Faranak Aghaei

Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

PURPOSE To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. METHODS The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. RESULTS In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC=0.85±0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96±0.03 (p<0.01). CONCLUSIONS This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

Applying a new quantitative global breast MRI feature analysis scheme to assess tumor response to chemotherapy.

To develop a new quantitative global kinetic breast magnetic resonance imaging (MRI) features analysis scheme and assess its feasibility to assess tumor response to neoadjuvant chemotherapy.

Computer-aided global breast MR image feature analysis for prediction of tumor response to chemotherapy: performance assessment

Dynamic contrast-enhanced breast magnetic resonance imaging (DCE-MRI) has been used increasingly in breast cancer diagnosis and assessment of cancer treatment efficacy. In this study, we applied a computer-aided detection (CAD) scheme to automatically segment breast regions depicting on MR images and used the kinetic image features computed from the global breast MR images acquired before neoadjuvant chemotherapy to build a new quantitative model to predict response of the breast cancer patients to the chemotherapy. To assess performance and robustness of this new prediction model, an image dataset involving breast MR images acquired from 151 cancer patients before undergoing neoadjuvant chemotherapy was retrospectively assembled and used. Among them, 63 patients had “complete response” (CR) to chemotherapy in which the enhanced contrast levels inside the tumor volume (pre-treatment) was reduced to the level as the normal enhanced background parenchymal tissues (post-treatment), while 88 patients had “partially response” (PR) in which the high contrast enhancement remain in the tumor regions after treatment. We performed the studies to analyze the correlation among the 22 global kinetic image features and then select a set of 4 optimal features. Applying an artificial neural network trained with the fusion of these 4 kinetic image features, the prediction model yielded an area under ROC curve (AUC) of 0.83±0.04. This study demonstrated that by avoiding tumor segmentation, which is often difficult and unreliable, fusion of kinetic image features computed from global breast MR images without tumor segmentation can also generate a useful clinical marker in predicting efficacy of chemotherapy.

Developing a unique portable device to non-invasively detect bio-electrochemical characteristics of human tissues

The objective of this study is to develop and test a unique portable device that aims to non-invasively detect bio-electrochemical characteristics of human tissues. For this purpose, we designed and developed a new portable Bio-impedance Spectroscopy (BIS) system utilizing active probe technique as measurement technique for bioelectrical features. This BIS system includes the integrated current source and output voltage signal detection sensors. Active probes are placed on the skin surface of the targeted human organ tissues to directly detect bioimpedance signals. Bio-impedance spectrum was measured by applying electrical currents over a range of frequencies (10kHz − 3MHz). The spectrum was then quantitatively analyzed to produce new biomarkers based on bio-electrochemical characteristics of human tissues. These new bioelectrical markers aim to accurately and reproducibly predict and/or detect human diseases (including cancer). To address the feasibility of this new research technique, we conducted a comprehensive evaluation of new BIS device with its calibration techniques and phantom study. Results showed that the computed bioelectrical marker values monotonically change corresponding to tissue compositions. In this research, we demonstrated how to compute independent and dependent bioelectrical features to be implemented on machine learning (ML) models that can improve our understanding of disease or cancer risk state. The study suggested that using this new device has potential for different applications, including the noninvasive assessment of breast density and the detection of asymmetrical focal areas between two bilateral breasts, which may eventually help more accurately predict breast cancer risk.

Association between background parenchymal enhancement of breast MRI and BIRADS rating change in the subsequent screening

