Diffusion-weighted magnetic resonance imaging in diagnosing graft dysfunction : a non-invasive alternative to renal biopsy.

The thesis is divided into three parts. The first part focuses on background information including how the kidney functions, diseases, and available kidney disease treatment strategies. In addition, the thesis provides information on imaging instruments and how they can be used to diagnose renal graft dysfunction. The second part focuses on elucidating the parameters linked with highly accurate diagnosis of rejection. Four parameters categories were tested: clinical biomarkers alone, individual mean apparent diffusion coefficient (ADC) at 11-different b- values, mean ADCs of certain groups of b-value, and fusion of clinical biomarkers and all b-values. The most accurate model was found to be when the b-value of b=100 s/mm2 and b=700 s/mm2 were fused. The third part of this thesis focuses on a study that uses Diffusion-Weighted MRI to diagnose and differentiate two types of renal rejection. The system was found to correctly differentiate the two types of rejection with a 98% accuracy. The last part of this thesis concludes the work that has been done and states the possible trends and future avenues

Role of machine learning in early diagnosis of kidney diseases.

Machine learning (ML) and deep learning (DL) approaches have been used as indispensable tools in modern artificial intelligence-based computer-aided diagnostic (AIbased CAD) systems that can provide non-invasive, early, and accurate diagnosis of a given medical condition. These AI-based CAD systems have proven themselves to be reproducible and have the generalization ability to diagnose new unseen cases with several diseases and medical conditions in different organs (e.g., kidneys, prostate, brain, liver, lung, breast, and bladder). In this dissertation, we will focus on the role of such AI-based CAD systems in early diagnosis of two kidney diseases, namely: acute rejection (AR) post kidney transplantation and renal cancer (RC). A new renal computer-assisted diagnostic (Renal-CAD) system was developed to precisely diagnose AR post kidney transplantation at an early stage. The developed Renal-CAD system perform the following main steps: (1) auto-segmentation of the renal allograft from surrounding tissues from diffusion weighted magnetic resonance imaging (DW-MRI) and blood oxygen level-dependent MRI (BOLD-MRI), (2) extraction of image markers, namely: voxel-wise apparent diffusion coefficients (ADCs) are calculated from DW-MRI scans at 11 different low and high b-values and then represented as cumulative distribution functions (CDFs) and extraction of the transverse relaxation rate (R2*) values from the segmented kidneys using BOLD-MRI scans at different echotimes, (3) integration of multimodal image markers with the associated clinical biomarkers, serum creatinine (SCr) and creatinine clearance (CrCl), and (4) diagnosing renal allograft status as nonrejection (NR) or AR by utilizing these integrated biomarkers and the developed deep learning classification model built on stacked auto-encoders (SAEs). Using a leaveone- subject-out cross-validation approach along with SAEs on a total of 30 patients with transplanted kidney (AR = 10 and NR = 20), the Renal-CAD system demonstrated 93.3% accuracy, 90.0% sensitivity, and 95.0% specificity in differentiating AR from NR. Robustness of the Renal-CAD system was also confirmed by the area under the curve value of 0.92. Using a stratified 10-fold cross-validation approach, the Renal-CAD system demonstrated its reproduciblity and robustness with a diagnostic accuracy of 86.7%, sensitivity of 80.0%, specificity of 90.0%, and AUC of 0.88. In addition, a new renal cancer CAD (RC-CAD) system for precise diagnosis of RC at an early stage was developed, which incorporates the following main steps: (1) estimating the morphological features by applying a new parametric spherical harmonic technique, (2) extracting appearance-based features, namely: first order textural features are calculated and second order textural features are extracted after constructing the graylevel co-occurrence matrix (GLCM), (3) estimating the functional features by constructing wash-in/wash-out slopes to quantify the enhancement variations across different contrast enhanced computed tomography (CE-CT) phases, (4) integrating all the aforementioned features and modeling a two-stage multilayer perceptron artificial neural network (MLPANN) classifier to classify the renal tumor as benign or malignant and identify the malignancy subtype. On a total of 140 RC patients (malignant = 70 patients (ccRCC = 40 and nccRCC = 30) and benign angiomyolipoma tumors = 70), the developed RC-CAD system was validated using a leave-one-subject-out cross-validation approach. The developed RC-CAD system achieved a sensitivity of 95.3% ± 2.0%, a specificity of 99.9% ± 0.4%, and Dice similarity coefficient of 0.98 ± 0.01 in differentiating malignant from benign renal tumors, as well as an overall accuracy of 89.6% ± 5.0% in the sub-typing of RCC. The diagnostic abilities of the developed RC-CAD system were further validated using a randomly stratified 10-fold cross-validation approach. The results obtained using the proposed MLP-ANN classification model outperformed other machine learning classifiers (e.g., support vector machine, random forests, and relational functional gradient boosting) as well as other different approaches from the literature. In summary, machine and deep learning approaches have shown potential abilities to be utilized to build AI-based CAD systems. This is evidenced by the promising diagnostic performance obtained by both Renal-CAD and RC-CAD systems. For the Renal- CAD, the integration of functional markers extracted from multimodal MRIs with clinical biomarkers using SAEs classification model, potentially improved the final diagnostic results evidenced by high accuracy, sensitivity, and specificity. The developed Renal-CAD demonstrated high feasibility and efficacy for early, accurate, and non-invasive identification of AR. For the RC-CAD, integrating morphological, textural, and functional features extracted from CE-CT images using a MLP-ANN classification model eventually enhanced the final results in terms of accuracy, sensitivity, and specificity, making the proposed RC-CAD a reliable noninvasive diagnostic tool for RC. The early and accurate diagnosis of AR or RC will help physicians to provide early intervention with the appropriate treatment plan to prolong the life span of the diseased kidney, increase the survival chance of the patient, and thus improve the healthcare outcome in the U.S. and worldwide

