Patient-specific, mechanistic models of tumor growth incorporating artificial intelligence and big data

Despite the remarkable advances in cancer diagnosis, treatment, and management that have occurred over the past decade, malignant tumors remain a major public health problem. Further progress in combating cancer may be enabled by personalizing the delivery of therapies according to the predicted response for each individual patient. The design of personalized therapies requires patient-specific information integrated into an appropriate mathematical model of tumor response. A fundamental barrier to realizing this paradigm is the current lack of a rigorous, yet practical, mathematical theory of tumor initiation, development, invasion, and response to therapy. In this review, we begin by providing an overview of different approaches to modeling tumor growth and treatment, including mechanistic as well as data-driven models based on ``big data" and artificial intelligence. Next, we present illustrative examples of mathematical models manifesting their utility and discussing the limitations of stand-alone mechanistic and data-driven models. We further discuss the potential of mechanistic models for not only predicting, but also optimizing response to therapy on a patient-specific basis. We then discuss current efforts and future possibilities to integrate mechanistic and data-driven models. We conclude by proposing five fundamental challenges that must be addressed to fully realize personalized care for cancer patients driven by computational models.

Training a universal instance segmentation network for live cell images of various cell types and imaging modalities

We share our recent findings in an attempt to train a universal segmentation network for various cell types and imaging modalities. Our method was built on the generalized U-Net architecture, which allows the evaluation of each component individually. We modified the traditional binary training targets to include three classes for direct instance segmentation. Detailed experiments were performed regarding training schemes, training settings, network backbones, and individual modules on the segmentation performance. Our proposed training scheme draws minibatches in turn from each dataset, and the gradients are accumulated before an optimization step. We found that the key to training a universal network is all-time supervision on all datasets, and it is necessary to sample each dataset in an unbiased way. Our experiments also suggest that there might exist common features to define cell boundaries across cell types and imaging modalities, which could allow application of trained models to totally unseen datasets. A few training tricks can further boost the segmentation performance, including uneven class weights in the cross-entropy loss function, well-designed learning rate scheduler, larger image crops for contextual information, and additional loss terms for unbalanced classes. We also found that segmentation performance can benefit from group normalization layer and Atrous Spatial Pyramid Pooling module, thanks to their more reliable statistics estimation and improved semantic understanding, respectively. We participated in the 6th Cell Tracking Challenge (CTC) held at IEEE International Symposium on Biomedical Imaging (ISBI) 2021 using one of the developed variants. Our method was evaluated as the best runner up during the initial submission for the primary track, and also secured the 3rd place in an additional round of competition in preparation for the summary publication.