Dataset Information

Three-dimensional Image-based Mechanical Modeling for Predicting the Response of Breast Cancer to Neoadjuvant Therapy.

ABSTRACT: The use of quantitative medical imaging data to initialize and constrain mechanistic mathematical models of tumor growth has demonstrated a compelling strategy for predicting therapeutic response. More specifically, we have demonstrated a data-driven framework for prediction of residual tumor burden following neoadjuvant therapy in breast cancer that uses a biophysical mathematical model combining reaction-diffusion growth/therapy dynamics and biomechanical effects driven by early time point imaging data. Whereas early work had been based on a limited dimensionality reduction (two-dimensional planar modeling analysis) to simplify the numerical implementation, in this work, we extend our framework to a fully volumetric, three-dimensional biophysical mathematical modeling approach in which parameter estimates are generated by an inverse problem based on the adjoint state method for numerical efficiency. In an in silico performance study, we show accurate parameter estimation with error less than 3% as compared to ground truth. We apply the approach to patient data from a patient with pathological complete response and a patient with residual tumor burden and demonstrate technical feasibility and predictive potential with direct comparisons between imaging data observation and model predictions of tumor cellularity and volume. Comparisons to our previous two-dimensional modeling framework reflect enhanced model prediction of residual tumor burden through the inclusion of additional imaging slices of patient-specific data.

SUBMITTER: Weis JA

PROVIDER: S-EPMC5193147 | biostudies-other | 2017 Feb

REPOSITORIES: biostudies-other

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Three-dimensional Image-based Mechanical Modeling for Predicting the Response of Breast Cancer to Neoadjuvant Therapy.

Weis Jared A JA Miga Michael I MI Yankeelov Thomas E TE

Computer methods in applied mechanics and engineering 20160901

The use of quantitative medical imaging data to initialize and constrain mechanistic mathematical models of tumor growth has demonstrated a compelling strategy for predicting therapeutic response. More specifically, we have demonstrated a data-driven framework for prediction of residual tumor burden following neoadjuvant therapy in breast cancer that uses a biophysical mathematical model combining reaction-diffusion growth/therapy dynamics and biomechanical effects driven by early time point ima ...[more]

PMID: 28042181

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Project description:BackgroundNeoadjuvant chemotherapy (NAC) is the standard treatment for early-stage triple negative breast cancer (TNBC). The primary endpoint of NAC is a pathological complete response (pCR). NAC results in pCR in only 30-40% of TNBC patients. Tumor-infiltrating lymphocytes (TILs), Ki67 and phosphohistone H3 (pH3) are a few known biomarkers to predict NAC response. Currently, systematic evaluation of the combined value of these biomarkers in predicting NAC response is lacking. In this study, the predictive value of markers derived from H&E and IHC stained biopsy tissue was comprehensively evaluated using a supervised machine learning (ML)-based approach. Identifying predictive biomarkers could help guide therapeutic decisions by enabling precise stratification of TNBC patients into responders and partial or non-responders.MethodsSerial sections from core needle biopsies (n = 76) were stained with H&E and immunohistochemically for the Ki67 and pH3 markers, followed by whole-slide image (WSI) generation. The serial section stains in H&E stain, Ki67 and pH3 markers formed WSI triplets for each patient. The resulting WSI triplets were co-registered with H&E WSIs serving as the reference. Separate mask region-based CNN (MRCNN) models were trained with annotated H&E, Ki67 and pH3 images for detecting tumor cells, stromal and intratumoral TILs (sTILs and tTILs), Ki67+, and pH3+ cells. Top image patches with a high density of cells of interest were identified as hotspots. Best classifiers for NAC response prediction were identified by training multiple ML models and evaluating their performance by accuracy, area under curve, and confusion matrix analyses.ResultsHighest prediction accuracy was achieved when hotspot regions were identified by tTIL counts and each hotspot was represented by measures of tTILs, sTILs, tumor cells, Ki67+, and pH3+ features. Regardless of the hotspot selection metric, a complementary use of multiple histological features (tTILs, sTILs) and molecular biomarkers (Ki67 and pH3) resulted in top ranked performance at the patient level.ConclusionsOverall, our results emphasize that prediction models for NAC response should be based on biomarkers in combination rather than in isolation. Our study provides compelling evidence to support the use of ML-based models to predict NAC response in patients with TNBC.

Project description:Accurate three-dimensional (3D) reconstruction of myocardial infarct geometry is crucial to patient-specific modeling of the heart aimed at providing therapeutic guidance in ischemic cardiomyopathy. However, myocardial infarct imaging is clinically performed using two-dimensional (2D) late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) techniques, and a method to build accurate 3D infarct reconstructions from the 2D LGE-CMR images has been lacking. The purpose of this study was to address this need.The authors developed a novel methodology to reconstruct 3D infarct geometry from segmented low-resolution (Lo-res) clinical LGE-CMR images. Their methodology employed the so-called logarithm of odds (LogOdds) function to implicitly represent the shape of the infarct in segmented image slices as LogOdds maps. These 2D maps were then interpolated into a 3D image, and the result transformed via the inverse of LogOdds to a binary image representing the 3D infarct geometry. To assess the efficacy of this method, the authors utilized 39 high-resolution (Hi-res) LGE-CMR images, including 36 in vivo acquisitions of human subjects with prior myocardial infarction and 3 ex vivo scans of canine hearts following coronary ligation to induce infarction. The infarct was manually segmented by trained experts in each slice of the Hi-res images, and the segmented data were downsampled to typical clinical resolution. The proposed method was then used to reconstruct 3D infarct geometry from the downsampled images, and the resulting reconstructions were compared with the manually segmented data. The method was extensively evaluated using metrics based on geometry as well as results of electrophysiological simulations of cardiac sinus rhythm and ventricular tachycardia in individual hearts. Several alternative reconstruction techniques were also implemented and compared with the proposed method.The accuracy of the LogOdds method in reconstructing 3D infarct geometry, as measured by the Dice similarity coefficient, was 82.10% ± 6.58%, a significantly higher value than those of the alternative reconstruction methods. Among outcomes of electrophysiological simulations with infarct reconstructions generated by various methods, the simulation results corresponding to the LogOdds method showed the smallest deviation from those corresponding to the manual reconstructions, as measured by metrics based on both activation maps and pseudo-ECGs.The authors have developed a novel method for reconstructing 3D infarct geometry from segmented slices of Lo-res clinical 2D LGE-CMR images. This method outperformed alternative approaches in reproducing expert manual 3D reconstructions and in electrophysiological simulations.

Dataset Information

Three-dimensional Image-based Mechanical Modeling for Predicting the Response of Breast Cancer to Neoadjuvant Therapy.

Publications

Three-dimensional Image-based Mechanical Modeling for Predicting the Response of Breast Cancer to Neoadjuvant Therapy.

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