Ahmed Abdulkadir

Rongguang Wang, Vishnu Bashyam, Zhijian Yang et al.

Generative adversarial networks (GANs) are one powerful type of deep learning models that have been successfully utilized in numerous fields. They belong to a broader family called generative methods, which generate new data with a probabilistic model by learning sample distribution from real examples. In the clinical context, GANs have shown enhanced capabilities in capturing spatially complex, nonlinear, and potentially subtle disease effects compared to traditional generative methods. This review appraises the existing literature on the applications of GANs in imaging studies of various neurological conditions, including Alzheimer's disease, brain tumors, brain aging, and multiple sclerosis. We provide an intuitive explanation of various GAN methods for each application and further discuss the main challenges, open questions, and promising future directions of leveraging GANs in neuroimaging. We aim to bridge the gap between advanced deep learning methods and neurology research by highlighting how GANs can be leveraged to support clinical decision making and contribute to a better understanding of the structural and functional patterns of brain diseases.

Ahmad Chaddad, Qizong lu, Jiali Li et al.

Artificial intelligence (AI) continues to transform data analysis in many domains. Progress in each domain is driven by a growing body of annotated data, increased computational resources, and technological innovations. In medicine, the sensitivity of the data, the complexity of the tasks, the potentially high stakes, and a requirement of accountability give rise to a particular set of challenges. In this review, we focus on three key methodological approaches that address some of the particular challenges in AI-driven medical decision making. (1) Explainable AI aims to produce a human-interpretable justification for each output. Such models increase confidence if the results appear plausible and match the clinicians expectations. However, the absence of a plausible explanation does not imply an inaccurate model. Especially in highly non-linear, complex models that are tuned to maximize accuracy, such interpretable representations only reflect a small portion of the justification. (2) Domain adaptation and transfer learning enable AI models to be trained and applied across multiple domains. For example, a classification task based on images acquired on different acquisition hardware. (3) Federated learning enables learning large-scale models without exposing sensitive personal health information. Unlike centralized AI learning, where the centralized learning machine has access to the entire training data, the federated learning process iteratively updates models across multiple sites by exchanging only parameter updates, not personal health data. This narrative review covers the basic concepts, highlights relevant corner-stone and state-of-the-art research in the field, and discusses perspectives.

Peng Yan, Ahmed Abdulkadir, Paul-Philipp Luley et al.

Automating the monitoring of industrial processes has the potential to enhance efficiency and optimize quality by promptly detecting abnormal events and thus facilitating timely interventions. Deep learning, with its capacity to discern non-trivial patterns within large datasets, plays a pivotal role in this process. Standard deep learning methods are suitable to solve a specific task given a specific type of data. During training, deep learning demands large volumes of labeled data. However, due to the dynamic nature of the industrial processes and environment, it is impractical to acquire large-scale labeled data for standard deep learning training for every slightly different case anew. Deep transfer learning offers a solution to this problem. By leveraging knowledge from related tasks and accounting for variations in data distributions, the transfer learning framework solves new tasks with little or even no additional labeled data. The approach bypasses the need to retrain a model from scratch for every new setup and dramatically reduces the labeled data requirement. This survey first provides an in-depth review of deep transfer learning, examining the problem settings of transfer learning and classifying the prevailing deep transfer learning methods. Moreover, we delve into applications of deep transfer learning in the context of a broad spectrum of time series anomaly detection tasks prevalent in primary industrial domains, e.g., manufacturing process monitoring, predictive maintenance, energy management, and infrastructure facility monitoring. We discuss the challenges and limitations of deep transfer learning in industrial contexts and conclude the survey with practical directions and actionable suggestions to address the need to leverage diverse time series data for anomaly detection in an increasingly dynamic production environment.

Zhijian Yang, Junhao Wen, Ahmed Abdulkadir et al.

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and SNP data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-driven neuroimaging phenotypes.

Pascal J. Sager, Benjamin Meyer, Peng Yan et al.

