BackgroundIn this study, we evaluated the ability of radiomic textural analysis of intratumoral and peritumoral regions on pretreatment breast cancer dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathological complete response (pCR) to neoadjuvant chemotherapy (NAC).MethodsA total of 117 patients who had received NAC were retrospectively analyzed. Within the intratumoral and peritumoral regions of T1-weighted contrast-enhanced MRI scans, a total of 99 radiomic textural features were computed at multiple phases. Feature selection was used to identify a set of top pCR-associated features from within a training set (n = 78), which were then used to train multiple machine learning classifiers to predict the likelihood of pCR for a given patient. Classifiers were then independently tested on 39 patients. Experiments were repeated separately among hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+, HER2−) and triple-negative or HER2+ (TN/HER2+) tumors via threefold cross-validation to determine whether receptor status-specific analysis could improve classification performance.ResultsAmong all patients, a combined intratumoral and peritumoral radiomic feature set yielded a maximum AUC of 0.78 ± 0.030 within the training set and 0.74 within the independent testing set using a diagonal linear discriminant analysis (DLDA) classifier. Receptor status-specific feature discovery and classification enabled improved prediction of pCR, yielding maximum AUCs of 0.83 ± 0.025 within the HR+, HER2− group using DLDA and 0.93 ± 0.018 within the TN/HER2+ group using a naive Bayes classifier. In HR+, HER2− breast cancers, non-pCR was characterized by elevated peritumoral heterogeneity during initial contrast enhancement. However, TN/HER2+ tumors were best characterized by a speckled enhancement pattern within the peritumoral region of nonresponders. Radiomic features were found to strongly predict pCR independent of choice of classifier, suggesting their robustness as response predictors.ConclusionsThrough a combined intratumoral and peritumoral radiomics approach, we could successfully predict pCR to NAC from pretreatment breast DCE-MRI, both with and without a priori knowledge of receptor status. Further, our findings suggest that the radiomic features most predictive of response vary across different receptor subtypes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0846-1) contains supplementary material, which is available to authorized users.

Purpose: To evaluate ability of radiomic (computer-extracted imaging) features to distinguish non-small cell lung cancer adenocarcinomas from granulomas at noncontrast CT. Materials and Methods: For this retrospective study, screening or standard diagnostic noncontrast CT images were collected for 290 patients (mean age, 68 years; range, 18–92 years; 125 men [mean age, 67 years; range, 18–90 years] and 165 women [mean age, 68 years; range, 33–92 years]) from two institutions between 2007 and 2013. Histopathologic analysis was available for one nodule per patient. Corresponding nodule of interest was identified on CT axial images by a radiologist with manually annotation. Nodule shape, wavelet (Gabor), and texture-based (Haralick and Laws energy) features were extracted from intra- and perinodular regions. Features were pruned to train machine learning classifiers with 145 patients. In a test set of 145 patients, classifier results were compared against a convolutional neural network (CNN) and diagnostic readings of two radiologists. Results: Support vector machine classifier with intranodular radiomic features achieved an area under the receiver operating characteristic curve (AUC) of 0.75 on the test set. Combining radiomics of intranodular with perinodular regions improved the AUC to 0.80. On the same test set, CNN resulted in an AUC of 0.76. Radiologist readers achieved AUCs of 0.61 and 0.60, respectively. Conclusion: Radiomic features from intranodular and perinodular regions of nodules can distinguish non-small cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT. Summary Perinodular and intranodular radiomic features corresponding to texture and shape (radiomics) were evaluated to distinguish nonsmall cell lung cancer adenocarcinomas from benign granulomas at noncontrast CT.

Objective Despite 90% Glioblastoma (GBM) recurrences occurring in the peritumoral brain zone (PBZ), its contribution in patient survival is poorly understood. The current study leverages computerized texture (i.e. radiomic) analysis to evaluate the efficacy of PBZ features from preoperative MRI in predicting long (>18-months) versus short-term (<7-months) survival in GBM. Methods 65 patient exams (29 short-term, 36 long-term) with Gadolinium-contrast T1w, FLAIR, T2w sequences from the Cancer Imaging Archive were employed. An expert manually segmented each study as: enhancing lesion, PBZ, and tumour necrosis. 402 radiomic features (capturing co-occurrence, gray-level dependence, directional gradients) was obtained for each region. Evaluation was performed using 3-fold cross validation, such that a subset of studies was used to select the most predictive features, and the remaining subset was used to evaluate their efficacy in predicting survival. Results A subset of 10 radiomic “peritumoral” MRI features, suggestive of intensity heterogeneity and textural patterns, was found to be predictive of survival (p = 1.47 × 10−5), as compared to features from enhancing tumour, necrotic regions, and known clinical factors. Conclusion Our preliminary analysis suggests that radiomic features from the PBZ on routine pre-operative MRI may be predictive of long-, versus short-term survival in GBM.

