We provide examples and highlights of Advanced Normalization Tools (ANTS) that address practical problems in real data. A variety of image and point similarity metrics and elastic, diffeomorphic, affine and other variations of transformation models are available.

The Advanced Normalizations Tools ecosystem, known as ANTsX, consists of multiple open-source software libraries which house top-performing algorithms used worldwide by scientific and research communities for processing and analyzing biological and medical imaging data. The base software library, ANTs, is built upon, and contributes to, the NIH-sponsored Insight Toolkit. Founded in 2008 with the highly regarded Symmetric Normalization image registration framework, the ANTs library has since grown to include additional functionality. Recent enhancements include statistical, visualization, and deep learning capabilities through interfacing with both the R statistical project (ANTsR) and Python (ANTsPy). Additionally, the corresponding deep learning extensions ANTsRNet and ANTsPyNet (built on the popular TensorFlow/Keras libraries) contain several popular network architectures and trained models for specific applications. One such comprehensive application is a deep learning analog for generating cortical thickness data from structural T1-weighted brain MRI, both cross-sectionally and longitudinally. These pipelines significantly improve computational efficiency and provide comparable-to-superior accuracy over multiple criteria relative to the existing ANTs workflows and simultaneously illustrate the importance of the comprehensive ANTsX approach as a framework for medical image analysis.

While aggregation of neuroimaging datasets from multiple sites and scanners can yield increased statistical power, it also presents challenges due to systematic scanner effects. This unwanted technical variability can introduce noise and bias into estimation of biological variability of interest. We propose a method for harmonizing longitudinal multi-scanner imaging data based on ComBat, a method originally developed for genomics and later adapted to cross-sectional neuroimaging data. Using longitudinal cortical thickness measurements from 663 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study, we demonstrate the presence of additive and multiplicative scanner effects in various brain regions. We compare estimates of the association between diagnosis and change in cortical thickness over time using three versions of the ADNI data: unharmonized data, data harmonized using cross-sectional ComBat, and data harmonized using longitudinal ComBat. In simulation studies, we show that longitudinal ComBat is more powerful for detecting longitudinal change than cross-sectional ComBat and controls the type I error rate better than unharmonized data with scanner included as a covariate. The proposed method would be useful for other types of longitudinal data requiring harmonization, such as genomic data, or neuroimaging studies of neurodevelopment, psychiatric disorders, or other neurological diseases.

Accurate segmentation of different sub-regions of gliomas including peritumoral edema, necrotic core, enhancing and non-enhancing tumor core from multimodal MRI scans has important clinical relevance in diagnosis, prognosis and treatment of brain tumors. However, due to the highly heterogeneous appearance and shape, segmentation of the sub-regions is very challenging. Recent development using deep learning models has proved its effectiveness in the past several brain segmentation challenges as well as other semantic and medical image segmentation problems. Most models in brain tumor segmentation use a 2D/3D patch to predict the class label for the center voxel and variant patch sizes and scales are used to improve the model performance. However, it has low computation efficiency and also has limited receptive field. U-Net is a widely used network structure for end-to-end segmentation and can be used on the entire image or extracted patches to provide classification labels over the entire input voxels so that it is more efficient and expect to yield better performance with larger input size. Furthermore, instead of picking the best network structure, an ensemble of multiple models, trained on different dataset or different hyperparameters, can generally improve the segmentation performance. In this study we propose to use an ensemble of 3D U-Nets with different hyper-parameters for brain tumor segmentation. Preliminary results showed effectiveness of this model. In addition, we developed a linear model for survival prediction using extracted imaging and non-imaging features, which, despite the simplicity, can effectively reduce overfitting and regression errors.