The Role of Radiomics and AI Technologies in the Segmentation, Detection, and Management of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary hepatic neoplasm. Thanks to recent advances in computed tomography (CT) and magnetic resonance imaging (MRI), there is potential to improve detection, segmentation, discrimination from HCC mimics, and monitoring of therapeutic response. Radiomics, artificial intelligence (AI), and derived tools have already been applied in other areas of diagnostic imaging with promising results. In this review, we briefly discuss the current clinical applications of radiomics and AI in the detection, segmentation, and management of HCC. Moreover, we investigate their potential to reach a more accurate diagnosis of HCC and to guide proper treatment planning

Medical Image Analytics (Radiomics) with Machine/Deeping Learning for Outcome Modeling in Radiation Oncology

Image-based quantitative analysis (radiomics) has gained great attention recently. Radiomics possesses promising potentials to be applied in the clinical practice of radiotherapy and to provide personalized healthcare for cancer patients. However, there are several challenges along the way that this thesis will attempt to address. Specifically, this thesis focuses on the investigation of repeatability and reproducibility of radiomics features, the development of new machine/deep learning models, and combining these for robust outcomes modeling and their applications in radiotherapy. Radiomics features suffer from robustness issues when applied to outcome modeling problems, especially in head and neck computed tomography (CT) images. These images tend to contain streak artifacts due to patients’ dental implants. To investigate the influence of artifacts for radiomics modeling performance, we firstly developed an automatic artifact detection algorithm using gradient-based hand-crafted features. Then, comparing the radiomics models trained on ‘clean’ and ‘contaminated’ datasets. The second project focused on using hand-crafted radiomics features and conventional machine learning methods for the prediction of overall response and progression-free survival for Y90 treated liver cancer patients. By identifying robust features and embedding prior knowledge in the engineered radiomics features and using bootstrapped LASSO to select robust features, we trained imaging and dose based models for the desired clinical endpoints, highlighting the complementary nature of this information in Y90 outcomes prediction. Combining hand-crafted and machine learnt features can take advantage of both expert domain knowledge and advanced data-driven approaches (e.g., deep learning). Thus, we proposed a new variational autoencoder network framework that modeled radiomics features, clinical factors, and raw CT images for the prediction of intrahepatic recurrence-free and overall survival for hepatocellular carcinoma (HCC) patients in this third project. The proposed approach was compared with widely used Cox proportional hazard model for survival analysis. Our proposed methods achieved significant improvement in terms of the prediction using the c-index metric highlighting the value of advanced modeling techniques in learning from limited and heterogeneous information in actuarial prediction of outcomes. Advances in stereotactic radiation therapy (SBRT) has led to excellent local tumor control with limited toxicities for HCC patients, but intrahepatic recurrence still remains prevalent. As an extension of the third project, we not only hope to predict the time to intrahepatic recurrence, but also the location where the tumor might recur. This will be clinically beneficial for better intervention and optimizing decision making during the process of radiotherapy treatment planning. To address this challenging task, firstly, we proposed an unsupervised registration neural network to register atlas CT to patient simulation CT and obtain the liver’s Couinaud segments for the entire patient cohort. Secondly, a new attention convolutional neural network has been applied to utilize multimodality images (CT, MR and 3D dose distribution) for the prediction of high-risk segments. The results showed much improved efficiency for obtaining segments compared with conventional registration methods and the prediction performance showed promising accuracy for anticipating the recurrence location as well. Overall, this thesis contributed new methods and techniques to improve the utilization of radiomics for personalized radiotherapy. These contributions included new algorithm for detecting artifacts, a joint model of dose with image heterogeneity, combining hand-crafted features with machine learnt features for actuarial radiomics modeling, and a novel approach for predicting location of treatment failure.PHDApplied PhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163092/1/liswei_1.pd

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society

Identification of cancer hallmarks in patients with non-metastatic colon cancer after surgical resection

