Machine learning with the TCGA-HNSC dataset: improving usability by addressing inconsistency, sparsity, and high-dimensionality.

BACKGROUND: In the era of precision oncology and publicly available datasets, the amount of information available for each patient case has dramatically increased. From clinical variables and PET-CT radiomics measures to DNA-variant and RNA expression profiles, such a wide variety of data presents a multitude of challenges. Large clinical datasets are subject to sparsely and/or inconsistently populated fields. Corresponding sequencing profiles can suffer from the problem of high-dimensionality, where making useful inferences can be difficult without correspondingly large numbers of instances. In this paper we report a novel deployment of machine learning techniques to handle data sparsity and high dimensionality, while evaluating potential biomarkers in the form of unsupervised transformations of RNA data. We apply preprocessing, MICE imputation, and sparse principal component analysis (SPCA) to improve the usability of more than 500 patient cases from the TCGA-HNSC dataset for enhancing future oncological decision support for Head and Neck Squamous Cell Carcinoma (HNSCC). RESULTS: Imputation was shown to improve prognostic ability of sparse clinical treatment variables. SPCA transformation of RNA expression variables reduced runtime for RNA-based models, though changes to classifier performance were not significant. Gene ontology enrichment analysis of gene sets associated with individual sparse principal components (SPCs) are also reported, showing that both high- and low-importance SPCs were associated with cell death pathways, though the high-importance gene sets were found to be associated with a wider variety of cancer-related biological processes. CONCLUSIONS: MICE imputation allowed us to impute missing values for clinically informative features, improving their overall importance for predicting two-year recurrence-free survival by incorporating variance from other clinical variables. Dimensionality reduction of RNA expression profiles via SPCA reduced both computation cost and model training/evaluation time without affecting classifier performance, allowing researchers to obtain experimental results much more quickly. SPCA simultaneously provided a convenient avenue for consideration of biological context via gene ontology enrichment analysis.

Air trapping and airflow obstruction in newborn cystic fibrosis piglets.

RATIONALE: Air trapping and airflow obstruction are being increasingly identified in infants with cystic fibrosis. These findings are commonly attributed to airway infection, inflammation, and mucus buildup. OBJECTIVES: To learn if air trapping and airflow obstruction are present before the onset of airway infection and inflammation in cystic fibrosis. METHODS: On the day they are born, piglets with cystic fibrosis lack airway infection and inflammation. Therefore, we used newborn wild-type piglets and piglets with cystic fibrosis to assess air trapping, airway size, and lung volume with inspiratory and expiratory X-ray computed tomography scans. Micro-computed tomography scanning was used to assess more distal airway sizes. Airway resistance was determined with a mechanical ventilator. Mean linear intercept and alveolar surface area were determined using stereologic methods. MEASUREMENTS AND MAIN RESULTS: On the day they were born, piglets with cystic fibrosis exhibited air trapping more frequently than wild-type piglets (75% vs. 12.5%, respectively). Moreover, newborn piglets with cystic fibrosis had increased airway resistance that was accompanied by luminal size reduction in the trachea, mainstem bronchi, and proximal airways. In contrast, mean linear intercept length, alveolar surface area, and lung volume were similar between both genotypes. CONCLUSIONS: The presence of air trapping, airflow obstruction, and airway size reduction in newborn piglets with cystic fibrosis before the onset of airway infection, inflammation, and mucus accumulation indicates that cystic fibrosis impacts airway development. Our findings suggest that early airflow obstruction and air trapping in infants with cystic fibrosis might, in part, be caused by congenital airway abnormalities.

Lumbar and Thoracic Vertebrae Segmentation in CT Scans Using a 3D Multi-Object Localization and Segmentation CNN.