Even though 1 in 6 men in the US, in their lifetime are expected to be diagnosed with prostate cancer (CaP), only 1 in 37 is expected to die on account of it. Consequently, among many men diagnosed with CaP, there has been a recent trend to resort to active surveillance (wait and watch) if diagnosed with a lower Gleason score on biopsy, as opposed to seeking immediate treatment. Some researchers have recently identified imaging markers for low and high grade CaP on multi-parametric (MP) magnetic resonance (MR) imaging (such as T2 weighted MR imaging (T2w MRI) and MR spectroscopy (MRS)). In this paper, we present a novel computerized decision support system (DSS), called Semi Supervised Multi Kernel Graph Embedding (SeSMiK-GE), that quantitatively combines structural, and metabolic imaging data for distinguishing (a) benign versus cancerous, and (b) high- versus low-Gleason grade CaP regions from in vivo MP-MRI. A total of 29 1.5 Tesla endorectal pre-operative in vivo MP MRI (T2w MRI, MRS) studies from patients undergoing radical prostatectomy were considered in this study. Ground truth for evaluation of the SeSMiK-GE classifier was obtained via annotation of disease extent on the preoperative imaging by visually correlating the MRI to the ex vivo whole mount histologic specimens. The SeSMiK-GE framework comprises of three main modules: (1) multi-kernel learning, (2) semi-supervised learning, and (3) dimensionality reduction, which are leveraged for the construction of an integrated low dimensional representation of the different imaging and non-imaging MRI protocols. Hierarchical classifiers for diagnosis and Gleason grading of CaP are then constructed within this unified low dimensional representation. Step 1 of the hierarchical classifier employs a random forest classifier in conjunction with the SeSMiK-GE based data representation and a probabilistic pairwise Markov Random Field algorithm (which allows for imposition of local spatial constraints) to yield a voxel based classification of CaP presence. The CaP region of interest identified in Step 1 is then subsequently classified as either high or low Gleason grade CaP in Step 2. Comparing SeSMiK-GE with unimodal T2w MRI, MRS classifiers and a commonly used feature concatenation (COD) strategy, yielded areas (AUC) under the receiver operative curve (ROC) of (a) 0.89 ± 0.09 (SeSMiK), 0.54 ± 0.18 (T2w MRI), 0.61 ± 0.20 (MRS), and 0.64 ± 0.23 (COD) for distinguishing benign from CaP regions, and (b) 0.84 ± 0.07 (SeSMiK),0.54 ± 0.13 (MRI), 0.59 ± 0.19 (MRS), and 0.62 ± 0.18 (COD) for distinguishing high and low grade CaP using a leave one out cross-validation strategy, all evaluations being performed on a per voxel basis. Our results suggest that following further rigorous validation, SeSMiK-GE could be developed into a powerful diagnostic and prognostic tool for detection and grading of CaP in vivo and in helping to determine the appropriate treatment option. Identifying low grade disease in vivo might allow CaP patients to opt for active surveillance rather than...

In this paper, we introduce a new radiomic descriptor, Co-occurrence of Local Anisotropic Gradient Orientations (CoLlAGe) for capturing subtle differences between benign and pathologic phenotypes which may be visually indistinguishable on routine anatomic imaging. CoLlAGe seeks to capture and exploit local anisotropic differences in voxel-level gradient orientations to distinguish similar appearing phenotypes. CoLlAGe involves assigning every image voxel an entropy value associated with the co-occurrence matrix of gradient orientations computed around every voxel. The hypothesis behind CoLlAGe is that benign and pathologic phenotypes even though they may appear similar on anatomic imaging, will differ in their local entropy patterns, in turn reflecting subtle local differences in tissue microarchitecture. We demonstrate CoLlAGe’s utility in three clinically challenging classification problems: distinguishing (1) radiation necrosis, a benign yet confounding effect of radiation treatment, from recurrent tumors on T1-w MRI in 42 brain tumor patients, (2) different molecular sub-types of breast cancer on DCE-MRI in 65 studies and (3) non-small cell lung cancer (adenocarcinomas) from benign fungal infection (granulomas) on 120 non-contrast CT studies. For each of these classification problems, CoLlAGE in conjunction with a random forest classifier outperformed state of the art radiomic descriptors (Haralick, Gabor, Histogram of Gradient Orientations).

