Human Knowledge Integrated Multi-modal Learning for Single Source Domain Generalization
Organizations: Impact Lab, Arizona State University
Abstract
Generalizing image classification across domains remains challenging in critical tasks such as fundus image-based diabetic retinopathy (DR) grading and resting-state fMRI seizure onset zone (SOZ) detection. When domains differ in unknown causal factors, achieving cross-domain generalization is difficult, and there is no established methodology to objectively assess such differences without direct metadata or protocol-level information from data collectors, which is typically inaccessible. We first introduce domain conformal bounds (DCB), a theoretical framework to evaluate whether domains diverge in unknown causal factors. Building on this, we propose GenEval, a multimodal Vision Language Models (VLM) approach that combines foundational models (e.g., MedGemma-4B) with human knowledge via Low-Rank Adaptation (LoRA) to bridge causal gaps and enhance single-source domain generalization (SDG). Across eight DR and two SOZ datasets, GenEval achieves superior SDG performance, with average accuracy of 69.2% (DR) and 81% (SOZ), outperforming the strongest baselines by 9.4% and 1.8%, respectively.
Figures & tables
| Method | Aptos | EyePACS | Messidor | Messidor 2 | p value |
|---|---|---|---|---|---|
| MMD [ 51 ] | 49.3 1.0 | 69.3 1.1 | 64.1 4.8 | 69.6 0.6 | 0.3 |
| CDANN [ 52 ] | 48.1 0.7 | 73.1 0.3 | 55.8 1.8 | 61.2 1.3 | 0.9 |
| SD-ViT [ 73 ] | 46.5 0.8 | 71.1 0.7 | 63.9 0.9 | 71.4 0.2 | 0.2 |
| SPSD-ViT [ 27 ] | 51.6 1.1 | 73.3 0.4 | 64.0 1.4 | 72.9 0.1 | 0.09 |
| ERM-ViT [ 75 ] | 48.5 0.9 | 70.7 1.7 | 62.7 1.6 | 69.5 2.5 | NA |
| GenEval (Ours) | 73.46 | 83.18 | 67.70 | 79.64 |
| Key LoRA hyperparameters |
| Adapter rank ( ) = 16; scaling factor ( ) = 16; LoRA dropout = 0.05; target modules = { q_proj, k_proj, v_proj, o_proj, up_proj, down_proj, gate_proj }; modules to save = { lm_head, embed_tokens }; trainable params = 95M (2.4% of 4B); task type = CAUSAL_LM . |
| Training time (hh:mm:ss) |
| Single domain: A = 01:03:35; E = 10:14:20; M1 = 00:20:41; M2 = 00:34:11. |
| Multi domain: A+E+M1 = 12:01:30; A+E+M2 = 12:23:19; A+M1+M2 = 01:58:43; E+M1+M2 = 11:18:07. |
| Inference time |
| Single domain: 423.96 ± 33.52 ms [383.14, 458.72]; Multi domain: 385.46 ± 29.24 ms [359.71, 427.35]. |
| Sou rce | Target | Best Baseline | Baseline Accuracy | K SDCD | D SDCD | GenEval | K + D SDCD |
|---|---|---|---|---|---|---|---|
| Mess | Aptos | SPSD-ViT [ 27 ] | 48.3 % | 92.7% | 16% | 56.0% | 98.03% |
| idor | Messidor2 | SPSD-ViT [ 27 ] | 62.2% | 99.1% | 87.1% | 65.18% | 99.14% |
| EyePACS | SPSD-ViT [ 27 ] | 57.4% | 17.02% | 36.4% | 80.04% | 94.94% | |
| Mess | Aptos | SPSD-ViT [ 27 ] | 52.8% | 32.1 % | 17.7% | 69.69% | 76.3% |