Radiation treatment of cancers like prostate or cervix cancer requires considering nearby bone structures like vertebrae. In this work, we present and validate a novel automated method for the 3D segmentation of individual lumbar and thoracic vertebra in computed tomography (CT) scans. It is based on a single, low-complexity convolutional neural network (CNN) architecture which works well even if little application-specific training data are available. It is based on volume patch-based processing, enabling the handling of arbitrary scan sizes. For each patch, it performs segmentation and an estimation of up to three vertebrae center locations in one step, which enables utilizing an advanced post-processing scheme to achieve high segmentation accuracy, as required for clinical use. Overall, 1763 vertebrae were used for the performance assessment. On 26 CT scans acquired for standard radiation treatment planning, a Dice coefficient of 0.921 ± 0.047 (mean ± standard deviation) and a signed distance error of 0.271 ± 0.748 mm was achieved. On the large-sized publicly available VerSe2020 data set with 129 CT scans depicting lumbar and thoracic vertebrae, the overall Dice coefficient was 0.940 ± 0.065 and the signed distance error was 0.109 ± 0.301 mm. A comparison to other methods that have been validated on VerSe data showed that our approach achieved a better overall segmentation performance.

Stensen's Duct Dynamic Anatomy Assessed with Sialography.

Objectives: The presence of a catheter required for contrast infusion during sialography obscures imaging of the distal duct. Static imaging via cone beam computed tomography and magnetic resonance sialography fails to address changes that occur dynamically to the anatomy of the flexible salivary ductal system. We aim to identify dynamic changes to the parotid gland by introducing a novel approach to analyze the full extent of Stensen's duct based on dynamic infusion digital sialography. Methods: Retrospective chart review of a single-center consecutive series of 409 parotid sialograms performed between April 2008 and June 2023 permitted selection of a contemporary series including seven normal sialograms and seven sialograms with stricture(s). Dynamic (fluoroscopic) infusion (iopamidol/gadolinium) sialograms were assessed through blinded review by two radiologists employing the institution's picture archiving and communication (PACS) system (©2023 Koninklijke Philips N.V., Amsterdam, Netherlands). Measurements determined changes, in two dimensions, to the angle of the masseteric bend and duct length while the catheter was in place (repose), during catheter withdrawal (stretch), and during recoil after withdrawal. Differences in median lengths and angles of Stensen's duct between the three time points were compared using Wilcoxon matched-pairs signed rank and Mann-Whitney tests. Results: Fourteen patients [median age (IQR), 55 years (24.7); 10 women] were evaluated. The median angle of the masseteric bend was 117.7° in repose versus 155.4° during catheter withdrawal (P < .001, n = 14). The median distance measured from the Stensen's duct orifice to the first major ductal bifurcation was 81.5 mm (IQR = 12.3) in repose. The median percent increase in length from repose to stretch was 6.3% (P < .001, n = 14). Conclusions: Dynamic infusion digital sialography with fluoroscopic recording during catheter removal permits assessment of the distal duct unobstructed by the presence of a catheter. The technique also identifies the dynamic nature and varying length and angulation of Stensen's duct.

Head and Neck Cancer Segmentation in FDG PET Images: Performance Comparison of Convolutional Neural Networks and Vision Transformers.

Convolutional neural networks (CNNs) have a proven track record in medical image segmentation. Recently, Vision Transformers were introduced and are gaining popularity for many computer vision applications, including object detection, classification, and segmentation. Machine learning algorithms such as CNNs or Transformers are subject to an inductive bias, which can have a significant impact on the performance of machine learning models. This is especially relevant for medical image segmentation applications where limited training data are available, and a model's inductive bias should help it to generalize well. In this work, we quantitatively assess the performance of two CNN-based networks (U-Net and U-Net-CBAM) and three popular Transformer-based segmentation network architectures (UNETR, TransBTS, and VT-UNet) in the context of HNC lesion segmentation in volumetric [F-18] fluorodeoxyglucose (FDG) PET scans. For performance assessment, 272 FDG PET-CT scans of a clinical trial (ACRIN 6685) were utilized, which includes a total of 650 lesions (primary: 272 and secondary: 378). The image data used are highly diverse and representative for clinical use. For performance analysis, several error metrics were utilized. The achieved Dice coefficient ranged from 0.833 to 0.809 with the best performance being achieved by CNN-based approaches. U-Net-CBAM, which utilizes spatial and channel attention, showed several advantages for smaller lesions compared to the standard U-Net. Furthermore, our results provide some insight regarding the image features relevant for this specific segmentation application. In addition, results highlight the need to utilize primary as well as secondary lesions to derive clinically relevant segmentation performance estimates avoiding biases.

