Quantitative Analysis of Dynamic Contrast-Enhanced Magnetic Resonance Breast Images: Optimization of the Time-to-Peak as a Diagnostic Indicator

Dynamic contrast-enhanced MRI (DCE-MRI) has been widely used in the diagnosis of breast cancer and as an aid in the management of this disease. Although DCE-MRI has a high sensitivity for the detection of malignant breast lesions, distinguishing malignant from benign lesions is more challenging for this method and may depend to some extent on how the images are analysed. Although clinical assessment of these images typically involves qualitative assessment by an expert, there is growing interest in the development of quantitative and automated methods to assist the expert assessment. This thesis involves the quantitative analysis of a particular empirical feature of the time evolution of the DCE-MRI signal known as the time-to-peak ( 7 ^ ) . In particular, this thesis investigates die feasibility of applying measures sensitive to 7 ^ heterogeneity as indicators for malignancy in breast DCE-MRI. Breast lesions in this study were automatically segmented by K-means clustering. Voxel- by-voxel 7\u27peak values were extracted using an empirical model. The / 1th percentile values (p = 10, 20...) of the 7’peak distribution within each lesion, as well as the fractional and absolute hot spot volumes were determined, where hot spot volume refers to the volume of tissue with 7 ^ less than a threshold value. Using the area under the receiver operating characteristic curve (AUC), these measures were tested as indicators for differentiating fibroadenomas from invasive lesions and from ductal carcinoma in situ, as well as for differentiating non-fibroadenoma benign lesions from these malignant lesions. For differentiating fibroadenomas from malignant lesions, low percentile values (p = 10) provided high diagnostic performance. At the optimal threshold (3 min), the hot spot volume provided high diagnostic performance. However, non-fibroadenoma benign lesions were quite difficult to distinguish from malignant lesions. This thesis demonstrates that quantitative analysis of the 7’peak distribution can be optimized for diagnostic performance providing indicators sensitive to intra-lesion r peak heterogeneity

Quantification of tumour heterogenity in MRI

Cancer is the leading cause of death that touches us all, either directly or indirectly. It is estimated that the number of newly diagnosed cases in the Netherlands will increase to 123,000 by the year 2020. General Dutch statistics are similar to those in the UK, i.e. over the last ten years, the age-standardised incidence rate1 has stabilised at around 355 females and 415 males per 100,000. Figure 1 shows the cancer incidence per gender. In the UK, the rise in lifetime risk of cancer is more than one in three and depends on many factors, including age, lifestyle and genetic makeup

