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Dasari Naga Raju

Publications and source records attributed to Dasari Naga Raju.

6 recordsLinked to original sources

TIRA: Tumor Immune Representation Adaptation for Zero-Shot Cross-Cancer MSI and TMB Prediction

Microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB-H) are clinically relevant biomarkers, yet their histopathological prediction remains challenging when models are transferred across morphologically distinct cancer types. Immune-associated spatial patterns can persist across cancers despite these morphological differences, but foundation-model-based predictors trained on a single cancer do not explicitly use this information, limiting cross-cancer generalization. To address this limitation, we propose TIRA (Tumor Immune Representation Adaptation), a target-free framework that refines frozen foundation-model representations using spatial immune topology, without requiring target-domain data during model development or test-time adaptation. TIRA uses a topology-supervised biology representation to condition tile-level attention while pooling only morphological features for joint MSI and TMB prediction. We train TIRA on TCGA-COAD+READ and evaluate it zero-shot on CPTAC-COAD, TCGA-STAD, TCGA-UCEC, and CPTAC-UCEC, covering cross-site, cross-cancer, and combined cross-cancer-site distribution shifts under UNI2, CONCH, and Virchow2. With UNI2, TIRA improved zero-shot AUROC on TCGA-STAD from 0.633 to 0.766 for MSI and from 0.651 to 0.772 for TMB. Source-derived spatial immune topology improved the cross-cancer robustness of frozen pathology foundation-model representations.

cs.CV↗

State-Aware Interaction MIL for Rare Joint Molecular Phenotype Prediction in Colorectal Cancer and Lung Adenocarcinoma

Joint molecular phenotype prediction is complicated by small joint-positive populations and overlapping histological features across alternative molecular states. Existing computational pathology approaches typically predict biomarkers independently or formulate the joint-positive phenotype as a binary endpoint. Independent prediction does not model interactions between biomarker-specific histological representations, whereas binary joint prediction collapses the double-negative and two single-positive configurations into a single negative class. We propose State-Aware Interaction MIL, a weakly supervised method that preserves biomarker-specific histological representations, models their interaction, and supervises the complete four-state molecular configuration. We evaluate the proposed approach for joint BRAF+/MSI+ prediction in colorectal cancer and EGFR+/TP53+ prediction in lung adenocarcinoma using frozen UNI2-h and CONCH pathology foundation-model representations. With UNI2-h, State-Aware Interaction MIL achieved an average precision of 0.5566 in colorectal cancer (joint-positive prevalence 6.8%) compared with 0.5161 for NaiveMTL, and 0.2784 in lung adenocarcinoma (joint-positive prevalence 8.6%) compared with 0.2525 for IndependentPair. With CONCH, State-Aware achieved an average precision of 0.4410 compared with 0.3932 for DirectJoint in colorectal cancer and 0.1659 compared with 0.1226 for DirectJoint in lung adenocarcinoma. These results indicate that pathology foundation-model representations contain predictive information for rare joint molecular phenotypes and that preserving biomarker-specific representations within a structured molecular-state formulation can improve prediction of these phenotypes from histopathology.

cs.CV↗

Conserved Immune Topology Improves Pathology Foundation Model Generalization for Cross-Cancer MSI-H Prediction

Pathology foundation models integrated with multiple instance learning achieve competitive accuracy within single-cancer cohorts, yet cross-cancer generalization remains unresolved due to organ-specific histological and architectural differences. In this paper, we propose Conserved Immune Topology (CIT), a lightweight spatial representation for cross-cancer MSI-H prediction that augments foundation-model embeddings with biologically motivated immune descriptors. CIT uses unsupervised clustering to identify immune-associated tiles, then encodes tertiary lymphoid structures, peritumoral immune reactions, multi-scale tumor-infiltrating lymphocyte density, and immune-tumor mixing from frozen foundation-model embeddings and tile coordinates without requiring annotations or target-domain data. The proposed method was evaluated under cross-site and cross-cancer settings using CPTAC-COAD and TCGA-STAD cohorts, which introduce scanner variability, distribution shifts, and organ-specific architectural variations. Zero-shot cross-cancer transfer with CIT increased TransMIL AUC from 0.6627 to 0.7161, an absolute gain of 0.0534 (p=0.003), with consistent improvements across all three MIL aggregators. These results suggest that spatial immune topology provides potentially an organ-invariant representation for MSI-H prediction, supporting cross-cancer generalization of pathology foundation models.

cs.CV↗

GD-MIL: Grade-Disentangled Multiple Instance Learning for Multimodal Biochemical Recurrence Prediction in Prostate Cancer