Computer-aided lymph node segmentation in volumetric CT data.

PURPOSE: The purpose of this work was to develop and validate a computer-aided method for the 3D segmentation of lymph nodes in CT images. The proposed method can be utilized to facilitate applications like biopsy planning, image guided radiation treatment, or assessment of response to therapy. METHODS: An optimal surface finding based lymph node segmentation method was developed. Based on the approximate center point of a lymph node of interest, a graph is generated, which represents the local neighborhood around the lymph node at discrete locations (graph nodes). A cost function is calculated based on a weighted edge and region homogeneity term. By means of optimization, a surface-based segmentation of the lymph node is derived. In addition, an interactive segmentation refinement algorithm was developed, which allows the user to quickly correct segmentation errors, if needed. For assessment of segmentation accuracy, 111 lymph nodes of mediastinum, abdomen, head/neck, and axillary regions from 35 volumetric CT scans were utilized. For accuracy analysis, lymph nodes were divided into three test sets based on lymph node size and spatial resolution of the CT scan. The average lymph node size for test set I, II, and III was 1056, 1621, and 501 mm(3), respectively. Spatial resolution of test set II was lower than for test sets I and III. To generate an independent reference standard for comparison, all 111 lymph nodes were segmented by an expert with a live wire approach. RESULTS: All test sets were segmented with the proposed approach. Out of the 111 lymph nodes, 40 cases (36%) required computer-aided refinement of initial segmentation results. The refinement typically required 10 s per lymph node. The mean and standard deviation of the Dice coefficient for final segmentations was 0.847 ± 0.061, 0.836 ± 0.058, and 0.809 ± 0.070 for test sets I, II, and II, respectively. The average signed surface distance error was 0.023 ± 0.171, 0.394 ± 0.189, and 0.001 ± 0.146 mm for test sets I, II, and II, respectively. The time required for locating the approximate center point of a target lymph node in a scan, generating an initial OSF segmentation, and refining the segmentation, if needed, is typically less than one minute. CONCLUSIONS: Segmentation of lymph nodes in volumetric CT images is a challenging task due to partial volume effects, nearby strong edges, neighboring structures with similar intensity profiles and potentially inhomogeneous density of lymph nodes. The presented approach addresses many of these obstacles. In the majority of cases investigated, the initial segmentation method delivered results that did not require further processing. In addition, the computer-aided segmentation refinement framework was found to be effective in dealing with potentially occurring segmentation errors.

Liver segmentation in contrast enhanced CT data using graph cuts and interactive 3D segmentation refinement methods.

