antspymm

ANTsPyMM

processing utilities for timeseries/multichannel images - mostly neuroimaging

the outputs of these processes can be used for data inspection/cleaning/triage as well for interrogating hypotheses.

this package also keeps track of the latest preferred algorithm variations for production environments.

install the dev version by calling (within the source directory):

python3 -m  build .

or install the latest release via

pip install antspymm

what this will do

ANTsPyMM will process several types of brain MRI into tabular form as well as normalized (standard template) space. The processing includes:

• T1wHier uses hierarchical processing from ANTsPyT1w organized around these measurements

  • CIT168 template 10.1101/211201

  • Desikan Killiany Tourville (DKT) 10.3389/fnins.2012.00171

  • basal forebrain (Avants et al HBM 2022 abstract)

  • other regions (eg MTL) 10.1101/2023.01.17.23284693

  • also produces jacobian data

• rsfMRI: resting state functional MRI

  • uses a recent homotopic parcellation to estimate network specific correlations

  • f/ALFF 10.1016/j.jneumeth.2008.04.012

  • percent absolute fluctuation

• NM2DMT: neuromelanin mid-brain images

  • CIT168 template 10.1101/211201

• DTI: DWI diffusion weighted images organized via:

  • CIT168 template 10.1101/211201

  • JHU atlases 10.1016/j.neuroimage.2008.07.009 10.1016/j.neuroimage.2007.07.053

  • DKT for cortical to cortical tractography estimates based on DiPy

• T2Flair: flair for white matter hyperintensity

  • https://pubmed.ncbi.nlm.nih.gov/30908194/

  • https://pubmed.ncbi.nlm.nih.gov/30125711/

  • https://pubmed.ncbi.nlm.nih.gov/35088930/

• T1w: voxel-based cortical thickness (DiReCT) 10.1016/j.neuroimage.2008.12.016

Results of these processes are plentiful; processing for a single subject will all modalities will take around 2 hours on an average laptop.

• documentation of functions here.

• data dictionary here.

• notes on QC here

achieved through four steps (recommended approach):

1. organize data in NRG format

2. perform blind QC

3. compute outlierness per modality and select optimally matched modalities ( steps 3.1 and 3.2 )

4. run the main antspymm function

formal description

Overview

The Advanced Normalization Tools Ecosystem (ANTsX) is a collection of interrelated, open-source software libraries for biological and medical image processing 1 and analysis built on the NIH’s Insight Toolkit (ITK). ANTsX has demonstrated significant applicability for a variety of organ systems, species, and imaging modalities 2 3 4. ANTsX-based processing of multi-modality studies utilizes the Python-based ANTsPyMM library. This includes structural (T1-w, DTI, FLAIR), functional (fMRI), and perfusion (ASL) modalities.

T1-weighted MRI

T1-weighted MRI processing has been previously described 1 2. It is coordinated by ANTsPyT1w, a sub-component of ANTsPyMM, and includes tools for image registration, segmentation, and super-resolution as customized for the human brain. Processing components include preprocessing (denoising + bias correction), brain extraction, sis-tissue parenchymal parcellation (CSF, gray matter, white matter, deep gray matter, brain stem, and cerebellum), and cortical parcellation for morphological quantitation. Derived measurements are tabulated by the neuroanatomical coordinates defined above and include cortical and subcortical measurements and morphological measurements of the hippocampus, basal forebrain and cerebellum.

Diffusion

Diffusion processing. ANTsPyMM couples the ANTsX toolkit with the Diffusion Imaging in Python (Dipy) library for the processing and analysis of diffusion MRI 1. The former is used for motion correction and normalization to corresponding T1-w images. Output consists of QC images, the motion corrected diffusion series, RGB images, FA, mean diffusion and dense tractography as well as tractography-based connectivity matrices. Tabular summary of these metrics are written to csv.

Resting-state fMRI

The rsfMRI processing computes a robust summary of resting-state fMRI time series data and corrects for motion artifacts, extracts temporal statistics, and computes functional connectivity across the brain. The analysis pipeline incorporates advanced techniques for noise reduction, temporal derivative calculation, signal standardization, and the calculation of functional connectivity between brain regions using Yeo homotopic labels. This provides researchers with cleaned, standardized, and biologically meaningful data for further analysis of brain network activity.

