Radiomic analysis has shown significant potential for predicting treatment response to neoadjuvant therapy in rectal cancers via routine MRI, though primarily based off a single acquisition plane or single region of interest. To exploit intuitive clinical and biological aspects of tumor extent on MRI, we present a novel multi-plane, multi-region radiomics framework to more comprehensively characterize and interrogate treatment response on MRI. Our framework was evaluated on a cohort of 71 T2-weighted axial and coronal MRIs from patients diagnosed with rectal cancer and who underwent chemoradiation. 2D radiomic features were extracted from three regions of interest (tumor, fat proximal to tumor, and perirectal fat) across axial and coronal planes, with a two-stage feature selection scheme designed to identify descriptors associated with pathologic complete response. When evaluated via a quadratic discriminant analysis classifier, our multi-plane, multi-region radiomics model outperformed single-plane or single-region feature sets with an area under the ROC curve (AUC) of 0.80 ± 0.03 in discovery and AUC=0.65 in hold-out validation. Uniquely, the optimal feature set comprised descriptors from across multiple planes (axial, coronal) as well as multiple regions (tumor, proximal fat, perirectal fat). Our multi-plane, multi-region radiomics framework may thus enable more comprehensive phenotyping of treatment response on MRI, potentially finding application for improved personalization of therapeutic and surgical interventions in rectal cancers.
With increasing promise of radiomics and deep learning approaches in capturing subtle patterns associated with disease response on routine MRI, there is an opportunity to more closely combine components from both approaches within a single architecture. We present a novel approach to integrating multi-scale, multi-oriented wavelet networks (WN) into a convolutional neural network (CNN) architecture, termed a deep hybrid convolutional wavelet network (DHCWN). The proposed model comprises the wavelet neurons (wavelons) that use the shift and scale parameters of a mother wavelet function as its building units. Whereas the activation functions in a typical CNN are fixed and monotonic (e.g. ReLU), the activation functions of the proposed DHCWN are wavelet functions that are flexible and significantly more stable during optimization. The proposed DHCWN was evaluated using a multi-institutional cohort of 153 pre-treatment rectal cancer MRI scans to predict pathologic response to neoadjuvant chemoradiation. When compared to typical CNN and a multilayer wavelet perceptron (DWN-MLP) 2D and 3D architectures, our novel DHCWN yielded significantly better performance in predicting pathologic complete response (achieving a maximum accuracy of 91.23% and a maximum AUC of 0.79), across multi-institutional discovery and hold-out validation cohorts. Interpretability evaluation of all three architectures via Grad-CAM and Shapley visualizations revealed DHCWNs best captured complex texture patterns within tumor regions on MRI as associated with pathologic complete response classification. The proposed DHCWN thus offers a significantly more extensible, interpretable, and integrated solution for characterizing predictive signatures via routine imaging data.
KEYWORDS: Feature extraction, Magnetic resonance imaging, Visualization, Inflammation, Surgery, Proteins, Feature selection, Control systems, Performance modeling, In vivo imaging
Pediatric Crohn’s disease (pCD) is a chronic relapsing-remitting inflammatory disease of the gastrointestinal tract, where there is a significant need for non-invasive comprehensive markers to accurately target clinical interventions. While Magnetic Resonance Enterography (MRE) is often used to localize pCD in vivo, it is still limited in predicting treatment response and capturing pCD phenotypes. The goal of this study was to identify radiomic features on baseline MRE associated with disease activity and treatment outcomes in pCD, as well as investigate potential associations of radiomics with serum-based pCD subtypes. Baseline MRE scans were acquired from 45 pediatric subjects (including healthy controls and pCD patients) where the latter was further sub-grouped into responders (stable after treatment) and non-responders (required surgery or had active disease 2+ years after treatment initiation). Radiomic features were extracted from the terminal ileum on a per-voxel basis from MRE and evaluated via a multi-stage feature selection scheme for identifying disease presence and patient outcomes separately. A Random Forest (RF) classifier achieved an area under the ROC curve (AUC) of 0.83 in distinguishing diseased patients from healthy subjects and an AUC of 0.85 in distinguishing nonresponders from responders; in leave-one-out cross-validation. Top-ranked Gabor and Laws radiomic features were found to be significantly correlated with serum pCD phenotypes including anemia, inflammation risk, vitamin deficiency, and immune activity. Radiomic features may therefore offer the ability to better characterize pCD phenotypes and predict patient outcomes, which could then be effectively treated via targeted interventions.
