Optimization and validation of the DESIGNER preprocessing pipeline for clinical diffusion MRI in white matter aging

Various diffusion MRI (dMRI) preprocessing pipelines are currently available to yield more accurate diffusion parameters. Here, we evaluated accuracy and robustness of the optimized Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline in a large clinical dMRI dataset and using ground-truth phantoms. DESIGNER, a preprocessing pipeline targeting various imaging artifacts in diffusion MRI data, has been modified to improve denoising and target Gibbs ringing for partial Fourier acquisitions. We compared the revised DESIGNER (Dv2) (including denoising, Gibbs removal, correction for motion, echo planar imaging (EPI) distortion, and eddy currents) against the original DESIGNER (Dv1) pipeline, minimal preprocessing (including correction for motion, EPI distortion, and eddy currents only), and no preprocessing on a large clinical dMRI dataset of 524 control subjects with ages between 25 and 75 years old. We evaluated the effect of specific processing steps on age correlations in white matter with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) metrics. We also evaluated the added effect of minimal Gaussian smoothing to deal with noise and to reduce outliers in parameter maps compared to DESIGNER-v2's noise removal method. Moreover, Dv2's updated noise and Gibbs removal methods were assessed using a ground truth dMRI phantom to evaluate accuracy. Results show age correlations of DTI and DKI metrics in white matter were affected by the preprocessing pipeline, causing systematic differences in absolute parameter values and loss or gain of statistical significance. Both in clinical dMRI and ground-truth phantoms, Dv2 pipeline resulted in the smallest number of outlier voxels and improved accuracy in DTI and DKI metrics as noise was reduced and Gibbs removal was improved. Thus, DESIGNER-v2 provides more accurate and robust DTI and DKI parameter maps by targeting common artifacts present in dMRI data acquired in clinical settings, as compared to no preprocessing or minimal preprocessing.