Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis.

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[1] § Methods › MRI data preprocessing ↔ alps.sh, lines 1–42 · score 0.91 · MRtrix3, JHU ICBM FA, Diffusion weighted images, FA maps, perivascular space, pipeline
[2] § Methods › Statistical analyses ↔ alps.sh, lines 1–42 · score 0.56 · FA template, JHU ICBM, pipeline, transformations, maps, FSL

Paper

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The authors' code

Shell · 757 lines · 56 KB · MIT · 2 matches

#! /bin/bash
#############################################################
# Giuseppe Barisano - [email hidden]
#############################################################
##### Computing diffusion along perivascular spaces (ALPS) from diffusion-weighted images #####
# REQUIRES: - FSL v. 6.0.3 or newer (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FslInstallation)
# - MRtrix3 (https://www.mrtrix.org/download/)
# This script assumes that FSL and MRtrix3 are in your $PATH.
# initial directories and parameters
#script_folder="${ALPSDIR}"
script_folder="$( cd -- "$( dirname -- "${BASH_SOURCE[0]:-$0}"; )" &> /dev/null && pwd 2> /dev/null; )";
# inputs # 1 or 2 dwi files (if 2, they should be of opposite phase encoding direction, e.g., PA and AP)
# REQUIRED INPUTS
dwi1=''
bval1=''
bvec1=''
# Optional input for eddy current correction
json1='' # .json files with details about the diffusion sequence. Tested with .json files generated from dcm2niix https://github.com/rordenlab/dcm2niix)
# Optional second dwi inputs (needs to have opposite phase encoding direction and the first volume of both dwi1 and dwi2 must be a B0 image)
dwi2=''
bval2=''
bvec2=''
json2=''
# optional inputs with default options
denoise=1 # perform the denoise and unringing
rois=2.5 # perform the ROI analysis using the provided ROIs of 2.5 mm radius drawn on JHU-ICBM-FA-1mm.nii.gz
template=1 #use the FSL's JHU-ICBM-FA-1mm.nii.gz as FA template or FSL's MNI template if the structural MRI data is provided.
skip=0 #perform all the steps of the pipeline.
eddy=1 #try to use eddy_cpu
warp=0 #perform linear registration of the FA map to the template.
freg=1 #if the analysis is done on template space, by default it will use FSL's flirt or applywarp to transform the TENSOR file to the template.
struct='' #structural MRI data (can be either a T1-weighted or a T2-weighted image, no FLAIR, no PD)
weight=1 #if a structural MRI data is provided, by default it will be considered a T1-weighted image.
print_usage() {
printf "\nUsage: alps.sh \n\
-a DWI \n\
-b BVAL \n\
-c BVEC \n\
-m METADATA (.json file) \n\
-i DWI (second input with opposite phase encoding) \n\
-j BVAL of second input (MUST BE DEFINED if second dwi input -i is defined) \n\
-k BVEC of second input (MUST BE DEFINED if second dwi input -i is defined) \n\
-n METADATA (.json file) of second input (MUST BE DEFINED if second dwi input -i is defined) \n\
-d DENOISING \n\
-e EDDY (specify which eddy program to use)
-r ROIS \n\
-t TEMPLATE \n\
-v VOLUMETRIC structural MRI data \n\
-h WeigHt of the volumetric structural MRI data \n\
-w WARP the reconstructed FA map to the template \n\
-f Use flirt or applywarp or vecreg to transform the TENSOR file to the template \n\
-s SKIP preprocessing and DTI fitting, i.e. perform ONLY ROI analysis \n\
-o OUTPUT_DIR_NAME \n"
printf "\nDefault values: \n\
-d DENOISING [default = 1]; 0=skip; 1=both denoise and unringing; 2=only denoise; 3=only unringing. \n\
-e EDDY [default = 1]; 0=skip eddy (not recommended); 1=use ${FSLDIR}/bin/eddy_cpu; 2=use ${FSLDIR}/bin/eddy; 3=use ${FSLDIR}/bin/eddy_correct;
alternatively, the user can specify which eddy program to use (e.g., eddy_cuda). The binary file specified by the user must be located in ${FSLDIR}/bin/ (do not include \"${FSLDIR}/bin/\" in the command, just the name of the binary file)\n\
-r ROIS [default = 2.5]; 0=skip ROI analysis; 2.5=ROI analysis with provided ROIs drawn on JHU-ICBM-FA-1mm;
alternatively, a positive number (non-integer numbers are acceptable, e.g., 2.5) that is the radius of the new sphere ROIs that you want to use for ALPS calculation. They will be generated on the default FSL's JHU/MNI 1mm template space and will be available in the output folder.
alternatively, a comma-separated list of 4 custom ROI nifti files can be specified.
ROIs need to be in the following order: 1) LEFT and 2) RIGHT PROJECTION FIBERS (superior corona radiata), 3) LEFT and 4) RIGHT ASSOCIATION FIBERS (superior longitudinal fasciculus)\n\
-t TEMPLATE [default = 1]; 0=ROI analysis in NATIVE space; 1=ROI analysis with FSL's JHU-ICBM-FA-1mm (if no structural MRI data input), MNI_T1_1mm (if structural data input is a T1) or JHU-ICBM-T2-1mm (if structural data input is a T2); \n\
alternatively, the user can specify a template to use. \n\
-v VOLUMETRIC structural MRI data: specify a structural MRI data (a T1w or T2w NIFTI file) to be used for registration of the FA map to the template;
-h weight of the structural MRI data [default = 1]; 1=T1-weighted image; 2=T2-weighted image (no PD, no FLAIR).
-w WARP [default = 0]; 0=perform linear registration of the reconstructed FA map to the template; 1=perform ONLY non-linear registration (warping) of the reconstructed FA map to the template using FSL's suggested default parameters (not recommended). \n\
2=perform linear (flirt) + non-linear registration (fnirt); option -w is ignored when a structural MRI is used (-v is not empty).
-f method to transform the TENSOR to the template [default = 1]; 1=use flirt (or applywarp if WARP is 1 or 2 or -V is not empty) to transform the TENSOR to the template; \n\
2=use FSL's vecreg to transform the TENSOR to the template.
-s Option to skip preprocessing and DTI fitting, i.e. performs ONLY ROI analysis [default = 0]; 0 = all the steps are performed; 1= ONLY ROI analysis is performed;
If -s 1, then -o MUST BE DEFINED and MUST CORRESPOND TO THE FOLDER WHERE dxx.nii.gz, dyy.nii.gz and dzz.nii.gz ARE LOCATED. \n\
-o OUTPUT_DIR_NAME [default = 1]; default option will create a folder called \"alps\" located in the directory of the (first) input. \n\
\nExample with 1 input: sh alps.sh -a dwi.nii.gz -b id.bval -c id.bvec -m id.json -d 1 -o alps\n\
\nExample with 2 inputs with opposite phase encoding direction: sh alps.sh -a dwi_PA.nii.gz -b id_PA.bval -c id_PA.bvec -m id_PA.json -i dwi_AP.nii.gz -j id_AP.bval -k id_AP.bvec -n id_AP.json -d 1 -o alps\n"
}
while getopts 'a:b:c:m:i:j:k:n:d:e:r:t:v:h:w:f:s:o:' flag; do
case "${flag}" in
a) dwi1="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
b) bval1="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
c) bvec1="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
m) json1="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
i) dwi2="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
j) bval2="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
k) bvec2="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
n) json2="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
d) denoise="${OPTARG}" ;;
e) eddy="${OPTARG}" ;;
r) rois="${OPTARG}" ;;
t) template="${OPTARG}" ;;
v) struct="$(echo "$(cd "$(dirname "${OPTARG}")" && pwd)/$(basename "${OPTARG}")")" ;;
h) weight="${OPTARG}" ;;
w) warp="${OPTARG}" ;;
f) freg="${OPTARG}" ;;
s) skip="${OPTARG}" ;;
o) output_dir_name="${OPTARG}" ;;
*) print_usage
exit 1 ;;
esac
done
#INITIAL CHECKS
#INPUTS
if [ $skip -eq 0 ]; then #check the inputs only if are needed
if [ $OPTIND -eq 1 ]; then echo "ERROR! No options were passed"; print_usage; exit 1; fi
if [ ! $dwi1 ]; then echo "ERROR! input dwi (-a) is not defined."; print_usage; exit 1; fi
