ENIGMA-DTI Skeletonization

Protocols

• ENIGMA-TBSS protocol (PDF format)
• ENIGMA-TBSS protocol (Word format)
• Once DTI data have been pre-processed, use the protocol above to map your images onto the ENIGMA-DTI FA template and project the skeleton.
• Do not forget to QC your images after FA maps have been registered! Misaligned images can cause problems with the overall GWAS and are difficult to detect once skeletonized.
• Use the script here to check the values of the projection distances . Make sure there are no outliers!

  ROI extraction from FA images

• ENIGMA-ROI extraction protocol (PDF format)
• ENIGMA-ROI extraction protocol (Word format)
• Use the above link to extract regions of interest from the skeletons and calculate the average FA within them.

**** An important note **** in the analysis is that the ROI labeled "IFO" is actually different that the same ROI under the most current FSL JHU Atlas label. This was different in the older JHU atlas used to create the template and make the protocols. Please note this will not play a role in ENIGMA-DTI GWAS as we will not be using this ROI for GWAS (it is very small) but it may be considered for disorder studies.
If groups choose to use these measures for their own analysis, please be advised that this should be uncinate according to the current atlas. To avoid confusion, we will NOT switch the labels back, but we will keep this warning so you can carefully examine your data.

ENIGMA-DTI Software tools for ENIGMA processing Quality Control:

• ENIGMA FA/Skel check: Check FA Registrations and make sure skeletons are correct.
• ENIGMA DTI SummaryStats protocol: Check the distribution of your ROIs and look for outliers.

More DTI tools:

• TrackVis: Tractography and visualization
• Camino: Tractography and DTI toolbox
• FSL: Many image processing tools used throughout ENIGMA-DTI protocols
• email me to add your favorite tools here.

Skeletonization of diffusivity measures including mean, axial and radial diffusivity (MD, L1, RD) 

If you would like to skeletonize non-FA diffusivity measures including mean (MD), axial (AD/L1) and/or radial diffusivity (RD) and then extract relevant ROI information from them according to the ENIGMA-DTI template, please follow the instructions provided at the below link:

• ENIGMA-DTI diffusivity protocol (links to new page)

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Analysis

We will be performing 2 large scale GWAS:

1. for all healthy controls and patient populations
2. for all healthy controls only
3. a 3rd GWAS for all patient populations without controls will be performed as a possible follow-up analysis

GWAS will be performed for the average FA value in the following regions of interest:

For samples without related individuals, associations will be run using Mach.

To account for relatedness within family-based datasets, we recommend and provide instructions for running merlin-offline a part of the Merlin package here .

All related and necessary software will be downloaded as part of the scripts, so no need to download them from here now!

Please follow the following link to access scripts for running the DTI-GWAS:

DTI GWAS Analysis

Easy to use SCRIPTS

Use this script after skeletonizing your FA images to check the mean and max projection distances to the skeleton:

#!/bin/sh
# Emma Sprooten for ENIGMA-DTI
# run in a new directory eg. Proj_Dist/
# create a text file containing paths to your masked FA maps
# output in Proj_Dist.txt

# make sure you have FSL5!!!

###### USER INPUTS ###############
## insert main folder where you ran TBSS
## just above "stats/" and "FA/"
maindir="/enigmaDTI/TBSS/run_tbss/"
list=`find $maindir -wholename "*/FA/*_masked_FA.nii.gz"`

## insert full path to mean_FA, skeleton mask and distance map
## based on ENIGMA-DTI protocol this should be:
mean_FA="/enigmaDTI/TBSS/ENIGMA_targets/mean_FA_MyMasked.nii.gz"
mask="/enigmaDTI/TBSS/ENIGMA_targets/mean_FA_skeleton_MyMasked.nii.gz"
dst_map="/enigmaDTI/TBSS/ENIGMA_targets/enigma_skeleton_mask_dst.nii.gz"

##############
### from here it should be working without further adjustments

rm Proj_Dist.txt
echo "ID" "Mean_Squared" "Max_Squared" >> Proj_Dist.txt


## for each FA map
    for FAmap in ${list}   
    do
	base=`echo $FAmap | awk 'BEGIN {FS="/"}; {print $NF}' | awk 'BEGIN {FS="_"}; {print $1}'`
        dst_out="dst_vals_"$base""

	# get Proj Dist images
        tbss_skeleton -d -i $mean_FA -p 0.2 $dst_map $FSLDIR/data/standard/LowerCingulum_1mm $FAmap $dst_out

	#X direction
	Xout=""squared_X_"$base"
	file=""$dst_out"_search_X.nii.gz"
	fslmaths $file -mul $file $Xout

	#Y direction
	Yout=""squared_Y_"$base"
	file=""$dst_out"_search_Y.nii.gz"
	fslmaths $file -mul $file $Yout

	#Z direction
        Zout=""squared_Z_"$base"
        file=""$dst_out"_search_Z.nii.gz"
	fslmaths $file -mul $file $Zout

	#Overall displacement
	Tout="Total_ProjDist_"$base""
	fslmaths $Xout -add $Yout -add $Zout $Tout

	# store extracted distances
	mean=`fslstats -t $Tout -k $mask -m`  
	max=`fslstats -t $Tout -R | awk '{print $2}'`
        echo "$base $mean $max" >> Proj_Dist.txt

        # remove X Y Z images
        ## comment out for debugging
        rm ./dst_vals_*.nii.gz
        rm ./squared_*.nii.gz

	echo "file $Tout done"
    done

The ENIGMA DTI Support emails are sent to:

• Josh Faskowitz (USC, CA, USA)
• Sean Hatton (Sydney, Australia)
• Neda Jahanshad (USC, CA, USA)
• Sinead Kelly (Dublin, Ireland)
• Peter Kochunov (U Maryland, MD, USA)
• Bennett Landman (Vanderbilt, TN, USA)
• Herve Lemaitre (Paris, France)
• Rene Mandl (Utrecht, Netherlands)
• Emma Sprooten (Yale U, CT, USA)
• Chris Whelan (Dublin, Ireland)
• Marcel Zwiers (Nijmegen, Netherlands)