Agents for computer use (ACUs) are an emerging class of systems capable of executing complex tasks on digital devices - such as desktops, mobile phones, and web platforms - given instructions in natural language. These agents can automate tasks by controlling software via low-level actions like mouse clicks and touchscreen gestures. However, despite rapid progress, ACUs are not yet mature for everyday use. In this survey, we investigate the state-of-the-art, trends, and research gaps in the development of practical ACUs. We provide a comprehensive review of the ACU landscape, introducing a unifying taxonomy spanning three dimensions: (I) the domain perspective, characterizing agent operating contexts; (II) the interaction perspective, describing observation modalities (e.g., screenshots, HTML) and action modalities (e.g., mouse, keyboard, code execution); and (III) the agent perspective, detailing how agents perceive, reason, and learn. We review 87 ACUs and 33 datasets across foundation model-based and classical approaches through this taxonomy. Our analysis identifies six major research gaps: insufficient generalization, inefficient learning, limited planning, low task complexity in benchmarks, non-standardized evaluation, and a disconnect between research and practical conditions. To address these gaps, we advocate for: (a) vision-based observations and low-level control to enhance generalization; (b) adaptive learning beyond static prompting; (c) effective planning and reasoning methods and models; (d) benchmarks that reflect real-world task complexity; (e) standardized evaluation based on task success; (f) aligning agent design with real-world deployment constraints. Together, our taxonomy and analysis establish a foundation for advancing ACU research toward general-purpose agents for robust and scalable computer use.

Benjamin Meyer, Lukas Tuggener, Sascha Hänzi et al.

Many document types use intrinsic, convention-driven structures that serve to encode precise and structured information, such as the conventions governing engineering drawings. However, state-of-the-art approaches treat document recognition as a mere computer vision problem, neglecting these underlying document-type-specific structural properties, making them dependent on sub-optimal heuristic post-processing and rendering many less frequent or more complicated document types inaccessible to modern document recognition. We suggest a novel perspective that frames document recognition as a transcription task from a document to a record. This implies a natural grouping of documents based on the intrinsic structure inherent in their transcription, where related document types can be treated (and learned) similarly. We propose a method to design structure-specific inductive biases for the underlying machine-learned end-to-end document recognition systems, and a respective base transformer architecture that we successfully adapt to different structures. We demonstrate the effectiveness of the so-found inductive biases in extensive experiments with progressively complex record structures from monophonic sheet music, shape drawings, and simplified engineering drawings. By integrating an inductive bias for unrestricted graph structures, we train the first-ever successful end-to-end model to transcribe engineering drawings to their inherently interlinked information. Our approach is relevant to inform the design of document recognition systems for document types that are less well understood than standard OCR, OMR, etc., and serves as a guide to unify the design of future document foundation models.

Peng Yan, Ahmed Abdulkadir, Gerrit A. Schatte et al.

To go from (passive) process monitoring to active process control, an effective AI system must learn about the behavior of the complex system from very limited training data, forming an ad-hoc digital twin with respect to process inputs and outputs that captures the consequences of actions on the process's world. We propose a novel methodology based on learning world models that disentangles process parameters in the learned latent representation, allowing for fine-grained control. Representation learning is driven by the latent factors influencing the processes through contrastive learning within a joint embedding predictive architecture. This makes changes in representations predictable from changes in inputs and vice versa, facilitating interpretability of key factors responsible for process variations, paving the way for effective control actions to keep the process within operational bounds. The effectiveness of our method is validated on the example of plastic injection molding, demonstrating practical relevance in proposing specific control actions for a notoriously unstable process.

Junhao Wen, Cynthia H. Y. Fu, Duygu Tosun et al.