if [ ! $bval1 ]; then echo "ERROR! bval (-b) is not defined."; print_usage; exit 1; fi
if [ ! $bvec1 ]; then echo "ERROR! bvec (-c) is not defined."; print_usage; exit 1; fi
if [ ! -f "${dwi1}" ]; then echo "ERROR! input $dwi1 does not exist."; exit 1; fi
if [ ! -f "${bval1}" ]; then echo "ERROR! bval file $bval1 does not exist."; exit 1; fi
if [ ! -f "${bvec1}" ]; then echo "ERROR! bvec file $bvec1 does not exist."; exit 1; fi
#OUTPUT ALPS CHECK
if [ -f "${outdir}/alps.stat/alps.csv" ] && [ ! -z "`tail -n 1 "${outdir}/alps.stat/alps.csv" | tr -d ,`" ]; then echo "ERROR! Final output alps.csv already exists and is not empty! Remove/rename the output folder in order to re-run the pipeline with input $dwi1"; exit 1; fi;
# create output directory
if [ ! $output_dir_name ]; then
#study_folder="$(dirname "${dwi1}")"
study_folder=`echo "$(cd "$(dirname -- "${dwi1}")" >/dev/null; pwd -P)"`
outdir="${study_folder}/alps"
else
outdir="${output_dir_name}"
fi
echo "create output directory: ${outdir}"
mkdir -p "${outdir}"
#exec > "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt 2>&1
exec > >(tee -a "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt) 2> >(tee -a "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt >&2)
#if [ ! $json1 ]; then echo "ERROR! metadata .json file (-m) is not defined."; print_usage; exit 1; fi
#CHECK FOR DWI2. Hashtagged, because:
#bvec2 is not used,
#bval2 might be skipped if the user verified that the first volume is a B0 volume
#json2 might be skipped if the user verified that the PE direction is opposite to that of dwi1.
#if [ $dwi2 ]; then if [ ! $bval2 ] || [ ! $bvec2 ] || [ ! $json2 ]; then echo "ERROR! dwi2 (-i) is defined, but bval (-j), bvec (-k), and/or metadata .json file (-n) of the second input is/are not defined."; print_usage; exit 1; fi; fi;
#if [ $bval2 ]; then if [ ! $dwi2 ] || [ ! $bvec2 ] || [ ! $json2 ]; then echo "ERROR! bval (-j) of the second input is defined, but dwi2 (-i), bvec (-k), and/or metadata .json file (-n) of the second input is/are not defined."; print_usage; exit 1; fi; fi;
#if [ $bvec2 ]; then if [ ! $dwi2 ] || [ ! $bval2 ] || [ ! $json2 ]; then echo "ERROR! bvec (-k) of the second input is defined, but dwi2 (-i), bval (-j), and/or metadata .json file (-n) of the second input is/are not defined."; print_usage; exit 1; fi; fi;
#if [ $json2 ]; then if [ ! $dwi2 ] || [ ! $bval2 ] || [ ! $bvec2 ]; then echo "ERROR! metadata .json file (-n) of the second input is defined, but dwi2 (-i), bval (-j), and/or bvec (-k) of the second input is/are not defined."; print_usage; exit 1; fi; fi;
if [ $dwi2 ]; then
if [ ! -f "${dwi2}" ]; then echo "ERROR! second input $dwi2 does not exist."; exit 1; fi;
#if [ $bval2 ]; then if [ ! -f "${bval2}" ]; then echo "ERROR! bval file $bval2 of second input does not exist."; exit 1; fi; fi;
#if [ ! -f "${bvec2}" ]; then echo "ERROR! bvec file $bvec2 of second input does not exist."; exit 1; fi;
#if [ $json2 ]; then if [ ! -f "${json2}" ]; then echo "ERROR! metadata .json file $json2 of second input does not exist."; exit 1; fi; fi;
fi
elif [ $skip -eq 1 ]; then
if [ ! $output_dir_name ]; then echo "ERROR! Option -s is set to 1, therefore option -o MUST BE DEFINED and MUST CORRESPOND TO THE FOLDER WHERE dxx.nii.gz, dyy.nii.gz and dzz.nii.gz ARE LOCATED."; exit 1; fi;
outdir="${output_dir_name}"
#exec > "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt 2>&1
exec > >(tee -a "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt) 2> >(tee -a "${outdir}"/alps_$(date +"%Y-%m-%d_%H-%M-%S")_log.txt >&2)
fi
#ROIS & TEMPLATE
if [ "$rois" != "0" ]; then
if [ "$rois" == "2.5" ]; then
echo "ROI analysis with default ROIs"
rois="${script_folder}/ROIs_JHU_ALPS/L_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/L_SLF.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SLF.nii.gz"
roption=$rois
elif [[ "$rois" =~ ^-?([0-9]+\.?[0-9]*|\.[0-9]+)$ ]]; then
radius=$rois
echo "ROI analysis with user-defined spheric ROIs with radius $radius mm"
rois="${script_folder}/ROIs_JHU_ALPS/L_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/L_SLF.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SLF.nii.gz" #only needed to pass the check below
roption=$radius
else
echo "ROI analysis with user-defined ROIs: $rois"
roption=$rois
fi
n_rois=`echo $rois | awk -F '[,]' '{print NF}'`
if [ $n_rois -ne 4 ]; then echo "ERROR! The number of ROIs is not equal to 4. The string of ROIs must include only 4 elements separated by 3 commas. Please double check that exactly 4 elements and no more than 3 commas are present in your string of ROIs (e.g., no commas is present in file/directory names."; exit 1; fi;
proj_L=`echo "$rois" | cut -d "," -f1`
proj_R=`echo "$rois" | cut -d "," -f2`
assoc_L=`echo "$rois" | cut -d "," -f3`
assoc_R=`echo "$rois" | cut -d "," -f4`
if [ ! -f "${proj_L}" ]; then echo "ERROR! Cannot find the following ROI file: ${proj_L}"; exit 1; fi;
if [ ! -f "${proj_R}" ]; then echo "ERROR! Cannot find the following ROI file: ${proj_R}"; exit 1; fi;
if [ ! -f "${assoc_L}" ]; then echo "ERROR! Cannot find the following ROI file: ${assoc_L}"; exit 1; fi;
if [ ! -f "${assoc_R}" ]; then echo "ERROR! Cannot find the following ROI file: ${assoc_R}"; exit 1; fi;
if [ "$template" != "0" ]; then #analysis in template space. Double check that the template exists.
#conditional for existence of structural MRI data.
if [ ! -z $struct ]; then
if [ ! -f "$struct" ]; then echo "ERROR! User specified to use $struct as structural MRI data, but I could not find it. Please double-check that the file exists."; exit 1; fi;
fi
#conditional for template selection
if [ "$template" == "1" ]; then
if [ -f ${FSLDIR}/data/standard/MNI152_T1_1mm_brain_mask_dil.nii.gz ]; then
template_mask="--refmask=${FSLDIR}/data/standard/MNI152_T1_1mm_brain_mask_dil.nii.gz "
#used only for fnirt (warp > 0 or !-z struct)
fi
if [ -z $struct ]; then
echo "Default FA template will be used: JHU-ICBM-FA-1mm.nii.gz"
template=${FSLDIR}/data/atlases/JHU/JHU-ICBM-FA-1mm.nii.gz
template_abbreviation=JHU-FA
elif [ ! -z $struct ]; then
if [ $weight == "1" ]; then
echo "The structural MRI $struct is a T1-weighted image, therefore the default template that will be used is: MNI152_T1_1mm"
template=${FSLDIR}/data/standard/MNI152_T1_1mm_brain.nii.gz
template_abbreviation=MNI152_T1_1mm
smri="t1w"
elif [ $weight == "2" ]; then
echo "The structural MRI $struct is a T2-weighted image, therefore the default template that will be used is: JHU-ICBM-T2-1mm"
template=${FSLDIR}/data/atlases/JHU/JHU-ICBM-T2-1mm.nii.gz
template_abbreviation=JHU-ICBM-T2-1mm
smri="t2w"
elif [ $weight -ne 1 ] && [ $weight -ne 2 ] && [ "$template" != "0" ] && [ "$template" != "1" ] ; then
echo "ERROR! A structural MRI data has been specified, but the user needs to specify with the option -h whether this is T1-weighted (-h 1) or T2-weighted (-h 2) in order to select a default template. \n\
The only allowed option for -h are 1 or 2. Alternatively, the user can specify the file template to use, and the option -h will be ignored."; exit 1;
fi
fi
else
template="$(echo "$(cd "$(dirname "${template}")" && pwd)/$(basename "${template}")")"
echo "User specified template: $template"
template_abbreviation=template
fi
if [ ! -f "${template}" ]; then echo "ERROR! Cannot find the template "$template". The template file must exist if -t option is not 0."; exit 1; fi;
if [ $warp -ne 0 ] && [ $warp -ne 1 ] && [ $warp -ne 2 ]; then echo "ERROR! The option specified with -w is $warp, which is not an allowed option. -w must be equal to 0 (for linear registration) or 1 (for non-linear registration)."; exit 1; fi;