Biochemical recurrence (BCR) after radical prostatectomy is a critical endpoint in prostate cancer, yet risk stratification relies almost entirely on variables dominated by Gleason grade. Whether H&E whole slide images (WSIs) carry prognostic signal beyond grade, and whether multiple instance learning (MIL) can recover it, remains unsettled. A key obstacle is that many pipelines select model checkpoints on the evaluation fold, artificially inflating concordance. We construct a rigorous benchmark on TCGA-PRAD (487 patients, 101 BCR events) using strict out-of-fold scoring over five-fold cross-validation repeated across five seeds. The choice of MIL aggregator (ABMIL, CLAM, TransMIL, PatchGCN) has little effect (C-index 0.61-0.64 with UNI2-h), while the feature extractor is the dominant factor (ResNet50 0.566 versus pathology foundation models up to 0.639). A clinical Cox model on grade, stage, and age reaches 0.687; no imaging-only model significantly outperforms it (p > 0.10). We introduce Grade-Disentangled MIL (GD-MIL), a gated-attention MIL encoder trained with a gradient-reversal grade adversary that encourages the slide representation to be invariant to Gleason grade before late fusion with clinical variables. GD-MIL achieves C-index 0.704, significantly outperforming both the clinical baseline (delta-c = +0.029, p = 0.0005) and the best imaging-only model (delta-c = +0.062, p = 0.039), suggesting H&E morphology contains prognostic information complementary to grade. A median risk split yields log-rank p < 0.0001 separation in BCR-free survival (~20% vs ~70% at five years).

cs.CV↗

Biological Spatial Priors Regularize Foundation Model Representations for Cross-Site MSI Generalization in Colorectal Cancer

Predicting microsatellite instability (MSI) status from routine hematoxylin and eosin (H&E) whole slide images (WSIs) offers a practical alternative to molecular testing, but models trained at one institution tend to generalize poorly to slides acquired at a different site. Foundation model representations, despite their generality, still encode site-specific texture alongside the conserved biological morphology underlying MSI. We investigate whether tile-level spatial priors derived from known MSI histology can guide these representations toward more site-invariant features. We introduce a biologically motivated spatial prior based on peripheral distance encoding, reflecting the Crohn's-like peripheral lymphocytic reaction at the tumor invasive margin, and evaluate a secondary local immune neighborhood encoding reflecting the lymphocyte-to-tumor ratio in each tile's immediate spatial neighborhood. Both priors are injected into a TransMIL aggregator before self-attention, allowing the transformer to integrate spatial biological context with UNI2-h or Virchow2 features across all attention layers. We evaluate six foundation model and MIL aggregator combinations as a reference, then assess the effect of each spatial prior. Training on TCGA-COAD (137 slides) and evaluating externally on TCGA-READ (50 slides) without retraining, peripheral distance encoding achieves MSI AUC 0.959 +/- 0.012 on COAD and MSS specificity 1.000 on READ, compared to 0.957 and 0.939 for the strongest reference configuration. Local immune neighborhood encoding achieves comparable internal AUC but lower cross-site specificity, suggesting margin proximity encodes a more site-invariant biological signal than local immune density. Results suggest biologically grounded spatial priors act as regularizers that reduce reliance on site-specific imaging patterns.

eess.IV↗

Exploring Self-Supervised Learning with U-Net Masked Autoencoders and EfficientNet-B7 for Improved Gastrointestinal Abnormality Classification in Video Capsule Endoscopy

Video Capsule Endoscopy (VCE) has become an indispensable diagnostic tool for gastrointestinal (GI) disorders due to its non-invasive nature and ability to capture high-resolution images of the small intestine. However, the enormous volume of data generated during a single procedure makes manual inspection labor-intensive, time-consuming, and prone to inter-observer variability. Automated analysis using deep learning offers a promising solution, but its effectiveness is often limited by data imbalance and the high cost of labeled medical data. In this work, we propose a novel framework that combines self-supervised learning through a U-Net-based masked autoencoder with supervised feature extraction using EfficientNet-B7 for multi-class abnormality classification in VCE images. The U-Net model is first trained in a self-supervised manner using Gaussian noise removal and masked reconstruction to learn robust visual representations without requiring annotations. The learned encoder features are then fused with EfficientNet-B7 features to form a rich, discriminative representation for classification. We evaluate our approach on the Capsule Vision 2024 Challenge dataset consisting of ten abnormality classes and a dominant normal class. Experimental results demonstrate that the proposed fusion framework achieves a validation accuracy of 94\%, outperforming standalone architectures and attention-based fusion variants. The study highlights the effectiveness of self-supervised representation learning and feature fusion in addressing class imbalance and improving diagnostic accuracy in real-world medical imaging scenarios.

cs.CV↗