Several preprocessing steps are included in the ANTsPyMM processing of resting state fMRI (rsfMRI) data. First, motion correction is used to align the time series to a series specific fMRI template. Distortion correction to t1 is also performed along with brain extraction. The temporal derivative is calculated to quantify changes over time in the signal, followed by the temporal standard deviation (tSTD), which computes the variability across time for each voxel. This is done to identify regions of interest with significant signal variation. The CompCor matrix 1 is computed using temporal standard deviation thresholds, which helps remove noise by identifying high-variance regions. Additionally, motion correction is a central part of the pipeline, where metrics like framewise displacement (FD) and motion-induced signal changes (DVARS) are calculated to detect and correct for artifacts caused by subject movement. Bandpass filtering is applied to focus the analysis on brain signals within specific frequency ranges, and censoring is used to exclude high-motion time points from the analysis, ensuring cleaner data. The preprocessing concludes with the calculation of summary statistics, including measures of signal-to-noise ratio (SNR) and motion effects, which are compiled into a dictionary for further use.

The next step in the pipeline involves computing functional connectivity through correlation matrices based on the Yeo homotopic labels, which group brain regions into homotopic (mirrored) areas across hemispheres. Time series data are averaged within each Yeo-labeled region, and pairwise correlation matrices are computed to assess the functional connectivity both within and between brain hemispheres. This allows for an in-depth analysis of large-scale brain networks, including symmetrical interactions between homotopic regions and connectivity within networks such as the default mode network, visual network, and others.

This provides a comprehensive framework for preprocessing resting-state fMRI data and analyzing functional connectivity across the brain. By combining robust noise reduction, motion correction, and correlation matrix computation, the pipeline ensures that the resulting data are suitable for high-quality research into brain network dynamics and resting-state connectivity. Through the use of Yeo homotopic labels and functional correlation matrices, the code offers a valuable tool for investigating symmetrical brain activity and network interactions in fMRI studies. By default, three different sets of processing parameters are employed. These were chosen based on an empirical evaluation of reproducibility in a traveling participant cohort.

ASL

ASL processing. Cerebral blood flow (CBF) is a critical parameter in understanding brain function and its alterations in various neurological conditions. Arterial spin labeling (ASL) MRI is a non-invasive technique that can measure CBF without the need for contrast agents. ANTsPyMM estimates CBF from ASL MRI data through a combination of image processing and mathematical modeling techniques 1. First, motion artifacts and outliers are removed from the time series data. Second, the preprocessed data is registered to the reference T1-w space using a rigid transformation optimized through the ANTs registration tools 2. Third, the six-tissue segmentation generated during the T1-w segmentation is used to partition the registered ASL data from which the CBF is estimated using a mathematical model that takes into account the ASL MRI signal, the labeling efficiency, and the longitudinal relaxation time of blood. Finally, the M0 image, which represents the equilibrium magnetization of brain tissue, is estimated using a separate mathematical model.

Magnetic resonance angiography

MRA processing and analysis. A precursor for quantitative measures of potential vascular irregularities is the segmentation derived from MR angiography. To extract these image-based quantitative measures (described below), we developed and trained a deep learning network as part of the ANTsXNet functional library. Training data was adapted from a publicly available resource 1 consisting of 42 subjects with vascular network segmentations and brain masks provided. A previously constructed high-resolution template was generated from the Human Connectome Project Young Adult cohort comprising T1-w, T2-w, and FA modalities using ANTs functionality 2 3 and served as the prediction space for network training. Prior spatial information was included by warping all vascular segmentations to the template space, averaged, spatially smoothed, and renormalized to the intensity range [0,1]. Aggressive data augmentation was used to generate additional data in real time during training consisting of random spatial linear and deformable transformations, random Gaussian additive noise, random histogram-based intensity warping 4, and simulated bias field based on the popular N4 algorithm 5. The functionality is available as open-source in both the R-based ANTsRNet (brainMraVesselSegmentation(...)) and Python-based ANTsPyNet (brain_mra_vessel_segmentation(...)).