if [ $freg -ne 1 ] && [ $freg -ne 2 ]; then echo "ERROR! The option specified with -f is $freg, which is not an allowed option. -f must be equal to 1 (for using FSL's flirt and/or applywarp depending on -w) or 2 (for using FSL's vecreg)."; exit 1; fi;
fi
fi
#OPTIONS
if [ "$denoise" != "0" ] && [ "$denoise" != "1" ] && [ "$denoise" != "2" ] && [ "$denoise" != "3" ]; then echo "-d option is equal to $denoise, which is not an allowed option. -d must be equal to 0, 1, 2, or 3, or skipped (which corresponds to -d 1)."; print_usage; exit 1; fi;
if [ "$eddy" == "1" ] && [ ! -f "${FSLDIR}/bin/eddy_cpu" ]; then echo "-e option (eddy) is equal to $eddy (default), which means using ${FSLDIR}/bin/eddy_cpu, but ${FSLDIR}/bin/eddy_cpu cannot be found. -e must be equal to 0 (skip eddy correction, not recommended) 1 (use ${FSLDIR}/bin/eddy_cpu), 2 (use ${FSLDIR}/bin/eddy), 3 (use ${FSLDIR}/bin/eddy_correct), or skipped (default value = 1). If the user wants to use a specific eddy program, this must be located in ${FSLDIR}/bin/"; print_usage; exit 1; fi;
if [ "$eddy" == "2" ] && [ ! -f "${FSLDIR}/bin/eddy" ]; then echo "-e option (eddy) is equal to $eddy (default), which means using ${FSLDIR}/bin/eddy, but ${FSLDIR}/bin/eddy cannot be found. -e must be equal to 0 (skip eddy correction, not recommended) 1 (use ${FSLDIR}/bin/eddy_cpu), 2 (use ${FSLDIR}/bin/eddy), 3 (use ${FSLDIR}/bin/eddy_correct), or skipped (default value = 1). If the user wants to use a specific eddy program, this must be located in ${FSLDIR}/bin/"; print_usage; exit 1; fi;
if [ "$eddy" == "3" ] && [ ! -f "${FSLDIR}/bin/eddy_correct" ]; then echo "-e option (eddy) is equal to $eddy (default), which means using ${FSLDIR}/bin/eddy_correct, but ${FSLDIR}/bin/eddy_correct cannot be found. -e must be equal to 0 (skip eddy correction, not recommended) 1 (use ${FSLDIR}/bin/eddy_cpu), 2 (use ${FSLDIR}/bin/eddy), 3 (use ${FSLDIR}/bin/eddy_correct), or skipped (default value = 1). If the user wants to use a specific eddy program, this must be located in ${FSLDIR}/bin/"; print_usage; exit 1; fi;
if [ "$eddy" != "0" ] && [ "$eddy" != "1" ] && [ "$eddy" != "2" ] && [ "$eddy" != "3" ] && [ ! -f "${FSLDIR}/bin/$eddy" ]; then echo "-e option (eddy) is equal to $eddy, but ${FSLDIR}/bin/$eddy cannot be found. -e must be equal to 0 (skip eddy correction, not recommended) or 1 (use eddy_cpu if available, or eddy if not), or skipped (default value = 1). If the user wants to use a specific eddy program, this must be located in ${FSLDIR}/bin/"; print_usage; exit 1; fi;
if [ "$skip" != "0" ] && [ "$skip" != "1" ]; then echo "-s option is equal to $skip, which is not an allowed option. -s must be equal to 0 or 1, or skipped (default value = 0)."; print_usage; exit 1; fi;
#running check
echo -e "Running ALPS with the following parameters: \n
-a $dwi1 \n
-b $bval1 \n
-c $bvec1 \n
-m $json1 \n
-i $dwi2 \n
-j $bval2 \n
-k $bvec2 \n
-n $json2 \n
-d $denoise \n
-e $eddy \n
-r $roption \n
-t $template \n
-v $struct \n
-h $weight \n
-w $warp \n
-f $freg \n
-s $skip \n
-o $output_dir_name"
# 1. PREPROCESSING (Denoising, unringing, Topup for Opposite EPI acquisitions, Eddy)
if [ $skip -eq 0 ]; then
#copy bval and bvec files into output directory
cp "$bvec1" "${outdir}/bvec1"
cp "$bval1" "${outdir}/bval1"
cd "${outdir}"
## Denoising and/or unringing
if [ $denoise -ne 0 ]; then
if [ $denoise -eq 1 ]; then
echo "Denoising and unringing $dwi1"
dwidenoise "$dwi1" "${outdir}/dwi1.denoised.nii.gz"
mrdegibbs "${outdir}/dwi1.denoised.nii.gz" "${outdir}/dwi1.denoised.unring.nii.gz"
dwi1_processed="${outdir}/dwi1.denoised.unring.nii.gz"
fi
if [ $denoise -eq 2 ]; then
echo "Denoising $dwi1"
dwidenoise "$dwi1" "${outdir}/dwi1.denoised.nii.gz"
dwi1_processed="${outdir}/dwi1.denoised.nii.gz"
fi
if [ $denoise -eq 3 ]; then
echo "Unringing $dwi1"
mrdegibbs "$dwi1" "${outdir}/dwi1.unring.nii.gz"
dwi1_processed="${outdir}/dwi1.unring.nii.gz"
fi
else
echo "Denoising and unringing skipped by the user (-d 0 option)"
dwi1_processed="${dwi1}"
fi
# IF YOU HAVE A METADATA (JSON) FILE, THEN YOU CAN RUN EDDY with eddy_cpu
if [ -f "${json1}" ]; then
# ACQUISITION PARAMETERS OF FIRST INPUT (REQUIRED FOR EDDY)
#scanner1=$(jq -r '.Manufacturer' "$json1") # -r gives you the raw output
#scanner1=$(cat "${json1}" | grep -w Manufacturer | cut -d ' ' -f2 | tr -d ',')
scanner1=$(cat "${json1}" | awk -F'"' '/"Manufacturer"/ {print $4}')
if [[ "$scanner1" == *"Philips"* ]]
then
#PEdir1=$(jq -r '.PhaseEncodingAxis' "$json1")
#PEdir1=$(cat "${json1}" | grep -w PhaseEncodingAxis | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
PEdir1=$(cat "${json1}" | awk -F'"' '/"PhaseEncodingAxis"/ {print $4}')
TotalReadoutTime1=0.1 #this assumes that the readout time is identical for all acquisitions on the Philips scanner. A "realistic" read-out time is ~50-100ms (and eddy accepts 10-200ms). So use 0.1 (i.e., 100 ms), not 1.
else
#PEdir1=$(jq -r '.PhaseEncodingDirection' "$json1")
#TotalReadoutTime1=$(jq -r '.TotalReadoutTime' "$json1")
#PEdir1=$(cat "${json1}" | grep -w PhaseEncodingDirection | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
#TotalReadoutTime1=$(cat "${json1}" | grep -w TotalReadoutTime | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
PEdir1=$(cat "${json1}" | awk -F'"' '/"PhaseEncodingDirection"/ {print $4}')
TotalReadoutTime1=$(cat "${json1}" | grep -w TotalReadoutTime | cut -d ':' -f2 | cut -d ',' -f1 | xargs)
fi
if [ "$PEdir1" = i ]; then printf "1 0 0 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
elif [ "$PEdir1" = i- ]; then printf "-1 0 0 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
elif [ "$PEdir1" = j ]; then printf "0 1 0 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
elif [ "$PEdir1" = j- ]; then printf "0 -1 0 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
elif [ "$PEdir1" = k ]; then printf "0 0 1 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
elif [ "$PEdir1" = k- ]; then printf "0 0 -1 $TotalReadoutTime1" > "${outdir}/acqparams.txt";
fi
#IF YOU HAVE A SECOND DWI
if [ "$dwi2" ]; then
echo "2nd DWI is available"
#if [[ "$dwi2" == *".nii" ]]; then gzip "$dwi2"; fi
if [ $denoise -eq 1 ]; then
echo "Denoising and unringing $dwi2"
dwidenoise "$dwi2" "${outdir}/dwi2.denoised.nii.gz"
mrdegibbs "${outdir}/dwi2.denoised.nii.gz" "${outdir}/dwi2.denoised.unring.nii.gz"
dwi2_processed="${outdir}/dwi2.denoised.unring.nii.gz"
elif [ $denoise -eq 2 ]; then
echo "Denoising $dwi2"
dwidenoise "$dwi2" "${outdir}/dwi2.denoised.nii.gz"
dwi2_processed="${outdir}/dwi2.denoised.nii.gz"
elif [ $denoise -eq 3 ]; then
echo "Unringing $dwi2"
mrdegibbs "$dwi2" "${outdir}/dwi2.unring.nii.gz"
dwi2_processed="${outdir}/dwi2.unring.nii.gz"
elif [ $denoise -eq 0 ]; then
dwi2_processed="${dwi2}"
fi
##
if [ "$json2" ]; then
#scanner2=$(jq -r '.Manufacturer' "$json2")
#scanner2=$(cat "${json2}" | grep -w Manufacturer | cut -d ' ' -f2 | tr -d ',')
scanner2=$(cat "${json2}" | awk -F'"' '/"Manufacturer"/ {print $4}')
if [[ "$scanner2" == *"Philips"* ]]
then
#PEdir2=$(jq -r '.PhaseEncodingAxis' "$json2")- #added "-" to make it opposite to the PEdir1. #Philips scans json files generated with dcm2niix have a problem where the PEdirection is the same (j) even though it is not.
#PEdir2=$(cat "${json2}" | grep -w PhaseEncodingAxis | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
PEdir2=$(cat "${json2}" | awk -F'"' '/"PhaseEncodingAxis"/ {print $4}')
TotalReadoutTime2=0.1 #this assumes that the readout time is identical for all acquisitions on the Philips scanner. A "realistic" read-out time is ~50-100ms (and eddy accepts 10-200ms). So use 0.1 (i.e., 100 ms), not 1.
else
