Auditing Sybil: Explaining Deep Lung Cancer Risk Prediction Through Generative Interventional Attributions

Lung cancer remains the leading cause of cancer mortality, driving the development of automated screening tools to alleviate radiologist workload. Standing at the frontier of this effort is Sybil, a deep learning model capable of predicting future risk solely from computed tomography (CT) with high precision. However, despite extensive clinical validation, current assessments rely purely on observational metrics. This correlation-based approach overlooks the model's actual reasoning mechanism, necessitating a shift to causal verification to ensure robust decision-making before clinical deployment. We propose S(H)NAP, a model-agnostic auditing framework that constructs generative interventional attributions validated by expert radiologists. By leveraging realistic 3D diffusion bridge modeling to systematically modify anatomical features, our approach isolates object-specific causal contributions to the risk score. Providing the first interventional audit of Sybil, we demonstrate that while the model often exhibits behavior akin to an expert radiologist, differentiating malignant pulmonary nodules from benign ones, it suffers from critical failure modes, including dangerous sensitivity to clinically unjustified artifacts and a distinct radial bias.

BioNIC: Biologically Inspired Neural Network for Image Classification Using Connectomics Principles

We present BioNIC, a multi-layer feedforward neural network for emotion classification, inspired by detailed synaptic connectivity graphs from the MICrONs dataset. At a structural level, we incorporate architectural constraints derived from a single cortical column of the mouse Primary Visual Cortex(V1): connectivity imposed via adjacency masks, laminar organization, and graded inhibition representing inhibitory neurons. At the functional level, we implement biologically inspired learning: Hebbian synaptic plasticity with homeostatic regulation, Layer Normalization, data augmentation to model exposure to natural variability in sensory input, and synaptic noise to model neural stochasticity. We also include convolutional layers for spatial processing, mimicking retinotopic mapping. The model performance is evaluated on the Facial Emotion Recognition task FER-2013 and compared with a conventional baseline. Additionally, we investigate the impacts of each biological feature through a series of ablation experiments. While connectivity was limited to a single cortical column and biologically relevant connections, BioNIC achieved performance comparable to that of conventional models, with an accuracy of 59.77 $\pm$ 0.27% on FER-2013. Our findings demonstrate that integrating constraints derived from connectomics is a computationally plausible approach to developing biologically inspired artificial intelligence systems. This work also highlights the potential of new generation peta-scale connectomics data in advancing both neuroscience modeling and artificial intelligence.

Projection Embedded Diffusion Bridge for CT Reconstruction from Incomplete Data

Reconstructing CT images from incomplete projection data remains challenging due to the ill-posed nature of the problem. Diffusion bridge models have recently shown promise in restoring clean images from their corresponding Filtered Back Projection (FBP) reconstructions, but incorporating data consistency into these models remains largely underexplored. Incorporating data consistency can improve reconstruction fidelity by aligning the reconstructed image with the observed projection data, and can enhance detail recovery by integrating structural information contained in the projections. In this work, we propose the Projection Embedded Diffusion Bridge (PEDB). PEDB introduces a novel reverse stochastic differential equation (SDE) to sample from the distribution of clean images conditioned on both the FBP reconstruction and the incomplete projection data. By explicitly conditioning on the projection data in sampling the clean images, PEDB naturally incorporates data consistency. We embed the projection data into the score function of the reverse SDE. Under certain assumptions, we derive a tractable expression for the posterior score. In addition, we introduce a free parameter to control the level of stochasticity in the reverse process. We also design a discretization scheme for the reverse SDE to mitigate discretization error. Extensive experiments demonstrate that PEDB achieves strong performance in CT reconstruction from three types of incomplete data, including sparse-view, limited-angle, and truncated projections. For each of these types, PEDB outperforms evaluated state-of-the-art diffusion bridge models across standard, noisy, and domain-shift evaluations.