Purpose To determine the feasibility of radiomic (computer extracted texture) features in differentiating radiation necrosis (RN) from recurrent brain tumors on routine MRI (Gadolinium (Gd)-T1w, T2w, FLAIR). Methods A retrospective study of brain tumor MRI obtained after 9-months (or later) post-radio-chemotherapy was collected from two institutions. In total, 58 patient studies were analyzed, consisting of a training (N = 43) cohort from one institution and an independent test (N = 15) cohort from another, with surgical histologic findings confirmed by an experienced neuropathologist at the respective institutions. Brain lesions on MRI were manually annotated by an expert neuro-radiologist. A set of radiomic features was extracted for every lesion on each MRI sequence: Gd-T1w, T2w, FLAIR. Feature selection was employed to identify the top 5 most discriminating features for every MRI sequence on the training cohort. These features were then evaluated on the test cohort via a support vector machine (SVM) classifier. The classification performance was compared against diagnostic reads by two expert neuro-radiologists, who had access to the same MRI sequences (Gd-T1w, T2w, and FLAIR) as the classifier. Results On the training cohort, the area under the receiver operating characteristic curve (AUC) was highest for FLAIR with 0.79, 95% CI [0.77, 0.81] for primary (N =22), and 0.79, 95% CI [0.75, 0.83], for metastatic subgroups (N = 21). Of the 15 studies in the holdout cohort, the SVM classifier identified 12 of 15 studies correctly, while neuro-radiologist 1 diagnosed 7 of 15, and neuro-radiologist 2 diagnosed 8 of 15 studies correctly, respectively. Discussion Our preliminary results appear to suggest that radiomic features may provide complementary diagnostic information on routine MRI sequences that may improve distinction of RN from recurrence, both for primary and metastatic brain tumors.

Hypoxia, a characteristic trait of Glioblastoma (GBM), is known to cause resistance to chemo-radiation treatment and is linked with poor survival. There is hence an urgent need to non-invasively characterize tumor hypoxia to improve GBM management. We hypothesized that (a) radiomic texture descriptors can capture tumor heterogeneity manifested as a result of molecular variations in tumor hypoxia, on routine treatment naïve MRI, and (b) these imaging based texture surrogate markers of hypoxia can discriminate GBM patients as short-term (STS), mid-term (MTS), and long-term survivors (LTS). 115 studies (33 STS, 41 MTS, 41 LTS) with gadolinium-enhanced T1-weighted MRI (Gd-T1w) and T2-weighted (T2w) and FLAIR MRI protocols and the corresponding RNA sequences were obtained. After expert segmentation of necrotic, enhancing, and edematous/nonenhancing tumor regions for every study, 30 radiomic texture descriptors were extracted from every region across every MRI protocol. Using the expression profile of 21 hypoxia-associated genes, a hypoxia enrichment score (HES) was obtained for the training cohort of 85 cases. Mutual information score was used to identify a subset of radiomic features that were most informative of HES within 3-fold cross-validation to categorize studies as STS, MTS, and LTS. When validated on an additional cohort of 30 studies (11 STS, 9 MTS, 10 LTS), our results revealed that the most discriminative features of HES were also able to distinguish STS from LTS (p = 0.003).

Rationale and Objectives To develop a computerized data integration framework (MaWERiC) for quantitatively combining structural and metabolic information from different Magnetic Resonance (MR) imaging modalities. Materials and Methods In this paper, we present a novel computerized support system that we call Multimodal Wavelet Embedding Representation for data Combination (MaWERiC) which (1) employs wavelet theory and dimensionality reduction for providing a common, uniform representation of the different imaging (T2-w) and non-imaging (spectroscopy) MRI channels, and (2) leverages a random forest classifier for automated prostate cancer detection on a per voxel basis from combined 1.5 Tesla in vivo MRI and MRS. Results A total of 36 1.5 T endorectal in vivo T2-w MRI, MRS patient studies were evaluated on a per-voxel via MaWERiC, using a three-fold cross validation scheme across 25 iterations. Ground truth for evaluation of the results was obtained via ex-vivo whole-mount histology sections which served as the gold standard for expert radiologist annotations of prostate cancer on a per-voxel basis. The results suggest that MaWERiC based MRS-T2-w meta-classifier (mean AUC, μ = 0.89 ± 0.02) significantly outperformed (i) a T2-w MRI (employing wavelet texture features) classifier (μ = 0.55± 0.02), (ii) a MRS (employing metabolite ratios) classifier (μ= 0.77 ± 0.03), (iii) a decision-fusion classifier, obtained by combining individual T2-w MRI and MRS classifier outputs (μ = 0.85 ± 0.03) and (iv) a data combination scheme involving combination of metabolic MRS and MR signal intensity features (μ = 0.66± 0.02). Conclusion A novel data integration framework, MaWERiC, for combining imaging and non-imaging MRI channels was presented. Application to prostate cancer detection via combination of T2-w MRI and MRS data demonstrated significantly higher AUC and accuracy values compared to the individual T2-w MRI, MRS modalities and other data integration strategies.