#PEdir2=$(jq -r '.PhaseEncodingDirection' "$json2")
#TotalReadoutTime2=$(jq -r '.TotalReadoutTime' "$json2")
#PEdir2=$(cat "${json2}" | grep -w PhaseEncodingDirection | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
#TotalReadoutTime2=$(cat "${json2}" | grep -w TotalReadoutTime | cut -d ' ' -f2 | tr -d ',' | tr -d '"')
PEdir2=$(cat "${json2}" | awk -F'"' '/"PhaseEncodingDirection"/ {print $4}')
TotalReadoutTime2=$(cat "${json2}" | grep -w TotalReadoutTime | cut -d ':' -f2 | cut -d ',' -f1 | xargs)
fi
else #if you don't have a json2 file, then assume that the PEdir2 is opposite to PEdir1 and that the TotalReadoutTime2 is equal to TotalReadoutTime1
if [[ "${PEdir1}" == *"-"* ]]; then PEdir2=$(echo ${PEdir1} | tr -d '-')
else PEdir2="${PEdir1}-"
fi
TotalReadoutTime2=$TotalReadoutTime1
fi
# ACQUISITION PARAMETERS (ADDED TO THE PREVIOUS FILE)
if [ "$PEdir2" = i ]; then printf "\n1 0 0 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
elif [ "$PEdir2" = i- ]; then printf "\n-1 0 0 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
elif [ "$PEdir2" = j ]; then printf "\n0 1 0 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
elif [ "$PEdir2" = j- ]; then printf "\n0 -1 0 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
elif [ "$PEdir2" = k ]; then printf "\n0 0 1 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
elif [ "$PEdir2" = k- ]; then printf "\n0 0 -1 $TotalReadoutTime2" >> "${outdir}/acqparams.txt";
fi
#TOPUP (only if PEdir1 = PEdir2- and both DWI datasets have B0 images as first volume)
b0_dwi1=`head -c 1 "$bval1"`
if [ "$bval2" ]; then #if you don't have a bval2 file, then assume it equal to b0_dwi1, that should be 0.
b0_dwi2=`head -c 1 "$bval2"`
else
b0_dwi2=$b0_dwi1
fi
if [ "${PEdir1}" == "${PEdir2}-" ] || [ "${PEdir2}" == "${PEdir1}-" ] && ([ "${b0_dwi1}" == "${b0_dwi2}" ] && [ "${b0_dwi1}" == "0" ]);
then
b0_1="${outdir}/b0_first_direction.nii.gz"
b0_2="${outdir}/b0_second_direction.nii.gz"
fslroi "$dwi1_processed" "$b0_1" 0 1
fslroi "$dwi2_processed" "$b0_2" 0 1
#check dimensions of b0_1 and b0_2 because sometimes they are different and needs to be coregistered for fslmerge to work
dim1_1=`fslhd "$b0_1" | grep dim1 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
dim2_1=`fslhd "$b0_1" | grep dim2 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
dim3_1=`fslhd "$b0_1" | grep dim3 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
dim1_2=`fslhd "$b0_2" | grep dim1 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
dim2_2=`fslhd "$b0_2" | grep dim2 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
dim3_2=`fslhd "$b0_2" | grep dim3 | tr -s ' ' | cut -d " " -f2 | head -n 1` #tr with the squeeze option makes all consecutive whitespaces equal to 1 whitespace
if [ "${dim1_1}" != "${dim1_2}" ] || [ "${dim2_1}" != "${dim2_2}" ] || [ "${dim3_1}" != "${dim3_2}" ];
then
flirt -in "${b0_2}" -ref "${b0_1}" -out "${outdir}/b0_second_direction_reg" -omat "${outdir}/b0_2.in.b0_1.mat" -bins 256 -cost corratio -searchrx -90 90 -searchry -90 90 -searchrz -90 90 -dof 6
b0_2="${outdir}/b0_second_direction_reg.nii.gz"
echo "b0_2 registered to b0_1"
fi
fslmerge -t "${outdir}/both_b0" "$b0_1" "$b0_2"
temp=`fslhd "${dwi1}" | grep dim3`
dimtmp=( $temp )
n_slices=${dimtmp[1]}
echo "Running FSL TOPUP"
if [ $((n_slices%2)) -eq 0 ] #even number of slices
then
topup --imain=both_b0 --datain=acqparams.txt --config=b02b0.cnf --out=my_topup_results --iout=my_hifi_b0 #which will upon completion create the two files my_topup_results_fieldcoef.nii.gz (an estimate of the susceptibility induced off-resonance field), my_topup_results_movpar.txt and the non-distorted space my_hifi_b0.nii.gz
else #odd number of slices, use a different configuration file (https://www.jiscmail.ac.uk/cgi-bin/webadmin?A2=FSL;6c4c9591.2002)
b02b0_1=`find /${FSLDIR} -name "b02b0_1.cnf" | head -n 1` #the location is usually ${FSLDIR}/src/topup/flirtsch/b02b0_1.cnf
if [ -z $b02b0_1 ]; then echo "ERROR! Could not find the configuration file required for running TOPUP on data with odd number of slices (your input has $n_slices slices). Should be in $FSLDIR."; exit 1;
else
topup --imain=both_b0 --datain=acqparams.txt --config=${b02b0_1} --out=my_topup_results --iout=my_hifi_b0 #which will upon completion create the two files my_topup_results_fieldcoef.nii.gz (an estimate of the susceptibility induced off-resonance field), my_topup_results_movpar.txt and the non-distorted space my_hifi_b0.nii.gz
fi
fi
# Processing of topup output
fslmaths my_hifi_b0 -Tmean my_hifi_b0
bet2 my_hifi_b0 b0_brain -m
#EDDY
if [ $eddy == "0" ]; then echo "EDDY skipped by the user (-e option is equal to $eddy)";
else
echo "Running EDDY with TOPUP RESULTS"
temp=`fslhd "${dwi1}" | grep dim4`
dimtmp=( $temp )
n_vol=${dimtmp[1]}
indx=""
for ((i=1; i<=$n_vol; i+=1)); do indx="$indx 1"; done
echo $indx > index.txt
if [ $eddy == "1" ] && [ -f ${FSLDIR}/bin/eddy_cpu ]; then
echo "Found eddy_cpu! Running ${FSLDIR}/bin/eddy_cpu with default options"
eddy_cpu --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --topup=my_topup_results --out=eddy_corrected_data
elif [ $eddy == "2" ] && [ -f ${FSLDIR}/bin/eddy ]; then
echo "Running ${FSLDIR}/bin/eddy with default options";
eddy --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --topup=my_topup_results --out=eddy_corrected_data
elif [ $eddy == "3" ] && [ -f ${FSLDIR}/bin/eddy_correct ]; then
echo "Running ${FSLDIR}/bin/eddy_correct with default options";
eddy_correct "$dwi1_processed" eddy_corrected_data 0 trilinear
else echo "Eddy with user-specified eddy program ${FSLDIR}/bin/$eddy"
"${FSLDIR}/bin/$eddy" --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --topup=my_topup_results --out=eddy_corrected_data
fi
fi
elif [ "${PEdir1}" != "${PEdir2}-" ] || [ "${PEdir2}" != "${PEdir1}-" ] || [ "${b0_dwi1}" != "${b0_dwi2}" ]; then
fslroi "$dwi1_processed" "${outdir}/b0" 0 1
bet2 "${outdir}/b0" "${outdir}/b0_brain" -m
#EDDY
if [ $eddy == "0" ]; then echo "EDDY skipped by the user (-e option is equal to $eddy)";
else
echo "Running EDDY (NO TOPUP) because PE directions are not opposite or b0 images are different"
temp=`fslhd "${dwi1}" | grep dim4`
dimtmp=( $temp )
n_vol=${dimtmp[1]}
indx=""
for ((i=1; i<=$n_vol; i+=1)); do indx="$indx 1"; done
echo $indx > index.txt
if [ $eddy == "1" ] && [ -f ${FSLDIR}/bin/eddy_cpu ]; then
echo "Found eddy_cpu! Running ${FSLDIR}/bin/eddy_cpu with default options"
eddy_cpu --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
elif [ $eddy == "2" ] && [ -f ${FSLDIR}/bin/eddy ]; then
echo "Running ${FSLDIR}/bin/eddy with default options";
eddy --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
elif [ $eddy == "3" ] && [ -f ${FSLDIR}/bin/eddy_correct ]; then
echo "Running ${FSLDIR}/bin/eddy_correct with default options";
eddy_correct "$dwi1_processed" eddy_corrected_data 0 trilinear
else echo "Eddy with user-specified eddy program ${FSLDIR}/bin/$eddy"
"${FSLDIR}/bin/$eddy" --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
fi
fi
fi
elif [ ! "$dwi2" ]; then
fslroi "$dwi1_processed" "${outdir}/b0" 0 1
bet2 "${outdir}/b0" "${outdir}/b0_brain" -m
#EDDY
if [ $eddy == "0" ]; then echo "EDDY skipped by the user (-e option is equal to $eddy)";
else
echo "Running EDDY only (NO TOPUP) because there is no dwi2"
temp=`fslhd "${dwi1}" | grep dim4`
dimtmp=( $temp )
n_vol=${dimtmp[1]}
indx=""
for ((i=1; i<=$n_vol; i+=1)); do indx="$indx 1"; done
echo $indx > index.txt
if [ $eddy == "1" ] && [ -f ${FSLDIR}/bin/eddy_cpu ]; then
echo "Found eddy_cpu! Running ${FSLDIR}/bin/eddy_cpu with default options"
eddy_cpu --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