Advanced perfusion quantification methods for dynamic PET and MRI data modelling

The functionality of tissues is guaranteed by the capillaries, which supply the microvascular network providing a considerable surface area for exchanges between blood and tissues. Microcirculation is affected by any pathological condition and any change in the blood supply can be used as a biomarker for the diagnosis of lesions and the optimization of the treatment. Nowadays, a number of techniques for the study of perfusion in vivo and in vitro are available. Among the several imaging modalities developed for the study of microcirculation, the analysis of the tissue kinetics of intravenously injected contrast agents or tracers is the most widely used technique. Tissue kinetics can be studied using different modalities: the positive enhancement of the signal in the computed tomography and in the ultrasound dynamic contrast enhancement imaging; T1-weighted MRI or the negative enhancement of T2* weighted MRI signal for the dynamic susceptibility contrast imaging or, finally, the uptake of radiolabelled tracers in dynamic PET imaging. Here we will focus on the perfusion quantification of dynamic PET and MRI data. The kinetics of the contrast agent (or the tracer) can be analysed visually, to define qualitative criteria but, traditionally, quantitative physiological parameters are extracted with the implementation of mathematical models. Serial measurements of the concentration of the tracer (or of the contrast agent) in the tissue of interest, together with the knowledge of an arterial input function, are necessary for the calculation of blood flow or perfusion rates from the wash-in and/or wash-out kinetic rate constants. The results depend on the acquisition conditions (type of imaging device, imaging mode, frequency and total duration of the acquisition), the type of contrast agent or tracer used, the data pre-processing (motion correction, attenuation correction, correction of the signal into concentration) and the data analysis method. As for the MRI, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique that can be used to measure properties of tissue microvasculature. It is sensitive to differences in blood volume and vascular permeability that can be associated with tumour angiogenesis. DCE-MRI has been investigated for a range of clinical oncologic applications (breast, prostate, cervix, liver, lung, and rectum) including cancer detection, diagnosis, staging, and assessment of treatment response. Tumour microvascular measurements by DCE-MRI have been found to correlate with prognostic factors (such as tumour grade, microvessel density, and vascular endothelial growth factor expression) and with recurrence and survival outcomes. Furthermore, DCE-MRI changes measured during treatment have been shown to correlate with outcome, suggesting a role as a predictive marker. The accuracy of DCE-MRI relies on the ability to model the pharmacokinetics of an injected contrast agent using the signal intensity changes on sequential magnetic resonance images. DCE-MRI data are usually quantified with the application of the pharmacokinetic two-compartment Tofts model (also known as the standard model), which represents the system with the plasma and tissue (extravascular extracellular space) compartments and with the contrast reagent exchange rates between them. This model assumes a negligible contribution from the vascular space and considers the system in, what-is-known as, the fast exchange limit, assuming infinitely fast transcytolemmal water exchange kinetics. In general, the number, as well as any assumption about the compartments, depends on the properties of the contrast agent used (mainly gadolinium) together with the tissue physiology or pathology studied. For this reason, the choice of the model is crucial in the analysis of DCE-MRI data. The value of PET in clinical oncology has been demonstrated with studies in a variety of cancers including colorectal carcinomas, lung tumours, head and neck tumours, primary and metastatic brain tumours, breast carcinoma, lymphoma, melanoma, bone cancers, and other soft-tissue cancers. PET studies of tumours can be performed for several reasons including the quantification of tumour perfusion, the evaluation of tumour metabolism, the tracing of radiolabelled cytostatic agents. In particular, the kinetic analysis of PET imaging has showed, in the past few years, an increasing value in tumour diagnosis, as well as in tumour therapy, through providing additional indicative parameters. Many authors have showed the benefit of kinetic analysis of anticancer drugs after labelling with radionuclide in measuring the specific therapeutic effect bringing to light the feasibility of applying the kinetic analysis to the dynamic acquisition. Quantification methods can involve visual analysis together with compartmental modelling and can be applied to a wide range of different tracers. The increased glycolysis in the most malignancies makes 18F-FDG-PET the most common diagnostic method used in tumour imaging. But, PET metabolic alteration in the target tissue can depend by many other factors. For example, most types of cancer are characterized by increased choline transport and by the overexpression of choline kinase in highly proliferating cells in response to enhanced demand of phosphatidylcholine (prostate, breast, lung, ovarian and colon cancers). This effect can be diagnosed with choline-based tracers as the 18Ffluoromethylcholine (18F-FCH), or the even more stable 18F-D4-Choline. Cellular proliferation is also imaged with 18F-fluorothymidine (FLT), which is trapped within the cytosol after being mono phosphorylated by thymidine kinase-1 (TK1), a principal enzyme in the salvage pathway of DNA synthesis. 18F-FLT has been found to be useful for noninvasive assessment of the proliferation rate of several types of cancer and showed high reproducibility and accuracy in breast and lung cancer tumours. The aim of this thesis is the perfusion quantification of dynamic PET and MRI data of patients with lung, brain, liver, prostate and breast lesions with the application of advanced models. This study covers a wide range of imaging methods and applications, presenting a novel combination of MRI-based perfusion measures with PET kinetic modelling parameters in oncology. It assesses the applicability and stability of perfusion quantification methods, which are not currently used in the routine clinical practice. The main achievements of this work include: 1) the assessment of the stability of perfusion quantification of D4-Choline and 18F-FLT dynamic PET data in lung and liver lesions, respectively (first applications in the literature); 2) the development of a model selection in the analysis of DCE-MRI data of primary brain tumours (first application of the extended shutter speed model); 3) the multiparametric analysis of PET and MRI derived perfusion measurements of primary brain tumour and breast cancer together with the integration of immuohistochemical markers in the prediction of breast cancer subtype (analysis of data acquired on the hybrid PET/MRI scanner). The thesis is structured as follows: - Chapter 1 is an introductive chapter on cancer biology. Basic concepts, including the causes of cancer, cancer hallmarks, available cancer treatments, are described in this first chapter. Furthermore, there are basic concepts of brain, breast, prostate and lung cancers (which are the lesions that have been analysed in this work). - Chapter 2 is about Positron Emission Tomography. After a brief introduction on the basics of PET imaging, together with data acquisition and reconstruction methods, the chapter focuses on PET in the clinical settings. In particular, it shows the quantification techniques of static and dynamic PET data and my results of the application of graphical methods, spectral analysis and compartmental models on dynamic 18F-FDG, 18F-FLT and 18F-D4- Choline PET data of patients with breast, lung cancer and hepatocellular carcinoma. - Chapter 3 is about Magnetic Resonance Imaging. After a brief introduction on the basics of MRI, the chapter focuses on the quantification of perfusion weighted MRI data. In particular, it shows the pharmacokinetic models for the quantification of dynamic contrast enhanced MRI data and my results of the application of the Tofts, the extended Tofts, the shutter speed and the extended shutter speed models on a dataset of patients with brain glioma. - Chapter 4 introduces the multiparametric imaging techniques, in particular the combined PET/CT and the hybrid PET/MRI systems. The last part of the chapter shows the applications of perfusion quantification techniques on a multiparametric study of breast tumour patients, who simultaneously underwent DCE-MRI and 18F-FDG PET on a hybrid PET/MRI scanner. Then the results of a predictive study on the same dataset of breast tumour patients integrated with immunohistochemical markers. Furthermore, the results of a multiparametric study on DCE-MRI and 18F-FCM brain data acquired both on a PET/CT scanner and on an MR scanner, separately. Finally, it will show the application of kinetic analysis in a radiomic study of patients with prostate cancer

