Gagandeep Singh

Jason Vega, Gagandeep Singh

A frustratingly easy technique known as the prefilling attack has been shown to effectively circumvent the safety alignment of frontier LLMs by simply prefilling the assistant response with an affirmative prefix before decoding. In response, recent work proposed a supervised fine-tuning (SFT) defense using data augmentation to achieve a \enquote{deep} safety alignment, allowing the model to generate natural language refusals immediately following harmful prefills. Unfortunately, we show in this work that the "deep" safety alignment produced by such an approach is in fact not very deep. A generalization of the prefilling attack, which we refer to as the Rank-Assisted Prefilling (RAP) attack, can effectively extract harmful content from models fine-tuned with the data augmentation defense by selecting low-probability "harmful" tokens from the top 20 predicted next tokens at each step (thus ignoring high-probability "refusal" tokens). We argue that this vulnerability is enabled due to the "gaming" of the SFT objective when the target distribution entropies are low, where low fine-tuning loss is achieved by shifting large probability mass to a small number of refusal tokens while neglecting the high ranks of harmful tokens. We then propose a new perspective on achieving deep safety alignment by matching the token ranks of the target distribution, rather than their probabilities. This perspective yields a surprisingly simple fix to the data augmentation defense based on regularizing the attention placed on harmful prefill tokens, an approach we call PRefill attEntion STOpping (PRESTO). Adding PRESTO yields up to a 4.7x improvement in the mean StrongREJECT score under RAP attacks across three popular open-source LLMs, with low impact to model utility.

Fan Wang, Zhilin Zou, Nicole Sakla et al.

Characterization of breast parenchyma in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a challenging task owing to the complexity of underlying tissue structures. Existing quantitative approaches, like radiomics and deep learning models, lack explicit quantification of intricate and subtle parenchymal structures, including fibroglandular tissue. To address this, we propose a novel topological approach that explicitly extracts multi-scale topological structures to better approximate breast parenchymal structures, and then incorporates these structures into a deep-learning-based prediction model via an attention mechanism. Our topology-informed deep learning model, \emph{TopoTxR}, leverages topology to provide enhanced insights into tissues critical for disease pathophysiology and treatment response. We empirically validate \emph{TopoTxR} using the VICTRE phantom breast dataset, showing that the topological structures extracted by our model effectively approximate the breast parenchymal structures. We further demonstrate \emph{TopoTxR}'s efficacy in predicting response to neoadjuvant chemotherapy. Our qualitative and quantitative analyses suggest differential topological behavior of breast tissue in treatment-naïve imaging, in patients who respond favorably to therapy as achieving pathological complete response (pCR) versus those who do not. In a comparative analysis with several baselines on the publicly available I-SPY 1 dataset (N=161, including 47 patients with pCR and 114 without) and the Rutgers proprietary dataset (N=120, with 69 patients achieving pCR and 51 not), \emph{TopoTxR} demonstrates a notable improvement, achieving a 2.6\% increase in accuracy and a 4.6\% enhancement in AUC compared to the state-of-the-art method.

Moinak Bhattacharya, Judy Huang, Amna F. Sher et al.

Accurately predicting immunotherapy response in Non-Small Cell Lung Cancer (NSCLC) remains a critical unmet need. Existing radiomics and deep learning-based predictive models rely primarily on pre-treatment imaging to predict categorical response outcomes, limiting their ability to capture the complex morphological and textural transformations induced by immunotherapy. This study introduces ImmunoDiff, an anatomy-aware diffusion model designed to synthesize post-treatment CT scans from baseline imaging while incorporating clinically relevant constraints. The proposed framework integrates anatomical priors, specifically lobar and vascular structures, to enhance fidelity in CT synthesis. Additionally, we introduce a novel cbi-Adapter, a conditioning module that ensures pairwise-consistent multimodal integration of imaging and clinical data embeddings, to refine the generative process. Additionally, a clinical variable conditioning mechanism is introduced, leveraging demographic data, blood-based biomarkers, and PD-L1 expression to refine the generative process. Evaluations on an in-house NSCLC cohort treated with immune checkpoint inhibitors demonstrate a 21.24% improvement in balanced accuracy for response prediction and a 0.03 increase in c-index for survival prediction. Code will be released soon.