Colon cancer is one of the most common cancers in the world, and the therapeutic workflow is dependent on the TNM staging system and the presence of clinical risk factors. However, in the case of patients with non-metastatic disease, evaluating the benefit of adjuvant chemotherapy is a clinical challenge. Radiomics could be seen as a non-invasive novel imaging biomarker able to outline tumor phenotype and to predict patient prognosis by analyzing preoperative medical images. Radiomics might provide decisional support for oncologists with the goal to reduce the number of arbitrary decisions in the emerging era of personalized medicine. To date, much evidence highlights the strengths of radiomics in cancer workup, but several aspects limit the use of radiomics methods as routine. The study aimed to develop a radiomic model able to identify high-risk colon cancer by analyzing pre-operative CT scans. The study population comprised 148 patients: 108 with non-metastatic colon cancer were retrospectively enrolled from January 2015 to June 2020, and 40 patients were used as the external validation cohort. The population was divided into two groups—High-risk and No-risk—following the presence of at least one high-risk clinical factor. All patients had baseline CT scans, and 3D cancer segmentation was performed on the portal phase by two expert radiologists using open-source software (3DSlicer v4.10.2). Among the 107 radiomic features extracted, stable features were selected to evaluate the inter-class correlation (ICC) (cut-off ICC > 0.8). Stable features were compared between the two groups (T-test or Mann–Whitney), and the significant features were selected for univariate and multivariate logistic regression to build a predictive radiomic model. The radiomic model was then validated with an external cohort. In total, 58/108 were classified as High-risk and 50/108 as No-risk. A total of 35 radiomic features were stable (0.81 ≤ ICC <  0.92). Among these, 28 features were significantly different between the two groups (p < 0.05), and only 9 features were selected to build the radiomic model. The radiomic model yielded an AUC of 0.73 in the internal cohort and 0.75 in the external cohort. In conclusion, the radiomic model could be seen as a performant, non-invasive imaging tool to properly stratify colon cancers with high-risk diseas

Deep learning for image-based liver analysis — A comprehensive review focusing on malignant lesions

Deep learning-based methods, in particular, convolutional neural networks and fully convolutional networks are now widely used in the medical image analysis domain. The scope of this review focuses on the analysis using deep learning of focal liver lesions, with a special interest in hepatocellular carcinoma and metastatic cancer; and structures like the parenchyma or the vascular system. Here, we address several neural network architectures used for analyzing the anatomical structures and lesions in the liver from various imaging modalities such as computed tomography, magnetic resonance imaging and ultrasound. Image analysis tasks like segmentation, object detection and classification for the liver, liver vessels and liver lesions are discussed. Based on the qualitative search, 91 papers were filtered out for the survey, including journal publications and conference proceedings. The papers reviewed in this work are grouped into eight categories based on the methodologies used. By comparing the evaluation metrics, hybrid models performed better for both the liver and the lesion segmentation tasks, ensemble classifiers performed better for the vessel segmentation tasks and combined approach performed better for both the lesion classification and detection tasks. The performance was measured based on the Dice score for the segmentation, and accuracy for the classification and detection tasks, which are the most commonly used metrics.publishedVersio

MR Imaging Texture Analysis in the Abdomen and Pelvis

Texture analysis (TA) is a form of radiomics and refers to quantitative measurements of the histogram, distribution and/or relationship of pixel intensities or gray scales within a region of interest on an image. TA can be applied to MRI of the abdomen and pelvis, with the main strength being quantitative analysis of pixel intensities and heterogeneity rather than subjective/qualitative analysis. There are multiple limitations of MR texture analysis (MRTA) including a dependency on image acquisition and reconstruction parameters, non-standardized approaches without or with image filtration, diverse software methods and applications, and statistical challenges relating numerous texture analysis results to clinical outcomes in retrospective pilot studies with small sample sizes. Despite these limitations, there is a growing body of literature supporting MRTA. In this review, the application of MRTA to the abdomen and pelvis will be discussed, including tissue or tumor characterization and response evaluation or prediction of outcomes in various tumors