Although breast magnetic resonance imaging (MRI) has been used as a breast cancer screening modality for high-risk women, its cancer detection yield remains low (i.e., ≤ 3%). Thus, increasing breast MRI screening efficacy and cancer detection yield is an important clinical issue in breast cancer screening. In this study, we investigated association between the background parenchymal enhancement (BPE) of breast MRI and the change of diagnostic (BIRADS) status in the next subsequent breast MRI screening. A dataset with 65 breast MRI screening cases was retrospectively assembled. All cases were rated BIRADS-2 (benign findings). In the subsequent screening, 4 cases were malignant (BIRADS-6), 48 remained BIRADS-2 and 13 were downgraded to negative (BIRADS-1). A computer-aided detection scheme was applied to process images of the first set of breast MRI screening. Total of 33 features were computed including texture feature and global BPE features. Texture features were computed from either a gray-level co-occurrence matrix or a gray level run length matrix. Ten global BPE features were also initially computed from two breast regions and bilateral difference between the left and right breasts. Box-plot based analysis shows positive association between texture features and BIRADS rating levels in the second screening. Furthermore, a logistic regression model was built using optimal features selected by a CFS based feature selection method. Using a leave-one-case-out based cross-validation method, classification yielded an overall 75% accuracy in predicting the improvement (or downgrade) of diagnostic status (to BIRAD-1) in the subsequent breast MRI screening. This study demonstrated potential of developing a new quantitative imaging marker to predict diagnostic status change in the short-term, which may help eliminate a high fraction of unnecessary repeated breast MRI screenings and increase the cancer detection yield.

Applying a new mammographic imaging marker to predict breast cancer risk

Identifying and developing new mammographic imaging markers to assist prediction of breast cancer risk has been attracting extensive research interest recently. Although mammographic density is considered an important breast cancer risk, its discriminatory power is lower for predicting short-term breast cancer risk, which is a prerequisite to establish a more effective personalized breast cancer screening paradigm. In this study, we presented a new interactive computer-aided detection (CAD) scheme to generate a new quantitative mammographic imaging marker based on the bilateral mammographic tissue density asymmetry to predict risk of cancer detection in the next subsequent mammography screening. An image database involving 1,397 women was retrospectively assembled and tested. Each woman had two digital mammography screenings namely, the “current” and “prior” screenings with a time interval from 365 to 600 days. All “prior” images were originally interpreted negative. In “current” screenings, these cases were divided into 3 groups, which include 402 positive, 643 negative, and 352 biopsy-proved benign cases, respectively. There is no significant difference of BIRADS based mammographic density ratings between 3 case groups (p < 0.6). When applying the CAD-generated imaging marker or risk model to classify between 402 positive and 643 negative cases using “prior” negative mammograms, the area under a ROC curve is 0.70±0.02 and the adjusted odds ratios show an increasing trend from 1.0 to 8.13 to predict the risk of cancer detection in the “current” screening. Study demonstrated that this new imaging marker had potential to yield significantly higher discriminatory power to predict short-term breast cancer risk.

Computer-aided classification of breast masses using contrast-enhanced digital mammograms

By taking advantages of both mammography and breast MRI, contrast-enhanced digital mammography (CEDM) has emerged as a new promising imaging modality to improve efficacy of breast cancer screening and diagnosis. The primary objective of study is to develop and evaluate a new computer-aided detection and diagnosis (CAD) scheme of CEDM images to classify between malignant and benign breast masses. A CEDM dataset consisting of 111 patients (33 benign and 78 malignant) was retrospectively assembled. Each case includes two types of images namely, low-energy (LE) and dual-energy subtracted (DES) images. First, CAD scheme applied a hybrid segmentation method to automatically segment masses depicting on LE and DES images separately. Optimal segmentation results from DES images were also mapped to LE images and vice versa. Next, a set of 109 quantitative image features related to mass shape and density heterogeneity was initially computed. Last, four multilayer perceptron-based machine learning classifiers integrated with correlationbased feature subset evaluator and leave-one-case-out cross-validation method was built to classify mass regions depicting on LE and DES images, respectively. Initially, when CAD scheme was applied to original segmentation of DES and LE images, the areas under ROC curves were 0.7585±0.0526 and 0.7534±0.0470, respectively. After optimal segmentation mapping from DES to LE images, AUC value of CAD scheme significantly increased to 0.8477±0.0376 (p<0.01). Since DES images eliminate overlapping effect of dense breast tissue on lesions, segmentation accuracy was significantly improved as compared to regular mammograms, the study demonstrated that computer-aided classification of breast masses using CEDM images yielded higher performance.