Moinak Bhattacharya, Saumya Gupta, Annie Singh et al.

Accurate brain tumor diagnosis relies on the assessment of multiple Magnetic Resonance Imaging (MRI) sequences. However, in clinical practice, the acquisition of certain sequences may be affected by factors like motion artifacts or contrast agent contraindications, leading to suboptimal outcome, such as poor image quality. This can then affect image interpretation by radiologists. Synthesizing high quality MRI sequences has thus become a critical research focus. Though recent advancements in controllable generative AI have facilitated the synthesis of diagnostic quality MRI, ensuring anatomical accuracy remains a significant challenge. Preserving critical structural relationships between different anatomical regions is essential, as even minor structural or topological inconsistencies can compromise diagnostic validity. In this work, we propose BrainMRDiff, a novel topology-preserving, anatomy-guided diffusion model for synthesizing brain MRI, leveraging brain and tumor anatomies as conditioning inputs. To achieve this, we introduce two key modules: Tumor+Structure Aggregation (TSA) and Topology-Guided Anatomy Preservation (TGAP). TSA integrates diverse anatomical structures with tumor information, forming a comprehensive conditioning mechanism for the diffusion process. TGAP enforces topological consistency during reverse denoising diffusion process; both these modules ensure that the generated image respects anatomical integrity. Experimental results demonstrate that BrainMRDiff surpasses existing baselines, achieving performance improvements of 23.33% on the BraTS-AG dataset and 33.33% on the BraTS-Met dataset. Code will be made publicly available soon.

Moinak Bhattacharya, Gagandeep Singh, Prateek Prasanna

Accurately modeling the spatiotemporal evolution of tumor morphology from baseline imaging is a pre-requisite for developing digital twin frameworks that can simulate disease progression and treatment response. Most existing approaches primarily characterize tumor growth while neglecting the concomitant alterations in adjacent anatomical structures. In reality, tumor evolution is highly non-linear and heterogeneous, shaped not only by therapeutic interventions but also by its spatial context and interaction with neighboring tissues. Therefore, it is critical to model tumor progression in conjunction with surrounding anatomy to obtain a comprehensive and clinically relevant understanding of disease dynamics. We introduce a mathematically grounded framework that unites mechanistic partial differential equations with differentiable deep learning. Anatomy is represented as a multi-class probability field on the simplex and evolved by a cross-diffusion reaction-diffusion system that enforces inter-class competition and exclusivity. A differentiable implicit-explicit scheme treats stiff diffusion implicitly while handling nonlinear reaction and event terms explicitly, followed by projection back to the simplex. To further enhance global plausibility, we introduce a topology regularizer that simultaneously enforces centerline preservation and penalizes region overlaps. The approach is validated on synthetic datasets and a clinical dataset. On synthetic benchmarks, our method achieves state-of-the-art accuracy while preserving topology, and also demonstrates superior performance on the clinical dataset. By integrating PDE dynamics, topology-aware regularization, and differentiable solvers, this work establishes a principled path toward anatomy-to-anatomy generation for digital twins that are visually realistic, anatomically exclusive, and topologically consistent.

Moinak Bhattacharya, Angelica P. Kurtz, Fabio M. Iwamoto et al.

