Ductal in-situ carcinoma (DCIS) is a non-invasive proliferation that lacks the ability to metastasize. Over the past four decades, DCIS diagnoses have increased ten-fold, with treatments nearly as aggressive as those for small low-grade invasive breast cancer. In this study, we evaluate the potential of identifying intrinsic imaging phenotype of DCIS using radiomic signatures from breast DCE-MRI. The rationale is that such phenotypes may capture aspects of the heterogeneity of DCIS that can aid in identifying indolent from aggressive disease to better stratify patients for improved disease management. An initial analysis was performed on eighty- two DCIS cases from the ECOG-ACRIN E4112 trial. The Cancer Phenomics Toolkit (CapTK) was used to extract a total of 95 3-D radiomic features from each primary lesion volume in pre-treatment, pre-operative breast DCE-MRI images. Features were first filtered for robustness across the heterogeneous clinical sites of DCE-MRI acquisition and features deemed non-robust (59) were discarded. Dimensionality reduction was performed with the remaining thirty-six features via principle component analysis (PCA). Unsupervised hierarchical clustering of the resulting five principal components (PCs) capturing 85% of the original feature variance was applied. Two significant intrinsic DCIS radiomic phenotypes were identified (p<0.001). Our hypothesis is that DCIS imaging biomarkers could improve prognostic ability more reliably than biopsy alone. These findings will be further explored in the expanded analysis of ECOG-ACRIN E4112 trial.
Convolutional neural networks (CNN) are increasingly used for image classification tasks. In general, the architectures of these networks are set ad hoc with little justification for selecting various components, such as the number of layers, layer depth, and convolution settings. In this work, we develop a structured approach to explore and select architectures that provide optimal classification performance. This was developed with an IRB-approved data set with 9,216 2-D maximum intensity projection (MIP) MRI breast images, containing breast cancer malignant or benign classes. This data set was divided into 7,372 training, 922 validation, and 922 test images. The architecture search method employs a genetic algorithm to find optimal ResNet-based classification architectures through crossover and mutation. Each generation, new model architectures are created from the genetic algorithm and trained with supervised machine learning. This search method identifies the model with the highest area under the ROC curve (AUC). The genetic algorithm produced an optimal model architecture which classifies malignancy in images with 76% accuracy and achieves an AUC score of .83. This approach offers a rational framework for automatic architecture exploration, potentially leading to a set of more efficient and generalizable CNN-based classifiers.
Glioblastoma (GBM), the most aggressive primary brain tumor, is primarily diagnosed and monitored using gadoliniumenhanced T1-weighted and T2-weighted (T2W) magnetic resonance imaging (MRI). Hyperintensity on T2W images is understood to correspond with vasogenic edema and infiltrating tumor cells. GBM’s inherent heterogeneity and resulting non-specific MRI image features complicate assessing treatment response. To better understand treatment response, we propose creating a patient-specific untreated virtual imaging control (UVIC), which represents an individual tumor’s growth if it had not been treated, for comparison with actual post-treatment images. We generated a T2W MRI UVIC by combining a patient-specific mathematical model of tumor growth with a multi-compartmental MRI signal equation. GBM growth was mathematically modeled using the previously developed Proliferation-Invasion-Hypoxia-Necrosis- Angiogenesis-Edema (PIHNA-E) model, which simulated tumor as being comprised of three cellular phenotypes: normoxic, hypoxic and necrotic cells interacting with a vasculature species, angiogenic factors and extracellular fluid. Within the PIHNA-E model, both hypoxic and normoxic cells emitted angiogenic factors, which recruited additional vessels and caused the vessels to leak, allowing fluid, or edema, to escape into the extracellular space. The model’s output was spatial volume fraction maps for each glioma cell type and edema/extracellular space. Volume fraction maps and corresponding T2 values were then incorporated into a multi-compartmental Bloch signal equation to create simulated T2W images. T2 values for individual compartments were estimated from the literature and a normal volunteer. T2 maps calculated from simulated images had normal white matter, normal gray matter, and tumor tissue T2 values within range of literature values.
KEYWORDS: Magnetic resonance imaging, Breast, Diagnostics, Data modeling, Tumors, Tumor growth modeling, Temporal resolution, Biopsy, Breast cancer, Data acquisition
Comparative preliminary analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data collected in the International Breast MR Consortium 6883 multicenter trial was performed to distinguish benign and malignant breast tumors. Prebiopsy DCE-MRI data from 45 patients with suspicious breast lesions were obtained. Semiquantitative mean signal-enhancement ratio (SERmean) was calculated for all lesions, and quantitative pharmacokinetic, parameters Ktrans, kep, and ve, were calculated for the subset with available T1 maps (n=35). Diagnostic performance was estimated for DCE-MRI parameters and compared to standard clinical MRI assessment. Quantitative and semiquantitative metrics discriminated benign and malignant lesions, with receiver operating characteristic area under the curve (AUC) values of 0.71, 0.70, and 0.82 for Ktrans, kep, and SERmean, respectively (p<0.05). At equal 94% sensitivity, the specificity and positive predictive value of SERmean (53% and 63%, respectively) and Ktrans (42% and 58%) were higher than clinical MRI assessment (32% and 54%). A multivariable model combining SERmean and clinical MRI assessment had an AUC value of 0.87. Quantitative pharmacokinetic and semiquantitative analyses of DCE-MRI improves discrimination of benign and malignant breast tumors, with our findings suggesting higher diagnostic accuracy using SERmean. SERmean has potential to help reduce unnecessary biopsies resulting from routine breast imaging.
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