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This report addresses the technical aspects of de-identification of medical images of human subjects and biospecimens, such that re-identification risk of ethical, moral, and legal concern is sufficiently reduced to allow unrestricted public sharing for any purpose, regardless of the jurisdiction of the source and distribution sites. All medical images, regardless of the mode of acquisition, are considered, though the primary emphasis is on those with accompanying data elements, especially those encoded in formats in which the data elements are embedded, particularly Digital Imaging and Communications in Medicine (DICOM). These images include image-like objects such as Segmentations, Parametric Maps, and Radiotherapy (RT) Dose objects. The scope also includes related non-image objects, such as RT Structure Sets, Plans and Dose Volume Histograms, Structured Reports, and Presentation States. Only de-identification of publicly released data is considered, and alternative approaches to privacy preservation, such as federated learning for artificial intelligence (AI) model development, are out of scope, as are issues of privacy leakage from AI model sharing. Only technical issues of public sharing are addressed.

The transition of an epithelial layer from a stationary, quiescent state to a highly migratory, dynamic state is required for wound healing, development, and regeneration. This transition, known as the unjamming transition (UJT), is responsible for epithelial fluidization and collective migration. Previous theoretical models have primarily focused on the UJT in flat epithelial layers, neglecting the effects of strong surface curvature characteristic of the epithelium textit{in vivo}. In this study, we investigate the role of surface curvature on tissue plasticity and cellular migration using a vertex model embedded on a spherical surface. Our findings reveal that increasing curvature promotes the UJT by reducing the energy barriers to cellular rearrangements. Higher curvature favors cell intercalation, mobility, and self-diffusivity, resulting in epithelial structures that are malleable and migratory when small, but become more rigid and stationary as they grow. Together, these results provide a conceptual framework to better understand how cell shape, cell propulsion, and tissue geometry contribute to tissue malleability, remodeling, and stabilization.

This work investigates use of equivariant neural networks as efficient and high-performance frameworks for image reconstruction and denoising in nuclear medicine. Our work aims to tackle limitations of conventional Convolutional Neural Networks (CNNs), which require significant training. We investigated equivariant networks, aiming to reduce CNN's dependency on specific training sets. Specifically, we implemented and evaluated equivariant spherical CNNs (SCNNs) for 2- and 3-dimensional medical imaging problems. Our results demonstrate superior quality and computational efficiency of SCNNs in both image reconstruction and denoising benchmark problems. Furthermore, we propose a novel approach to employ SCNNs as a complement to conventional image reconstruction tools, enhancing the outcomes while reducing reliance on the training set. Across all cases, we observed significant decrease in computational cost by leveraging the inherent inclusion of equivariant representatives while achieving the same or higher quality of image processing using SCNNs compared to CNNs. Additionally, we explore the potential of SCNNs for broader tomography applications, particularly those requiring rotationally variant representation.

Recent studies of genotype-phenotype (GP) maps have reported universally enhanced phenotypic robustness to genotype mutations, a feature essential to evolution. Virtually all of these studies make a simplifying assumption that each genotype-represented as a sequence-maps deterministically to a single phenotype, such as a discrete structure. Here, we introduce probabilistic genotype-phenotype (PrGP) maps, where each genotype maps to a vector of phenotype probabilities, as a more realistic and universal language for investigating robustness in a variety of physical, biological, and computational systems. We study three model systems to show that PrGP maps offer a generalized framework which can handle uncertainty emerging from various physical sources: (1) thermal fluctuation in RNA folding, (2) external field disorder in spin glass ground state finding, and (3) superposition and entanglement in quantum circuits, which are realized experimentally on IBM quantum computers. In all three cases, we observe a novel biphasic robustness scaling which is enhanced relative to random expectation for more frequent phenotypes and approaches random expectation for less frequent phenotypes. We derive an analytical theory for the behavior of PrGP robustness, and we demonstrate that the theory is highly predictive of empirical robustness.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well-annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied clinical environments and providing personalized volumetric reports to patients undergoing BM treatment.

Previously, Barlow and Attneave hypothesised a link between biological vision and information maximisation. Following Shannon, information was defined using the probability of natural images. Several physiological and psychophysical phenomena have been derived from principles like info-max, efficient coding, or optimal denoising. However, it remains unclear how this link is expressed in mathematical terms from image probability. Classical derivations were subjected to strong assumptions on the probability models and on the behaviour of the sensors. Moreover, the direct evaluation of the hypothesis was limited by the inability of classical image models to deliver accurate estimates of the probability. Here, we directly evaluate image probabilities using a generative model for natural images, and analyse how probability-related factors can be combined to predict the sensitivity of state-of-the-art subjective image quality metrics, a proxy for human perception. We use information theory and regression analysis to find a simple model that when combining just two probability-related factors achieves 0.77 correlation with subjective metrics. This probability-based model is validated in two ways: through direct comparison with the opinion of real observers in a subjective quality experiment, and by reproducing basic trends of classical psychophysical facts such as the Contrast Sensitivity Function, the Weber-law, and contrast masking.