Role of deep learning techniques in non-invasive diagnosis of human diseases.

Machine learning, a sub-discipline in the domain of artificial intelligence, concentrates on algorithms able to learn and/or adapt their structure (e.g., parameters) based on a set of observed data. The adaptation is performed by optimizing over a cost function. Machine learning obtained a great attention in the biomedical community because it offers a promise for improving sensitivity and/or specificity of detection and diagnosis of diseases. It also can increase objectivity of the decision making, decrease the time and effort on health care professionals during the process of disease detection and diagnosis. The potential impact of machine learning is greater than ever due to the increase in medical data being acquired, the presence of novel modalities being developed and the complexity of medical data. In all of these scenarios, machine learning can come up with new tools for interpreting the complex datasets that confront clinicians. Much of the excitement for the application of machine learning to biomedical research comes from the development of deep learning which is modeled after computation in the brain. Deep learning can help in attaining insights that would be impossible to obtain through manual analysis. Deep learning algorithms and in particular convolutional neural networks are different from traditional machine learning approaches. Deep learning algorithms are known by their ability to learn complex representations to enhance pattern recognition from raw data. On the other hand, traditional machine learning requires human engineering and domain expertise to design feature extractors and structure data. With increasing demands upon current radiologists, there are growing needs for automating the diagnosis. This is a concern that deep learning is able to address. In this dissertation, we present four different successful applications of deep learning for diseases diagnosis. All the work presented in the dissertation utilizes medical images. In the first application, we introduce a deep-learning based computer-aided diagnostic system for the early detection of acute renal transplant rejection. The system is based on the fusion of both imaging markers (apparent diffusion coefficients derived from diffusion-weighted magnetic resonance imaging) and clinical biomarkers (creatinine clearance and serum plasma creatinine). The fused data is then used as an input to train and test a convolutional neural network based classifier. The proposed system is tested on scans collected from 56 subjects from geographically diverse populations and different scanner types/image collection protocols. The overall accuracy of the proposed system is 92.9% with 93.3% sensitivity and 92.3% specificity in distinguishing non-rejected kidney transplants from rejected ones. In the second application, we propose a novel deep learning approach for the automated segmentation and quantification of the LV from cardiac cine MR images. We aimed at achieving lower errors for the estimated heart parameters compared to the previous studies by proposing a novel deep learning segmentation method. Using fully convolutional neural networks, we proposed novel methods for the extraction of a region of interest that contains the left ventricle, and the segmentation of the left ventricle. Following myocardial segmentation, functional and mass parameters of the left ventricle are estimated. Automated Cardiac Diagnosis Challenge dataset was used to validate our framework, which gave better segmentation, accurate estimation of cardiac parameters, and produced less error compared to other methods applied on the same dataset. Furthermore, we showed that our segmentation approach generalizes well across different datasets by testing its performance on a locally acquired dataset. In the third application, we propose a novel deep learning approach for automated quantification of strain from cardiac cine MR images of mice. For strain analysis, we developed a Laplace-based approach to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. Following tracking, the strain estimation is performed using the Lagrangian-based approach. This new automated system for strain analysis was validated by comparing the outcome of these analysis with the tagged MR images from the same mice. There were no significant differences between the strain data obtained from our algorithm using cine compared to tagged MR imaging. In the fourth application, we demonstrate how a deep learning approach can be utilized for the automated classification of kidney histopathological images. Our approach can classify four classes: the fat, the parenchyma, the clear cell renal cell carcinoma, and the unusual cancer which has been discovered recently, called clear cell papillary renal cell carcinoma. Our framework consists of three convolutional neural networks and the whole-slide kidney images were divided into patches with three different sizes to be inputted to the networks. Our approach can provide patch-wise and pixel-wise classification. Our approach classified the four classes accurately and surpassed other state-of-the-art methods such as ResNet (pixel accuracy: 0.89 Resnet18, 0.93 proposed). In conclusion, the results of our proposed systems demonstrate the potential of deep learning for the efficient, reproducible, fast, and affordable disease diagnosis

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

A non-invasive image based system for early diagnosis of prostate cancer.

