Reproducibility of lung nodule radiomic features: Multivariable and univariable investigations that account for interactions between CT acquisition and reconstruction parameters.

PURPOSE: Recent studies have demonstrated a lack of reproducibility of radiomic features in response to variations in CT parameters. In addition, reproducibility of radiomic features has not been well established in clinical datasets. We aimed to investigate the effects of a wide range of CT acquisition and reconstruction parameters on radiomic features in a realistic setting using clinical low dose lung cancer screening cases. We performed univariable and multivariable explorations to consider the effects of individual parameters and the simultaneous interactions between three different acquisition/reconstruction parameters of radiation dose level, reconstructed slice thickness, and kernel. METHOD: A cohort of 89 lung cancer screening patients were collected that each had a solid lung nodule >4mm diameter. A computational pipeline was used to perform a simulation of dose reduction of the raw projection data, collected from patient scans. This was followed by reconstruction of raw data with weighted filter back projection (wFBP) algorithm and automatic lung nodule detection and segmentation using a computer-aided detection tool. For each patient, 36 different image datasets were created corresponding to dose levels of 100%, 50%, 25%, and 10% of the original dose level, three slice thicknesses of 0.6 mm, 1 mm, and 2 mm, as well as three reconstruction kernels of smooth, medium, and sharp. For each nodule, 226 well-known radiomic features were calculated at each image condition. The reproducibility of radiomic features was first evaluated by measuring the intercondition agreement of the feature values among the 36 image conditions. Then in a series of univariable analyses, the impact of individual CT parameters was assessed by selecting subsets of conditions with one varying and two constant CT parameters. In each subset, intraparameter agreements were assessed. Overall concordance correlation coefficient (OCCC) served as the measure of agreement. An OCCC ≥ 0.9 implied strong agreement and reproducibility of radiomic features in intercondition or intraparameter comparisons. Furthermore, the interaction of CT parameters in impacting radiomic feature values was investigated via ANOVA. RESULTS: All included radiomic features lacked intercondition reproducibility (OCCC < 0.9) among all the 36 conditions. Out of 226 radiomic features analyzed, only 17 and 18 features were considered reproducible (OCCC ≥ 0.9) to dose and kernel variation, respectively, within the corresponding condition subsets. Slice thickness demonstrated the largest impact on radiomic feature values where only one to five features were reproducible at a few condition subsets. ANOVA revealed significant interactions (P < 0.05) between CT parameters affecting the variability of >50% of radiomic features. CONCLUSION: We systematically explored the multidimensional space of CT parameters in affecting lung nodule radiomic features. Univariable and multivariable analyses of this study not only showed the lack of reproducibility of the majority of radiomic features but also revealed existing interactions among CT parameters, meaning that the effect of individual CT parameters on radiomic features can be conditional upon other CT acquisition and reconstruction parameters. Our findings advise on careful radiomic feature selection and attention to the inclusion criteria for CT image acquisition protocols within the datasets of radiomic studies.

Technical Note: Design and implementation of a high-throughput pipeline for reconstruction and quantitative analysis of CT image data.

PURPOSE: With recent substantial improvements in modern computing, interest in quantitative imaging with CT has seen a dramatic increase. As a result, the need to both create and analyze large, high-quality datasets of clinical studies has increased as well. At present, no efficient, widely available method exists to accomplish this. The purpose of this technical note is to describe an open-source high-throughput computational pipeline framework for the reconstruction and analysis of diagnostic CT imaging data to conduct large-scale quantitative imaging studies and to accelerate and improve quantitative imaging research. METHODS: The pipeline consists of two, primary "blocks": reconstruction and analysis. Reconstruction is carried out via a graphics processing unit (GPU) queuing framework developed specifically for the pipeline that allows a dataset to be reconstructed using a variety of different parameter configurations such as slice thickness, reconstruction kernel, and simulated acquisition dose. The analysis portion then automatically analyzes the output of the reconstruction using "modules" that can be combined in various ways to conduct different experiments. Acceleration of analysis is achieved using cluster processing. Efficiency and performance of the pipeline are demonstrated using an example 142 subject lung screening cohort reconstructed 36 different ways and analyzed using quantitative emphysema scoring techniques. RESULTS: The pipeline reconstructed and analyzed the 5112 reconstructed datasets in approximately 10 days, a roughly 72× speedup over previous efforts using the scanner for reconstructions. Tightly coupled pipeline quality assurance software ensured proper performance of analysis modules with regard to segmentation and emphysema scoring. CONCLUSIONS: The pipeline greatly reduced the time from experiment conception to quantitative results. The modular design of the pipeline allows the high-throughput framework to be utilized for other future experiments into different quantitative imaging techniques. Future applications of the pipeline being explored are robustness testing of quantitative imaging metrics, data generation for deep learning, and use as a test platform for image-processing techniques to improve clinical quantitative imaging.

Fusion of Quantitative Image and Genomic Biomarkers to Improve Prognosis Assessment of Early Stage Lung Cancer Patients.

OBJECTIVE: This study aims to develop a new quantitative image feature analysis scheme and investigate its role along with two genomic biomarkers, namely protein expression of the excision repair cross-complementing 1 genes and a regulatory subunit of ribonucleotide reductase (RRM1), in predicting cancer recurrence risk of stage I nonsmall-cell lung cancer (NSCLC) patients after surgery. METHODS: By using chest computed tomography images, we developed a computer-aided detection scheme to segment lung tumors and computed tumor-related image features. After feature selection, we trained a Naïve Bayesian network-based classifier using eight image features and a multilayer perceptron classifier using two genomic biomarkers to predict cancer recurrence risk, respectively. Two classifiers were trained and tested using a dataset with 79 stage I NSCLC cases, a synthetic minority oversampling technique and a leave-one-case-out validation method. A fusion method was also applied to combine prediction scores of two classifiers. RESULTS: Areas under ROC curves (AUC) values are 0.78 ± 0.06 and 0.68 ± 0.07 when using the image feature and genomic biomarker-based classifiers, respectively. AUC value significantly increased to 0.84 ± 0.05 ( ) when fusion of two classifier-generated prediction scores using an equal weighting factor. CONCLUSION: A quantitative image feature-based classifier yielded significantly higher discriminatory power than a genomic biomarker-based classifier in predicting cancer recurrence risk. Fusion of prediction scores generated by the two classifiers further improved prediction performance. SIGNIFICANCE: We demonstrated a new approach that has potential to assist clinicians in more effectively managing stage I NSCLC patients to reduce cancer recurrence risk.