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Abstract Alzheimer’s Disease (AD) is a progressive neurodegenerative disease and the leading cause of dementia. Early diagnosis is critical for patients to benefit from potential intervention and treatment. The retina has emerged as a plausible diagnostic site for AD detection owing to its anatomical connection with the brain. However, existing AI models for this purpose have yet to provide a rational explanation behind their decisions and have not been able to infer the stage of the disease’s progression. Along this direction, we propose a novel model-agnostic explainable-AI framework, called Granu$$\underline{la}$$ $\underline{\mathrm{la}}$r Neuron-le$$\underline{v}$$ $\underline{v}$el Expl$$\underline{a}$$ $\underline{a}$iner (LAVA), an interpretation prototype that probes into intermediate layers of the Convolutional Neural Network (CNN) models to directly assess the continuum of AD from the retinal imaging without the need for longitudinal or clinical evaluations. This innovative approach aims to validate retinal vasculature as a biomarker and diagnostic modality for evaluating Alzheimer’s Disease. Leveraged UK Biobank cognitive tests and vascular morphological features demonstrate significant promise and effectiveness of LAVA in identifying AD stages across the progression continuum. 

Abstract Whole-head segmentation from Magnetic Resonance Images (MRI) establishes the foundation for individualized computational models using finite element method (FEM). This foundation paves the path for computer-aided solutions in fields such as non-invasive brain stimulation. Most current automatic head segmentation tools are developed using healthy young adults. Thus, they may neglect the older population that is more prone to age-related structural decline such as brain atrophy. In this work, we present a new deep learning method called GRACE, which stands for General, Rapid, And Comprehensive whole-hEad tissue segmentation. GRACE is trained and validated on a novel dataset that consists of 177 manually corrected MR-derived reference segmentations that have undergone meticulous manual review. Each T1-weighted MRI volume is segmented into 11 tissue types, including white matter, grey matter, eyes, cerebrospinal fluid, air, blood vessel, cancellous bone, cortical bone, skin, fat, and muscle. To the best of our knowledge, this work contains the largest manually corrected dataset to date in terms of number of MRIs and segmented tissues. GRACE outperforms five freely available software tools and a traditional 3D U-Net on a five-tissue segmentation task. On this task, GRACE achieves an average Hausdorff Distance of 0.21, which exceeds the runner-up at an average Hausdorff Distance of 0.36. GRACE can segment a whole-head MRI in about 3 seconds, while the fastest software tool takes about 3 minutes. In summary, GRACE segments a spectrum of tissue types from older adults’ T1-MRI scans at favorable accuracy and speed. The trained GRACE model is optimized on older adult heads to enable high-precision modeling in age-related brain disorders. To support open science, the GRACE code and trained weights are made available online and open to the research community at https://github.com/lab-smile/GRACE. 

Parkinson’s disease is the world’s fastest-growing neurological disorder. Research to elucidate the mechanisms of Parkinson’s disease and automate diagnostics would greatly improve the treatment of patients with Parkinson’s disease. Current diagnostic methods are expensive and have limited availability. Considering the insidious and preclinical onset and progression of the disease, a desirable screening should be diagnostically accurate even before the onset of symptoms to allow medical interventions. We highlight retinal fundus imaging, often termed a window to the brain, as a diagnostic screening modality for Parkinson’s disease. We conducted a systematic evaluation of conventional machine learning and deep learning techniques to classify Parkinson’s disease from UK Biobank fundus imaging. Our results suggest Parkinson’s disease individuals can be differentiated from age and gender-matched healthy subjects with 68% accuracy. This accuracy is maintained when predicting either prevalent or incident Parkinson’s disease. Explainability and trustworthiness are enhanced by visual attribution maps of localized biomarkers and quantified metrics of model robustness to data perturbations. 