PURPOSE: Liver segmentation is an important prerequisite for the assessment of liver cancer treatment options like tumor resection, image-guided radiation therapy (IGRT), radiofrequency ablation, etc. The purpose of this work was to evaluate a new approach for liver segmentation. METHODS: A graph cuts segmentation method was combined with a three-dimensional virtual reality based segmentation refinement approach. The developed interactive segmentation system allowed the user to manipulate volume chunks and∕or surfaces instead of 2D contours in cross-sectional images (i.e, slice-by-slice). The method was evaluated on twenty routinely acquired portal-phase contrast enhanced multislice computed tomography (CT) data sets. An independent reference was generated by utilizing a currently clinically utilized slice-by-slice segmentation method. After 1 h of introduction to the developed segmentation system, three experts were asked to segment all twenty data sets with the proposed method. RESULTS: Compared to the independent standard, the relative volumetric segmentation overlap error averaged over all three experts and all twenty data sets was 3.74%. Liver segmentation required on average 16 min of user interaction per case. The calculated relative volumetric overlap errors were not found to be significantly different [analysis of variance (ANOVA) test, p = 0.82] between experts who utilized the proposed 3D system. In contrast, the time required by each expert for segmentation was found to be significantly different (ANOVA test, p = 0.0009). Major differences between generated segmentations and independent references were observed in areas were vessels enter or leave the liver and no accepted criteria for defining liver boundaries exist. In comparison, slice-by-slice based generation of the independent standard utilizing a live wire tool took 70.1 min on average. A standard 2D segmentation refinement approach applied to all twenty data sets required on average 38.2 min of user interaction and resulted in statistically not significantly different segmentation error indices (ANOVA test, significance level of 0.05). CONCLUSIONS: All three experts were able to produce liver segmentations with low error rates. User interaction time savings of up to 71% compared to a 2D refinement approach demonstrate the utility and potential of our approach. The system offers a range of different tools to manipulate segmentation results, and some users might benefit from a longer learning phase to develop efficient segmentation refinement strategies. The presented approach represents a generally applicable segmentation approach that can be applied to many medical image segmentation problems.

Automated measurement of uptake in cerebellum, liver, and aortic arch in full-body FDG PET/CT scans.

PURPOSE: The purpose of this work was to develop and validate fully automated methods for uptake measurement of cerebellum, liver, and aortic arch in full-body PET/CT scans. Such measurements are of interest in the context of uptake normalization for quantitative assessment of metabolic activity and/or automated image quality control. METHODS: Cerebellum, liver, and aortic arch regions were segmented with different automated approaches. Cerebella were segmented in PET volumes by means of a robust active shape model (ASM) based method. For liver segmentation, a largest possible hyperellipsoid was fitted to the liver in PET scans. The aortic arch was first segmented in CT images of a PET/CT scan by a tubular structure analysis approach, and the segmented result was then mapped to the corresponding PET scan. For each of the segmented structures, the average standardized uptake value (SUV) was calculated. To generate an independent reference standard for method validation, expert image analysts were asked to segment several cross sections of each of the three structures in 134 F-18 fluorodeoxyglucose (FDG) PET/CT scans. For each case, the true average SUV was estimated by utilizing statistical models and served as the independent reference standard. RESULTS: For automated aorta and liver SUV measurements, no statistically significant scale or shift differences were observed between automated results and the independent standard. In the case of the cerebellum, the scale and shift were not significantly different, if measured in the same cross sections that were utilized for generating the reference. In contrast, automated results were scaled 5% lower on average although not shifted, if FDG uptake was calculated from the whole segmented cerebellum volume. The estimated reduction in total SUV measurement error ranged between 54.7% and 99.2%, and the reduction was found to be statistically significant for cerebellum and aortic arch. CONCLUSIONS: With the proposed methods, the authors have demonstrated that automated SUV uptake measurements in cerebellum, liver, and aortic arch agree with expert-defined independent standards. The proposed methods were found to be accurate and showed less intra- and interobserver variability, compared to manual analysis. The approach provides an alternative to manual uptake quantification, which is time-consuming. Such an approach will be important for application of quantitative PET imaging to large scale clinical trials.

Quantification of uptake in pelvis F-18 FLT PET-CT images using a 3D localization and segmentation CNN.