Periventricular spaces and white matter hyperintensities

Traditional measures for indicating abnormal vascular morphology can then be calculated, such as tortuosity 1. For example, tight vascular coils (i.e., high tortuosity) are often associated with the presence of malignant tumors. From the centerline of the vessel segmentation, various tortuosity measures have been proposed including 1) distance metric: the ratio of the length of the centerline to the distance between the two endpoints, 2) inflection count metric: the distance metric multiplied by the number of the inflection points (i.e., a point of minimum total curvature), 3) sum of angles metric: the integrated total curvature normalized by total path length.

For quantitative assessment of enlarged perivascular spaces, we employ functionality made publicly available through the ANTsX toolkit. Specifically, previous published research 2 has been ported to the ANTsXNet library and will be used for segmenting enlarged perivascular spaces. Using both T1 and FLAIR modalities, a trained deep learning U-net neural network was trained using 40 datasets in which all visible perivascular spaces were manually annotated by an expert. An ensemble of trained weights is used to produce the final probability image. Previous work in MRI super resolution 3 will be used to explore the possible output enhancement. PVS segmentation results will be tabulated per lobe using separate ANTsXNet functionality 4.

Similar functionality exists for segmentation of white matter hyperintensities and will be included in the MRI processing for this project. Several algorithms have been ported to ANTsXNet from previous research from multiple groups to complement existing capabilities 5 6 7. Regional tabulation will also depend on the lobar segmentation within the white matter as with the PVS segmentation results.

first time setup

import antspyt1w
import antspymm
antspyt1w.get_data(force_download=True)
antspymm.get_data(force_download=True)

NOTE: get_data has a force_download option to make sure the latest package data is installed.

NOTE: some functions in antspynet will download deep network model weights on the fly. if one is containerizing, then it would be worth running a test case through in the container to make sure all the relevant weights are pre-downloaded.

NOTE: an example process for BIDS data on a cluster is here. this repo is also a good place to try to learn how to use this tool.

example processing

see the latest help but this snippet gives an idea of how one might use the package:

import os
os.environ["TF_NUM_INTEROP_THREADS"] = "8"
os.environ["TF_NUM_INTRAOP_THREADS"] = "8"
os.environ["ITK_GLOBAL_DEFAULT_NUMBER_OF_THREADS"] = "8"

import antspymm
import antspyt1w
import antspynet
import ants

... i/o code here ...

tabPro, normPro = antspymm.mm(
    t1,
    hier,
    nm_image_list = mynm,
    rsf_image = rsf,
    dw_image = dwi,
    bvals = bval_fname,
    bvecs = bvec_fname,
    flair_image = flair,
    do_tractography=False,
    do_kk=False,
    do_normalization=True,
    verbose=True )

antspymm.write_mm( '/tmp/test_output', t1wide, tabPro, normPro )

blind quality control

this package also provides tools to identify the best multi-modality image set at a given visit.

the code below provides guidance on how to automatically qc, filter and match multiple modality images at each time point. these tools are based on standard unsupervised approaches and are not perfect so we recommend using the associated plotting/visualization techniques to check the quality characterizations for each modality.

## run the qc on all images - requires a relatively large sample per modality to be effective
## then aggregate
qcdf=pd.DataFrame()
for fn in fns:
  qcdf=pd.concat( [qcdf,antspymm.blind_image_assessment(fn)], axis=0)
qcdfa=antspymm.average_blind_qc_by_modality(qcdf,verbose=True) ## reduce the time series qc
qcdfaol=antspymm.outlierness_by_modality(qcdfa) # estimate outlier scores
print( qcdfaol.shape )
print( qcdfaol.keys )
matched_mm_data=antspymm.match_modalities( qcdfaol  )

or just get modality-specific outlierness "by hand" then match mm:

import antspymm
import pandas as pd
mymods = antspymm.get_valid_modalities( )
alldf = pd.DataFrame()
for n in range(len(mymods)):
    m=mymods[n]
    jj=antspymm.collect_blind_qc_by_modality("qc/*"+m+"*csv")
    jjj=antspymm.average_blind_qc_by_modality(jj,verbose=False).dropna(axis=1) ## reduce the time series qc
    jjj=antspymm.outlierness_by_modality( jjj, verbose=False)
    alldf = pd.concat( [alldf, jjj ], axis=0 )
    jjj.to_csv( "mm_outlierness_"+m+".csv")
    print(m+" done")
# write the joined data out
alldf.to_csv( "mm_outlierness.csv", index=False )
# find the best mm collection
matched_mm_data=antspymm.match_modalities( alldf, verbose=True )
matched_mm_data.to_csv( "matched_mm_data.csv", index=False )
matched_mm_data['negative_outlier_factor'] = 1.0 - matched_mm_data['ol_loop'].astype("float")
matched_mm_data2 = antspymm.highest_quality_repeat( matched_mm_data, 'subjectID', 'date', qualityvar='negative_outlier_factor')
matched_mm_data2.to_csv( "matched_mm_data2.csv", index=False )