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation method that applies neuromodulatory effects to the brain via low-intensity, direct current. It has shown possible positive effects in areas such as depression, substance use disorder, anxiety, and pain. Unfortunately, mixed trial results have delayed the field’s progress. Electrical current field approximation provides a way for tDCS researchers to estimate how an individual will respond to specific tDCS parameters. Publicly available physics-based stimulators have led to much progress; however, they can be error-prone, susceptible to quality issues (e.g., poor segmentation), and take multiple hours to run. Digital functional twins provide a method of estimating brain function in response to stimuli using computational methods. We seek to implement this idea for individualized tDCS. Hence, this work provides a proof-of-concept for generating electrical field maps for tDCS directly from T1-weighted magnetic resonance images (MRIs). Our deep learning method employs special loss regularizations to improve the model’s generalizability and calibration across individual scans and electrode montages. Users may enter a desired electrode montage in addition to the unique MRI for a custom output. Our dataset includes 442 unique individual heads from individuals across the adult lifespan. The pipeline can generate results on the scale of minutes, unlike physics-based systems that can take 1–3 hours. Overall, our methods will help streamline the process of individual current dose estimations for improved tDCS interventions. To support open science, the code that is associated with this paper is available at: https://github.com/lab-smile/tDCS-DT. 

The burgeoning field of brain health research increasingly leverages artificial intelligence (AI) to analyze and interpret neuroimaging data. Medical foundation models have shown promise of superior performance with better sample efficiency. This work introduces a novel approach towards creating 3-dimensional (3D) medical foundation models for multimodal neuroimage segmentation through self-supervised training. Our approach involves a novel two-stage pretraining approach using vision transformers. The first stage encodes anatomical structures in generally healthy brains from the large-scale unlabeled neuroimage dataset of multimodal brain magnetic resonance imaging (MRI) images from 41,400 participants. This stage of pertaining focuses on identifying key features such as shapes and sizes of different brain structures. The second pretraining stage identifies disease-specific attributes, such as geometric shapes of tumors and lesions and spatial placements within the brain. This dual-phase methodology significantly reduces the extensive data requirements usually necessary for AI model training in neuroimage segmentation with the flexibility to adapt to various imaging modalities. We rigorously evaluate our model, BrainSegFounder, using the Brain Tumor Segmentation (BraTS) challenge and Anatomical Tracings of Lesions After Stroke v2.0 (ATLAS v2.0) datasets. BrainSegFounder demonstrates a significant performance gain, surpassing the achievements of the previous winning solutions using fully supervised learning. Our findings underscore the impact of scaling up both the model complexity and the volume of unlabeled training data derived from generally healthy brains. Both of these factors enhance the accuracy and predictive capabilities of the model in neuroimage segmentation tasks. Our pretrained models and code are at https://github.com/lab-smile/BrainSegFounder. 

Recent neuroimaging studies have shown that the visual cortex plays an important role in representing the affective significance of visual input. The origin of these affect-specific visual representations is debated: they are intrinsic to the visual system versus they arise through reentry from frontal emotion processing structures such as the amygdala. We examined this problem by combining convolutional neural network (CNN) models of the human ventral visual cortex pre-trained on ImageNet with two datasets of affective images. Our results show that in all layers of the CNN models, there were artificial neurons that responded consistently and selectively to neutral, pleasant, or unpleasant images and lesioning these neurons by setting their output to zero or enhancing these neurons by increasing their gain led to decreased or increased emotion recognition performance respectively. These results support the idea that the visual system may have the intrinsic ability to represent the affective significance of visual input and suggest that CNNs offer a fruitful platform for testing neuroscientific theories. 

Model calibration measures the agreement between the predicted probability estimates and the true correctness likelihood. Proper model calibration is vital for high-risk applications. Unfortunately, modern deep neural networks are poorly calibrated, compromising trustworthiness and reliability. Medical image segmentation particularly suffers from this due to the natural uncertainty of tissue boundaries. This is exasperated by their loss functions, which favor overconfidence in the majority classes. We address these challenges with DOMINO, a domain-aware model calibration method that leverages the semantic confusability and hierarchical similarity between class labels. Our experiments demonstrate that our DOMINO-calibrated deep neural networks outperform non-calibrated models and state-of-the-art morphometric methods in head image segmentation. Our results show that our method can consistently achieve better calibration, higher accuracy, and faster inference times than these methods, especially on rarer classes. This performance is attributed to our domain-aware regularization to inform semantic model calibration. These findings show the importance of semantic ties between class labels in building confidence in deep learning models. The framework has the potential to improve the trustworthiness and reliability of generic medical image segmentation models. The code for this article is available at: https://github.com/lab-smile/DOMINO.