Tractography with T1-weighted MRI and associated anatomical constraints on clinical quality diffusion MRI

Diffusion MRI (dMRI) streamline tractography, the gold standard for in vivo estimation of brain white matter (WM) pathways, has long been considered indicative of macroscopic relationships with WM microstructure. However, recent advances in tractography demonstrated that convolutional recurrent neural networks (CoRNN) trained with a teacher-student framework have the ability to learn and propagate streamlines directly from T1 and anatomical contexts. Training for this network has previously relied on high-resolution dMRI. In this paper, we generalize the training mechanism to traditional clinical resolution data, which allows generalizability across sensitive and susceptible study populations. We train CoRNN on a small subset of the Baltimore Longitudinal Study of Aging (BLSA), which better resembles clinical protocols. Then, we define a metric, termed the epsilon ball seeding method, to compare T1 tractography and traditional diffusion tractography at the streamline level. Under this metric, T1 tractography generated by CoRNN reproduces diffusion tractography with approximately two millimeters of error.

Unsupervised Discovery of Clinical Disease Signatures Using Probabilistic Independence

Insufficiently precise diagnosis of clinical disease is likely responsible for many treatment failures, even for common conditions and treatments. With a large enough dataset, it may be possible to use unsupervised machine learning to define clinical disease patterns more precisely. We present an approach to learning these patterns by using probabilistic independence to disentangle the imprint on the medical record of causal latent sources of disease. We inferred a broad set of 2000 clinical signatures of latent sources from 9195 variables in 269,099 Electronic Health Records. The learned signatures produced better discrimination than the original variables in a lung cancer prediction task unknown to the inference algorithm, predicting 3-year malignancy in patients with no history of cancer before a solitary lung nodule was discovered. More importantly, the signatures' greater explanatory power identified pre-nodule signatures of apparently undiagnosed cancer in many of those patients.

Nucleus subtype classification using inter-modality learning

Understanding the way cells communicate, co-locate, and interrelate is essential to understanding human physiology. Hematoxylin and eosin (H&E) staining is ubiquitously available both for clinical studies and research. The Colon Nucleus Identification and Classification (CoNIC) Challenge has recently innovated on robust artificial intelligence labeling of six cell types on H&E stains of the colon. However, this is a very small fraction of the number of potential cell classification types. Specifically, the CoNIC Challenge is unable to classify epithelial subtypes (progenitor, endocrine, goblet), lymphocyte subtypes (B, helper T, cytotoxic T), or connective subtypes (fibroblasts, stromal). In this paper, we propose to use inter-modality learning to label previously un-labelable cell types on virtual H&E. We leveraged multiplexed immunofluorescence (MxIF) histology imaging to identify 14 subclasses of cell types. We performed style transfer to synthesize virtual H&E from MxIF and transferred the higher density labels from MxIF to these virtual H&E images. We then evaluated the efficacy of learning in this approach. We identified helper T and progenitor nuclei with positive predictive values of $0.34 \pm 0.15$ (prevalence $0.03 \pm 0.01$) and $0.47 \pm 0.1$ (prevalence $0.07 \pm 0.02$) respectively on virtual H&E. This approach represents a promising step towards automating annotation in digital pathology.

Evaluation of Mean Shift, ComBat, and CycleGAN for Harmonizing Brain Connectivity Matrices Across Sites

Connectivity matrices derived from diffusion MRI (dMRI) provide an interpretable and generalizable way of understanding the human brain connectome. However, dMRI suffers from inter-site and between-scanner variation, which impedes analysis across datasets to improve robustness and reproducibility of results. To evaluate different harmonization approaches on connectivity matrices, we compared graph measures derived from these matrices before and after applying three harmonization techniques: mean shift, ComBat, and CycleGAN. The sample comprises 168 age-matched, sex-matched normal subjects from two studies: the Vanderbilt Memory and Aging Project (VMAP) and the Biomarkers of Cognitive Decline Among Normal Individuals (BIOCARD). First, we plotted the graph measures and used coefficient of variation (CoV) and the Mann-Whitney U test to evaluate different methods' effectiveness in removing site effects on the matrices and the derived graph measures. ComBat effectively eliminated site effects for global efficiency and modularity and outperformed the other two methods. However, all methods exhibited poor performance when harmonizing average betweenness centrality. Second, we tested whether our harmonization methods preserved correlations between age and graph measures. All methods except for CycleGAN in one direction improved correlations between age and global efficiency and between age and modularity from insignificant to significant with p-values less than 0.05.