Late-life depression (LLD) is characterized by considerable heterogeneity in clinical manifestation. Unraveling such heterogeneity would aid in elucidating etiological mechanisms and pave the road to precision and individualized medicine. We sought to delineate, cross-sectionally and longitudinally, disease-related heterogeneity in LLD linked to neuroanatomy, cognitive functioning, clinical symptomatology, and genetic profiles. Multimodal data from a multicentre sample (N=996) were analyzed. A semi-supervised clustering method (HYDRA) was applied to regional grey matter (GM) brain volumes to derive dimensional representations. Two dimensions were identified, which accounted for the LLD-related heterogeneity in voxel-wise GM maps, white matter (WM) fractional anisotropy (FA), neurocognitive functioning, clinical phenotype, and genetics. Dimension one (Dim1) demonstrated relatively preserved brain anatomy without WM disruptions relative to healthy controls. In contrast, dimension two (Dim2) showed widespread brain atrophy and WM integrity disruptions, along with cognitive impairment and higher depression severity. Moreover, one de novo independent genetic variant (rs13120336) was significantly associated with Dim 1 but not with Dim 2. Notably, the two dimensions demonstrated significant SNP-based heritability of 18-27% within the general population (N=12,518 in UKBB). Lastly, in a subset of individuals having longitudinal measurements, Dim2 demonstrated a more rapid longitudinal decrease in GM and brain age, and was more likely to progress to Alzheimers disease, compared to Dim1 (N=1,413 participants and 7,225 scans from ADNI, BLSA, and BIOCARD datasets).

Gyujoon Hwang, Ahmed Abdulkadir, Guray Erus et al.

Neuroimaging biomarkers that distinguish between typical brain aging and Alzheimer's disease (AD) are valuable for determining how much each contributes to cognitive decline. Machine learning models can derive multi-variate brain change patterns related to the two processes, including the SPARE-AD (Spatial Patterns of Atrophy for Recognition of Alzheimer's Disease) and SPARE-BA (of Brain Aging) investigated herein. However, substantial overlap between brain regions affected in the two processes confounds measuring them independently. We present a methodology toward disentangling the two. T1-weighted MRI images of 4,054 participants (48-95 years) with AD, mild cognitive impairment (MCI), or cognitively normal (CN) diagnoses from the iSTAGING (Imaging-based coordinate SysTem for AGIng and NeurodeGenerative diseases) consortium were analyzed. First, a subset of AD patients and CN adults were selected based purely on clinical diagnoses to train SPARE-BA1 (regression of age using CN individuals) and SPARE-AD1 (classification of CN versus AD). Second, analogous groups were selected based on clinical and molecular markers to train SPARE-BA2 and SPARE-AD2: amyloid-positive (A+) AD continuum group (consisting of A+AD, A+MCI, and A+ and tau-positive CN individuals) and amyloid-negative (A-) CN group. Finally, the combined group of the AD continuum and A-/CN individuals was used to train SPARE-BA3, with the intention to estimate brain age regardless of AD-related brain changes. Disentangled SPARE models derived brain patterns that were more specific to the two types of the brain changes. Correlation between the SPARE-BA and SPARE-AD was significantly reduced. Correlation of disentangled SPARE-AD was non-inferior to the molecular measurements and to the number of APOE4 alleles, but was less to AD-related psychometric test scores, suggesting contribution of advanced brain aging to these scores.

Zhijian Yang, Ilya M. Nasrallah, Haochang Shou et al.

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a novel semi-supervised deep-clustering method, which dissects neuroanatomical heterogeneity, enabling identification of disease subtypes via their imaging signatures relative to controls. When applied to MRIs (2 studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified 4 neurodegenerative patterns/axes: P1, normal anatomy and highest cognitive performance; P2, mild/diffuse atrophy and more prominent executive dysfunction; P3, focal medial temporal atrophy and relatively greater memory impairment; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1$\rightarrow$P2$\rightarrow$P4 and P1$\rightarrow$P3$\rightarrow$P4. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered better yet complementary performance in predicting clinical progression, compared to amyloid/tau. These deep-learning derived biomarkers offer promise for precision diagnostics and targeted clinical trial recruitment.

Vishnu M. Bashyam, Jimit Doshi, Guray Erus et al.