Automated Characterisation and Classification of Liver Lesions From CT Scans

Cancer is a general term for a wide range of diseases that can affect any part of the body due to the rapid creation of abnormal cells that grow outside their normal boundaries. Liver cancer is one of the common diseases that cause the death of more than 600,000 each year. Early detection is important to diagnose and reduce the incidence of death. Examination of liver lesions is performed with various medical imaging modalities such as Ultrasound (US), Computer tomography (CT), and Magnetic resonance imaging (MRI). The improvements in medical imaging and image processing techniques have significantly enhanced the interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate. Moreover, CAD systems can help physician, as a second opinion, in characterising lesions and making the diagnostic decision. Thus, CAD systems have become an important research area. Particularly, these systems can provide diagnostic assistance to doctors to improve overall diagnostic accuracy. The traditional methods to characterise liver lesions and differentiate normal liver tissues from abnormal ones are largely dependent on the radiologists experience. Thus, CAD systems based on the image processing and artificial intelligence techniques gained a lot of attention, since they could provide constructive diagnosis suggestions to clinicians for decision making. The liver lesions are characterised through two ways: (1) Using a content-based image retrieval (CBIR) approach to assist the radiologist in liver lesions characterisation. (2) Calculating the high-level features that describe/ characterise the liver lesion in a way that is interpreted by humans, particularly Radiologists/Clinicians, based on the hand-crafted/engineered computational features (low-level features) and learning process. However, the research gap is related to the high-level understanding and interpretation of the medical image contents from the low-level pixel analysis, based on mathematical processing and artificial intelligence methods. In our work, the research gap is bridged if a relation of image contents to medical meaning in analogy to radiologist understanding is established. This thesis explores an automated system for the classification and characterisation of liver lesions in CT scans. Firstly, the liver is segmented automatically by using anatomic medical knowledge, histogram-based adaptive threshold and morphological operations. The lesions and vessels are then extracted from the segmented liver by applying AFCM and Gaussian mixture model through a region growing process respectively. Secondly, the proposed framework categorises the high-level features into two groups; the first group is the high-level features that are extracted from the image contents such as (Lesion location, Lesion focality, Calcified, Scar, ...); the second group is the high-level features that are inferred from the low-level features through machine learning process to characterise the lesion such as (Lesion density, Lesion rim, Lesion composition, Lesion shape,...). The novel Multiple ROIs selection approach is proposed, in which regions are derived from generating abnormality level map based on intensity difference and the proximity distance for each voxel with respect to the normal liver tissue. Then, the association between low-level, high-level features and the appropriate ROI are derived by assigning the ability of each ROI to represents a set of lesion characteristics. Finally, a novel feature vector is built, based on high-level features, and fed into SVM for lesion classification. In contrast with most existing research, which uses low-level features only, the use of high-level features and characterisation helps in interpreting and explaining the diagnostic decision. The methods are evaluated on a dataset containing 174 CT scans. The experimental results demonstrated that the efficacy of the proposed framework in the successful characterisation and classification of the liver lesions in CT scans. The achieved average accuracy was 95:56% for liver lesion characterisation. While the lesion’s classification accuracy was 97:1% for the entire dataset. The proposed framework is developed to provide a more robust and efficient lesion characterisation framework through comprehensions of the low-level features to generate semantic features. The use of high-level features (characterisation) helps in better interpretation of CT liver images. In addition, the difference-of-features using multiple ROIs were developed for robust capturing of lesion characteristics in a reliable way. This is in contrast to the current research trend of extracting the features from the lesion only and not paying much attention to the relation between lesion and surrounding area. The design of the liver lesion characterisation framework is based on the prior knowledge of the medical background to get a better and clear understanding of the liver lesion characteristics in medical CT images

Targeted Anti-Angiogenic Therapy in Metastatic Renal Cell Carcinoma and Methodological Improvements in Assessment of Therapeutic Response with Imaging Biomarkers