elif [ $eddy == "2" ] && [ -f ${FSLDIR}/bin/eddy ]; then
echo "Running ${FSLDIR}/bin/eddy with default options";
eddy --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
elif [ $eddy == "3" ] && [ -f ${FSLDIR}/bin/eddy_correct ]; then
echo "Running ${FSLDIR}/bin/eddy_correct with default options";
eddy_correct "$dwi1_processed" eddy_corrected_data 0 trilinear
else echo "Eddy with user-specified eddy program ${FSLDIR}/bin/$eddy"
"${FSLDIR}/bin/$eddy" --imain="$dwi1_processed" --mask=b0_brain_mask --acqp=acqparams.txt --index=index.txt --bvecs=bvec1 --bvals=bval1 --out=eddy_corrected_data
fi
fi
fi
elif [ ! -f "${json1}" ] && [ $eddy == "3" ]; then
echo "Running ${FSLDIR}/bin/eddy_correct with default options";
eddy_correct "$dwi1_processed" eddy_corrected_data 0 trilinear
fi
# 2. FIT TENSOR
if [ -f "${outdir}/eddy_corrected_data.nii.gz" ]; then
echo "starting DTI FITTING on eddy corrected data"
if [ -f "${outdir}/eddy_corrected_data.eddy_rotated_bvecs" ]; then
echo "Using eddy_rotated_bvecs"
dtifit --data=eddy_corrected_data.nii.gz --out=dti --mask=b0_brain_mask.nii.gz --bvecs=eddy_corrected_data.eddy_rotated_bvecs --bvals=bval1 --save_tensor
else
dtifit --data=eddy_corrected_data.nii.gz --out=dti --mask=b0_brain_mask.nii.gz --bvecs=bvec1 --bvals=bval1 --save_tensor
fi
else
if [ -f "${dwi1_processed}" ]; then
fslroi "$dwi1_processed" "${outdir}/b0" 0 1
bet2 "${outdir}/b0" "${outdir}/b0_brain" -m
echo "starting DTI FITTING on preprocessed diffusion data (denoised and/or unringed, NO TOPUP, NO eddy correction)"
dtifit --data="${dwi1_processed}" --out=dti --mask=b0_brain_mask.nii.gz --bvecs=bvec1 --bvals=bval1 --save_tensor
else
fslroi "$dwi1" "${outdir}/b0" 0 1
bet2 "${outdir}/b0" "${outdir}/b0_brain" -m
echo "starting DTI FITTING on input diffusion data (NO preprocessing (denoising/unringing), NO TOPUP, NO eddy correction)"
dtifit --data="${dwi1}" --out=dti --mask=b0_brain_mask.nii.gz --bvecs=bvec1 --bvals=bval1 --save_tensor
fi
fi
echo "DTI FITTING completed!"
#fslsplit "${outdir}/dti_tensor.nii.gz"
#cp "${outdir}/vol0000.nii.gz" "${outdir}/dxx.nii.gz"
#cp "${outdir}/vol0003.nii.gz" "${outdir}/dyy.nii.gz"
#cp "${outdir}/vol0005.nii.gz" "${outdir}/dzz.nii.gz"
elif [ $skip -eq 1 ]; then
echo "Preprocessing and DTI fitting skipped by the user (-s 1 option). ONLY ROI ANALYSIS IS PERFORMED. Checking all required inputs are available..."
if [ -f "${outdir}/alps.stat/alps.csv" ] && [ ! -z "`tail -n 1 "${outdir}/alps.stat/alps.csv" | tr -d ,`" ]; then echo "ERROR! Final output alps.csv already exists and is not empty! Remove/rename the "alps.stat" folder or the "alps.stat/alps.csv" file in order to run the ROI analysis only (-s 1) in ${outdir}"; exit 1; fi;
if [ -f "${outdir}/dti_FA.nii.gz" ]; then echo "dti_FA.nii.gz is available for ROI analysis"; else echo "ERROR! Cannot find ${outdir}/dti_FA.nii.gz, needed for ROI analysis. Double check that ${outdir}/dti_FA.nii.gz exists; if it does not exist, consider running the whole alps script (-s 0, default option)"; exit 1; fi
if [ -f "${outdir}/dti_tensor.nii.gz" ]; then echo "dti_tensor.nii.gz is available for ROI analysis"; else echo "ERROR! Cannot find ${outdir}/dti_tensor.nii.gz, needed for ROI analysis. Double check that ${outdir}/dti_tensor.nii.gz exists; if it does not exist, consider running the whole alps script (-s 0, default option)"; exit 1; fi
#if [ -f "${outdir}/dxx.nii.gz" ]; then echo "dxx.nii.gz is available for ROI analysis"; else echo "ERROR! Cannot find ${outdir}/dxx.nii.gz, needed for ROI analysis. Double check that ${outdir}/dxx.nii.gz exists; if it does not exist, consider running the whole alps script (-s 0, default option)"; exit 1; fi
#if [ -f "${outdir}/dyy.nii.gz" ]; then echo "dyy.nii.gz is available for ROI analysis"; else echo "ERROR! Cannot find ${outdir}/dyy.nii.gz, needed for ROI analysis. Double check that ${outdir}/dyy.nii.gz exists; if it does not exist, consider running the whole alps script (-s 0, default option)"; exit 1; fi
#if [ -f "${outdir}/dyy.nii.gz" ]; then echo "dzz.nii.gz is available for ROI analysis"; else echo "ERROR! Cannot find ${outdir}/dzz.nii.gz, needed for ROI analysis. Double check that ${outdir}/dzz.nii.gz exists; if it does not exist, consider running the whole alps script (-s 0, default option)"; exit 1; fi
fi
# 3. ROI ANALYSIS
if [ "$rois" != "0" ]
then
if [ -z $radius ]; then
iteration=0
for r in $(echo $rois | tr -s ',' ' '); do
iteration=$((iteration+1))
cp "$r" "${outdir}/"$(basename "$(basename "$r" .gz)" .nii)"_in_${template_abbreviation}.nii.gz";
if [ $iteration -eq 1 ]; then
cp "${outdir}/"$(basename "$(basename "$r" .gz)" .nii)"_in_${template_abbreviation}.nii.gz" "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
else
fslmaths "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz" -add "${outdir}/"$(basename "$(basename "$r" .gz)" .nii)"_in_${template_abbreviation}.nii.gz" "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
fi
done
cluster -t 1 -i "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz" -o "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
#cp "${script_folder}/ROIs_JHU_ALPS/all_ROIs.nii.gz" "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
else #generate spheric ROIs in template space
if [ "${template}" == "0" ]; then template_roi=${FSLDIR}/data/atlases/JHU/JHU-ICBM-FA-1mm.nii.gz; template_abbreviation=JHU-FA; else template_roi="${template}"; fi
fslmaths "${template_roi}" -mul 0 -add 1 -roi 116 1 110 1 99 1 0 1 -kernel sphere $radius -fmean -bin "${outdir}/L_SCR_in_${template_abbreviation}.nii.gz" -odt float
fslmaths "${template_roi}" -mul 0 -add 1 -roi 64 1 110 1 99 1 0 1 -kernel sphere $radius -fmean -bin "${outdir}/R_SCR_in_${template_abbreviation}.nii.gz" -odt float
fslmaths "${template_roi}" -mul 0 -add 1 -roi 128 1 110 1 99 1 0 1 -kernel sphere $radius -fmean -bin "${outdir}/L_SLF_in_${template_abbreviation}.nii.gz" -odt float
fslmaths "${template_roi}" -mul 0 -add 1 -roi 52 1 110 1 99 1 0 1 -kernel sphere $radius -fmean -bin "${outdir}/R_SLF_in_${template_abbreviation}.nii.gz" -odt float
fslmaths "${outdir}/L_SCR_in_${template_abbreviation}.nii.gz" -add "${outdir}/R_SCR_in_${template_abbreviation}.nii.gz" -add "${outdir}/L_SLF_in_${template_abbreviation}.nii.gz" -add "${outdir}/R_SLF_in_${template_abbreviation}.nii.gz" -bin "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
cluster -t 1 -i "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz" -o "${outdir}/all_ROIs_in_${template_abbreviation}.nii.gz"
fi
rois="${outdir}/L_SCR_in_${template_abbreviation}.nii.gz","${outdir}/R_SCR_in_${template_abbreviation}.nii.gz","${outdir}/L_SLF_in_${template_abbreviation}.nii.gz","${outdir}/R_SLF_in_${template_abbreviation}.nii.gz"
proj_L="${outdir}/L_SCR_in_${template_abbreviation}.nii.gz"
proj_R="${outdir}/R_SCR_in_${template_abbreviation}.nii.gz"
assoc_L="${outdir}/L_SLF_in_${template_abbreviation}.nii.gz"
assoc_R="${outdir}/R_SLF_in_${template_abbreviation}.nii.gz"
#ROIs
echo "starting ROI analysis with projection fibers "$(basename "$proj_L")" (LEFT) and "$(basename "$proj_R")" (RIGHT), and association fibers "$(basename "$assoc_L")" (LEFT) and "$(basename "$assoc_R")" (RIGHT)"
#TEMPLATE
if [ "$template" != "0" ]; then #analysis in template space
if [ -f "$struct" ]; then #if you have structural MRI data
echo "Linear (flirt) + Non-Linear (fnirt) registration to template via structural scan";
cp "$struct" "${outdir}/${smri}.nii.gz"
#hashtagged the following 2 lines because bet2 does not work super well in all struct MRI scans.
#bet2 "${outdir}/${smri}.nii.gz" "${outdir}/${smri}_brain" -m #this is used for flirt dti2struct and flirt struct2template