PURPOSE: The purpose of this work was to develop and validate a deep convolutional neural network (CNN) approach for the automated pelvis segmentation in computed tomography (CT) scans to enable the quantification of active pelvic bone marrow by means of Fluorothymidine F-18 (FLT) tracer uptake measurement in positron emission tomography (PET) scans. This quantification is a critical step in calculating bone marrow dose for radiopharmaceutical therapy clinical applications as well as external beam radiation doses. METHODS: An approach for the combined localization and segmentation of the pelvis in CT volumes of varying sizes, ranging from full-body to pelvis CT scans, was developed that utilizes a novel CNN architecture in combination with a random sampling strategy. The method was validated on 34 planning CT scans and 106 full-body FLT PET-CT scans using a cross-validation strategy. Specifically, two different training and CNN application options were studied, quantitatively assessed, and statistically compared. RESULTS: The proposed method was able to successfully locate and segment the pelvis in all test cases. On all data sets, an average Dice coefficient of 0.9396 ± $\pm$ 0.0182 or better was achieved. The relative tracer uptake measurement error ranged between 0.065% and 0.204%. The proposed approach is time-efficient and shows a reduction in runtime of up to 95% compared to a standard U-Net-based approach without a localization component. CONCLUSIONS: The proposed method enables the efficient calculation of FLT uptake in the pelvis. Thus, it represents a valuable tool to facilitate bone marrow preserving adaptive radiation therapy and radiopharmaceutical dose calculation. Furthermore, the method can be adapted to process other bone structures as well as organs.

Noise-Based Image Harmonization Significantly Increases Repeatability and Reproducibility of Radiomics Features in PET Images: A Phantom Study.

For multicenter clinical studies, characterizing the robustness of image-derived radiomics features is essential. Features calculated on PET images have been shown to be very sensitive to image noise. The purpose of this work was to investigate the efficacy of a relatively simple harmonization strategy on feature robustness and agreement. A purpose-built texture pattern phantom was scanned on 10 different PET scanners in 7 institutions with various different image acquisition and reconstruction protocols. An image harmonization technique based on equalizing a contrast-to-noise ratio was employed to generate a "harmonized" alongside a "standard" dataset for a reproducibility study. In addition, a repeatability study was performed with images from a single PET scanner of variable image noise, varying the binning time of the reconstruction. Feature agreement was measured using the intraclass correlation coefficient (ICC). In the repeatability study, 81/93 features had a lower ICC on the images with the highest image noise as compared to the images with the lowest image noise. Using the harmonized dataset significantly improved the feature agreement for five of the six investigated feature classes over the standard dataset. For three feature classes, high feature agreement corresponded with higher sensitivity to the different patterns, suggesting a way to select suitable features for predictive models.

A unified framework for simultaneous assessment of accuracy, between-, and within-reader variability of image segmentations.

Medical imaging is utilized in a wide range of clinical applications. To enable a detailed quantitative analysis, medical images must often be segmented to label (delineate) structures of interest; for example, a tumor. Frequently, manual segmentation is utilized in clinical practice (e.g., in radiation oncology) to define such structures of interest. However, it can be quite time consuming and subject to substantial between-, and within-reader variability. A more reproducible, less variable, and more time efficient segmentation approach is likely to improve medical treatment. This potential has spurred the development of segmentation algorithms which harness computational power. Segmentation algorithms' widespread use is limited due to difficulty in quantifying their performance relative to manual segmentation, which itself is subject to variation. This paper presents a statistical model which simultaneously estimates segmentation method accuracy, and between- and within-reader variability. The model is simultaneously fit for multiple segmentation methods within a unified Bayesian framework. The Bayesian model is compared to other methods used in literature via a simulation study, and application to head and neck cancer PET/CT data. The modeling framework is flexible and can be employed in numerous comparison applications. Several alternate applications are discussed in the paper.

The fractal geometry of bronchial trees differs by strain in mice.

Fractal biological structures are pervasive throughout the plant and animal kingdoms, with the mammalian lung being a quintessential example. The lung airway and vascular trees are generated during embryogenesis from a small set of building codes similar to Turing mechanisms that create robust trees ideally suited to their functions. Whereas the blood flow pattern generated by these fractal trees has been shown to be genetically determined, the geometry of the trees has not. We explored a newly established repository providing high-resolution bronchial trees from the four most commonly studied laboratory mice (B6C3F1, BALB/c, C57BL/6 and CD-1). The data fit a fractal model well for all animals with the fractal dimensions ranging from 1.54 to 1.67, indicating that the conducting airway of mice can be considered a self-similar and space-filling structure. We determined that the fractal dimensions of these airway trees differed by strain but not sex, reinforcing the concept that airway branching patterns are encoded within the DNA. The observations also highlight that future study design and interpretations may need to consider differences in airway geometry between mouse strains.NEW & NOTEWORTHY Similar to larger mammals such as humans, the geometries of the bronchial tree in mice are fractal structures that have repeating patterns from the trachea to the terminal branches. The airway geometries of the four most commonly studied mice are different and need to be considered when comparing results that employ different mouse strains. This variability in mouse airway geometries should be incorporated into computer models exploring toxicology and aerosol deposition in mouse models.

lapdMouse: associating lung anatomy with local particle deposition in mice.

