Daniel R. Thedens

Erendiz Tarakci, Joseph Mandeville, Fahmeed Hyder et al.

Rodent stroke models are important for evaluating treatments and understanding the pathophysiology and behavioral changes of brain ischemia, and magnetic resonance imaging (MRI) is a valuable tool for measuring outcome in preclinical studies. Brain extraction is an essential first step in most neuroimaging pipelines; however, it can be challenging in the presence of severe pathology and when dataset quality is highly variable. Convolutional neural networks (CNNs) can improve accuracy and reduce operator time, facilitating high throughput preclinical studies. As part of an ongoing preclinical stroke imaging study, we developed a deep-learning mouse brain extraction tool by using a U-net CNN. While previous studies have evaluated U-net architectures, we sought to evaluate their practical performance across data types. We ask how performance is affected with data across: six imaging centers, two time points after experimental stroke, and across four MRI contrasts. We trained, validated, and tested a typical U-net model on 240 multimodal MRI datasets including quantitative multi-echo T2 and apparent diffusivity coefficient (ADC) maps, and performed qualitative evaluation with a large preclinical stroke database (N=1,368). We describe the design and development of this system, and report our findings linking data characteristics to segmentation performance. We consistently found high accuracy and ability of the U-net architecture to generalize performance in a range of 95-97% accuracy, with only modest reductions in performance based on lower fidelity imaging hardware and brain pathology. This work can help inform the design of future preclinical rodent imaging studies and improve their scalability and reliability.

Ryan P. Cabeen, Joseph Mandeville, Fahmeed Hyder et al.

While ischemic stroke is a leading cause of death worldwide, there has been little success translating putative cerebroprotectants from rodent preclinical trials to human patients. We investigated computational image-based assessment tools for practical improvement of the quality, scalability, and outlook for large scale preclinical screening for potential therapeutic interventions in rodent models. We developed, evaluated, and deployed a pipeline for image-based stroke outcome quantification for the Stroke Preclinical Assessment Network (SPAN), a multi-site, multi-arm, multi-stage study evaluating a suite of cerebroprotectant interventions. Our fully automated pipeline combines state-of-the-art algorithmic and data analytic approaches to assess stroke outcomes from multi-parameter MRI data collected longitudinally from a rodent model of middle cerebral artery occlusion (MCAO), including measures of infarct volume, brain atrophy, midline shift, and data quality. We applied our approach to 1,368 scans and report population level results of lesion extent and longitudinal changes from injury. We validated our system by comparison with both manual annotations of coronal MRI slices and tissue sections from the same brain, using crowdsourcing from blinded stroke experts from the network. Our results demonstrate the efficacy and robustness of our image-based stroke assessments. The pipeline may provide a promising resource for ongoing rodent preclinical studies conducted by SPAN and other networks in the future.

Zhihui Guo, Honghai Zhang, Zhi Chen et al.

Automated segmentation of individual calf muscle compartments from 3D magnetic resonance (MR) images is essential for developing quantitative biomarkers for muscular disease progression and its prediction. Achieving clinically acceptable results is a challenging task due to large variations in muscle shape and MR appearance. Although deep convolutional neural networks (DCNNs) achieved improved accuracy in various image segmentation tasks, certain problems such as utilizing long-range information and incorporating high-level constraints remain unsolved. We present a novel fully convolutional network (FCN), called FilterNet, that utilizes contextual information in a large neighborhood and embeds edge-aware constraints for individual calf muscle compartment segmentations. An encoder-decoder architecture with flexible backbone blocks is used to systematically enlarge convolution receptive field and preserve information at all resolutions. Edge positions derived from the FCN output muscle probability maps are explicitly regularized using kernel-based edge detection in an end-to-end optimization framework. Our FilterNet was evaluated on 40 T1-weighted MR images of 10 healthy and 30 diseased subjects by 4-fold cross-validation. Mean DICE coefficients of 88.00%--91.29% and mean absolute surface positioning errors of 1.04--1.66 mm were achieved for the five 3D muscle compartments.