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: Tumors, Magnetic resonance imaging, Cancer, Feature extraction, Surgery, Medical research, In vivo imaging, Diffusion, Data analysis, Oncology, Machine learning, Pattern recognition, Image analysis
Dynamic contrast-enhanced (DCE) MRI is increasingly used to stage and evaluate rectal cancer extent in vivo in order to plan and target interventions for locally advanced tumors. The major clinical challenge faced with rectal cancers today is to personalize interventions through early identification of patients will benefit from neoadjuvant chemoradiation (nCRT) alone and who will benefit from aggressive surgery (with adjuvant radiation) instead; via baseline imaging. In this study, we evaluated texture kinetic features of rectal tumors using baseline DCE MRI scans, in order to predict pathologic tumor stage regression in response to nCRT. Our texture kinetics approach utilized a combination of texture features (from multiple DCE uptake phases) and polynomial curve fitting to uniquely quantify spatiotemporal patterns of lesion texture during contrast uptake and diffusion that were different between responders and non-responders to nCRT. We utilized a cohort of 48 rectal cancer patients for whom pre-nCRT 3 T DCE MRI was available, including pre-, early-, and delayed-enhancement phases. All DCE MRI phases were processed for motion and spatial alignment artifacts via rigid co-registration, and the tumor ROI on all 3 contrast phases was normalized with respect to non-enhancing muscle. 191 texture features were extracted from each of 3 contrast phases separately, following which each feature was plotted with respect to time to yield a feature enhancement curve. Polynomial fitting was applied to each feature enhancement curve to result in a vector of coefficients which was considered the texture kinetic representation of that feature. All 191 features were evaluated in terms of their texture kinetic representation as well as the raw feature enhancement, for predicting pathologically regressed tumor stages (ypT0-2) from non-regressed tumors (ypT3-4) via a cross-validated QDA classifier. Texture kinetics of gradient XY enhancement yielded the best overall AUC=0:762±0:053, which was significantly higher than any feature enhancement representation (best AUC=0:696±0:050). Texture kinetic representations also outperformed their corresponding raw feature enhancement representations in 54.5% of the features compared, and performed significantly worse in only 13% of the comparisons. Non-invasive guidance of interventions in rectal cancers could therefore be enhanced through the use of texture kinetic features from DCE MRI, which may better characterize spatiotemporal differences between responders and non-responders on baseline imaging.
Tumor downstaging after neoadjuvant chemoradiation (CRT) in rectal cancer patients is typically assessed via Magnetic Resonance Imaging (MRI) in order to determine follow-up surgical interventions, but is associated with marked inter-reader variability and limited performance. While radiomic features have shown promise for evaluating chemoradiation response and tumor stage in rectal cancers, there is a need to determine how reproducible these features are across different MRI scanners and acquisitions. In this study, we evaluated radiomic feature reproducibility in terms of feature instability within a uniquely curated true healthy" rectum cohort in order to construct a stability-informed radiomic classifier for differentiating poorly from markedly down-staged rectal tumors after chemoradiation in a multi-site setting. We utilized a cohort of 156 patients, with (a) 74 MRIs visualizing the healthy rectum, (b) 52 post-CRT MRI scans in the discovery cohort, and (c) 30 post-CRT MRI scans in a second-site validation cohort; the latter 2 being from rectal cancer patients. 764 radiomic features were extracted from within the entire rectal wall on each MRI scan. Feature instability was used to quantify how reproducible each radiomic feature was between the discovery cohort and the healthy rectum cohort, using locations along the rectum that were spatially distinct from the treated tumor region. From the resulting stability-informed" feature set, the most relevant features were identified to distinguish pathologic tumor stage groups in the discovery cohort via a QDA classifier with cross-validation to ensure robustness. The top 4 radiomic features were then evaluated in hold-out fashion on scans from the validation cohort. We found that utilizing a stability-informed radiomic model (which comprised features that were reproducible in 100% of all comparisons) was significantly more accurate in identifying pathological tumor stage regression in both discovery (AUC=0:66 ± 0:09) and validation (AUC=0.73) cohorts, compared to a basic radiomic model that used all extracted features (AUC=0:60 ± 0:07 in discovery, AUC=0.62 in validation). Evaluating feature instability with respect to healthy rectal tissue may thus enhance the performance of radiomic models in characterizing pathologic downstaging in rectal cancers, via MRI.