Functional Magnetic Resonance Imaging of Breast Cancer

This thesis examines the use of magnetic resonance imaging (MRI) techniques in the detection of breast cancer and the prediction of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT). This thesis compares the diagnostic performance of diffusion-weighted imaging (DWI) models in the breast using a systematic review and meta-analysis. Advanced diffusion models have been proposed that may improve the performance of standard DWI using the apparent diffusion coefficient (ADC) to discriminate between malignant and benign breast lesions. Pooling the results from 73 studies, comparable diagnostic accuracy is shown using the ADC and parameters from the intra-voxel incoherent motion (IVIM) and diffusion tensor imaging (DTI) models. This work highlights a lack of standardisation in DWI protocols and methodology. Conventional acquisition techniques used in DWI often suffer from image artefacts and low spatial resolution. A multi-shot DWI technique, multiplexed sensitivity encoding (MUSE), can improve the image quality of DWI. A MUSE protocol has been optimised through a series of phantom experiments and validated in 20 patients. Comparing MUSE to conventional DWI, statistically significant improvements are shown in distortion and blurring metrics and qualitative image quality metrics such as lesion conspicuity and diagnostic confidence, increasing the clinical utility of DWI. This thesis investigates the use of dynamic contrast-enhanced MRI (DCE-MRI) in the detection of breast cancer and the prediction of pCR. Abbreviated MRI (ABB-MRI) protocols have gained increasing attention for the detection of breast cancer, acquiring a shortened version of a full diagnostic protocol (FDP-MRI) in a fraction of the time, reducing the cost of the examination. The diagnostic performance of abbreviated and full diagnostic protocols is systematically compared using a meta-analysis. Pooling 13 studies, equivalent diagnostic accuracy is shown for ABB-MRI in cohorts enriched with cancers, and lower but not significantly different diagnostic performance is shown in screening cohorts. Higher order imaging features derived from pre-treatment DCE-MRI could be used to predict pCR and inform decisions regarding targeted treatment, avoiding unnecessary toxicity. Using data from 152 patients undergoing NACT, radiomics features are extracted from baseline DCE-MRI and machine learning models trained to predict pCR with moderate accuracy. The stability of feature selection using logistic regression classification is demonstrated and a comparison of models trained using features from different time points in the dynamic series demonstrates that a full dynamic series enables the most accurate prediction of pCR.GE Healthcare funded PhD Studentshi