#flirt -ref "${outdir}/${smri}_brain.nii.gz" -in "${outdir}/dti_FA.nii.gz" -dof 6 -omat "${outdir}/dti2struct.mat"
if [ $weight == "1" ]; then
flirt -ref "${outdir}/${smri}.nii.gz" -in "${outdir}/dti_FA.nii.gz" -dof 6 -out "${outdir}/dti_FA_2_${smri}.nii.gz" -omat "${outdir}/dti2struct.mat"
elif [ $weight == "2" ]; then #if it's a T2, it's better to align the b0 volume rather than the FA, because the b0 contrast is more similar to T2.
if [ -f "${outdir}/b0.nii.gz" ]; then
flirt -ref "${outdir}/${smri}.nii.gz" -in "${outdir}/b0.nii.gz" -dof 6 -out "${outdir}/b0_2_${smri}.nii.gz" -omat "${outdir}/dti2struct.mat"
else #in case you don't have b0 (i.e., you skipped the preprocessing, and are only doing ROI analysis with a dti_FA map ready)
flirt -ref "${outdir}/${smri}.nii.gz" -in "${outdir}/dti_FA.nii.gz" -dof 6 -out "${outdir}/dti_FA_2_${smri}.nii.gz" -omat "${outdir}/dti2struct.mat"
fi
fi
if [ -f "${outdir}/b0_brain_mask.nii.gz" ]; then
flirt -in "${outdir}/b0_brain_mask.nii.gz" -ref "${outdir}/${smri}.nii.gz" -interp nearestneighbour -out "${outdir}/b0_brain_mask_2_struct.nii.gz" -init "${outdir}/dti2struct.mat" -applyxfm
fslmaths "${outdir}/${smri}.nii.gz" -mul "${outdir}/b0_brain_mask_2_struct.nii.gz" "${outdir}/${smri}_brain.nii.gz"
else #in case you don't have b0_brain_mask (i.e., you skipped the preprocessing, and are only doing ROI analysis)
bet2 "${outdir}/dti_FA.nii.gz" "${outdir}/dti_FA_brain" -m
flirt -in "${outdir}/dti_FA_brain_mask.nii.gz" -ref "${outdir}/${smri}.nii.gz" -interp nearestneighbour -out "${outdir}/dti_FA_brain_mask_2_struct.nii.gz" -init "${outdir}/dti2struct.mat" -applyxfm
fslmaths "${outdir}/${smri}.nii.gz" -mul "${outdir}/dti_FA_brain_mask_2_struct.nii.gz" "${outdir}/${smri}_brain.nii.gz"
fi
flirt -ref "${template}" -in "${outdir}/${smri}_brain.nii.gz" -omat "${outdir}/struct2template_aff.mat"
fnirt --in="${outdir}/${smri}.nii.gz" --aff="${outdir}/struct2template_aff.mat" --cout="${outdir}/struct2template_warps" \
--ref="${template}" ${template_mask}--imprefm=1 \
--impinm=1 --imprefval=0 --impinval=0 --subsamp=4,4,2,2,1,1 --miter=5,5,5,5,5,10 --infwhm=8,6,5,4.5,3,2 --reffwhm=8,6,5,4,2,0 \
--lambda=300,150,100,50,40,30 --estint=1,1,1,1,1,0 --applyrefmask=1,1,1,1,1,1 --applyinmask=1 --warpres=10,10,10 --ssqlambda=1 \
--regmod=bending_energy --intmod=global_non_linear_with_bias --intorder=5 --biasres=50,50,50 --biaslambda=10000 --refderiv=0
applywarp --in="${outdir}/dti_FA.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"
applywarp --in="${outdir}/dti_MD.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dti_MD_to_${template_abbreviation}.nii.gz"
if [ "$freg" == "1" ]; then echo "Transformation of the tensor to the template with applywarp";
applywarp --in="${outdir}/dti_tensor.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dxx.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dxx_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dyy.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dyy_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dzz.nii.gz" --ref="${template}" --warp="${outdir}/struct2template_warps" --premat="${outdir}/dti2struct.mat" --out="${outdir}/dzz_in_${template_abbreviation}.nii.gz"
elif [ "$freg" == "2" ]; then echo "Transformation of the tensor to the template with vecreg";
vecreg -i "${outdir}/dti_tensor.nii.gz" -r "${template}" -o "${outdir}/dti_tensor_in_struct.nii.gz" -t "${outdir}/dti2struct.mat"
vecreg -i "${outdir}/dti_tensor_in_struct.nii.gz" -r "${template}" -o "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" -w "${outdir}/struct2template_warps"
fi
else
if [ "$warp" == "0" ]; then
if [ ! -f "${outdir}/dti_FA_to_${template_abbreviation}.nii.gz" ]; then
echo "Linear registration to template with flirt and default options";
flirt -in "${outdir}/dti_FA.nii.gz" -ref "${template}" -out "${outdir}/dti_FA_to_${template_abbreviation}.nii.gz" -omat "${outdir}/FA_to_${template_abbreviation}.mat" -bins 256 -cost corratio -searchrx -90 90 -searchry -90 90 -searchrz -90 90 -dof 12;
flirt -in "${outdir}/dti_MD.nii.gz" -ref "${template}" -out "${outdir}/dti_MD_to_${template_abbreviation}.nii.gz" -init "${outdir}/FA_to_${template_abbreviation}.mat" -applyxfm;
else echo "dti_FA registered to template exists and will NOT be overwritten: ${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"; fi
if [ ! -f "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" ]; then
if [ "$freg" == "1" ]; then echo "Transformation of the tensor to the template with flirt";
flirt -in "${outdir}/dti_tensor.nii.gz" -ref "${template}" -out "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" -init "${outdir}/FA_to_${template_abbreviation}.mat" -applyxfm
#flirt -in "${outdir}/dxx.nii.gz" -ref "${template}" -out "${outdir}/dxx_in_${template_abbreviation}.nii.gz" -init "${outdir}/FA_to_${template_abbreviation}.mat" -applyxfm
#flirt -in "${outdir}/dyy.nii.gz" -ref "${template}" -out "${outdir}/dyy_in_${template_abbreviation}.nii.gz" -init "${outdir}/FA_to_${template_abbreviation}.mat" -applyxfm
#flirt -in "${outdir}/dzz.nii.gz" -ref "${template}" -out "${outdir}/dzz_in_${template_abbreviation}.nii.gz" -init "${outdir}/FA_to_${template_abbreviation}.mat" -applyxfm
elif [ "$freg" == "2" ]; then echo "Transformation of the tensor to the template with vecreg";
vecreg -i "${outdir}/dti_tensor.nii.gz" -r "${template}" -o "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" -t "${outdir}/FA_to_${template_abbreviation}.mat"
#vecreg -i "${outdir}/dxx.nii.gz" -r "${template}" -o "${outdir}/dxx_in_${template_abbreviation}.nii.gz" -t "${outdir}/FA_to_${template_abbreviation}.mat"
#vecreg -i "${outdir}/dyy.nii.gz" -r "${template}" -o "${outdir}/dyy_in_${template_abbreviation}.nii.gz" -t "${outdir}/FA_to_${template_abbreviation}.mat"
#vecreg -i "${outdir}/dzz.nii.gz" -r "${template}" -o "${outdir}/dzz_in_${template_abbreviation}.nii.gz" -t "${outdir}/FA_to_${template_abbreviation}.mat"
fi
else echo "dti_tensor registered to template exists and will NOT be overwritten: ${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"; fi
elif [ "$warp" == "1" ]; then
if [ ! -f "${outdir}/dti_FA_to_${template_abbreviation}.nii.gz" ]; then
echo "Non-Linear registration to template with fnirt and default options (cf. fsl/etc/flirtsch/FA_2_FMRIB58_1mm.cnf)";
fnirt --in="${outdir}/dti_FA.nii.gz" --ref="${template}" ${template_mask}--cout="${outdir}/FA_to_${template_abbreviation}_warps" --imprefm=1 --impinm=1 --imprefval=0 --impinval=0 --subsamp=8,4,2,2 \
--miter=5,5,5,5 --infwhm=12,6,2,2 --reffwhm=12,6,2,2 --lambda=300,75,30,30 --estint=1,1,1,0 --warpres=10,10,10 --ssqlambda=1 \
--regmod=bending_energy --intmod=global_linear --refderiv=0
applywarp --in="${outdir}/dti_FA.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"
applywarp --in="${outdir}/dti_MD.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_MD_to_${template_abbreviation}.nii.gz"
else echo "dti_FA registered to template exists and will NOT be overwritten: ${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"; fi
if [ ! -f "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" ]; then
if [ "$freg" == "1" ]; then echo "Transformation of the tensor to the template with applywarp";
applywarp --in="${outdir}/dti_tensor.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dxx.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dxx_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dyy.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dyy_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dzz.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dzz_in_${template_abbreviation}.nii.gz"
