Abstract
OBJECTIVES: To construct a pathomics-based machine learning model to enhance the diagnostic efficacy of LungPro navigational bronchoscopy for peripheral pulmonary lesions and to optimize the management strategy for LungPro-diagnosed negative lesions. METHODS: Clinical data and hematoxylin and eosin (H&E)-stained whole slide images (WSIs) were collected from 144 consecutive patients undergoing LungPro virtual bronchoscopy at a single institution between January 2022 and December 2023. Patients were stratified into diagnosis-positive and diagnosis-negative cohorts based on histopathological or etiological confirmation. An artificial intelligence (AI) model was developed and validated using 94 diagnosis-positive cases. Logistic regression (LR) identified associations between clinical/imaging characteristics and malignant pulmonary lesion risk factors. We implemented a convolutional neural network (CNN) with weakly supervised learning to extract image-level features, followed by multiple instance learning (MIL) for patient-level feature aggregation. Multiple machine learning (ML) algorithms were applied to model the extracted features. A multimodal diagnostic framework integrating clinical, imaging, and pathomics data were subsequently developed and evaluated on 50 LungPro-negative patients to assess the framework's diagnostic performance and predictive validity. RESULTS: Univariable and multivariable logistic regression analyses identified that age, lesion boundary and mean computed tomography (CT) attenuation were independent risk factors for malignant peripheral pulmonary lesions (P < 0.05). A histopathological model using a MIL fusion strategy showed strong diagnostic performance for lung cancer, with area under the curve (AUC) values of 0.792 (95% CI 0.680-0.903) in the training cohort and 0.777 (95% CI 0.531-1.000) in the test cohort. Combining predictive clinical features with pathological characteristics enhanced diagnostic yield for peripheral pulmonary lesions to 0.848 (95% CI 0.6945-1.0000). In patients with initially negative LungPro biopsy results, the model identified 20 of 28 malignant lesions (sensitivity: 71.43%) and 15 of 22 benign lesions (specificity: 68.18%). Class activation mapping (CAM) validated the model by highlighting key malignant features, including conspicuous nucleoli and nuclear atypia. CONCLUSIONS: The fusion diagnostic model that incorporates clinical and pathomic features markedly enhances the diagnostic accuracy of LungPro in this retrospective cohort. This model aids in the detection of subtle malignant characteristics, thereby offering evidence to support precise and targeted therapeutic interventions for lesions that LungPro classifies as negative in clinical settings.