Beyond mammography : an evaluation of complementary modalities in breast imaging

Breast cancer is the main cause of cancer death among women worldwide and the goal of mammography screening is to reduce breast cancer-specific mortality. The reduction of the sensitivity of mammography for detecting cancer among women with dense breasts requires the use of complementary methods for this subset of women. Three of the projects in this thesis examine the performance of such complementary methods and a fourth study investigates the association between the biomarker BPE (background parenchymal enhancement) and risk factors for breast cancer. In study 1, we prospectively compared the sensitivity and specificity of Automated Breast Volume Scanner (ABVS) with handheld ultrasound for detection of breast cancer among women with a suspicious mammographic finding who were recalled after attending the population-based mammography screening program. We performed both methods on 113 women and found 26 malignant lesions. Analysis was performed in two categories: breasts with a suspicious screening mammography and breasts with a negative screening mammography. In the first category (n=118) the sensitivity of both methods was 88% (p=1.0), the specificity of handheld ultrasound was 93.5 % and ABVS was 89.2%. The difference in specificity was not statistically significant (p=0.29). For breasts without a suspicious mammographic finding, the sensitivity of handheld ultrasound and ABVS was 100% (p=1.0), the specificity was 100% and 94.1% respectively. The difference in specificity was statistically significant (p=0.03). In summary, ABVS has similar sensitivity to handheld ultrasound, but lower specificity in breasts with a negative mammogram. In study 2, we explored the incremental cancer detection rate when adding a threedimensional infrared imaging (3DIRI) score to screening mammography among women with dense breasts (Volpara volumetric density >6 % on the previous mammography examination) who attended the population-based mammography screening program. Women with a negative mammogram and positive 3DIRI score were triaged for a DCEMRI examination to verify the presence of cancer. Of 1727 participants, 7 women had a mammography-detected breast cancer. Among women with a negative mammogram and a positive infrared imaging (n=219), an additional 6 cancers in 5 women were detected on MRI resulting in an incremental cancer detection rate of 22.5 per 1000. Among women with a negative mammography and infrared examination, one woman was diagnosed with breast cancer during the two-year follow-up. The study does not provide information on the proportion of cancers that might have been detected had MRI been performed among women with a negative mammogram and 3DIRI score. Consequently, this study does not shed light on the diagnostic accuracy of infrared imaging or whether using an infrared risk score is the optimal method for identifying women who would benefit from additional imaging modalities. In study 3, we used MRI examinations of study 2 among women without breast cancer (n=214) to explore the association between BPE at DCE-MRI and a large array of risk factors for breast cancer. Thanks to the Karma database, we had unique access to data from self-reporting questionnaires on risk factors. BPE and mammographic density were assessed visually by three radiologists and BPE was further dichotomized into low and high. We created categorical variables for other risk factors. We calculated the univariable associations between BPE and each risk factor and fitted an adjusted logistic regression model. In the adjusted model, we found a negative association with age (p=0.002), and a positive association with BMI (p=0.03). There was a statistically significant association with systemic progesterone (p=0.03) but since only five participants used progesterone preparations, the result is uncertain. Although the likelihood for high BPE increased with increase in mammographic density, the association was not statistically significant (p=0.23). We were able to confirm earlier findings that BPE is associated with age, BMI and progesterone, but we could not find an association with other risk factors for breast cancer. In study 4, we compared the diagnostic accuracy, reading-time, and inter-rater agreement of an abbreviated protocol (aMRI) to the routine full protocol (fMRI) of contrast-enhanced breast MRI. The MRI examinations were performed before biopsy and among women who were not part of a surveillance program due to an increased familial risk of breast cancer. Analysis was performed on a per breast basis. Aggregated across three readers, the sensitivity and specificity were 93.0% and 91.7% for aMRI, and 92.0% and 94.3% for the fMRI. Using a generalized estimating equations approach to compare the two protocols, the difference in sensitivity was not statistically significant (p=0.840), and the difference in specificity was significant (p=0.003). There was a statistically significant difference in average reading time of 67 seconds for aMRI and 126 seconds for the fMRI (p= 0.000). The inter-rater agreement was 0.79 for aMRI and 0.83 for fMRI. We were able to demonstrate that the abbreviated protocol has similar sensitivity to the full protocol even if MRI is performed before biopsy and the images lack telltale signs of malignancy. In conclusion, this thesis provides new knowledge about the biomarker BPE, broadens our knowledge on the diagnostic accuracy of two different imaging modalities and highlights the importance of good study design for diagnostic accuracy studies