elif [ "$freg" == "2" ]; then echo "Transformation of the tensor to the template with vecreg";
vecreg -i "${outdir}/dti_tensor.nii.gz" -r "${template}" -o "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" -w "${outdir}/FA_to_${template_abbreviation}_warps"
fi
else echo "dti_tensor registered to template exists and will NOT be overwritten: ${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"; fi
elif [ "$warp" == "2" ]; then
if [ ! -f "${outdir}/dti_FA_to_${template_abbreviation}.nii.gz" ]; then
echo "Linear (flirt) + Non-Linear (fnirt) registration to template";
flirt -in "${outdir}/dti_FA.nii.gz" -ref "${template}" -omat "${outdir}/FA_to_${template_abbreviation}_aff.mat" -bins 256 -cost corratio -searchrx -90 90 -searchry -90 90 -searchrz -90 90 -dof 12
fnirt --in="${outdir}/dti_FA.nii.gz" --ref="${template}" ${template_mask}--aff="${outdir}/FA_to_${template_abbreviation}_aff.mat" \
--cout="${outdir}/FA_to_${template_abbreviation}_warps" --imprefm=1 --impinm=1 --imprefval=0 --impinval=0 --subsamp=8,4,2,2 \
--miter=5,5,5,5 --infwhm=12,6,2,2 --reffwhm=12,6,2,2 --lambda=300,75,30,30 --estint=1,1,1,0 --warpres=10,10,10 --ssqlambda=1 \
--regmod=bending_energy --intmod=global_linear --refderiv=0
applywarp --in="${outdir}/dti_FA.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"
applywarp --in="${outdir}/dti_MD.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_MD_to_${template_abbreviation}.nii.gz"
else echo "dti_FA registered to template exists and will NOT be overwritten: ${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"; fi
if [ ! -f "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" ]; then
if [ "$freg" == "1" ]; then echo "Transformation of the tensor to the template with applywarp";
applywarp --in="${outdir}/dti_tensor.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dxx.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dxx_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dyy.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dyy_in_${template_abbreviation}.nii.gz"
#applywarp --in="${outdir}/dzz.nii.gz" --ref="${template}" --warp="${outdir}/FA_to_${template_abbreviation}_warps" --out="${outdir}/dzz_in_${template_abbreviation}.nii.gz"
elif [ "$freg" == "2" ]; then echo "Transformation of the tensor to the template with vecreg";
vecreg -i "${outdir}/dti_tensor.nii.gz" -r "${template}" -o "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" -w "${outdir}/FA_to_${template_abbreviation}_warps"
fi
else echo "dti_tensor registered to template exists and will NOT be overwritten: ${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz"; fi
fi
fi
fslroi "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" "${outdir}/dxx_in_${template_abbreviation}.nii.gz" 0 1
fslroi "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" "${outdir}/dyy_in_${template_abbreviation}.nii.gz" 3 1
fslroi "${outdir}/dti_tensor_in_${template_abbreviation}.nii.gz" "${outdir}/dzz_in_${template_abbreviation}.nii.gz" 5 1
dxx="${outdir}/dxx_in_${template_abbreviation}.nii.gz"
dyy="${outdir}/dyy_in_${template_abbreviation}.nii.gz"
dzz="${outdir}/dzz_in_${template_abbreviation}.nii.gz"
fa="${outdir}/dti_FA_to_${template_abbreviation}.nii.gz"
md="${outdir}/dti_MD_to_${template_abbreviation}.nii.gz"
elif [ "$template" == "0" ]; then #analysis in native space
echo "ALPS analysis in native space"
fslroi "${outdir}/dti_tensor.nii.gz" "${outdir}/dxx.nii.gz" 0 1
fslroi "${outdir}/dti_tensor.nii.gz" "${outdir}/dyy.nii.gz" 3 1
fslroi "${outdir}/dti_tensor.nii.gz" "${outdir}/dzz.nii.gz" 5 1
dxx="${outdir}/dxx.nii.gz"
dyy="${outdir}/dyy.nii.gz"
dzz="${outdir}/dzz.nii.gz"
fa="${outdir}/dti_FA.nii.gz"
md="${outdir}/dti_MD.nii.gz"
#if [ "$rois" == "${script_folder}/ROIs_JHU_ALPS/L_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SCR.nii.gz,${script_folder}/ROIs_JHU_ALPS/L_SLF.nii.gz,${script_folder}/ROIs_JHU_ALPS/R_SLF.nii.gz" ]; then
template=${FSLDIR}/data/atlases/JHU/JHU-ICBM-FA-1mm.nii.gz
template_abbreviation=JHU-FA
flirt -ref "${outdir}/dti_FA.nii.gz" -in "${template}" -out "${outdir}/dti_FA_${template_abbreviation}_to_native.nii.gz" -omat "${outdir}/${template_abbreviation}_to_native.mat" -bins 256 -cost corratio -searchrx -90 90 -searchry -90 90 -searchrz -90 90 -dof 12
for r in $(echo $rois | tr -s ',' ' '); do
flirt -in "${r}" -ref "${outdir}/dti_FA.nii.gz" -out "${outdir}/"$(basename "$(basename "$(basename "$r" .gz)" .nii)" _in_${template_abbreviation})"_native.nii.gz" -init "${outdir}/${template_abbreviation}_to_native.mat" -applyxfm -interp nearestneighbour
done
proj_L=${outdir}/"$(basename "$(basename "$(basename "$(echo "${rois}" | cut -d ',' -f1)" .gz)" .nii)" _in_${template_abbreviation})"_native.nii.gz
proj_R=${outdir}/"$(basename "$(basename "$(basename "$(echo "${rois}" | cut -d ',' -f2)" .gz)" .nii)" _in_${template_abbreviation})"_native.nii.gz
assoc_L=${outdir}/"$(basename "$(basename "$(basename "$(echo "${rois}" | cut -d ',' -f3)" .gz)" .nii)" _in_${template_abbreviation})"_native.nii.gz
assoc_R=${outdir}/"$(basename "$(basename "$(basename "$(echo "${rois}" | cut -d ',' -f4)" .gz)" .nii)" _in_${template_abbreviation})"_native.nii.gz
fslmaths "${proj_L}" -add "${proj_R}" -add "${assoc_L}" -add "${assoc_R}" -bin "${outdir}/all_ROIs_native.nii.gz"
cluster -t 1 -i "${outdir}/all_ROIs_native.nii.gz" -o "${outdir}/all_ROIs_native.nii.gz"
#fi
fi
#GATHER STATS
mkdir -p "${outdir}/alps.stat"
echo "id,scanner,x_proj_L,x_assoc_L,y_proj_L,z_assoc_L,x_proj_R,x_assoc_R,y_proj_R,z_assoc_R,alps_L,alps_R,alps" > "${outdir}/alps.stat/alps.csv"
echo "id,scanner,diffusion_metric,proj_L,assoc_L,proj_R,assoc_R,mean_proj,mean_assoc" > "${outdir}/alps.stat/fa+md_alps.csv"
if [[ "$dwi1" == *".nii" ]]; then
id="$(basename "$dwi1" .nii)"
elif [[ $dwi1 == *".nii.gz" ]]; then
id="$(basename "$dwi1" .nii.gz)"
else
id="$(basename "$dwi1")"
fi
x_proj_L="$(fslstats "${dxx}" -k "${proj_L}" -m)"
x_assoc_L="$(fslstats "${dxx}" -k "${assoc_L}" -m)"
y_proj_L="$(fslstats "${dyy}" -k "${proj_L}" -m)"
z_assoc_L="$(fslstats "${dzz}" -k "${assoc_L}" -m)"
x_proj_R="$(fslstats "${dxx}" -k "${proj_R}" -m)"
x_assoc_R="$(fslstats "${dxx}" -k "${assoc_R}" -m)"
y_proj_R="$(fslstats "${dyy}" -k "${proj_R}" -m)"
z_assoc_R="$(fslstats "${dzz}" -k "${assoc_R}" -m)"
alps_L=`echo "(($x_proj_L+$x_assoc_L)/2)/(($y_proj_L+$z_assoc_L)/2)" | bc -l` #proj1 and assoc1 are left side, bc -l needed for decimal printing results
alps_R=`echo "(($x_proj_R+$x_assoc_R)/2)/(($y_proj_R+$z_assoc_R)/2)" | bc -l` #proj2 and assoc2 are right side, bc -l needed for decimal printing results
alps=`echo "($alps_R+$alps_L)/2" | bc -l`
echo "${id},${scanner1},${x_proj_L},${x_assoc_L},${y_proj_L},${z_assoc_L},${x_proj_R},${x_assoc_R},${y_proj_R},${z_assoc_R},${alps_L},${alps_R},${alps}" >> "${outdir}/alps.stat/alps.csv"
#FA and MD values from projection and association areas
for diff in "${fa}" "${md}"; do
pl="$(fslstats "${diff}" -k "${proj_L}" -m)"
pr="$(fslstats "${diff}" -k "${proj_R}" -m)"
al="$(fslstats "${diff}" -k "${assoc_L}" -m)"
ar="$(fslstats "${diff}" -k "${assoc_R}" -m)"
pmean=`echo "($pl+$pr)/2" | bc -l`
amean=`echo "($al+$ar)/2" | bc -l`
if [ "${diff}" == "${fa}" ]; then d="FA"; else d="MD"; fi
echo "${id},${scanner1},${d},${pl},${al},${pr},${ar},${pmean},${amean}" >> "${outdir}/alps.stat/fa+md_alps.csv"
done
elif [ "$rois" == "0" ]; then
echo "ROI analysis skipped by the user.";
fi
echo "Finito! Please cite this repository (https://github.com/gbarisano/alps/) and the paper:
Liu, X, Barisano, G, et al., Cross-Vendor Test-Retest Validation of Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) for Evaluating Glymphatic System Function, Aging and Disease (2023)"