an example on open neuro (BIDS) data

from : ANT PD see also this repo.

imagesBIDS/
└── ANTPD
    └── sub-RC4125
        └── ses-1
            ├── anat
            │   ├── sub-RC4125_ses-1_T1w.json
            │   └── sub-RC4125_ses-1_T1w.nii.gz
            ├── dwi
            │   ├── sub-RC4125_ses-1_dwi.bval
            │   ├── sub-RC4125_ses-1_dwi.bvec
            │   ├── sub-RC4125_ses-1_dwi.json
            │   └── sub-RC4125_ses-1_dwi.nii.gz
            └── func
                ├── sub-RC4125_ses-1_task-ANT_run-1_bold.json
                ├── sub-RC4125_ses-1_task-ANT_run-1_bold.nii.gz
                └── sub-RC4125_ses-1_task-ANT_run-1_events.tsv

import antspymm
import pandas as pd
import glob as glob
fns = glob.glob("imagesBIDS/ANTPD/sub-RC4125/ses-*/*/*gz")
fns.sort()
randid='000' # BIDS does not have unique image ids - so we assign one
studycsv = antspymm.generate_mm_dataframe(
    'ANTPD',
    'sub-RC4125',
    'ses-1',
    randid,
    'T1w',
    '/Users/stnava/data/openneuro/imagesBIDS/',
    '/Users/stnava/data/openneuro/processed/',
    t1_filename=fns[0],
    dti_filenames=[fns[1]],
    rsf_filenames=[fns[2]])
studycsv2 = studycsv.dropna(axis=1)
mmrun = antspymm.mm_csv( studycsv2, mysep='_' )

# aggregate the data after you've run on many subjects
# studycsv_all would be the vstacked studycsv2 data frames
zz=antspymm.aggregate_antspymm_results_sdf( studycsv_all, 
    subject_col='subjectID', date_col='date', image_col='imageID',  base_path=bd, 
    splitsep='_', idsep='-', wild_card_modality_id=True, verbose=True)

NRG example

NRG format details here

imagesNRG/
└── ANTPD
    └── sub-RC4125
        └── ses-1
            ├── DTI
            │   └── 000
            │       ├── ANTPD_sub-RC4125_ses-1_DTI_000.bval
            │       ├── ANTPD_sub-RC4125_ses-1_DTI_000.bvec
            │       ├── ANTPD_sub-RC4125_ses-1_DTI_000.json
            │       └── ANTPD_sub-RC4125_ses-1_DTI_000.nii.gz
            ├── T1w
            │   └── 000
            │       └── ANTPD_sub-RC4125_ses-1_T1w_000.nii.gz
            └── rsfMRI
                └── 000
                    └── ANTPD_sub-RC4125_ses-1_rsfMRI_000.nii.gz

import antspymm
import pandas as pd
import glob as glob
t1fn=glob.glob("imagesNRG/ANTPD/sub-RC4125/ses-*/*/*/*T1w*gz")[0]
# flair also takes a single image
dtfn=glob.glob("imagesNRG/ANTPD/sub-RC4125/ses-*/*/*/*DTI*gz")
rsfn=glob.glob("imagesNRG/ANTPD/sub-RC4125/ses-*/*/*/*rsfMRI*gz")
studycsv = antspymm.generate_mm_dataframe(
    'ANTPD',
    'sub-RC4125',
    'ses-1',
    '000',
    'T1w',
    '/Users/stnava/data/openneuro/imagesNRG/',
    '/Users/stnava/data/openneuro/processed/',
    t1fn,
    rsf_filenames=rsfn,
    dti_filenames=dtfn
)
studycsv2 = studycsv.dropna(axis=1)
mmrun = antspymm.mm_csv( studycsv2, mysep='_' )

Population studies

Large population studies may need more care to ensure everything is reproducibly organized and processed. In this case, we recommend:

1. blind qc

first run the blind qc function that would look like tests/blind_qc.py. this gives a quick view of the relevant data to be processed. it provides both figures and summary data for each 3D and 4D (potential) input image.