Morphological quantitation software in breast MRI: application to neoadjuvant chemotherapy patients

The work in this thesis examines the use of texture analysis techniques and shape descriptors to analyse MR images of the breast and their application as a potential quantitative tool for prognostic indication.Textural information is undoubtedly very heavily used in a radiologist’s decision making process. However, subtle variations in texture are often missed, thus by quantitatively analysing MR images the textural properties that would otherwise be impossible to discern by simply visually inspecting the image can be obtained. Texture analysis is commonly used in image classification of aerial and satellite photography, studies have also focussed on utilising texture in MRI especially in the brain. Recent research has focussed on other organs such as the breast wherein lesion morphology is known to be an important diagnostic and prognostic indicator. Recent work suggests benefits in assessing lesion texture in dynamic contrast-enhanced (DCE) images, especially with regards to changes during the initial enhancement and subsequent washout phases. The commonest form of analysis is the spatial grey-level dependence matrix method, but there is no direct evidence concerning the most appropriate pixel separation and number of grey levels to utilise in the required co-occurrence matrix calculations. The aim of this work is to systematically assess the efficacy of DCE-MRI based textural analysis in predicting response to chemotherapy in a cohort of breast cancer patients. In addition an attempt was made to use shape parameters in order to assess tumour surface irregularity, and as a predictor of response to chemotherapy.In further work this study aimed to texture map DCE MR images of breast patients utilising the co-occurrence method but on a pixel by pixel basis in order to determine threshold values for normal, benign and malignant tissue and ultimately creating functionality within the in house developed software to highlight hotspots outlining areas of interest (possible lesions). Benign and normal data was taken from MRI screening data and malignant data from patients referred with known malignancies.This work has highlighted that textural differences between groups (based on response, nodal status, triple negative and biopsy grade groupings) are apparent and appear to be most evident 1-3 minutes post-contrast administration. Whilst the large number of statistical tests undertaken necessitates a degree of caution in interpreting the results, the fact that significant differences for certain texture parameters and groupings are consistently observed is encouraging.With regards to shape analysis this thesis has highlighted that some differences between groups were seen in shape descriptors but that shape may be limited as a prognostic indicator. Using textural analysis gave a higher proportion of significant differences whilst shape analysis results showed inconsistency across time points.With regards to the mapping this work successfully analysed the texture maps for each case and established lesion detection is possible. The study successfully highlighted hotspots in the breast patients data post texture mapping, and has demonstrated the relationship between sensitivity and false positive rate via hotspot thresholding