alps.sh at commit e6f58e7, under MIT · at the source

Overview

Authors: Xin Jin^1,2, Yan Fu³, Ting Qiu⁴, Jianyu Li², Huixiong Zhang², Yifan Chen², Kewei Chen⁵, Yuanchao Zhang^1,2,5, Junling Wang^{6,7,8,9,10,11}, Xiaoping Yi^12,13,14, Lena Palaniyappan⁴, B Blair Braden⁵

ORCID iDs: Xin Jin, Lena Palaniyappan

14 affiliations

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, Sichuan P. R. China
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054 Sichuan P. R. China
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China
Douglas Mental Health University Institute, McGill University, Montreal, QC Canada
College of Health Solutions, Arizona State University, Phoenix, AZ 85287 USA
Department of Neurology, Xiangya Hospital, Central South University, Jiangxi. (National Regional Center for Neurological Diseases), Nanchang, 330038 Jiangxi P. R. China
National Clinical Research Center for Geriatric Diseases(Xiangya Hospital of Central South University), Changsha, 410008 Hunan P. R. China
Key Laboratory of Hunan Province for Neurodegenerative Disorders, Central South University, Changsha, 410008 Hunan P. R. China
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan P. R. China
Engineering Research Center of Hunan Province for Cognitive Impairment Disorders, Central South University, Changsha, 410008 Hunan P. R. China
Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, 410008 Hunan P. R. China
Department of Nuclear Medicine and Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, 404000 P. R. China
Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC) and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Chongqing University, Chongqing, 404000 P.R. China
School of Medicine, Chongqing University, Chongqing, 400030 P.R. China

Institutions: University of Electronic Science and Technology of China (China); Tongji Hospital (China); Huazhong University of Science and Technology (China); Douglas Mental Health University Institute (Canada); McGill University (Canada); Arizona State University (United States); Central South University (China); Xiangya Hospital Central South University (China); Chongqing University (China)

Journal: BMC medicine, volume 24, issue 1, article 405

Dates: received 29 January 2026; accepted 20 May 2026; published online 27 May 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1186/s12916-026-04948-z · PMID 42204548 · PMCID PMC13397807 · OpenAlex W7162590803

Open access: gold, a free copy (OpenAlex)

Status: code verified

Categories: structural MRI / diffusion (modality), human (organism), other condition (population), clinical / translational (subfield)

Methods: Connectivity, Statistics, fMRI & imaging

Keywords: ALS, Glymphatic system, White matter integrity, DTI-ALPS, Free-water fraction

MeSH: Amyotrophic Lateral Sclerosis*, Extracellular Fluid*, Glymphatic System*, White Matter*, Aged, Diffusion Tensor Imaging, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged (* major topic)

Topic: Cerebrospinal fluid and hydrocephalus (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex

Funding: Santé (CB-C2022); Scientific Research Program of FuRong Laboratory (No.2024PT5109); National Natural Science Foundation of China (U22A20377); Fundamental Research Funds for the Central Universities of Central South University (2024ZZTS0954); Project Program of National Clinical Research Center for Geriatric Disorders (No. 2022LNJJ09)

Citations: not cited yet (Europe PMC); 69 references in the paper

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration and prominent extra-motor involvement. Impaired clearance of neurotoxic proteins has led to increasing interest in the brain glymphatic system; however, its in vivo associations with brain microstructure and clinical heterogeneity remain incompletely understood.

Methods: One hundred forty-six patients with ALS and 149 demographically matched healthy controls (HCs) underwent multimodal MRI and comprehensive clinical assessments. Putative glymphatic function was quantified using diffusion tensor imaging along perivascular space (DTI-ALPS). Extracellular free water fraction (FWF) and free-water-corrected fractional anisotropy (fwcFA) were derived to characterize extracellular fluid and white matter microstructure. Group differences were assessed using vertex-wise and voxel-wise analyses with correction for multiple comparisons. Associations among imaging metrics and clinical measures were evaluated using correlation and serial mediation analyses.

Results: Compared with HCs, patients with ALS exhibited significantly reduced DTI-ALPS index, widespread increases in cortical FWF, bidirectional alterations in white matter FWF, and extensive reductions in fwcFA across major white matter tracts. Reduced DTI-ALPS was associated with changes in extracellular free water and white matter microstructural integrity, whereas FWF and fwcFA measures were associated with functional, cognitive, and emotional outcomes. Mediation analyses identified significant indirect associations between DTI-ALPS and both functional and cognitive measures through a pathway involving cortical FWF, white matter FWF, and fwcFA, although direct associations were not observed.

Conclusions: These findings provide in vivo evidence that putative glymphatic dysfunction co-occurs with extracellular fluid alterations, white matter microstructural changes, and clinical impairment in ALS. Multi-compartment diffusion imaging may offer complementary markers for characterizing brain microstructure and its clinical relevance in ALS.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12916-026-04948-z.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repository

Its files are read in the Code ↔ Paper reader above, with 2 matches between paragraphs and lines of code.

gbarisano/alps

License: MIT

State: the link answers, verified on 26 September 2026

Evidence: files inventoried

Commit: e6f58e7c1b882a799b613e91fe15bab940dc4cd3, 12 September 2025

Languages: Shell (1)

Size: 12 files, 1 script

Software Heritage: not archived

Found in: the text, “MRI data preprocessing”

Holds: README, license file

Not found: CITATION.cff, environment file, tests, continuous integration, documentation

Tools: FSL (1 file), MRtrix3 (1 file)

Availability: 1 check, the latest on 26 September 2026: the link answers

26 September 2026: the link answers

3 files

alps.sh, Shell, 757 lines, 2 matches
LICENSE, License, 21 lines
README.md, Text, 170 lines

At the source: github.com/gbarisano/alps/

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
1 script, each with its path and the digest of its content;
2 matches between paragraphs of the paper and lines of the code (method lexical-v1);
neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 12 authors, 5 keywords, 11 MeSH terms, 5 funders, 69 references.

Cite

This paper

Jin, X., Fu, Y., Qiu, T., Li, J., Zhang, H., Chen, Y., Chen, K., Zhang, Y., Wang, J., Yi, X., Palaniyappan, L., & Braden, B. B. (2026). Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis. BMC medicine, 24(1), 405. https://doi.org/10.1186/s12916-026-04948-z

BibTeX

@article{jin2026putative, author = {Jin, Xin and Fu, Yan and Qiu, Ting and Li, Jianyu and Zhang, Huixiong and Chen, Yifan and Chen, Kewei and Zhang, Yuanchao and Wang, Junling and Yi, Xiaoping and Palaniyappan, Lena and Braden, B Blair}, title = {{Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis}}, journal = {BMC medicine}, year = {2026}, month = may, volume = {24}, number = {1}, pages = {405}, publisher = {BioMed Central}, issn = {1741-7015}, doi = {10.1186/s12916-026-04948-z}, url = {https://doi.org/10.1186/s12916-026-04948-z}, pmid = {42204548}, pmcid = {PMC13397807} }

RIS

TY - JOUR AU - Jin, Xin AU - Fu, Yan AU - Qiu, Ting AU - Li, Jianyu AU - Zhang, Huixiong AU - Chen, Yifan AU - Chen, Kewei AU - Zhang, Yuanchao AU - Wang, Junling AU - Yi, Xiaoping AU - Palaniyappan, Lena AU - Braden, B Blair TI - Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis T2 - BMC medicine J2 - BMC Med PY - 2026 DA - 2026/05/27 VL - 24 IS - 1 SP - 405 SN - 1741-7015 PB - BioMed Central DO - 10.1186/s12916-026-04948-z UR - https://doi.org/10.1186/s12916-026-04948-z LA - en ER -

CSL-JSON

{ "id": "10.1186/s12916-026-04948-z", "type": "article-journal", "title": "Putative glymphatic dysfunction links extracellular fluid dysregulation to white matter degeneration and clinical impairment in amyotrophic lateral sclerosis", "container-title": "BMC medicine", "author": [ { "family": "Jin", "given": "Xin" }, { "family": "Fu", "given": "Yan" }, { "family": "Qiu", "given": "Ting" }, { "family": "Li", "given": "Jianyu" }, { "family": "Zhang", "given": "Huixiong" }, { "family": "Chen", "given": "Yifan" }, { "family": "Chen", "given": "Kewei" }, { "family": "Zhang", "given": "Yuanchao" }, { "family": "Wang", "given": "Junling" }, { "family": "Yi", "given": "Xiaoping" }, { "family": "Palaniyappan", "given": "Lena" }, { "family": "Braden", "given": "B Blair" } ], "container-title-short": "BMC Med", "volume": "24", "issue": "1", "page": "405", "DOI": "10.1186/s12916-026-04948-z", "PMID": "42204548", "PMCID": "PMC13397807", "ISSN": "1741-7015", "publisher": "BioMed Central", "URL": "https://doi.org/10.1186/s12916-026-04948-z", "language": "en", "issued": { "date-parts": [ [ 2026, 5, 27 ] ] } }

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