| idor2 | Messidor | SD-ViT [ 73 ] | 61.0% | 99.9% | 98.2% | 67.67% | 100.00% |
| EyePACS | SPSD-ViT [ 27 ] | 72.5% | 34.6% | 41.31% | 77.79% | 96.34% |
| Ablation | SDCD (%) | Accuracy (%) |
|---|---|---|
| no ablation | 59.000 | 65.01 |
| remove microaneurysms | 68.000 | 70.02 |
| remove hemorrhages, or exudates | 71.683 | 71.05 |
| remove venous beading | 82.765 | 73.21 |
| remove Neovascularization | 82.81 | 73.23 |
| Method | APTOS | Messidor | IDRiD | DeepDR | FGADR | RLDL | Avg |
|---|---|---|---|---|---|---|---|
| GDRNet | 52.8 | 65.7 | 70.0 | 40.0 | 7.5 | 44.3 | 46.7 |
| DECO | 59.7 | 70.1 | 74.8 | 40.3 | 9.9 | 49.3 | 50.68 |
| GenEval | 73.2 | 69.5 | 70.6 | 59.2 | 56.9 | 67.6 | 66.2 |
| VLM Method | APTOS | Messidor | Average |
|---|---|---|---|
| CLIP [ 64 ] | 44.3 | 39.6 | 41.9 |
| OrdinalCLIP [ 45 ] | 45.7 | 41.8 | 43.8 |
| CLIP-DR [ 87 ] | 46.3 | 47.3 | 46.8 |
| GenEval- (Ours) | 72.0 | 78.2 | 75.1 |
| Source | Target | CuPKL [ 37 ] | CuPKL Avg | GenEval | GenEval Avg |
|---|---|---|---|---|---|
| PCH | UNC | 82.3 | 88.1 | 91.0 | 90 |
| UNC | PCH | 93.8 | 89.0 |
| Dataset | Accuracy (%) | F1-Score (%) | Recall (%) |
|---|---|---|---|
| APTOS | 61.80 | 60.25 | 62.15 |
| EyePACS | 79.66 | 77.61 | 78.95 |
| Messidor | 67.92 | 67.58 | 69.44 |
| Messidor-2 | 77.52 | 75.78 | 76.71 |
| Average | 71.73 | 70.31 | 71.31 |
| Symptom | Key Observations and Diagnostic Relevance |
|---|---|
| Microaneurysms | Tiny red capillary dilations in the retina; earliest sign of mild NPDR. Their progression correlates with disease severity [ 9 ] . |
| Hemorrhages | Includes dark red dot/blot and flame-shaped types indicating microvascular leakage. Severe NPDR is marked by more than 20 hemorrhages in all quadrants; risk of PDR rises to 50% within a year [ 83 ] . |
| Hard Exudates | Sharp yellow lipid-rich deposits from chronic leakage, often in/near the macula. Indicative of risk for diabetic macular edema (DME), a major cause of vision loss [ 30 ] . |
| Cotton Wool Spots | Fluffy white retinal lesions caused by nerve-fiber-layer infarctions. Signify retinal ischemia in moderate to severe NPDR [ 72 ] . |
| Subhyaloid Hemorrhages | Boat- or D-shaped hemorrhages between the retina and the hyaloid face, typically from ruptured neovascular vessels. Hallmark of proliferative DR [ 12 ] . |
| Neovascularization | Fragile new vessel growth on the optic disc (NVD) or elsewhere on the retina (NVE). Defining trait of PDR; untreated cases face 60% vision loss within five years [ 22 ] . |
| Dataset | Micro. | Hemorr. | Exud. | Composite |
|---|---|---|---|---|
| APTOS | 42.3 5.1 | 48.6 4.7 | 61.2 5.4 | 51.0 4.2 |
| EyePACS | 46.1 4.3 | 54.0 4.9 | 65.8 5.0 | 55.2 4.1 |
| Messidor | 44.7 5.6 | 50.2 5.1 | 63.1 5.5 | 53.0 4.6 |