Neuro-oncology poses unique challenges for machine learning due to heterogeneous data and tumor complexity, limiting the ability of foundation models (FMs) to generalize across cohorts. Existing FMs also perform poorly in predicting uncommon molecular markers, which are essential for treatment response and risk stratification. To address these gaps, we developed a neuro-oncology specific FM with a distributionally robust loss function, enabling accurate estimation of tumor phenotypes while maintaining cross-institution generalization. We pretrained self-supervised backbones (BYOL, DINO, MAE, MoCo) on multi-institutional brain tumor MRI and applied distributionally robust optimization (DRO) to mitigate site and class imbalance. Downstream tasks included molecular classification of common markers (MGMT, IDH1, 1p/19q, EGFR), uncommon alterations (ATRX, TP53, CDKN2A/2B, TERT), continuous markers (Ki-67, TP53), and overall survival prediction in IDH1 wild-type glioblastoma at UCSF, UPenn, and CUIMC. Our method improved molecular prediction and reduced site-specific embedding differences. At CUIMC, mean balanced accuracy rose from 0.744 to 0.785 and AUC from 0.656 to 0.676, with the largest gains for underrepresented endpoints (CDKN2A/2B accuracy 0.86 to 0.92, AUC 0.73 to 0.92; ATRX AUC 0.69 to 0.82; Ki-67 accuracy 0.60 to 0.69). For survival, c-index improved at all sites: CUIMC 0.592 to 0.597, UPenn 0.647 to 0.672, UCSF 0.600 to 0.627. Grad-CAM highlighted tumor and peri-tumoral regions, confirming interpretability. Overall, coupling FMs with DRO yields more site-invariant representations, improves prediction of common and uncommon markers, and enhances survival discrimination, underscoring the need for prospective validation and integration of longitudinal and interventional signals to advance precision neuro-oncology.

Joseph Bae, Saarthak Kapse, Gagandeep Singh et al.

We predict mechanical ventilation requirement and mortality using computational modeling of chest radiographs (CXRs) for coronavirus disease 2019 (COVID-19) patients. This two-center, retrospective study analyzed 530 deidentified CXRs from 515 COVID-19 patients treated at Stony Brook University Hospital and Newark Beth Israel Medical Center between March and August 2020. DL and machine learning classifiers to predict mechanical ventilation requirement and mortality were trained and evaluated using patient CXRs. A novel radiomic embedding framework was also explored for outcome prediction. All results are compared against radiologist grading of CXRs (zone-wise expert severity scores). Radiomic and DL classification models had mAUCs of 0.78+/-0.02 and 0.81+/-0.04, compared with expert scores mAUCs of 0.75+/-0.02 and 0.79+/-0.05 for mechanical ventilation requirement and mortality prediction, respectively. Combined classifiers using both radiomics and expert severity scores resulted in mAUCs of 0.79+/-0.04 and 0.83+/-0.04 for each prediction task, demonstrating improvement over either artificial intelligence or radiologist interpretation alone. Our results also suggest instances where inclusion of radiomic features in DL improves model predictions, something that might be explored in other pathologies. The models proposed in this study and the prognostic information they provide might aid physician decision making and resource allocation during the COVID-19 pandemic.

Marwa Ismail, Virginia Hill, Volodymyr Statsevych et al.

A significant challenge in Glioblastoma (GBM) management is identifying pseudo-progression (PsP), a benign radiation-induced effect, from tumor recurrence, on routine imaging following conventional treatment. Previous studies have linked tumor lobar presence and laterality to GBM outcomes, suggesting that disease etiology and progression in GBM may be impacted by tumor location. Hence, in this feasibility study, we seek to investigate the following question: Can tumor location on treatment-naïve MRI provide early cues regarding likelihood of a patient developing pseudo-progression versus tumor recurrence? In this study, 74 pre-treatment Glioblastoma MRI scans with PsP (33) and tumor recurrence (41) were analyzed. First, enhancing lesion on Gd-T1w MRI and peri-lesional hyperintensities on T2w/FLAIR were segmented by experts and then registered to a brain atlas. Using patients from the two phenotypes, we construct two atlases by quantifying frequency of occurrence of enhancing lesion and peri-lesion hyperintensities, by averaging voxel intensities across the population. Analysis of differential involvement was then performed to compute voxel-wise significant differences (p-value<0.05) across the atlases. Statistically significant clusters were finally mapped to a structural atlas to provide anatomic localization of their location. Our results demonstrate that patients with tumor recurrence showed prominence of their initial tumor in the parietal lobe, while patients with PsP showed a multi-focal distribution of the initial tumor in the frontal and temporal lobes, insula, and putamen. These preliminary results suggest that lateralization of pre-treatment lesions towards certain anatomical areas of the brain may allow to provide early cues regarding assessing likelihood of occurrence of pseudo-progression from tumor recurrence on MRI scans.