Machine Learning-Based Reconstruction of 2D MRI for Quantitative Morphometry in Epilepsy

IntroductionStructural neuroimaging analyses require research quality images, acquired with costly MRI acquisitions. Isotropic (3D-T1) images are desirable for quantitative analyses, however a routine compromise in the clinical setting is to acquire anisotropic (2D-T1) analogues for qualitative visual inspection. ML (Machine learning-based) software have shown promise in addressing some of the limitations of 2D-T1 scans in research applications, yet their efficacy in quantitative research is generally poorly understood. Pathology-related abnormalities of the subcortical structures have previously been identified in idiopathic generalised epilepsy (IGE), which have been overlooked based on visual inspection, through the use of quantitative morphometric analyses. As such, IGE biomarkers present a suitable model in which to evaluate the applicability of image preprocessing methods. This study therefore explores subcortical structural biomarkers of IGE, first in our silver standard 3D-T1 scans, then in 2D-T1 scans that were either untransformed, resampled using a classical interpolation approach, or synthesised with a resolution and contrast agnostic ML model (the latter of which is compared to a separate model). Methods2D-T1 and 3D-T1 MRI scans were acquired during the same scanning session for 33 individuals with drug-responsive IGE (age mean 32.16 {+/-} SD = 14.20, male n = 14) and 42 individuals with drug-resistant IGE (31.76 {+/-} 11.12, 17), all diagnosed at the Walton Centre NHS Foundation Trust Liverpool, alongside 39 age- and sex-matched healthy controls (32.32 {+/-} 8.65, 16). The untransformed 2D-T1 scans were resampled into isotropic images using NiBabel (res-T1), and preprocessed into synthetic isotropic images using SynthSR (syn-T1). For the 3D-T1, 2D-T1, res-T1, and syn-T1 images, the recon-all command from FreeSurfer 8.0.0 was used to create parcellations of 174 anatomical regions (equivalent to the 174 regional parcellations provided as part of the DL+DiReCT pipeline), defined by the aseg and Destrieux atlases, and FSL run_first_all was used to segment subcortical surface shapes. The new ML FreeSurfer pipeline, recon-all-clinical, was also tested in the 2D-T1, 3D-T1, and res-T1 images. As a model comparison for SynthSR, the DL+DiReCT pipeline was used to provide segmentations of the 2D-T1 and res-T1 images, including estimates of regional volume and thickness. Spatial overlap and intraclass correlations between the morphometrics of the eight resulting parcellations were first determined, then subcortical surface shape abnormalities associated with IGE were identified by comparing the FSL run_first_all outputs of patients with controls. ResultsWhen standardised to the metrics derived from the 3D-T1 scans, cortical volume and thickness estimates trended lower for the 2D-T1, res-T1, syn-T1, and DL+DiReCT outputs, whereas subcortical volume estimates were more coherent. Dice coefficients revealed an acceptable spatial similarity between the cortices of the 3D-T1 scans and the other images overall, and was higher in the subcortical structures. Intraclass correlation coefficients were consistently lowest when metrics were computed for model-derived inputs, and estimates of thickness were less similar to the ground truth than those of volume. For the people with epilepsy, the 3D-T1 scans showed significant surface deflations across various subcortical structures when compared to healthy controls. Analysis of the 2D-T1 scans enabled the reliable detection of a subset of subcortical abnormalities, whereas analyses of the res-T1 and syn-T1 images were more prone to false-positive results. ConclusionsResampling and ML image synthesis methods do not currently attenuate partial volume effects resulting from low through plane resolution in anisotropic MRI scans, instead quantitative analyses using 2D-T1 scans should be interpreted with caution, and researchers should consider the potential implications of preprocessing. The recon-all-clinical pipeline is promising, but requires further evaluation, especially when considered as an alternative to the classical pipeline. Key PointsO_LISurface deviations indicative of regional atrophy and hypertrophy were identified in people with idiopathic generalised epilepsy. C_LIO_LIPartial volume effects are likely to attenuate subtle morphometric abnormalities, increasing the likelihood of erroneous inference. C_LIO_LIPriors in synthetic image creation models may render them insensitive to subtle biomarkers. C_LIO_LIResampling and machine-learning based image synthesis are not currently replacements for research quality acquisitions in quantitative MRI research. C_LIO_LIThe results of studies using synthetic images should be interpreted in a separate context to those using untransformed data. C_LI