To facilitate computational toxicology, we developed an approach for generating high-resolution lung-anatomy and particle-deposition mouse models. Major processing steps of our method include mouse preparation, serial block-face cryomicrotome imaging, and highly automated image analysis for generating three-dimensional (3D) mesh-based models and volume-based models of lung anatomy (airways, lobes, sublobes, and near-acini structures) that are linked to local particle-deposition measurements. Analysis resulted in 34 mouse models covering 4 different mouse strains (B6C3F1: 8, BALB/C: 11, C57Bl/6: 8, and CD-1: 7) as well as both sexes (16 male and 18 female) and different particle sizes [2 µm (n = 15), 1 µm (n = 16), and 0.5 µm (n = 3)]. On average, resulting mouse airway models had 1,616.9 ± 298.1 segments, a centerline length of 597.6 ± 59.8 mm, and 1,968.9 ± 296.3 outlet regions. In addition to 3D geometric lung models, matching detailed relative particle-deposition measurements are provided. All data sets are available online in the lapdMouse archive for download. The presented approach enables linking relative particle deposition to anatomical structures like airways. This will in turn improve the understanding of site-specific airflows and how they affect drug, environmental, or biological aerosol deposition.NEW & NOTEWORTHY Computer simulations of particle deposition in mouse lungs play an important role in computational toxicology. Until now, a limiting factor was the lack of high-resolution mouse lung models and measured local particle-deposition information, which are required for developing accurate modeling approaches (e.g., computational fluid dynamics). With the developed imaging and analysis approach, we address this issue and provide all of the raw and processed data in a publicly accessible repository.

A 3D deep convolutional neural network approach for the automated measurement of cerebellum tracer uptake in FDG PET-CT scans.

PURPOSE: The purpose of this work was to assess the potential of deep convolutional neural networks in automated measurement of cerebellum tracer uptake in F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans. METHODS: Three different three-dimensional (3D) convolutional neural network architectures (U-Net, V-Net, and modified U-Net) were implemented and compared regarding their performance in 3D cerebellum segmentation in FDG PET scans. For network training and testing, 134 PET scans with corresponding manual volumetric segmentations were utilized. For segmentation performance assessment, a fivefold cross-validation was used, and the Dice coefficient as well as signed and unsigned distance errors were calculated. In addition, standardized uptake value (SUV) uptake measurement performance was assessed by means of a statistical comparison to an independent reference standard. Furthermore, a comparison to a previously reported active-shape-model-based approach was performed. RESULTS: Out of the three convolutional neural networks investigated, the modified U-Net showed significantly better segmentation performance. It achieved a Dice coefficient of 0.911 ± 0.026, a signed distance error of 0.220 ± 0.103 mm, and an unsigned distance error of 1.048 ± 0.340 mm. When compared to the independent reference standard, SUV uptake measurements produced with the modified U-Net showed no significant error in slope and intercept. The estimated reduction in total SUV measurement error was 95.1%. CONCLUSIONS: The presented work demonstrates the potential of deep convolutional neural networks in automated SUV measurement of reference regions. While it focuses on the cerebellum, utilized methods can be generalized to other reference regions like the liver or aortic arch. Future work will focus on combining lesion and reference region analysis into one approach.

Quantitative Imaging Informatics for Cancer Research.

