Pfungst and Clever Hans: Identifying the unintended cues in a widely used Alzheimer's disease MRI dataset using explainable deep learning

Backgrounds. Deep neural networks have demonstrated high accuracy in classifying Alzheimer's disease (AD). This study aims to enlighten the underlying black-box nature and reveal individual contributions of T1-weighted (T1w) gray-white matter texture, volumetric information and preprocessing on classification performance. Methods. We utilized T1w MRI data from the Alzheimer's Disease Neuroimaging Initiative to distinguish matched AD patients (990 MRIs) from healthy controls (990 MRIs). Preprocessing included skull stripping and binarization at varying thresholds to systematically eliminate texture information. A deep neural network was trained on these configurations, and the model performance was compared using McNemar tests with discrete Bonferroni-Holm correction. Layer-wise Relevance Propagation (LRP) and structural similarity metrics between heatmaps were applied to analyze learned features. Results. Classification performance metrics (accuracy, sensitivity, and specificity) were comparable across all configurations, indicating a negligible influence of T1w gray- and white signal texture. Models trained on binarized images demonstrated similar feature performance and relevance distributions, with volumetric features such as atrophy and skull-stripping features emerging as primary contributors. Conclusions. We revealed a previously undiscovered Clever Hans effect in a widely used AD MRI dataset. Deep neural networks classification predominantly rely on volumetric features, while eliminating gray-white matter T1w texture did not decrease the performance. This study clearly demonstrates an overestimation of the importance of gray-white matter contrasts, at least for widely used structural T1w images, and highlights potential misinterpretation of performance metrics.

Unsupervised Skull Segmentation via Contrastive MR-to-CT Modality Translation

The skull segmentation from CT scans can be seen as an already solved problem. However, in MR this task has a significantly greater complexity due to the presence of soft tissues rather than bones. Capturing the bone structures from MR images of the head, where the main visualization objective is the brain, is very demanding. The attempts that make use of skull stripping seem to not be well suited for this task and fail to work in many cases. On the other hand, supervised approaches require costly and time-consuming skull annotations. To overcome the difficulties we propose a fully unsupervised approach, where we do not perform the segmentation directly on MR images, but we rather perform a synthetic CT data generation via MR-to-CT translation and perform the segmentation there. We address many issues associated with unsupervised skull segmentation including the unpaired nature of MR and CT datasets (contrastive learning), low resolution and poor quality (super-resolution), and generalization capabilities. The research has a significant value for downstream tasks requiring skull segmentation from MR volumes such as craniectomy or surgery planning and can be seen as an important step towards the utilization of synthetic data in medical imaging.

Domain Influence in MRI Medical Image Segmentation: spatial versus k-space inputs

Transformer-based networks applied to image patches have achieved cutting-edge performance in many vision tasks. However, lacking the built-in bias of convolutional neural networks (CNN) for local image statistics, they require large datasets and modifications to capture relationships between patches, especially in segmentation tasks. Images in the frequency domain might be more suitable for the attention mechanism, as local features are represented globally. By transforming images into the frequency domain, local features are represented globally. Due to MRI data acquisition properties, these images are particularly suitable. This work investigates how the image domain (spatial or k-space) affects segmentation results of deep learning (DL) models, focusing on attention-based networks and other non-convolutional models based on MLPs. We also examine the necessity of additional positional encoding for Transformer-based networks when input images are in the frequency domain. For evaluation, we pose a skull stripping task and a brain tissue segmentation task. The attention-based models used are PerceiverIO and a vanilla Transformer encoder. To compare with non-attention-based models, an MLP and ResMLP are also trained and tested. Results are compared with the Swin-Unet, the state-of-the-art medical image segmentation model. Experimental results show that using k-space for the input domain can significantly improve segmentation results. Also, additional positional encoding does not seem beneficial for attention-based networks if the input is in the frequency domain. Although none of the models matched the Swin-Unet's performance, the less complex models showed promising improvements with a different domain choice.

BrainMorph: A Foundational Keypoint Model for Robust and Flexible Brain MRI Registration

We present a keypoint-based foundation model for general purpose brain MRI registration, based on the recently-proposed KeyMorph framework. Our model, called BrainMorph, serves as a tool that supports multi-modal, pairwise, and scalable groupwise registration. BrainMorph is trained on a massive dataset of over 100,000 3D volumes, skull-stripped and non-skull-stripped, from nearly 16,000 unique healthy and diseased subjects. BrainMorph is robust to large misalignments, interpretable via interrogating automatically-extracted keypoints, and enables rapid and controllable generation of many plausible transformations with different alignment types and different degrees of nonlinearity at test-time. We demonstrate the superiority of BrainMorph in solving 3D rigid, affine, and nonlinear registration on a variety of multi-modal brain MRI scans of healthy and diseased subjects, in both the pairwise and groupwise setting. In particular, we show registration accuracy and speeds that surpass current state-of-the-art methods, especially in the context of large initial misalignments and large group settings. All code and models are available at https://github.com/alanqrwang/brainmorph.