Emerging Techniques in Breast MRI

As indicated throughout this chapter, there is a constant effort to move to more sensitive, specific, and quantitative methods for characterizing breast tissue via magnetic resonance imaging (MRI). In the present chapter, we focus on six emerging techniques that seek to quantitatively interrogate the physiological and biochemical properties of the breast. At the physiological scale, we present an overview of ultrafast dynamic contrast-enhanced MRI and magnetic resonance elastography which provide remarkable insights into the vascular and mechanical properties of tissue, respectively. Moving to the biochemical scale, magnetization transfer, chemical exchange saturation transfer, and spectroscopy (both “conventional” and hyperpolarized) methods all provide unique, noninvasive, insights into tumor metabolism. Given the breadth and depth of information that can be obtained in a single MRI session, methods of data synthesis and interpretation must also be developed. Thus, we conclude the chapter with an introduction to two very different, though complementary, methods of data analysis: (1) radiomics and habitat imaging, and (2) mechanism-based mathematical modeling

PET-MR Imaging of Hypoxia and Vascularity in Breast Cancer

Breast cancer is the most common cancer in the UK and in women globally. Imaging methods like mammography, ultrasound (US) and magnetic resonance imaging (MRI) play an important role in the diagnosis and management of breast cancer; they are generally utilised to provide anatomical or structural description of tumours in the clinical setting. It is widely accepted that the tumour microenvironment influences the phenotype, progression and treatment of breast cancer. This gave the impetus to move beyond tumour visualization in images to radiomics in order to provide additional disease characterisation and early biomarkers of tumour response. Due to their ability to assess physiological processes in vivo, positron emission tomography (PET) and MRI can provide non-invasive characterisation of the tumour microenvironment, including perfusion, vascular permeability, cellularity and hypoxia, which is associated with poor clinical outcome and metastasis. Clinical imaging studies in breast tumours have hitherto assessed tumour physiological parameters separately, with only few directly comparing data from these modalities. To this end, hybrid PET-MRI represents an attractive option as it can allow examination of functional processes and features of tumours simultaneously, while also conferring methodological advantages to the way imaging information is combined. The main aim of this thesis is to provide a better understanding of breast cancer pathophysiology using simultaneous PET and multi-parametric MRI. In particular, this work aims to explore relationships between imaging biomarkers of tumour vascularity measured by dynamic contrast-enhanced (DCE) MRI, cellularity using diffusion-weighted imaging (DWI) and hypoxic status using 18F-fluoromisonidazole (18F-FMISO) PET. Correlations between functional PET-MRI parameters and immunohistochemical (IHC) biomarkers of hypoxia and vascularity as well as MRI morphological tumour descriptors are also presented. The thesis concludes with an investigation of the utility of MRI markers of perfusion and surrogate markers of hypoxia to quantitatively monitor and predict pathological response in patients undergoing neoadjuvant chemotherapy (NACT) and provides projections for future work

Analysis of contrast-enhanced medical images.