Recent advances in the field of radiomics have enabled the development of a number of prognostic and predictive imaging-based tools for a variety of diseases. However, wider clinical adoption of these tools is contingent on their generalizability across multiple sites and scanners. This may be particularly relevant in the context of radiomic features derived from T1- or T2-weighted magnetic resonance images (MRIs), where signal intensity values are known to lack tissue-specific meaning and vary based on differing acquisition protocols between institutions. We present the first empirical study of benchmarking five different radiomic feature families in terms of both reproducibility and discriminability in a multisite setting, specifically, for identifying prostate tumors in the peripheral zone on MRI. Our cohort comprised 147 patient T2-weighted MRI datasets from four different sites, all of which are first preprocessed to correct for acquisition-related artifacts such as bias field, differing voxel resolutions, and intensity drift (nonstandardness). About 406 three-dimensional voxel-wise radiomic features from five different families (gray, Haralick, gradient, Laws, and Gabor) were evaluated in a cross-site setting to determine (a) how reproducible they are within a relatively homogeneous nontumor tissue region and (b) how well they could discriminate tumor regions from nontumor regions. Our results demonstrate that a majority of the popular Haralick features are reproducible in over 99% of all cross-site comparisons, as well as achieve excellent cross-site discriminability (classification accuracy of ≈0.8). By contrast, a majority of Laws features are highly variable across sites (reproducible in <75 % of all cross-site comparisons) as well as resulting in low cross-site classifier accuracies (<0.6), likely due to a large number of noisy filter responses that can be extracted. These trends suggest that only a subset of radiomic features and associated parameters may be both reproducible and discriminable enough for use within machine learning classifier schemes.
Detailed localization of the rectal wall after chemoradiation on standard-of-care post-chemoradiation (CRT) MRIs could enable more targeted follow-up interventions, but it is a challenging and laborious task for radiologists. This may be because the primary tumor site (i.e. primary" wall) and the remaining adjacent" wall areas depict visually overlapping intensity characteristics as a result of chemoradiation-induced noise and treatment effects. In this study, we present initial results for developing and optimizing fully convolutional networks (FCNs) to automatically segment the rectal wall on post-CRT MRIs. Our cohort comprised 50 post-CRT, T2-weighted MRIs from rectal cancer patients with expert annotations of the entire length of the rectal wall (with separate indications for extent of primary wall as well as adjacent wall). The FCN framework was designed to provide a pixel-wise segmentation of the rectal wall while utilizing the original T2w intensity images, and was tested on 20% of the cohort that was held-out from training. Our results showed that (a) the best-performing FCN for segmenting primary wall areas utilized a training set comprising primary wall sections alone (median DSC = 0.71), while (b) optimal segmentations of adjacent wall areas were achieved by an FCN trained on both primary and adjacent wall sections (median DSC = 0.68). Notably, the primary wall FCN performed poorly when applied to adjacent wall and vice versa; perhaps indicating that fundamental physiological differences exist between these wall areas that must be accounted for within automated CN segmentation approaches. FCNs may hence have to be optimized on a region-specific basis to obtain detailed, accurate delineations of the entire rectal wall on post-CRT T2w MRI, towards more targeted excision surgery and adjuvant therapy.
The recent advent of radiomics has enabled the development of prognostic and predictive tools which use routine imaging, but a key question that still remains is how reproducible these features may be across multiple sites and scanners. This is especially relevant in the context of MRI data, where signal intensity values lack tissue specific, quantitative meaning, as well as being dependent on acquisition parameters (magnetic field strength, image resolution, type of receiver coil). In this paper we present the first empirical study of the reproducibility of 5 different radiomic feature families in a multi-site setting; specifically, for characterizing prostate MRI appearance. Our cohort comprised 147 patient T2w MRI datasets from 4 different sites, all of which were first pre-processed to correct acquisition-related for artifacts such as bias field, differing voxel resolutions, as well as intensity drift (non-standardness). 406 3D voxel wise radiomic features were extracted and evaluated in a cross-site setting to determine how reproducible they were within a relatively homogeneous non-tumor tissue region; using 2 different measures of reproducibility: Multivariate Coefficient of Variation and Instability Score. Our results demonstrated that Haralick features were most reproducible between all 4 sites. By comparison, Laws features were among the least reproducible between sites, as well as performing highly variably across their entire parameter space. Similarly, the Gabor feature family demonstrated good cross-site reproducibility, but for certain parameter combinations alone. These trends indicate that despite extensive pre-processing, only a subset of radiomic features and associated parameters may be reproducible enough for use within radiomics-based machine learning classifier schemes.
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