CT-based Subchondral Bone Microstructural Analysis in Knee Osteoarthritis via MR-Guided Distillation Learning

Background: MR-based subchondral bone effectively predicts knee osteoarthritis. However, its clinical application is limited by the cost and time of MR. Purpose: We aim to develop a novel distillation-learning-based method named SRRD for subchondral bone microstructural analysis using easily-acquired CT images, which leverages paired MR images to enhance the CT-based analysis model during training. Materials and Methods: Knee joint images of both CT and MR modalities were collected from October 2020 to May 2021. Firstly, we developed a GAN-based generative model to transform MR images into CT images, which was used to establish the anatomical correspondence between the two modalities. Next, we obtained numerous patches of subchondral bone regions of MR images, together with their trabecular parameters (BV / TV, Tb. Th, Tb. Sp, Tb. N) from the corresponding CT image patches via regression. The distillation-learning technique was used to train the regression model and transfer MR structural information to the CT-based model. The regressed trabecular parameters were further used for knee osteoarthritis classification. Results: A total of 80 participants were evaluated. CT-based regression results of trabecular parameters achieved intra-class correlation coefficients (ICCs) of 0.804, 0.773, 0.711, and 0.622 for BV / TV, Tb. Th, Tb. Sp, and Tb. N, respectively. The use of distillation learning significantly improved the performance of the CT-based knee osteoarthritis classification method using the CNN approach, yielding an AUC score of 0.767 (95% CI, 0.681-0.853) instead of 0.658 (95% CI, 0.574-0.742) (p<.001). Conclusions: The proposed SRRD method showed high reliability and validity in MR-CT registration, regression, and knee osteoarthritis classification, indicating the feasibility of subchondral bone microstructural analysis based on CT images.

PrefixMol: Target- and Chemistry-aware Molecule Design via Prefix Embedding

Is there a unified model for generating molecules considering different conditions, such as binding pockets and chemical properties? Although target-aware generative models have made significant advances in drug design, they do not consider chemistry conditions and cannot guarantee the desired chemical properties. Unfortunately, merging the target-aware and chemical-aware models into a unified model to meet customized requirements may lead to the problem of negative transfer. Inspired by the success of multi-task learning in the NLP area, we use prefix embeddings to provide a novel generative model that considers both the targeted pocket's circumstances and a variety of chemical properties. All conditional information is represented as learnable features, which the generative model subsequently employs as a contextual prompt. Experiments show that our model exhibits good controllability in both single and multi-conditional molecular generation. The controllability enables us to outperform previous structure-based drug design methods. More interestingly, we open up the attention mechanism and reveal coupling relationships between conditions, providing guidance for multi-conditional molecule generation.