Early detection of human organ diseases is of great importance for the accurate diagnosis and institution of appropriate therapies. This can potentially prevent progression to end-stage disease by detecting precursors that evaluate organ functionality. In addition, it also assists the clinicians for therapy evaluation, tracking diseases progression, and surgery operations. Advances in functional and contrast-enhanced (CE) medical images enabled accurate noninvasive evaluation of organ functionality due to their ability to provide superior anatomical and functional information about the tissue-of-interest. The main objective of this dissertation is to develop a computer-aided diagnostic (CAD) system for analyzing complex data from CE magnetic resonance imaging (MRI). The developed CAD system has been tested in three case studies: (i) early detection of acute renal transplant rejection, (ii) evaluation of myocardial perfusion in patients with ischemic heart disease after heart attack; and (iii), early detection of prostate cancer. However, developing a noninvasive CAD system for the analysis of CE medical images is subject to multiple challenges, including, but are not limited to, image noise and inhomogeneity, nonlinear signal intensity changes of the images over the time course of data acquisition, appearances and shape changes (deformations) of the organ-of-interest during data acquisition, determination of the best features (indexes) that describe the perfusion of a contrast agent (CA) into the tissue. To address these challenges, this dissertation focuses on building new mathematical models and learning techniques that facilitate accurate analysis of CAs perfusion in living organs and include: (i) accurate mathematical models for the segmentation of the object-of-interest, which integrate object shape and appearance features in terms of pixel/voxel-wise image intensities and their spatial interactions; (ii) motion correction techniques that combine both global and local models, which exploit geometric features, rather than image intensities to avoid problems associated with nonlinear intensity variations of the CE images; (iii) fusion of multiple features using the genetic algorithm. The proposed techniques have been integrated into CAD systems that have been tested in, but not limited to, three clinical studies. First, a noninvasive CAD system is proposed for the early and accurate diagnosis of acute renal transplant rejection using dynamic contrast-enhanced MRI (DCE-MRI). Acute rejection–the immunological response of the human immune system to a foreign kidney–is the most sever cause of renal dysfunction among other diagnostic possibilities, including acute tubular necrosis and immune drug toxicity. In the U.S., approximately 17,736 renal transplants are performed annually, and given the limited number of donors, transplanted kidney salvage is an important medical concern. Thus far, biopsy remains the gold standard for the assessment of renal transplant dysfunction, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The diagnostic results of the proposed CAD system, based on the analysis of 50 independent in-vivo cases were 96% with a 95% confidence interval. These results clearly demonstrate the promise of the proposed image-based diagnostic CAD system as a supplement to the current technologies, such as nuclear imaging and ultrasonography, to determine the type of kidney dysfunction. Second, a comprehensive CAD system is developed for the characterization of myocardial perfusion and clinical status in heart failure and novel myoregeneration therapy using cardiac first-pass MRI (FP-MRI). Heart failure is considered the most important cause of morbidity and mortality in cardiovascular disease, which affects approximately 6 million U.S. patients annually. Ischemic heart disease is considered the most common underlying cause of heart failure. Therefore, the detection of the heart failure in its earliest forms is essential to prevent its relentless progression to premature death. While current medical studies focus on detecting pathological tissue and assessing contractile function of the diseased heart, this dissertation address the key issue of the effects of the myoregeneration therapy on the associated blood nutrient supply. Quantitative and qualitative assessment in a cohort of 24 perfusion data sets demonstrated the ability of the proposed framework to reveal regional perfusion improvements with therapy, and transmural perfusion differences across the myocardial wall; thus, it can aid in follow-up on treatment for patients undergoing the myoregeneration therapy. Finally, an image-based CAD system for early detection of prostate cancer using DCE-MRI is introduced. Prostate cancer is the most frequently diagnosed malignancy among men and remains the second leading cause of cancer-related death in the USA with more than 238,000 new cases and a mortality rate of about 30,000 in 2013. Therefore, early diagnosis of prostate cancer can improve the effectiveness of treatment and increase the patient’s chance of survival. Currently, needle biopsy is the gold standard for the diagnosis of prostate cancer. However, it is an invasive procedure with high costs and potential morbidity rates. Additionally, it has a higher possibility of producing false positive diagnosis due to relatively small needle biopsy samples. Application of the proposed CAD yield promising results in a cohort of 30 patients that would, in the near future, represent a supplement of the current technologies to determine prostate cancer type. The developed techniques have been compared to the state-of-the-art methods and demonstrated higher accuracy as shown in this dissertation. The proposed models (higher-order spatial interaction models, shape models, motion correction models, and perfusion analysis models) can be used in many of today’s CAD applications for early detection of a variety of diseases and medical conditions, and are expected to notably amplify the accuracy of CAD decisions based on the automated analysis of CE images