Assessing the therapeutic response of tumors to hypoxia-targeted prodrugs with an in silico approach.

Tumor hypoxia is commonly recognized as a condition stimulating the progress of the aggressive phenotype of tumor cells. Hypoxic tumor cells inhibit the delivery of cytotoxic drugs, causing hypoxic areas to receive insufficient amounts of anticancer agents, which results in adverse treatment responses. Being such an obstruction to conventional therapies for cancer, hypoxia might be considered a target to facilitate the efficacy of treatments in the resistive environment of tumor sites. In this regard, benefiting from prodrugs that selectively target hypoxic regions remains an effective approach. Additionally, combining hypoxia-activated prodrugs (HAPs) with conventional chemotherapeutic drugs has been used as a promising strategy to eradicate hypoxic cells. However, determining the appropriate sequencing and scheduling of the combination therapy is also of great importance in obtaining favorable results in anticancer therapy. Here, benefiting from a modeling approach, we study the efficacy of HAPs in combination with chemotherapeutic drugs on tumor growth and the treatment response. Different treatment schedules have been investigated to see the importance of determining the optimal schedule in combination therapy. The effectiveness of HAPs in varying hypoxic conditions has also been explored in the study. The model provides qualitative conclusions about the treatment response, as the maximal benefit is obtained from combination therapy with greater cell death for highly hypoxic tumors. It has also been observed that the antitumor effects of HAPs show a hypoxia-dependent profile.

Chemotherapy response prediction with diffuser elapser network.

In solid tumors, elevated fluid pressure and inadequate blood perfusion resulting from unbalanced angiogenesis are the prominent reasons for the ineffective drug delivery inside tumors. To normalize the heterogeneous and tortuous tumor vessel structure, antiangiogenic treatment is an effective approach. Additionally, the combined therapy of antiangiogenic agents and chemotherapy drugs has shown promising effects on enhanced drug delivery. However, the need to find the appropriate scheduling and dosages of the combination therapy is one of the main problems in anticancer therapy. Our study aims to generate a realistic response to the treatment schedule, making it possible for future works to use these patient-specific responses to decide on the optimal starting time and dosages of cytotoxic drug treatment. Our dataset is based on our previous in-silico model with a framework for the tumor microenvironment, consisting of a tumor layer, vasculature network, interstitial fluid pressure, and drug diffusion maps. In this regard, the chemotherapy response prediction problem is discussed in the study, putting forth a proof of concept for deep learning models to capture the tumor growth and drug response behaviors simultaneously. The proposed model utilizes multiple convolutional neural network submodels to predict future tumor microenvironment maps considering the effects of ongoing treatment. Since the model has the task of predicting future tumor microenvironment maps, we use two image quality evaluation metrics, which are structural similarity and peak signal-to-noise ratio, to evaluate model performance. We track tumor cell density values of ground truth and predicted tumor microenvironments. The model predicts tumor microenvironment maps seven days ahead with the average structural similarity score of 0.973 and the average peak signal ratio of 35.41 in the test set. It also predicts tumor cell density at the end day of 7 with the mean absolute percentage error of [Formula: see text].

Multi-ray medical ultrasound simulation without explicit speckle modelling.

PURPOSE: To develop a medical ultrasound (US) simulation method using T1-weighted magnetic resonance images (MRI) as the input that offers a compromise between low-cost ray-based and high-cost realistic wave-based simulations. METHODS: The proposed method uses a novel multi-ray image formation approach with a virtual phased array transducer probe. A domain model is built from input MR images. Multiple virtual acoustic rays are emerged from each element of the linear transducer array. Reflected and transmitted acoustic energy at discrete points along each ray is computed independently. Simulated US images are computed by fusion of the reflected energy along multiple rays from multiple transducers, while phase delays due to differences in distances to transducers are taken into account. A preliminary implementation using GPUs is presented. RESULTS: Preliminary results show that the multi-ray approach is capable of generating view point-dependent realistic US images with an inherent Rician distributed speckle pattern automatically. The proposed simulator can reproduce the shadowing artefacts and demonstrates frequency dependence apt for practical training purposes. We also have presented preliminary results towards the utilization of the method for real-time simulations. CONCLUSIONS: The proposed method offers a low-cost near-real-time wave-like simulation of realistic US images from input MR data. It can further be improved to cover the pathological findings using an improved domain model, without any algorithmic updates. Such a domain model would require lesion segmentation or manual embedding of virtual pathologies for training purposes.