DN-ODE: Data-driven neural-ODE modeling for breast cancer tumor dynamics and progression-free survivals.

Pharmacokinetic/Pharmacodynamic (PK/PD) modeling is crucial in the development of new drugs. However, traditional population-based PK/PD models encounter challenges when modeling for individual patients. We aim to explore the potential of constructing a pharmacodynamic model for individual breast cancer pharmacodynamics leveraging only limited data from early clinical trial phases. While previous studies on Neural Ordinary Differential Equations (ODEs) suggest promising results in clinical trial practices, they primarily focused on theoretical applications or independent PK/PD modeling. PD modeling from complex and irregular clinical trial data, especially when interacting with PK parameters, is still unclear. To achieve that, we introduce a Data-driven Neural Ordinary Differential Equation (DN-ODE) modeling for breast cancer tumor dynamics and progression-free survival data. To validate this approach, experiments are conducted with early-phase clinical trial data from the Amcenestrant (an oral treatment for breast cancer) dataset (AMEERA 1-2), aiming to predict pharmacodynamics in the later phase (AMEERA 3). DN-ODE model achieves RMSE scores of 8.78 and 0.21 in tumor size and progression-free survival, respectively, with R2 scores over 0.9 for each task. Compared to PK/PD methodologies, DN-ODE is able to predict robust individual tumor dynamics with only limited cycle data. We also introduce Principal Component Analysis visualizations for encoder results, demonstrating the DN-ODE's capability to discern individual distributions and diverse tumor growth patterns. Therefore, DN-ODE facilitates comprehensive drug efficacy assessments, pinpoints potential responders, and aids in trial design.

Knowledge distillation circumvents nonlinearity for optical convolutional neural networks.

In recent years, convolutional neural networks (CNNs) have enabled ubiquitous image processing applications. As such, CNNs require fast forward propagation runtime to process high-resolution visual streams in real time. This is still a challenging task even with state-of-the-art graphics and tensor processing units. The bottleneck in computational efficiency primarily occurs in the convolutional layers. Performing convolutions in the Fourier domain is a promising way to accelerate forward propagation since it transforms convolutions into elementwise multiplications, which are considerably faster to compute for large kernels. Furthermore, such computation could be implemented using an optical 4f system with orders of magnitude faster operation. However, a major challenge in using this spectral approach, as well as in an optical implementation of CNNs, is the inclusion of a nonlinearity between each convolutional layer, without which CNN performance drops dramatically. Here, we propose a spectral CNN linear counterpart (SCLC) network architecture and its optical implementation. We propose a hybrid platform with an optical front end to perform a large number of linear operations, followed by an electronic back end. The key contribution is to develop a knowledge distillation (KD) approach to circumvent the need for nonlinear layers between the convolutional layers and successfully train such networks. While the KD approach is known in machine learning as an effective process for network pruning, we adapt the approach to transfer the knowledge from a nonlinear network (teacher) to a linear counterpart (student), where we can exploit the inherent parallelism of light. We show that the KD approach can achieve performance that easily surpasses the standard linear version of a CNN and could approach the performance of the nonlinear network. Our simulations show that the possibility of increasing the resolution of the input image allows our proposed 4f optical linear network to perform more efficiently than a nonlinear network with the same accuracy on two fundamental image processing tasks: (i) object classification and (ii) semantic segmentation.

Incremental Learning Meets Transfer Learning: Application to Multi-site Prostate MRI Segmentation.

Many medical datasets have recently been created for medical image segmentation tasks, and it is natural to question whether we can use them to sequentially train a single model that (1) performs better on all these datasets, and (2) generalizes well and transfers better to the unknown target site domain. Prior works have achieved this goal by jointly training one model on multi-site datasets, which achieve competitive performance on average but such methods rely on the assumption about the availability of all training data, thus limiting its effectiveness in practical deployment. In this paper, we propose a novel multi-site segmentation framework called incremental-transfer learning (ITL), which learns a model from multi-site datasets in an end-to-end sequential fashion. Specifically, "incremental" refers to training sequentially constructed datasets, and "transfer" is achieved by leveraging useful information from the linear combination of embedding features on each dataset. In addition, we introduce our ITL framework, where we train the network including a site-agnostic encoder with pretrained weights and at most two segmentation decoder heads. We also design a novel site-level incremental loss in order to generalize well on the target domain. Second, we show for the first time that leveraging our ITL training scheme is able to alleviate challenging catastrophic forgetting problems in incremental learning. We conduct experiments using five challenging benchmark datasets to validate the effectiveness of our incremental-transfer learning approach. Our approach makes minimal assumptions on computation resources and domain-specific expertise, and hence constitutes a strong starting point in multi-site medical image segmentation.