| Messidor-2 | 49.0 4.8 | 56.3 4.5 | 68.4 4.7 | 57.0 3.9 |
| Mean | 45.5 | 52.3 | 64.6 | 54.1 |
| Method | EyePACS | Messidor | Messidor-2 | Average |
|---|---|---|---|---|
| DRGen [ 6 ] | 67.5 1.8 | 46.7 0.1 | 61.0 0.1 | 58.4 |
| ERM-ViT [ 75 ] | 67.8 1.4 | 45.5 0.2 | 58.8 0.4 | 57.3 |
| SD-ViT [ 73 ] | 72.0 0.8 | 45.4 0.1 | 58.5 0.2 | 58.6 |
| SPSD-ViT [ 27 ] | 71.4 0.8 | 45.6 0.1 | 58.8 0.2 | 58.6 |
| GenEval (Ours) | 77.8 0.8 | 49.0 0.2 | 64.0 0.2 | 63.6 |
| p value | 0.01 | 0.04 | 0.02 | 0.01 |
| Method | APTOS | EyePACS | Messidor-2 | Average |
|---|---|---|---|---|
| DRGen [ 6 ] | 41.7 4.3 | 43.1 7.9 | 44.8 0.9 | 43.2 |
| ERM-ViT [ 75 ] | 45.3 1.3 | 52.4 3.2 | 58.2 3.2 | 51.9 |
| SD-ViT [ 73 ] | 44.3 0.9 | 53.2 1.6 | 57.8 2.4 | 51.7 |
| SPSD-ViT [ 27 ] | 48.3 1.1 | 57.4 2.1 | 62.2 1.6 | 55.9 |
| GenEval (Ours) | 56.0 0.8 | 80.0 2.1 | 65.2 2.4 | 67.1 |
| p value | 0.01 | 0.01 | 0.03 | 0.01 |
| Method | APTOS | EyePACS | Messidor | Average |
|---|---|---|---|---|
| DRGen [ 6 ] | 40.9 3.9 | 69.3 1.0 | 61.3 0.8 | 57.7 |
| ERM-ViT [ 75 ] | 47.9 2.1 | 67.4 0.9 | 59.6 3.9 | 58.3 |
| SD-ViT [ 73 ] | 51.8 0.9 | 68.7 0.6 | 62.0 1.7 | 60.8 |
| SPSD-ViT [ 27 ] | 52.8 2.0 | 72.5 0.3 | 61.0 0.8 | 62.1 |
| GenEval (Ours) | 69.7 1.8 | 77.8 0.3 | 67.7 0.8 | 71.7 |
| p value | 0.01 | 0.03 | 0.02 | 0.01 |
| Symptom | Key Observations and Diagnostic Relevance |
|---|---|
| Single Activation | Large, isolated activation region; primary indicator of epileptogenic focus [ 36 ] . |
| Gray Matter Activation | Activation primarily in gray matter with minimal white matter overlap; characteristic neuronal seizure activity [ 36 ] . |
| Hemispheric Asymmetry | Unilateral or asymmetric activation patterns; seizure foci show lateralized activity [ 36 ] . |
| Temporal Consistency | Persistent activation patterns across multiple time points; epileptogenic regions maintain consistent activity [ 36 ] . |
| Network Isolation | Activation distinct from resting-state networks (RSN); independence indicates pathological activity [ 36 ] . |
| Spatial Localization | Focal activation confined to specific anatomical regions; spatially constrained patterns [ 36 ] . |
| Method | Acc (%) | Prec (%) | Rec (%) | F1 (%) |
|---|---|---|---|---|
| PCH | ||||
| CuPKL GPT-4o | 88.4 | 93.8 | 93.8 | 93.8 |
| GenEval | 81.0 | 93.0 | 86.0 | 89.0 |
| UNC | ||||
| CuPKL GPT-4o | 70.0 | 90.3 | 75.0 | 82.3 |
| GenEval | 83.0 | 93.0 | 88.0 | 91.0 |
| Source | Target | K SDCD (%) | D SDCD (%) | GenEval Acc. (%) |
|---|---|---|---|---|
| Messidor | APTOS | 93.10 | 16.00 | 56.20 |
| Messidor | Messidor2 | 98.70 | 87.10 | 65.10 |
| Messidor | EyePACS | 22.00 | 36.40 | 80.20 |
| Messidor2 | APTOS | 30.50 | 17.70 | 69.60 |
| Messidor2 | Messidor | 99.60 | 98.20 | 67.70 |
| Messidor2 | EyePACS | 38.20 | 41.31 | 77.90 |