2. collect outlierness measurements

the outlierness function gives one an idea of how each image relates to the others in terms of similarity. it may or may not succeed in detecting true outliers but does a reasonable job of providing some rank ordering of quality when there is repeated data. see tests/outlierness.py.

3. match the modalities for each subject and timepoint

this occurs at the end of tests/outlierness.py. the output of the function will select the best quality time point multiple modality collection and will define the antspymm cohort in a reproducible manner.

4. run the antspymm processing

for each subject/timepoint, one would run:

# ... imports above ...
studyfn="matched_mm_data2.csv"
df=pd.read_csv( studyfn )
index = 20 # 20th subject/timepoint
csvfns = df['filename']
csvrow = df[ df['filename'] == csvfns[index] ]
csvrow['projectID']='MyStudy'

############################################################################################
template = ants.image_read("~/.antspymm/PPMI_template0.nii.gz")
bxt = ants.image_read("~/.antspymm/PPMI_template0_brainmask.nii.gz")
template = template * bxt
template = ants.crop_image( template, ants.iMath( bxt, "MD", 12 ) )
studycsv2 = antspymm.study_dataframe_from_matched_dataframe(
        csvrow,
        rootdir + "nrgdata/data/",
        rootdir + "processed/", verbose=True)
mmrun = antspymm.mm_csv( studycsv2,
                        dti_motion_correct='SyN',
                        dti_denoise=True,
                        normalization_template=template,
                        normalization_template_output='ppmi',
                        normalization_template_transform_type='antsRegistrationSyNQuickRepro[s]',
                        normalization_template_spacing=[1,1,1])

5. aggregate results

if you have a large population study then the last step would look like this:

import antspymm
import glob as glob
import re
import pandas as pd
import os
df = pd.read_csv( "matched_mm_data2.csv" )
pdir='./processed/'
df['projectID']='MYSTUDY'
merged = antspymm.merge_wides_to_study_dataframe( df, pdir, verbose=False, report_missing=False, progress=100 )
print(merged.shape)
merged.to_csv("mystudy_results_antspymm.csv")

useful tools for converting dicom to nifti

• dcm2niix

• dicom2nifti

import dicom2nifti

dicom2nifti.convert_directory(dicom_directory, output_folder, compression=True, reorient=True)

• simpleitk

import SimpleITK as sitk
import sys
import os
import glob as glob
import ants
dd='dicom'
oo='dicom2nifti'
folders=glob.glob('dicom/*')
k=0
for f in folders:
    print(f)    
    reader = sitk.ImageSeriesReader()
    ff=glob.glob(f+"/*")
    dicom_names = reader.GetGDCMSeriesFileNames(ff[0])
    if len(ff) > 0:
        fnout='dicom2nifti/image_'+str(k).zfill(4)+'.nii.gz'
        if not exists(fnout):
            failed=False
            reader.SetFileNames(dicom_names)
            try:
                image = reader.Execute()
            except:
                failed=True
                pass
            if not failed:
                size = image.GetSpacing()
                print( image.GetMetaDataKeys( ) )
                print( size )
                sitk.WriteImage(image, fnout )
                img=ants.image_read( fnout )
                img=ants.iMath(img,'TruncateIntensity',0.02,0.98)
                ants.plot( img, nslices=21,ncol=7,axis=2, crop=True )
        else:
            print(f+ ": "+'empty')
    k=k+1

build docs

pdoc -o ./docs antspymm --html

ssl error

if you get an odd certificate error when calling force_download, try:

import ssl
ssl._create_default_https_context = ssl._create_unverified_context

to publish a release

before doing this - make sure you have a recent run of pip-compile pyproject.toml

rm -r -f build/ antspymm.egg-info/ dist/
python3 -m  build .
python3 -m pip install --upgrade twine
python3 -m twine upload --repository antspymm dist/*