Analysis of the BraTS 2023 Intracranial Meningioma Segmentation Challenge

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, T2/FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing T2/FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps.

Boosting Skull-Stripping Performance for Pediatric Brain Images

Skull-stripping is the removal of background and non-brain anatomical features from brain images. While many skull-stripping tools exist, few target pediatric populations. With the emergence of multi-institutional pediatric data acquisition efforts to broaden the understanding of perinatal brain development, it is essential to develop robust and well-tested tools ready for the relevant data processing. However, the broad range of neuroanatomical variation in the developing brain, combined with additional challenges such as high motion levels, as well as shoulder and chest signal in the images, leaves many adult-specific tools ill-suited for pediatric skull-stripping. Building on an existing framework for robust and accurate skull-stripping, we propose developmental SynthStrip (d-SynthStrip), a skull-stripping model tailored to pediatric images. This framework exposes networks to highly variable images synthesized from label maps. Our model substantially outperforms pediatric baselines across scan types and age cohorts. In addition, the <1-minute runtime of our tool compares favorably to the fastest baselines. We distribute our model at https://w3id.org/synthstrip.

Longitudinal Volumetric Study for the Progression of Alzheimer's Disease from Structural MR Images

Alzheimer's Disease (AD) is primarily an irreversible neurodegenerative disorder affecting millions of individuals today. The prognosis of the disease solely depends on treating symptoms as they arise and proper caregiving, as there are no current medical preventative treatments. For this purpose, early detection of the disease at its most premature state is of paramount importance. This work aims to survey imaging biomarkers corresponding to the progression of Alzheimer's Disease (AD). A longitudinal study of structural MR images was performed for given temporal test subjects selected randomly from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The pipeline implemented includes modern pre-processing techniques such as spatial image registration, skull stripping, and inhomogeneity correction. The temporal data across multiple visits spanning several years helped identify the structural change in the form of volumes of cerebrospinal fluid (CSF), grey matter (GM), and white matter (WM) as the patients progressed further into the disease. Tissue classes are segmented using an unsupervised learning approach using intensity histogram information. The segmented features thus extracted provide insights such as atrophy, increase or intolerable shifting of GM, WM and CSF and should help in future research for automated analysis of Alzheimer's detection with clinical domain explainability.

Brain MRI Segmentation using Template-Based Training and Visual Perception Augmentation

Deep learning models usually require sufficient training data to achieve high accuracy, but obtaining labeled data can be time-consuming and labor-intensive. Here we introduce a template-based training method to train a 3D U-Net model from scratch using only one population-averaged brain MRI template and its associated segmentation label. The process incorporated visual perception augmentation to enhance the model's robustness in handling diverse image inputs and mitigating overfitting. Leveraging this approach, we trained 3D U-Net models for mouse, rat, marmoset, rhesus, and human brain MRI to achieve segmentation tasks such as skull-stripping, brain segmentation, and tissue probability mapping. This tool effectively addresses the limited availability of training data and holds significant potential for expanding deep learning applications in image analysis, providing researchers with a unified solution to train deep neural networks with only one image sample.

The University of California San Francisco, Brain Metastases Stereotactic Radiosurgery (UCSF-BMSR) MRI Dataset

The University of California San Francisco Brain Metastases Stereotactic Radiosurgery (UCSF-BMSR) dataset is a public, clinical, multimodal brain MRI dataset consisting of 560 brain MRIs from 412 patients with expert annotations of 5136 brain metastases. Data consists of registered and skull stripped T1 post-contrast, T1 pre-contrast, FLAIR and subtraction (T1 pre-contrast - T1 post-contrast) images and voxelwise segmentations of enhancing brain metastases in NifTI format. The dataset also includes patient demographics, surgical status and primary cancer types. The UCSF-BSMR has been made publicly available in the hopes that researchers will use these data to push the boundaries of AI applications for brain metastases.

Attention-based convolutional neural network for perfusion T2-weighted MR images preprocessing

Accurate skull-stripping is crucial preprocessing in dynamic susceptibility contrast-enhanced perfusion magnetic resonance data analysis. The presence of non-brain tissues impacts the perfusion parameters assessment. In this study, we propose different integration strategies for the spatial and channel squeeze and excitation attention mechanism into the baseline U-Net+ResNet neural network architecture to provide automatic skull-striping i.e., Standard scSE, scSE-PRE, scSE-POST, and scSE Identity strategies of plugging of scSE block into the ResNet backbone. We comprehensively investigate the performance of skull-stripping in T2-star weighted MR images with abnormal brain anatomy. The comparison that utilizing any of the proposed strategies provides the robustness of skull-stripping. However, the scSE-POST integration strategy provides the best result with an average Dice Coefficient of 0.9810.