Surf2CT: Cascaded 3D Flow Matching Models for Torso 3D CT Synthesis from Skin Surface

We present Surf2CT, a novel cascaded flow matching framework that synthesizes full 3D computed tomography (CT) volumes of the human torso from external surface scans and simple demographic data (age, sex, height, weight). This is the first approach capable of generating realistic volumetric internal anatomy images solely based on external body shape and demographics, without any internal imaging. Surf2CT proceeds through three sequential stages: (1) Surface Completion, reconstructing a complete signed distance function (SDF) from partial torso scans using conditional 3D flow matching; (2) Coarse CT Synthesis, generating a low-resolution CT volume from the completed SDF and demographic information; and (3) CT Super-Resolution, refining the coarse volume into a high-resolution CT via a patch-wise conditional flow model. Each stage utilizes a 3D-adapted EDM2 backbone trained via flow matching. We trained our model on a combined dataset of 3,198 torso CT scans (approximately 1.13 million axial slices) sourced from Massachusetts General Hospital (MGH) and the AutoPET challenge. Evaluation on 700 paired torso surface-CT cases demonstrated strong anatomical fidelity: organ volumes exhibited small mean percentage differences (range from -11.1% to 4.4%), and muscle/fat body composition metrics matched ground truth with strong correlation (range from 0.67 to 0.96). Lung localization had minimal bias (mean difference -2.5 mm), and surface completion significantly improved metrics (Chamfer distance: from 521.8 mm to 2.7 mm; Intersection-over-Union: from 0.87 to 0.98). Surf2CT establishes a new paradigm for non-invasive internal anatomical imaging using only external data, opening opportunities for home-based healthcare, preventive medicine, and personalized clinical assessments without the risks associated with conventional imaging techniques.

Cascaded 3D Diffusion Models for Whole-body 3D 18-F FDG PET/CT synthesis from Demographics

We propose a cascaded 3D diffusion model framework to synthesize high-fidelity 3D PET/CT volumes directly from demographic variables, addressing the growing need for realistic digital twins in oncologic imaging, virtual trials, and AI-driven data augmentation. Unlike deterministic phantoms, which rely on predefined anatomical and metabolic templates, our method employs a two-stage generative process. An initial score-based diffusion model synthesizes low-resolution PET/CT volumes from demographic variables alone, providing global anatomical structures and approximate metabolic activity. This is followed by a super-resolution residual diffusion model that refines spatial resolution. Our framework was trained on 18-F FDG PET/CT scans from the AutoPET dataset and evaluated using organ-wise volume and standardized uptake value (SUV) distributions, comparing synthetic and real data between demographic subgroups. The organ-wise comparison demonstrated strong concordance between synthetic and real images. In particular, most deviations in metabolic uptake values remained within 3-5% of the ground truth in subgroup analysis. These findings highlight the potential of cascaded 3D diffusion models to generate anatomically and metabolically accurate PET/CT images, offering a robust alternative to traditional phantoms and enabling scalable, population-informed synthetic imaging for clinical and research applications.

OWT: A Foundational Organ-Wise Tokenization Framework for Medical Imaging

Recent advances in representation learning often rely on holistic, black-box embeddings that entangle multiple semantic components, limiting interpretability and generalization. These issues are especially critical in medical imaging. To address these limitations, we propose an Organ-Wise Tokenization (OWT) framework with a Token Group-based Reconstruction (TGR) training paradigm. Unlike conventional approaches that produce holistic features, OWT explicitly disentangles an image into separable token groups, each corresponding to a distinct organ or semantic entity. Our design ensures each token group encapsulates organ-specific information, boosting interpretability, generalization, and efficiency while allowing fine-grained control in downstream tasks. Experiments on CT and MRI datasets demonstrate the effectiveness of OWT in not only achieving strong image reconstruction and segmentation performance, but also enabling novel semantic-level generation and retrieval applications that are out of reach for standard holistic embedding methods. These findings underscore the potential of OWT as a foundational framework for semantically disentangled representation learning, offering broad scalability and applicability to real-world medical imaging scenarios and beyond.

Prediction of Frozen Region Growth in Kidney Cryoablation Intervention Using a 3D Flow-Matching Model

This study presents a 3D flow-matching model designed to predict the progression of the frozen region (iceball) during kidney cryoablation. Precise intraoperative guidance is critical in cryoablation to ensure complete tumor eradication while preserving adjacent healthy tissue. However, conventional methods, typically based on physics driven or diffusion based simulations, are computationally demanding and often struggle to represent complex anatomical structures accurately. To address these limitations, our approach leverages intraoperative CT imaging to inform the model. The proposed 3D flow matching model is trained to learn a continuous deformation field that maps early-stage CT scans to future predictions. This transformation not only estimates the volumetric expansion of the iceball but also generates corresponding segmentation masks, effectively capturing spatial and morphological changes over time. Quantitative analysis highlights the model robustness, demonstrating strong agreement between predictions and ground-truth segmentations. The model achieves an Intersection over Union (IoU) score of 0.61 and a Dice coefficient of 0.75. By integrating real time CT imaging with advanced deep learning techniques, this approach has the potential to enhance intraoperative guidance in kidney cryoablation, improving procedural outcomes and advancing the field of minimally invasive surgery.

