Li Ma

Wanling Gao, Yunyou Huang, Dandan Cui et al.

A profound gap persists between artificial intelligence (AI) and clinical practice in medicine, primarily due to the lack of rigorous and cost-effective evaluation methodologies. State-of-the-art and state-of-the-practice AI model evaluations are limited to laboratory studies on medical datasets or direct clinical trials with no or solely patient-centered controls. Moreover, the crucial role of clinicians in collaborating with AI, pivotal for determining its impact on clinical practice, is often overlooked. For the first time, we emphasize the critical necessity for rigorous and cost-effective evaluation methodologies for AI models in clinical practice, featuring patient/clinician-centered (dual-centered) AI randomized controlled trials (DC-AI RCTs) and virtual clinician-based in-silico trials (VC-MedAI) as an effective proxy for DC-AI RCTs. Leveraging 7500 diagnosis records from two-step inaugural DC-AI RCTs across 14 medical centers with 125 clinicians, our results demonstrate the necessity of DC-AI RCTs and the effectiveness of VC-MedAI. Notably, VC-MedAI performs comparably to human clinicians, replicating insights and conclusions from prospective DC-AI RCTs. We envision DC-AI RCTs and VC-MedAI as pivotal advancements, presenting innovative and transformative evaluation methodologies for AI models in clinical practice, offering a preclinical-like setting mirroring conventional medicine, and reshaping development paradigms in a cost-effective and fast-iterative manner. Chinese Clinical Trial Registration: ChiCTR2400086816.

Qiuli Wang, Yongxu Liu, Li Ma et al.

Histological Tertiary Lymphoid Structures (TLSs) are increasingly recognized for their correlation with the efficacy of immunotherapy in various solid tumors. Traditionally, the identification and characterization of TLSs rely on immunohistochemistry (IHC) staining techniques, utilizing markers such as CD20 for B cells. Despite the specificity of IHC, Hematoxylin-Eosin (H&E) staining offers a more accessible and cost-effective choice. Capitalizing on the prevalence of H&E staining slides, we introduce a novel Mask-Guided Adversarial Transfer Learning method designed for virtual pathological staining. This method adeptly captures the nuanced color variations across diverse tissue types under various staining conditions, such as nucleus, red blood cells, positive reaction regions, without explicit label information, and adeptly synthesizes realistic IHC-like virtual staining patches, even replicating the positive reaction. Further, we propose the Virtual IHC Pathology Analysis Network (VIPA-Net), an integrated framework encompassing a Mask-Guided Transfer Module and an H&E-Based Virtual Staining TLS Detection Module. VIPA-Net synergistically harnesses both H\&E staining slides and the synthesized virtual IHC patches to enhance the detection of TLSs within H&E Whole Slide Images (WSIs). We evaluate the network with a comprehensive dataset comprising 1019 annotated slides from The Cancer Genome Atlas (TCGA). Experimental results compellingly illustrate that the VIPA-Net substantially elevates TLS detection accuracy, effectively circumventing the need for actual CD20 staining across the public dataset.

Guangyao Chen, Peixi Peng, Li Ma et al.

Recently, the generalization behavior of Convolutional Neural Networks (CNN) is gradually transparent through explanation techniques with the frequency components decomposition. However, the importance of the phase spectrum of the image for a robust vision system is still ignored. In this paper, we notice that the CNN tends to converge at the local optimum which is closely related to the high-frequency components of the training images, while the amplitude spectrum is easily disturbed such as noises or common corruptions. In contrast, more empirical studies found that humans rely on more phase components to achieve robust recognition. This observation leads to more explanations of the CNN's generalization behaviors in both robustness to common perturbations and out-of-distribution detection, and motivates a new perspective on data augmentation designed by re-combing the phase spectrum of the current image and the amplitude spectrum of the distracter image. That is, the generated samples force the CNN to pay more attention to the structured information from phase components and keep robust to the variation of the amplitude. Experiments on several image datasets indicate that the proposed method achieves state-of-the-art performances on multiple generalizations and calibration tasks, including adaptability for common corruptions and surface variations, out-of-distribution detection, and adversarial attack.