PURPOSE: We summarize Quantitative Imaging Informatics for Cancer Research (QIICR; U24 CA180918), one of the first projects funded by the National Cancer Institute (NCI) Informatics Technology for Cancer Research program. METHODS: QIICR was motivated by the 3 use cases from the NCI Quantitative Imaging Network. 3D Slicer was selected as the platform for implementation of open-source quantitative imaging (QI) tools. Digital Imaging and Communications in Medicine (DICOM) was chosen for standardization of QI analysis outputs. Support of improved integration with community repositories focused on The Cancer Imaging Archive (TCIA). Priorities included improved capabilities of the standard, toolkits and tools, reference datasets, collaborations, and training and outreach. RESULTS: Fourteen new tools to support head and neck cancer, glioblastoma, and prostate cancer QI research were introduced and downloaded over 100,000 times. DICOM was amended, with over 40 correction proposals addressing QI needs. Reference implementations of the standard in a popular toolkit and standalone tools were introduced. Eight datasets exemplifying the application of the standard and tools were contributed. An open demonstration/connectathon was organized, attracting the participation of academic groups and commercial vendors. Integration of tools with TCIA was improved by implementing programmatic communication interface and by refining best practices for QI analysis results curation. CONCLUSION: Tools, capabilities of the DICOM standard, and datasets we introduced found adoption and utility within the cancer imaging community. A collaborative approach is critical to addressing challenges in imaging informatics at the national and international levels. Numerous challenges remain in establishing and maintaining the infrastructure of analysis tools and standardized datasets for the imaging community. Ideas and technology developed by the QIICR project are contributing to the NCI Imaging Data Commons currently being developed.

Multisite Technical and Clinical Performance Evaluation of Quantitative Imaging Biomarkers from 3D FDG PET Segmentations of Head and Neck Cancer Images.

Quantitative imaging biomarkers (QIBs) provide medical image-derived intensity, texture, shape, and size features that may help characterize cancerous tumors and predict clinical outcomes. Successful clinical translation of QIBs depends on the robustness of their measurements. Biomarkers derived from positron emission tomography images are prone to measurement errors owing to differences in image processing factors such as the tumor segmentation method used to define volumes of interest over which to calculate QIBs. We illustrate a new Bayesian statistical approach to characterize the robustness of QIBs to different processing factors. Study data consist of 22 QIBs measured on 47 head and neck tumors in 10 positron emission tomography/computed tomography scans segmented manually and with semiautomated methods used by 7 institutional members of the NCI Quantitative Imaging Network. QIB performance is estimated and compared across institutions with respect to measurement errors and power to recover statistical associations with clinical outcomes. Analysis findings summarize the performance impact of different segmentation methods used by Quantitative Imaging Network members. Robustness of some advanced biomarkers was found to be similar to conventional markers, such as maximum standardized uptake value. Such similarities support current pursuits to better characterize disease and predict outcomes by developing QIBs that use more imaging information and are robust to different processing factors. Nevertheless, to ensure reproducibility of QIB measurements and measures of association with clinical outcomes, errors owing to segmentation methods need to be reduced.

A Bayesian framework for performance assessment and comparison of imaging biomarker quantification methods.

Quantitative biomarkers derived from medical images are being used increasingly to help diagnose disease, guide treatment, and predict clinical outcomes. Measurement of quantitative imaging biomarkers is subject to bias and variability from multiple sources, including the scanner technologies that produce images, the approaches for identifying regions of interest in images, and the algorithms that calculate biomarkers from regions. Moreover, these sources may differ within and between the quantification methods employed by institutions, thus making it difficult to develop and implement multi-institutional standards. We present a Bayesian framework for assessing bias and variability in imaging biomarkers derived from different quantification methods, comparing agreement to a reference standard, studying prognostic performance, and estimating sample size for future clinical studies. The statistical methods are illustrated with data obtained from a positron emission tomography challenge conducted by members of the NCI's Quantitative Imaging Network program, in which tumor volumes were measured manually and with seven different semi-automated segmentation algorithms. Estimates and comparisons of bias and variability in the resulting measurements are provided along with an R software package for the technical performance analysis and an online web application for sample size and power analysis.

