction Voxelwise Gaussian radial basis RK4 10 million seeds 2 threads Tracts 20 Mean FA 0.559 Tracts 72 Mean FA 0.446

DTI, V50, b-value Comparison b = 800 s/mm2 b = 2000 s/mm2 Tracts 376 Mean FA 0.445 Tracts 458 Mean FA 0.408 All Tracts Center ROI Bottom left leg ROI Tracts 214 Mean FA 0.453 Tracts 70 Mean FA 0.414 -tracking parameters constant -[V50, 6b=0, b=800, 50slices, TR=10s, TE=100ms] -[V50, 6b=0, b=2000, 50slices, TR=10s, TE=100ms] -Parameters: Fiber threshold = 0.13 Step size (mm) = 1.198 Length constraint (mm): min = 30, max = 500 Max angle = 80 Smoothing = 0 Random direction Voxelwise Gaussian radial basis RK4 10 million seeds 2 threads Tracts 72 Mean FA 0.446 Tracts 82 Mean FA 0.430

DTI/HARDI comparison (ROI placed on center crossing) DTI, V50, b = 2000 s/mm2 HARDI, V50, b = 2000 s/mm2 In the classic diffusion ellipsoid tensor model, the information from the crossing tract just appears as noise or unexplained decreased anisotropy in a given voxel. HARDI calculates a distribution of multiple directions in a given voxel. We just want to know which direction lines turn up the maximum anisotropic diffusion measures. If there is a single tract, there will be just two maxima pointing in opposite directions. If two tracts cross in the voxel, there will be two pairs of maxima, and so on. HARDI resolves crossing fibers better than DTI

Phantom Orientation NO MATTER HOW YOU SLICE IT, orientation to the main magnetic field makes a difference. Best results obtained in phantoms aligned parallel to the main magnetic field. These differences might be related to orientation-dependent susceptibilities.

Phantom Susceptibility Bo -Field map shown of phantom… -The magnetic susceptibility of the phantom leads to field inhomogeneities which interfere with the imaging gradient fields resulting in local image distortions. -This discontinuity in susceptibility leads to two macroscopic effects in EPI: signal loss and geometric distortions. Susceptibility artifacts occur as the result of microscopic gradients or variations in the magnetic field strength that occurs near the interfaces of substance of different magnetic susceptibility. Large susceptibility artifacts are commonly seen surrounding ferromagnetic objects inside of diamagnetic materials (such as the human body). These gradients cause dephasing of spins and frequency shifts of the surrounding tissues. The net result are bright and dark areas with spatial distortion of surrounding anatomy. These artifacts are worst with long echo times and with gradient echo sequences. Long readout times are sensitive to main magnetic field inhomogeneities and magnetic susceptibility. A field map can be estimated from different scans acquired at different echo times. The phase difference between the acquired images is due to the different precession frequencies, which are related to the field map via a linear relation    Signal drop out typically occurs in gradient echo images, and thus is less of an issue for DW spin echo EPI. With respect to geometric distortion, however, field inhomogeneity behaves like a ‘background gradient’ that affects the phase of the measured signal.   The effects of susceptibility can be mitigated by combining EPI with parallel imaging to reduce the duration of the echo train and increasing the bandwidth. The magnetic field maps which were measured at a different orientation of the phantom to the main magnetic field. Note that the field was proportional to the angle between the main magnetic field and the fiber direction. Magnetic susceptibility is a dimensionless proportionality constant that indicates the degree of magnetization of a material in response to an applied magnetic field. If χ is positive, the material can be paramagnetic. In this case, the magnetic field in the material is strengthened by the induced magnetization. Alternatively, if χ is negative, the material is diamagnetic. As a result, the magnetic field in the material is weakened by the induced magnetization.

Human Analysis

Motion Correction in Diffusion Imaging Registration of intensity Rotation of the diffusion vector Actually scanned Starting designed vector position Registration and vector rotation Motion based on B0 images.

Motion Correction Procedure Acquire diffusion-weighted (DW) images Estimate the diffusion tensor Simulate DW images using tensor Motion detection by comparing the acquired and simulated DW images First MC step: Uses measured DWI (mDWI) and B0 image mutual information as a cost function to correct motion. (discontinuity index) This works well when mDWIs have similar intensities, but this isn’t necessarily the case. Second MC step: Use motion corrected image to estimate tensors (simulated tensors; sD). Third MC step: Generate simulated image by combining the sD and the B0 image. FourthMC step: Use mDWI and simulated image mutual information as a cost function to correct motion. This corrects for additional motion that is due to heterogeneous mDWI signal intensities, since the simulated images have the same intensity profile as the mDWIs.

Global Comparison No Motion Correction Motion Correction Anterior part most affected Metronome effect Spatially inhomogeneous Edges See Evaluating_MC_vs_NOMC.doc for parameter values

Cingulate Comparison No MC MC Tracts = 762 Tracts = 1208 Mean FA = 0.418 Tracts = 1208 Mean FA = 0.493 MC = motion corrected Cingulate ROI See Evaluating_MC_vs_NOMC.doc for parameter values

fMRI Paradigm Interested in using dorsolateral prefrontal cortex as a mask in tracking analysis DLPFC elicited by memory encoding (cue) 2s 8s Probe Cue Rest 18s Retention face working memory task created in ePrime a block of the task is shown this block was repeated 10 times with 10s fixation in the beginning and end of the run

Group Activation for Cue ROI: Dorsolateral Prefrontal Cortex R L z8

2 Patterns of Activation Participant 1 Participant 2

Crossing Fibers (HARDI, 128 Directions, b2000) Participant 1

Crossing Problem

Ventral-Rostral Fiber Redirection

Due to Rostral U-Fibers?

Take Home Messages Diffusion imaging dependent on: ROI, b-value, # of directions, & orientation Diffusion imaging particularly susceptible to subject motion Subject comparisons in diffusion imaging not trivial Tracking is a useful exploratory technique