Background: Drugs targeting angiogenic pathway remain the mainstay of treatment for metastatic renal cell carcinoma (mRCC). Tyrosine Kinase Inhibitors (TKI) as Sunitinib, Pazopanib as single agents and humanised monoclonal antibody bevacizumab (Bev) in combination with Interferon- α2a (IFN) have established as the first-line therapy for mRCC. Despite improvements in treatment, there are multiple questions which remain unanswered. In the combination of Bev and IFN, the respective role of each drug and whether any additional anti-angiogenic activity is gained by adding IFN to Bev remains unknown. As the clinical benefit obtained with these cytostatic agents does not always correlate with the conventional response assessment techniques as RECIST, it is necessary to reconsider the methods by which we assess benefit from these therapies. In this thesis, I report three studies aiming to answer these questions. Methods: With the clinical trial reported here, I explore whether Bev induced changes in vascular parameters measured by Dynamic Contrast Enhanced MRI (DCE-MRI) is significantly enhanced by the addition of IFN. In a phase II, randomised, open labelled, multicentre trial, treatment naïve mRCC patients were randomised to receive Bev on its own or in combination with a low dose (3MU) or standard dose (9MU) IFN. DCE-MRI was used to assess the changes in vascularity with the primary endpoint being, changes in transfer coefficient (Ktrans) after six weeks of treatment. I also report two retrospective imaging-based studies, using contrast-enhanced CT scans, performed to improve the methodology of response assessment for these antiangiogenic therapeutics. Here I explore the use of a) combining changes in size and arterial phase contrast enhancement measured using CT scan and b) changes in CT texture as methods of therapeutic response assessment in mRCC patients treated with TKI. Results: With the phase 2 clinical trial, we faced significant difficulty in recruitment as a result of restrictions in access to treatment in NHS, other competing studies and restrictions proposed by the DCE-MRI inclusion criteria. With slow recruitment, an unplanned analysis was performed after 21 patients were recruited. Analysis of primary endpoint showed no trend in the difference between arms with no correlation found between change in Ktrans and addition of IFN to bevacizumab. Effect size analysis performed due to the small numbers recruited failed to show any significance in the observed difference in Ktrans. Change in Ktrans and Kep may identify a group of patients likely to have PFS > 6 months, but this observation needs to evaluation in a larger sample size. Measuring size and change in arterial phase enhancement retrospectively using CT, a new criterion "modified" Choi, which prerequisite a combination of a decrease in arterial phase density by 15% and a decrease in size by 10% for response was proposed. Response assessment was measured with RECIST, Choi and modified Choi individually in 20 evaluable patients retrospectively and clinical benefit compared with Kaplan-Meier statistics and Log-Rank test. Response assessment as defined by the modified Choi criteria successfully identified patients who received clinical benefit from the treatment. Time to progression (TTP) was 448 days for the partial response and 89 days for stable disease as per the new criteria which were statistically significant with a p-value of 0.002. The second retrospective analysis explored the textural changes in enhanced CT scan. Performed in collaboration with researchers from Brighton University who developed the software algorithm used to assess changes in entropy and uniformity, 87 metastases from 39 patients with mRCC were analysed at baseline and after two cycles of TKI treatment. Textural parameters and response assessment criteria were correlated with TTP. After two cycles of TKI, the decrease in tumour entropy was 3%-45%, and increase in uniformity was 5%-21%. At a threshold change of -2% with uniformity, on a coarse scale of 2.5, the textural change was able to separate responders from non-responders. With Kaplan-Meier analysis comparing all four criteria, the percentage change in uniformity was statistically more significant than for RECIST, Choi, and Modified Choi criteria. Cox regression analysis showed that texture uniformity was an independent predictor of time to progression. Discussion: With the studies reported here, I was able to demonstrate the importance of improving the methodology in assessment of therapeutic response to targeted anti-angiogenic therapy in metastatic renal cell carcinoma. Even though the clinical trial, terminated early due to slow recruitment, did not reach its primary endpoint, changes in other vascular parameters as Kep combined with changes Ktrans showed tendency towards identifying a group of patients who derived clinical benefit of >6months with these therapies. This is particularly exciting as given the vascular stabilisation effect proposed for bevacizumab, the effusion parameter Kep may be a better tool in assessing response rather than Ktrans and warrants further assessment in a larger cohort. Modified choi criterion and textural analysis are two important methodological improvements in response assessment of cytostatic anti-angiogenic therapy. In the analyses reported here, both techniques have shown superiority over RECIST in response assessment and differentiating mRCC patients who is likely to gain clinical benefit by TKI therapy. Validation of these criteria on a larger patient cohort is important. As these criterions are assessed on standard enhanced CT scans, incorporating these criteria, especially modified choi criterion, as part of standard CT assessment could be performed and will provide a real world validation. Retrospective assessment using larger cohort of patients from previous phase 3 trials or inclusion of these parameters prospectively in phase 3 trials would also help us in evaluating these modalities further