QUANTITATIVE CT IMAGE FEATURE ANALYSIS FOR PREDICTING TUMOR RESPONSE TO CHEMOTHERAPY AT EARLY STAGE

In gynecologic oncology, ovarian cancer is the second leading cancer with highest mortality rate. Since most of the ovarian cancer patients are diagnosed at advanced stage occurred with metastatic tumors, chemotherapy is a necessary treating procedure after the aggressive surgery which removes the patient’s primary ovary tumor (Primary cytoreduction). However, currently, no method is able to effectively and efficiently predict the tumor response to the chemotherapy at an early stage (i.e. 4-6 weeks after the treatment). This study aims to investigate whether using quantitative image features computed from CT images enables to more accurately predict the response of ovarian cancer patients to chemotherapy. During the experiment, we retrospectively assembled a dataset involving 91 patients. Each patient had two sets of pre-and post-therapy (4-6 weeks follow-up) CT images. A computer-aided detection scheme was then developed, which is able to segment the metastatic tumors and computed image features. Next, we built two initial feature pools using image features computed from pre-therapy CT images only and image feature difference computed from both pre- and post-therapy images. The predicting performance of each feature was evaluated using the area under ROC curve, which is based on the criteria 6-month progression-free survival (PFS). Among these features, the optimal feature cluster was determined and an equal-weighted fusion method was used to generate a new image marker to predict PFS of the patients. The results indicate that the highest single feature AUC values are achieved as 0.6842 ± 0.0557 and 0.7705 ± 0.0495 respectively, which are computed from pre-therapy CT images only and both pre- and post-therapy CT images. When applying fusion-based image markers, AUC values significantly increased to 0.8103 ± 0.0447 and 0.8292 ±0.0431 (p < 0.05),respectively. This study demonstrated that it is feasible to predict patients’ early stage response to chemotherapy using quantitative image features computed from pre-therapy CT images. However, we can significantly improve the prediction performance when adding information from the 4-6 week follow-up CT images

Developing and Applying CAD-generated Image Markers to Assist Disease Diagnosis and Prognosis Prediction