Foundation Models for Biomedical Image Segmentation: A Survey

Recent advancements in biomedical image analysis have been significantly driven by the Segment Anything Model (SAM). This transformative technology, originally developed for general-purpose computer vision, has found rapid application in medical image processing. Within the last year, marked by over 100 publications, SAM has demonstrated its prowess in zero-shot learning adaptations for medical imaging. The fundamental premise of SAM lies in its capability to segment or identify objects in images without prior knowledge of the object type or imaging modality. This approach aligns well with tasks achievable by the human visual system, though its application in non-biological vision contexts remains more theoretically challenging. A notable feature of SAM is its ability to adjust segmentation according to a specified resolution scale or area of interest, akin to semantic priming. This adaptability has spurred a wave of creativity and innovation in applying SAM to medical imaging. Our review focuses on the period from April 1, 2023, to September 30, 2023, a critical first six months post-initial publication. We examine the adaptations and integrations of SAM necessary to address longstanding clinical challenges, particularly in the context of 33 open datasets covered in our analysis. While SAM approaches or achieves state-of-the-art performance in numerous applications, it falls short in certain areas, such as segmentation of the carotid artery, adrenal glands, optic nerve, and mandible bone. Our survey delves into the innovative techniques where SAM's foundational approach excels and explores the core concepts in translating and applying these models effectively in diverse medical imaging scenarios.

Super-Resolution Multi-Contrast Unbiased Eye Atlases With Deep Probabilistic Refinement

Eye morphology varies significantly across the population, especially for the orbit and optic nerve. These variations limit the feasibility and robustness of generalizing population-wise features of eye organs to an unbiased spatial reference. To tackle these limitations, we propose a process for creating high-resolution unbiased eye atlases. First, to restore spatial details from scans with a low through-plane resolution compared to a high in-plane resolution, we apply a deep learning-based super-resolution algorithm. Then, we generate an initial unbiased reference with an iterative metric-based registration using a small portion of subject scans. We register the remaining scans to this template and refine the template using an unsupervised deep probabilistic approach that generates a more expansive deformation field to enhance the organ boundary alignment. We demonstrate this framework using magnetic resonance images across four different MRI tissue contrasts, generating four atlases in separate spatial alignments. For each tissue contrast, we find a significant improvement in the average Dice score across four labeled regions compared to a standard registration framework consisting of rigid, affine, and deformable transformations. These results highlight the effective alignment of eye organs and boundaries using our proposed process. By combining super-resolution preprocessing and deep probabilistic models, we address the challenge of generating an eye atlas to serve as a standardized reference across a largely variable population.

RAISE -- Radiology AI Safety, an End-to-end lifecycle approach

The integration of AI into radiology introduces opportunities for improved clinical care provision and efficiency but it demands a meticulous approach to mitigate potential risks as with any other new technology. Beginning with rigorous pre-deployment evaluation and validation, the focus should be on ensuring models meet the highest standards of safety, effectiveness and efficacy for their intended applications. Input and output guardrails implemented during production usage act as an additional layer of protection, identifying and addressing individual failures as they occur. Continuous post-deployment monitoring allows for tracking population-level performance (data drift), fairness, and value delivery over time. Scheduling reviews of post-deployment model performance and educating radiologists about new algorithmic-driven findings is critical for AI to be effective in clinical practice. Recognizing that no single AI solution can provide absolute assurance even when limited to its intended use, the synergistic application of quality assurance at multiple levels - regulatory, clinical, technical, and ethical - is emphasized. Collaborative efforts between stakeholders spanning healthcare systems, industry, academia, and government are imperative to address the multifaceted challenges involved. Trust in AI is an earned privilege, contingent on a broad set of goals, among them transparently demonstrating that the AI adheres to the same rigorous safety, effectiveness and efficacy standards as other established medical technologies. By doing so, developers can instil confidence among providers and patients alike, enabling the responsible scaling of AI and the realization of its potential benefits. The roadmap presented herein aims to expedite the achievement of deployable, reliable, and safe AI in radiology.

Predicting Age from White Matter Diffusivity with Residual Learning

Imaging findings inconsistent with those expected at specific chronological age ranges may serve as early indicators of neurological disorders and increased mortality risk. Estimation of chronological age, and deviations from expected results, from structural MRI data has become an important task for developing biomarkers that are sensitive to such deviations. Complementary to structural analysis, diffusion tensor imaging (DTI) has proven effective in identifying age-related microstructural changes within the brain white matter, thereby presenting itself as a promising additional modality for brain age prediction. Although early studies have sought to harness DTI's advantages for age estimation, there is no evidence that the success of this prediction is owed to the unique microstructural and diffusivity features that DTI provides, rather than the macrostructural features that are also available in DTI data. Therefore, we seek to develop white-matter-specific age estimation to capture deviations from normal white matter aging. Specifically, we deliberately disregard the macrostructural information when predicting age from DTI scalar images, using two distinct methods. The first method relies on extracting only microstructural features from regions of interest. The second applies 3D residual neural networks (ResNets) to learn features directly from the images, which are non-linearly registered and warped to a template to minimize macrostructural variations. When tested on unseen data, the first method yields mean absolute error (MAE) of 6.11 years for cognitively normal participants and MAE of 6.62 years for cognitively impaired participants, while the second method achieves MAE of 4.69 years for cognitively normal participants and MAE of 4.96 years for cognitively impaired participants. We find that the ResNet model captures subtler, non-macrostructural features for brain age prediction.