Conventional and deep learning-based methods have shown great potential in the medical imaging domain, as means for deriving diagnostic, prognostic, and predictive biomarkers, and by contributing to precision medicine. However, these methods have yet to see widespread clinical adoption, in part due to limited generalization performance across various imaging devices, acquisition protocols, and patient populations. In this work, we propose a new paradigm in which data from a diverse range of acquisition conditions are "harmonized" to a common reference domain, where accurate model learning and prediction can take place. By learning an unsupervised image to image canonical mapping from diverse datasets to a reference domain using generative deep learning models, we aim to reduce confounding data variation while preserving semantic information, thereby rendering the learning task easier in the reference domain. We test this approach on two example problems, namely MRI-based brain age prediction and classification of schizophrenia, leveraging pooled cohorts of neuroimaging MRI data spanning 9 sites and 9701 subjects. Our results indicate a substantial improvement in these tasks in out-of-sample data, even when training is restricted to a single site.

Tanweer Rashid, Ahmed Abdulkadir, Ilya M. Nasrallah et al.

Lobar cerebral microbleeds (CMBs) and localized non-hemorrhage iron deposits in the basal ganglia have been associated with brain aging, vascular disease and neurodegenerative disorders. Particularly, CMBs are small lesions and require multiple neuroimaging modalities for accurate detection. Quantitative susceptibility mapping (QSM) derived from in vivo magnetic resonance imaging (MRI) is necessary to differentiate between iron content and mineralization. We set out to develop a deep learning-based segmentation method suitable for segmenting both CMBs and iron deposits. We included a convenience sample of 24 participants from the MESA cohort and used T2-weighted images, susceptibility weighted imaging (SWI), and QSM to segment the two types of lesions. We developed a protocol for simultaneous manual annotation of CMBs and non-hemorrhage iron deposits in the basal ganglia. This manual annotation was then used to train a deep convolution neural network (CNN). Specifically, we adapted the U-Net model with a higher number of resolution layers to be able to detect small lesions such as CMBs from standard resolution MRI. We tested different combinations of the three modalities to determine the most informative data sources for the detection tasks. In the detection of CMBs using single class and multiclass models, we achieved an average sensitivity and precision of between 0.84-0.88 and 0.40-0.59, respectively. The same framework detected non-hemorrhage iron deposits with an average sensitivity and precision of about 0.75-0.81 and 0.62-0.75, respectively. Our results showed that deep learning could automate the detection of small vessel disease lesions and including multimodal MR data (particularly QSM) can improve the detection of CMB and non-hemorrhage iron deposits with sensitivity and precision that is compatible with use in large-scale research studies.

Francesco La Rosa, Erin S Beck, Ahmed Abdulkadir et al.

The automated detection of cortical lesions (CLs) in patients with multiple sclerosis (MS) is a challenging task that, despite its clinical relevance, has received very little attention. Accurate detection of the small and scarce lesions requires specialized sequences and high or ultra-high field MRI. For supervised training based on multimodal structural MRI at 7T, two experts generated ground truth segmentation masks of 60 patients with 2014 CLs. We implemented a simplified 3D U-Net with three resolution levels (3D U-Net-). By increasing the complexity of the task (adding brain tissue segmentation), while randomly dropping input channels during training, we improved the performance compared to the baseline. Considering a minimum lesion size of 0.75 μL, we achieved a lesion-wise cortical lesion detection rate of 67% and a false positive rate of 42%. However, 393 (24%) of the lesions reported as false positives were post-hoc confirmed as potential or definite lesions by an expert. This indicates the potential of the proposed method to support experts in the tedious process of CL manual segmentation.

Özgün Çiçek, Ahmed Abdulkadir, Soeren S. Lienkamp et al.

This paper introduces a network for volumetric segmentation that learns from sparsely annotated volumetric images. We outline two attractive use cases of this method: (1) In a semi-automated setup, the user annotates some slices in the volume to be segmented. The network learns from these sparse annotations and provides a dense 3D segmentation. (2) In a fully-automated setup, we assume that a representative, sparsely annotated training set exists. Trained on this data set, the network densely segments new volumetric images. The proposed network extends the previous u-net architecture from Ronneberger et al. by replacing all 2D operations with their 3D counterparts. The implementation performs on-the-fly elastic deformations for efficient data augmentation during training. It is trained end-to-end from scratch, i.e., no pre-trained network is required. We test the performance of the proposed method on a complex, highly variable 3D structure, the Xenopus kidney, and achieve good results for both use cases.