DEVELOPING NOVEL COMPUTER-AIDED DETECTION AND DIAGNOSIS SYSTEMS OF MEDICAL IMAGES

Reading medical images to detect and diagnose diseases is often difficult and has large inter-reader variability. To address this issue, developing computer-aided detection and diagnosis (CAD) schemes or systems of medical images has attracted broad research interest in the last several decades. Despite great effort and significant progress in previous studies, only limited CAD schemes have been used in clinical practice. Thus, developing new CAD schemes is still a hot research topic in medical imaging informatics field. In this dissertation, I investigate the feasibility of developing several new innovative CAD schemes for different application purposes. First, to predict breast tumor response to neoadjuvant chemotherapy and reduce unnecessary aggressive surgery, I developed two CAD schemes of breast magnetic resonance imaging (MRI) to generate quantitative image markers based on quantitative analysis of global kinetic features. Using the image marker computed from breast MRI acquired pre-chemotherapy, CAD scheme enables to predict radiographic complete response (CR) of breast tumors to neoadjuvant chemotherapy, while using the imaging marker based on the fusion of kinetic and texture features extracted from breast MRI performed after neoadjuvant chemotherapy, CAD scheme can better predict the pathologic complete response (pCR) of the patients. Second, to more accurately predict prognosis of stroke patients, quantifying brain hemorrhage and ventricular cerebrospinal fluid depicting on brain CT images can play an important role. For this purpose, I developed a new interactive CAD tool to segment hemorrhage regions and extract radiological imaging marker to quantitatively determine the severity of aneurysmal subarachnoid hemorrhage at presentation and correlate the estimation with various homeostatic/metabolic derangements and predict clinical outcome. Third, to improve the efficiency of primary antibody screening processes in new cancer drug development, I developed a CAD scheme to automatically identify the non-negative tissue slides, which indicate reactive antibodies in digital pathology images. Last, to improve operation efficiency and reliability of storing digital pathology image data, I developed a CAD scheme using optical character recognition algorithm to automatically extract metadata from tissue slide label images and reduce manual entry for slide tracking and archiving in the tissue pathology laboratories. In summary, in these studies, we developed and tested several innovative approaches to identify quantitative imaging markers with high discriminatory power. In all CAD schemes, the graphic user interface-based visual aid tools were also developed and implemented. Study results demonstrated feasibility of applying CAD technology to several new application fields, which has potential to assist radiologists, oncologists and pathologists improving accuracy and consistency in disease diagnosis and prognosis assessment of using medical image

Evaluation of cancer outcome assessment using MRI: A review of deep-learning methods

Accurate evaluation of tumor response to treatment is critical to allow personalized treatment regimens according to the predicted response and to support clinical trials investigating new therapeutic agents by providing them with an accurate response indicator. Recent advances in medical imaging, computer hardware, and machine-learning algorithms have resulted in the increased use of these tools in the field of medicine as a whole and specifically in cancer imaging for detection and characterization of malignant lesions, prognosis, and assessment of treatment response. Among the currently available imaging techniques, magnetic resonance imaging (MRI) plays an important role in the evaluation of treatment assessment of many cancers, given its superior soft-tissue contrast and its ability to allow multiplanar imaging and functional evaluation. In recent years, deep learning (DL) has become an active area of research, paving the way for computer-assisted clinical and radiological decision support. DL can uncover associations between imaging features that cannot be visually identified by the naked eye and pertinent clinical outcomes. The aim of this review is to highlight the use of DL in the evaluation of tumor response assessed on MRI. In this review, we will first provide an overview of common DL architectures used in medical imaging research in general. Then, we will review the studies to date that have applied DL to magnetic resonance imaging for the task of treatment response assessment. Finally, we will discuss the challenges and opportunities of using DL within the clinical workflow

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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A refined molecular taxonomy of breast cancer

The current histoclinical breast cancer classification is simple but imprecise. Several molecular classifications of breast cancers based on expression profiling have been proposed as alternatives. However, their reliability and clinical utility have been repeatedly questioned, notably because most of them were derived from relatively small initial patient populations. We analyzed the transcriptomes of 537 breast tumors using three unsupervised classification methods. A core subset of 355 tumors was assigned to six clusters by all three methods. These six subgroups overlapped with previously defined molecular classes of breast cancer, but also showed important differences, notably the absence of an ERBB2 subgroup and the division of the large luminal ER+ group into four subgroups, two of them being highly proliferative. Of the six subgroups, four were ER+/PR+/AR+, one was ER−/PR−/AR+ and one was triple negative (AR−/ER−/PR−). ERBB2-amplified tumors were split between the ER−/PR−/AR+ subgroup and the highly proliferative ER+ LumC subgroup. Importantly, each of these six molecular subgroups showed specific copy-number alterations. Gene expression changes were correlated to specific signaling pathways. Each of these six subgroups showed very significant differences in tumor grade, metastatic sites, relapse-free survival or response to chemotherapy. All these findings were validated on large external datasets including more than 3000 tumors. Our data thus indicate that these six molecular subgroups represent well-defined clinico-biological entities of breast cancer. Their identification should facilitate the detection of novel prognostic factors or therapeutical targets in breast cancer