FLT PET Radiomics for Response Prediction to Chemoradiation Therapy in Head and Neck Squamous Cell Cancer.

Radiomics is an image analysis approach for extracting large amounts of quantitative information from medical images using a variety of computational methods. Our goal was to evaluate the utility of radiomic feature analysis from 18F-fluorothymidine positron emission tomography (FLT PET) obtained at baseline in prediction of treatment response in patients with head and neck cancer. Thirty patients with advanced-stage oropharyngeal or laryngeal cancer, treated with definitive chemoradiation therapy, underwent FLT PET imaging before treatment. In total, 377 radiomic features of FLT uptake and feature variants were extracted from volumes of interest; these features variants were defined by either the primary tumor or the total lesion burden, which consisted of the primary tumor and all FLT-avid nodes. Feature variants included normalized measurements of uptake, which were calculated by dividing lesion uptake values by the mean uptake value in the bone marrow. Feature reduction was performed using clustering to remove redundancy, leaving 172 representative features. Effects of these features on progression-free survival were modeled with Cox regression and P-values corrected for multiple comparisons. In total, 9 features were considered significant. Our results suggest that smaller, more homogenous lesions at baseline were associated with better prognosis. In addition, features extracted from total lesion burden had a higher concordance index than primary tumor features for 8 of the 9 significant features. Furthermore, total lesion burden features showed lower interobserver variability.

FDG PET based prediction of response in head and neck cancer treatment: Assessment of new quantitative imaging features.

INTRODUCTION: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is now a standard diagnostic imaging test performed in patients with head and neck cancer for staging, re-staging, radiotherapy planning, and outcome assessment. Currently, quantitative analysis of FDG PET scans is limited to simple metrics like maximum standardized uptake value, metabolic tumor volume, or total lesion glycolysis, which have limited predictive value. The goal of this work was to assess the predictive potential of new (i.e., nonstandard) quantitative imaging features on head and neck cancer outcome. METHODS: This retrospective study analyzed fifty-eight pre- and post-treatment FDG PET scans of patients with head and neck squamous cell cancer to calculate five standard and seventeen new features at baseline and post-treatment. Cox survival regression was used to assess the predictive potential of each quantitative imaging feature on disease-free survival. RESULTS: Analysis showed that the post-treatment change of the average tracer uptake in the rim background region immediately adjacent to the tumor normalized by uptake in the liver represents a novel PET feature that is associated with disease-free survival (HR 1.95; 95% CI 1.27, 2.99) and has good discriminative performance (c index 0.791). CONCLUSION: The reported findings define a promising new direction for quantitative imaging biomarker research in head and neck squamous cell cancer and highlight the potential role of new radiomics features in oncology decision making as part of precision medicine.

Pulmonary lobe separation in expiration chest CT scans based on subject-specific priors derived from inspiration scans.

Segmentation of pulmonary lobes in inspiration and expiration chest CT scan pairs is an important prerequisite for lobe-based quantitative disease assessment. Conventional methods process each CT scan independently, resulting typically in lower segmentation performance at expiration compared to inspiration. To address this issue, we present an approach, which utilizes CT scans at both respiratory states. It consists of two main parts: a base method that processes a single CT scan and an extended method that utilizes the segmentation result obtained on the inspiration scan as a subject-specific prior for segmentation of the expiration scan. We evaluated the methods on a diverse set of 40 CT scan pairs. In addition, we compare the performance of our method to a registration-based approach. On inspiration scans, the base method achieved an average distance error of 0.59, 0.64, and 0.91 mm for the left oblique, right oblique, and right horizontal fissures, respectively, when compared with expert-based reference tracings. On expiration scans, the base method's errors were 1.54, 3.24, and 3.34 mm, respectively. In comparison, utilizing proposed subject-specific priors for segmentation of expiration scans allowed decreasing average distance errors to 0.82, 0.79, and 1.04 mm, which represents a significant improvement ([Formula: see text]) compared with all other methods investigated.