Evaluating tumor regression of rectal cancers via MRI after standard-of-care chemoradiation therapy (CRT) remains highly challenging for radiologists. While the tumor region-of-interest (ROI) on post-CRT rectal MRI is difficult to localize, an underexplored region is the perirectal fat (surrounding tumor and rectum) where residual cancer cells and positive lymph nodes are known to be present. Recent studies have shown that physiologic environments surrounding tumor regions may provide complementary information that is predictive of response to CRT and patient survival. We present initial results of characterizing perirectal fat regions on MRI via radiomics, towards capturing sub-visual details related to rectal tumor or nodal response to CRT. A total of 37 rectal cancer patients for whom MRIs as well as pathologic tumor staging were available post-CRT were included in this study. Region-wise radiomic features were extracted from expert annotated perirectal fat regions and a 2-stage feature selection was employed to identify the most relevant features. Radiomic entropy of perirectal fat was found to be over-expressed in patients with poor tumor or nodal response post-CRT, albeit with different spatial distributions. In a leave-one-patient-out cross validation setting, a quadratic discriminant analysis (QDA) classifier trained on top radiomic features from the perirectal fat achieved AUCs of 0.77 (for differentiating incomplete vs marked tumor regression) and 0.75 (for differentiating lymph node positive from negative patients). By comparison, perirectal fat intensities achieved significantly poorer AUCs in both tasks. Our results indicate perirectal fat on post-CRT MRI may be highly relevant for evaluating CRT response and informing follow-on interventions in rectal cancers.
KEYWORDS: Magnetic resonance imaging, Tumors, Cancer, CRTs, Feature extraction, In vivo imaging, Medical research, Feature selection, Tissues, Lung cancer
A major clinical challenge in rectal cancer currently is non-invasive identification of tumor regression to standard- of-care neoadjuvant chemoradiation (CRT). Multi-parametric MRI is routinely acquired after CRT, but expert radiologists find it highly challenging to assess the degree of tumor regression on both T2-weighted (T2w) and Gadolinium contrast-enhanced (CE) MRI; resulting in poor agreement with gold-standard pathologic evaluation. In this study, we present initial results for integrating quantitative image appearance (radiomic) features from post-CRT T2w and CE MRI towards in vivo assessment of pathologic rectal tumor response to chemoradiation. 29 rectal cancer patients with post-CRT multi-parametric 3 T MRI (with T2w, initial and delayed CE phases) were included in this study. Through spatial co-registration, the treated region of the rectal wall was identified and annotated on T2w and all CE phases (as well as correcting for motion artifacts in CE MRI). 165 radiomic features (including Haralick, Gabor, Laws, Sobel/Kirsch) were separately extracted from each of T2w and 2 CE phases; within the entire rectal wall. The top 2 response-associated radiomic features for each of (a) T2w, (b) 2 CE phases, (c) combined T2w+CE phases were identified via feature selection and evaluated in a leave- one-patient-out cross validation setting. Integrating T2w and CE radiomic features was found to be markedly more accurate (AUC=0.93) for assessing post-CRT pathologic tumor stage, compared to T2w radiomic features (AUC=0.80) and CE radiomic features (AUC=0.63) individually. Top-ranked features captured heterogeneity of gradient responses on T2w MRI and macro-scale Gabor wavelet responses of contrast enhancement on CE MRI. Combining radiomic features from post-CRT T2w and CE MRI may hence enable more comprehensive evaluation of response to neoadjuvant therapy in rectal cancers, which can be used to better guide follow-up interventions.
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.
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