Association between mammogram density and background parenchymal enhancement of breast MRI

Breast density has been widely considered as an important risk factor for breast cancer. The purpose of this study is to examine the association between mammogram density results and background parenchymal enhancement (BPE) of breast MRI. A dataset involving breast MR images was acquired from 65 high-risk women. Based on mammography density (BIRADS) results, the dataset was divided into two groups of low and high breast density cases. The Low-Density group has 15 cases with mammographic density (BIRADS 1 and 2), while the High-density group includes 50 cases, which were rated by radiologists as mammographic density BIRADS 3 and 4. A computer-aided detection (CAD) scheme was applied to segment and register breast regions depicted on sequential images of breast MRI scans. CAD scheme computed 20 global BPE features from the entire two breast regions, separately from the left and right breast region, as well as from the bilateral difference between left and right breast regions. An image feature selection method namely, CFS method, was applied to remove the most redundant features and select optimal features from the initial feature pool. Then, a logistic regression classifier was built using the optimal features to predict the mammogram density from the BPE features. Using a leave-one-case-out validation method, the classifier yields the accuracy of 82% and area under ROC curve, AUC=0.81±0.09. Also, the box-plot based analysis shows a negative association between mammogram density results and BPE features in the MRI images. This study demonstrated a negative association between mammogram density and BPE of breast MRI images.

Applying a CAD-generated imaging marker to assess short-term breast cancer risk

Although whether using computer-aided detection (CAD) helps improve radiologists’ performance in reading and interpreting mammograms is controversy due to higher false-positive detection rates, objective of this study is to investigate and test a new hypothesis that CAD-generated false-positives, in particular, the bilateral summation of false-positives, is a potential imaging marker associated with short-term breast cancer risk. An image dataset involving negative screening mammograms acquired from 1,044 women was retrospectively assembled. Each case involves 4 images of craniocaudal (CC) and mediolateral oblique (MLO) view of the left and right breasts. In the next subsequent mammography screening, 402 cases were positive for cancer detected and 642 remained negative. A CAD scheme was applied to process all “prior” negative mammograms. Some features from CAD scheme were extracted, which include detection seeds, the total number of false-positive regions, an average of detection scores and the sum of detection scores in CC and MLO view images. Then the features computed from two bilateral images of left and right breasts from either CC or MLO view were combined. In order to predict the likelihood of each testing case being positive in the next subsequent screening, two logistic regression models were trained and tested using a leave-one-case-out based cross-validation method. Data analysis demonstrated the maximum prediction accuracy with an area under a ROC curve of AUC=0.65±0.017 and the maximum adjusted odds ratio of 4.49 with a 95% confidence interval of [2.95, 6.83]. The results also illustrated an increasing trend in the adjusted odds ratio and risk prediction scores (p<0.01). Thus, the study showed that CAD-generated false-positives might provide a new quantitative imaging marker to help assess short-term breast cancer risk.

Classification of Breast Masses Using a Computer-Aided Diagnosis Scheme of Contrast Enhanced Digital Mammograms

Contrast-enhanced digital mammography (CEDM) is a promising imaging modality in breast cancer diagnosis. This study aims to investigate how to optimally develop a computer-aided diagnosis (CAD) scheme of CEDM images to classify breast masses. A CEDM dataset of 111 patients was assembled, which includes 33 benign and 78 malignant cases. Each CEDM includes two types of images namely, low energy (LE) and dual-energy subtracted (DES) images. A CAD scheme was applied to segment mass regions depicting on LE and DES images separately. Optimal segmentation results generated from DES images were also mapped to LE images or vice versa. After computing image features, multilayer perceptron based machine learning classifiers that integrate with a correlation-based feature subset evaluator and leave-one-case-out cross-validation method were built to classify mass regions. When applying CAD to DES and LE images with original segmentation, areas under ROC curves (AUC) were 0.759 ± 0.053 and 0.753 ± 0.047, respectively. After mapping the mass regions optimally segmented on DES images to LE images, AUC significantly increased to 0.848 ± 0.038 (p < 0.01). Study demonstrated that DES images eliminated overlapping effect of dense breast tissue, which helps improve mass segmentation accuracy. The study demonstrated that applying a novel approach to optimally map mass region segmented from DES images to LE images enabled CAD to yield significantly improved performance.