Developing computer-aided detection and/or diagnosis (CAD) schemes has been an active research topic in medical imaging informatics (MII) with promising results in assisting clinicians in making better diagnostic and/or clinical decisions in the last two decades. To build robust CAD schemes, we need to develop state-of-the-art image processing and machine learning (ML) algorithms to optimize each step in the CAD pipeline, including detection and segmentation of the region of interest, optimal feature generation, followed by integration to ML classifiers. In my dissertation, I conducted multiple studies investigating the feasibility of developing several novel CAD schemes in the field of medicine concerning different purposes. The first study aims to investigate how to optimally develop a CAD scheme of contrast-enhanced digital mammography (CEDM) images to classify breast masses. CEDM includes both low energy (LE) and dual-energy subtracted (DES) images. A CAD scheme was applied to segment mass regions depicting 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 ML classifiers integrated with a correlation-based feature subset evaluator and leave-one-case-out cross-validation method were built to classify mass regions. The study demonstrated that DES images eliminated the overlapping effect of dense breast tissue, which helps improve mass segmentation accuracy. By mapping mass regions segmented from DES images to LE images, CAD yields significantly improved performance. The second study aims to develop a new quantitative image marker computed from the pre-intervention computed tomography perfusion (CTP) images and evaluate its feasibility to predict clinical outcome among acute ischemic stroke (AIS) patients undergoing endovascular mechanical thrombectomy after diagnosis of large vessel occlusion. A CAD scheme is first developed to pre-process CTP images of different scanning series for each study case, perform image segmentation, quantify contrast-enhanced blood volumes in bilateral cerebral hemispheres, and compute image features related to asymmetrical cerebral blood flow patterns based on the cumulative cerebral blood flow curves of two hemispheres. Next, image markers based on a single optimal feature and ML models fused with multi-features are developed and tested to classify AIS cases into two classes of good and poor prognosis based on the Modified Rankin Scale. The study results show that ML model trained using multiple features yields significantly higher classification performance than the image marker using the best single feature (p<0.01). This study demonstrates the feasibility of developing a new CAD scheme to predict the prognosis of AIS patients in the hyperacute stage, which has the potential to assist clinicians in optimally treating and managing AIS patients. The third study aims to develop and test a new CAD scheme to predict prognosis in aneurysmal subarachnoid hemorrhage (aSAH) patients using brain CT images. Each patient had two sets of CT images acquired at admission and prior to discharge. CAD scheme was applied to segment intracranial brain regions into four subregions, namely, cerebrospinal fluid (CSF), white matter (WM), gray matter (GM), and extraparenchymal blood (EPB), respectively. CAD then computed nine image features related to 5 volumes of the segmented sulci, EPB, CSF, WM, GM, and four volumetrical ratios to sulci. Subsequently, 16 ML models were built using multiple features computed either from CT images acquired at admission or prior to discharge to predict eight prognosis related parameters. The results show that ML models trained using CT images acquired at admission yielded higher accuracy to predict short-term clinical outcomes, while ML models trained using CT images acquired prior to discharge had higher accuracy in predicting long-term clinical outcomes. Thus, this study demonstrated the feasibility of predicting the prognosis of aSAH patients using new ML model-generated quantitative image markers. The fourth study aims to develop and test a new interactive computer-aided detection (ICAD) tool to quantitatively assess hemorrhage volumes. After loading each case, the ICAD tool first segments intracranial brain volume, performs CT labeling of each voxel. Next, contour-guided image-thresholding techniques based on CT Hounsfield Unit are used to estimate and segment hemorrhage-associated voxels (ICH). Next, two experienced neurology residents examine and correct the markings of ICH categorized into either intraparenchymal hemorrhage (IPH) or intraventricular hemorrhage (IVH) to obtain the true markings. Additionally, volumes and maximum two-dimensional diameter of each sub-type of hemorrhage are also computed for understanding ICH prognosis. The performance to segment hemorrhage regions between semi-automated ICAD and the verified neurology residents’ true markings is evaluated using dice similarity coefficient (DSC). The data analysis results in the study demonstrate that the new ICAD tool enables to segment and quantify ICH and other hemorrhage volumes with higher DSC. Finally, the fifth study aims to bridge the gap between traditional radiomics and deep learning systems by comparing and assessing these two technologies in classifying breast lesions. First, one CAD scheme is applied to segment lesions and compute radiomics features. In contrast, another scheme applies a pre-trained residual net architecture (ResNet50) as a transfer learning model to extract automated features. Next, the principal component algorithm processes both initially computed radiomics and automated features to create optimal feature vectors. Then, several support vector machine (SVM) classifiers are built using the optimized radiomics or automated features. This study indicates that (1) CAD built using only deep transfer learning yields higher classification performance than the traditional radiomic-based model, (2) SVM trained using the fused radiomics and automated features does not yield significantly higher AUC, and (3) radiomics and automated features contain highly correlated information in lesion classification. In summary, in all these studies, I developed and investigated several key concepts of CAD pipeline, including (i) pre-processing algorithms, (ii) automatic detection and segmentation schemes, (iii) feature extraction and optimization methods, and (iv) ML and data analysis models. All developed CAD models are embedded with interactive and visually aided graphical user interfaces (GUIs) to provide user functionality. These techniques present innovative approaches for building quantitative image markers to build optimal ML models. The study results indicate the underlying CAD scheme's potential application to assist radiologists in clinical settings for their assessments in diagnosing disease and improving their overall performance

A Comparison of Computer-Aided Diagnosis Schemes Optimized Using Radiomics and Deep Transfer Learning Methods

Objective: Radiomics and deep transfer learning are two popular technologies used to develop computer-aided detection and diagnosis (CAD) schemes of medical images. This study aims to investigate and to compare the advantages and the potential limitations of applying these two technologies in developing CAD schemes. Methods: A relatively large and diverse retrospective dataset including 3000 digital mammograms was assembled in which 1496 images depicted malignant lesions and 1504 images depicted benign lesions. Two CAD schemes were developed to classify breast lesions. The first scheme was developed using four steps namely, applying an adaptive multi-layer topographic region growing algorithm to segment lesions, computing initial radiomics features, applying a principal component algorithm to generate an optimal feature vector, and building a support vector machine classifier. The second CAD scheme was built based on a pre-trained residual net architecture (ResNet50) as a transfer learning model to classify breast lesions. Both CAD schemes were trained and tested using a 10-fold cross-validation method. Several score fusion methods were also investigated to classify breast lesions. CAD performances were evaluated and compared by the areas under the ROC curve (AUC). Results: The ResNet50 model-based CAD scheme yielded AUC = 0.85 ± 0.02, which was significantly higher than the radiomics feature-based CAD scheme with AUC = 0.77 ± 0.02 (p < 0.01). Additionally, the fusion of classification scores generated by the two CAD schemes did not further improve classification performance. Conclusion: This study demonstrates that using deep transfer learning is more efficient to develop CAD schemes and it enables a higher lesion classification performance than CAD schemes developed using radiomics-based technology

IDRiD: Diabetic Retinopathy – Segmentation and Grading Challenge

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