Abstract

We are developing imaging methods for a co-clinical trial investigating synergy between immunotherapy and radiotherapy. We perform longitudinal micro-computed tomography (micro-CT) of mice to detect lung metastasis after treatment. This work explores deep learning (DL) as a fast approach for automated lung nodule detection. We used data from control mice both with and without primary lung tumors. To augment the number of training sets, we have simulated data using real augmented tumors inserted into micro-CT scans. We employed a convolutional neural network (CNN), trained with four competing types of training data: (1) simulated only, (2) real only, (3) simulated and real, and (4) pretraining on simulated followed with real data. We evaluated our model performance using precision and recall curves, as well as receiver operating curves (ROC) and their area under the curve (AUC). The AUC appears to be almost identical (0.76–0.77) for all four cases. However, the combination of real and synthetic data was shown to improve precision by 8%. Smaller tumors have lower rates of detection than larger ones, with networks trained on real data showing better performance. Our work suggests that DL is a promising approach for fast and relatively accurate detection of lung tumors in mice.

Highlights

  • Published: 7 August 2021Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain

  • The clinical arm will lag behind the preclinical arm, allowing for real-time integration of animal data in the clinical trial which leads to improved study design and better outcomes for the clinical trial [3]

  • We evaluated the performance of our model for lung tumor detection using precision and recall curves, as well as receiver operating curves (ROC)

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Summary

Introduction

Small animal imaging has become essential in evaluating new cancer therapies as they are translated from the preclinical to clinical domain. Co-clinical trials are a growing application of small animal imaging where animal results are used to shape ongoing clinical trials [1,2]. In a co-clinical trial, an animal and a clinical arm are run in parallel to study the efficacy of a novel drug or therapy. We are developing quantitative imaging methods for use in the preclinical arm of a co-clinical trial investigating synergy between immunotherapy and radiotherapy for the treatment of soft tissue sarcoma [4,5]. A critical metric of therapeutic response in patients is metastasis-free survival determined through serial imaging of the lungs, the most common site for metastasis for this type of soft tissue sarcoma. Micro-CT has been successfully used to detect lung tumors and evaluate lung tumor burden in many mouse models [6,7]

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