Automated brain tumor segmentation methods have become well-established and reached performance levels offering clear clinical utility. These methods typically rely on four input magnetic resonance imaging (MRI) modalities: T1-weighted images with and without contrast enhancement, T2-weighted images, and FLAIR images. However, some sequences are often missing in clinical practice due to time constraints or image artifacts, such as patient motion. Consequently, the ability to substitute missing modalities and gain segmentation performance is highly desirable and necessary for the broader adoption of these algorithms in the clinical routine. In this work, we present the establishment of the Brain MR Image Synthesis Benchmark (BraSyn) in conjunction with the Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2023. The primary objective of this challenge is to evaluate image synthesis methods that can realistically generate missing MRI modalities when multiple available images are provided. The ultimate aim is to facilitate automated brain tumor segmentation pipelines. The image dataset used in the benchmark is diverse and multi-modal, created through collaboration with various hospitals and research institutions.

Patient recruitment is challenging for clinical trials. We introduce TrialGPT, an end-to-end framework for zero-shot patient-to-trial matching with large language models. TrialGPT comprises three modules: it first performs large-scale filtering to retrieve candidate trials (TrialGPT-Retrieval); then predicts criterion-level patient eligibility (TrialGPT-Matching); and finally generates trial-level scores (TrialGPT-Ranking). We evaluate TrialGPT on three cohorts of 183 synthetic patients with over 75,000 trial annotations. TrialGPT-Retrieval can recall over 90% of relevant trials using less than 6% of the initial collection. Manual evaluations on 1,015 patient-criterion pairs show that TrialGPT-Matching achieves an accuracy of 87.3% with faithful explanations, close to the expert performance. The TrialGPT-Ranking scores are highly correlated with human judgments and outperform the best-competing models by 43.8% in ranking and excluding trials. Furthermore, our user study reveals that TrialGPT can reduce the screening time by 42.6% in patient recruitment. Overall, these results have demonstrated promising opportunities for patient-to-trial matching with TriaGPT.

Firing across populations of neurons in many regions of the mammalian brain maintains a temporal memory, a neural timeline of the recent past. Behavioral results demonstrate that people can both remember the past and anticipate the future over an analogous internal timeline. This paper presents a mathematical framework for building this timeline of the future. We assume that the input to the system is a time series of symbols-sparse tokenized representations of the present-in continuous time. The goal is to record pairwise temporal relationships between symbols over a wide range of time scales. We assume that the brain has access to a temporal memory in the form of the real Laplace transform. Hebbian associations with a diversity of synaptic time scales are formed between the past timeline and the present symbol. The associative memory stores the convolution between the past and the present. Knowing the temporal relationship between the past and the present allows one to infer relationships between the present and the future. With appropriate normalization, this Hebbian associative matrix can store a Laplace successor representation and a Laplace predecessor representation from which measures of temporal contingency can be evaluated. The diversity of synaptic time constants allows for learning of non-stationary statistics as well as joint statistics between triplets of symbols. This framework synthesizes a number of recent neuroscientific findings including results from dopamine neurons in the mesolimbic forebrain.

Energy landscape analysis is a data-driven method to analyze multidimensional time series, including functional magnetic resonance imaging (fMRI) data. It has been shown to be a useful characterization of fMRI data in health and disease. It fits an Ising model to the data and captures the dynamics of the data as movement of a noisy ball constrained on the energy landscape derived from the estimated Ising model. In the present study, we examine test-retest reliability of the energy landscape analysis. To this end, we construct a permutation test that assesses whether or not indices characterizing the energy landscape are more consistent across different sets of scanning sessions from the same participant (i.e., within-participant reliability) than across different sets of sessions from different participants (i.e., between-participant reliability). We show that the energy landscape analysis has significantly higher within-participant than between-participant test-retest reliability with respect to four commonly used indices. We also show that a variational Bayesian method, which enables us to estimate energy landscapes tailored to each participant, displays comparable test-retest reliability to that using the conventional likelihood maximization method. The proposed methodology paves the way to perform individual-level energy landscape analysis for given data sets with a statistically controlled reliability.