Pseudoinverse Diffusion Models for Generative CT Image Reconstruction from Low Dose Data

Score-based diffusion models have significantly advanced generative deep learning for image processing. Measurement conditioned models have also been applied to inverse problems such as CT reconstruction. However, the conventional approach, culminating in white noise, often requires a high number of reverse process update steps and score function evaluations. To address this limitation, we propose an alternative forward process in score-based diffusion models that aligns with the noise characteristics of low-dose CT reconstructions, rather than converging to white noise. This method significantly reduces the number of required score function evaluations, enhancing efficiency and maintaining familiar noise textures for radiologists, Our approach not only accelerates the generative process but also retains CT noise correlations, a key aspect often criticized by clinicians for deep learning reconstructions. In this work, we rigorously define a matrix-controlled stochastic process for this purpose and validate it through computational experiments. Using a dataset from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC), we simulate low-dose CT measurements and train our model, comparing it with a baseline scalar diffusion process and conditional diffusion model. Our results demonstrate the superiority of our pseudoinverse diffusion model in terms of efficiency and the ability to produce high-quality reconstructions that are familiar in texture to medical professionals in a low number of score function evaluations. This advancement paves the way for more efficient and clinically practical diffusion models in medical imaging, particularly beneficial in scenarios demanding rapid reconstructions or lower radiation exposure.

Rethinking Visual Counterfactual Explanations Through Region Constraint

Visual counterfactual explanations (VCEs) have recently gained immense popularity as a tool for clarifying the decision-making process of image classifiers. This trend is largely motivated by what these explanations promise to deliver -- indicate semantically meaningful factors that change the classifier's decision. However, we argue that current state-of-the-art approaches lack a crucial component -- the region constraint -- whose absence prevents from drawing explicit conclusions, and may even lead to faulty reasoning due to phenomenons like confirmation bias. To address the issue of previous methods, which modify images in a very entangled and widely dispersed manner, we propose region-constrained VCEs (RVCEs), which assume that only a predefined image region can be modified to influence the model's prediction. To effectively sample from this subclass of VCEs, we propose Region-Constrained Counterfactual Schr\"odinger Bridges (RCSB), an adaptation of a tractable subclass of Schr\"odinger Bridges to the problem of conditional inpainting, where the conditioning signal originates from the classifier of interest. In addition to setting a new state-of-the-art by a large margin, we extend RCSB to allow for exact counterfactual reasoning, where the predefined region contains only the factor of interest, and incorporating the user to actively interact with the RVCE by predefining the regions manually.

Hallucination Index: An Image Quality Metric for Generative Reconstruction Models

Generative image reconstruction algorithms such as measurement conditioned diffusion models are increasingly popular in the field of medical imaging. These powerful models can transform low signal-to-noise ratio (SNR) inputs into outputs with the appearance of high SNR. However, the outputs can have a new type of error called hallucinations. In medical imaging, these hallucinations may not be obvious to a Radiologist but could cause diagnostic errors. Generally, hallucination refers to error in estimation of object structure caused by a machine learning model, but there is no widely accepted method to evaluate hallucination magnitude. In this work, we propose a new image quality metric called the hallucination index. Our approach is to compute the Hellinger distance from the distribution of reconstructed images to a zero hallucination reference distribution. To evaluate our approach, we conducted a numerical experiment with electron microscopy images, simulated noisy measurements, and applied diffusion based reconstructions. We sampled the measurements and the generative reconstructions repeatedly to compute the sample mean and covariance. For the zero hallucination reference, we used the forward diffusion process applied to ground truth. Our results show that higher measurement SNR leads to lower hallucination index for the same apparent image quality. We also evaluated the impact of early stopping in the reverse diffusion process and found that more modest denoising strengths can reduce hallucination. We believe this metric could be useful for evaluation of generative image reconstructions or as a warning label to inform radiologists about the degree of hallucinations in medical images.