Prostate cancer is the second most fatal cancer experienced by American males. The average American male has a 16.15% chance of developing prostate cancer, which is 8.38% higher than lung cancer, the second most likely cancer. The current in-vitro techniques that are based on analyzing a patients blood and urine have several limitations concerning their accuracy. In addition, the prostate Specific Antigen (PSA) blood-based test, has a high chance of false positive diagnosis, ranging from 28%-58%. Yet, biopsy remains the gold standard for the assessment of prostate cancer, but only as the last resort because of its invasive nature, high cost, and potential morbidity rates. The major limitation of the relatively small needle biopsy samples is the higher possibility of producing false positive diagnosis. Moreover, the visual inspection system (e.g., Gleason grading system) is not quantitative technique and different observers may classify a sample differently, leading to discrepancies in the diagnosis. As reported in the literature that the early detection of prostate cancer is a crucial step for decreasing prostate cancer related deaths. Thus, there is an urgent need for developing objective, non-invasive image based technology for early detection of prostate cancer. The objective of this dissertation is to develop a computer vision methodology, later translated into a clinically usable software tool, which can improve sensitivity and specificity of early prostate cancer diagnosis based on the well-known hypothesis that malignant tumors are will connected with the blood vessels than the benign tumors. Therefore, using either Diffusion Weighted Magnetic Resonance imaging (DW-MRI) or Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI), we will be able to interrelate the amount of blood in the detected prostate tumors by estimating either the Apparent Diffusion Coefficient (ADC) in the prostate with the malignancy of the prostate tumor or perfusion parameters. We intend to validate this hypothesis by demonstrating that automatic segmentation of the prostate from either DW-MRI or DCE-MRI after handling its local motion, provides discriminatory features for early prostate cancer diagnosis. The proposed CAD system consists of three majors components, the first two of which constitute new research contributions to a challenging computer vision problem. The three main components are: (1) A novel Shape-based segmentation approach to segment the prostate from either low contrast DW-MRI or DCE-MRI data; (2) A novel iso-contours-based non-rigid registration approach to ensure that we have voxel-on-voxel matches of all data which may be more difficult due to gross patient motion, transmitted respiratory effects, and intrinsic and transmitted pulsatile effects; and (3) Probabilistic models for the estimated diffusion and perfusion features for both malignant and benign tumors. Our results showed a 98% classification accuracy using Leave-One-Subject-Out (LOSO) approach based on the estimated ADC for 30 patients (12 patients diagnosed as malignant; 18 diagnosed as benign). These results show the promise of the proposed image-based diagnostic technique as a supplement to current technologies for diagnosing prostate cancer

A non-invasive diagnostic system for early assessment of acute renal transplant rejection.

Early diagnosis of acute renal transplant rejection (ARTR) is of immense importance for appropriate therapeutic treatment administration. Although the current diagnostic technique is based on renal biopsy, it is not preferred due to its invasiveness, recovery time (1-2 weeks), and potential for complications, e.g., bleeding and/or infection. In this thesis, a computer-aided diagnostic (CAD) system for early detection of ARTR from 4D (3D + b-value) diffusion-weighted (DW) MRI data is developed. The CAD process starts from a 3D B-spline-based data alignment (to handle local deviations due to breathing and heart beat) and kidney tissue segmentation with an evolving geometric (level-set-based) deformable model. The latter is guided by a voxel-wise stochastic speed function, which follows from a joint kidney-background Markov-Gibbs random field model accounting for an adaptive kidney shape prior and for on-going visual kidney-background appearances. A cumulative empirical distribution of apparent diffusion coefficient (ADC) at different b-values of the segmented DW-MRI is considered a discriminatory transplant status feature. Finally, a classifier based on deep learning of a non-negative constrained stacked auto-encoder is employed to distinguish between rejected and non-rejected renal transplants. In the “leave-one-subject-out” experiments on 53 subjects, 98% of the subjects were correctly classified (namely, 36 out of 37 rejected transplants and 16 out of 16 nonrejected ones). Additionally, a four-fold cross-validation experiment was performed, and an average accuracy of 96% was obtained. These experimental results hold promise of the proposed CAD system as a reliable non-invasive diagnostic tool

Fast and robust hybrid framework for infant brain classification from structural MRI : a case study for early diagnosis of autism.

The ultimate goal of this work is to develop a computer-aided diagnosis (CAD) system for early autism diagnosis from infant structural magnetic resonance imaging (MRI). The vital step to achieve this goal is to get accurate segmentation of the different brain structures: whitematter, graymatter, and cerebrospinal fluid, which will be the main focus of this thesis. The proposed brain classification approach consists of two major steps. First, the brain is extracted based on the integration of a stochastic model that serves to learn the visual appearance of the brain texture, and a geometric model that preserves the brain geometry during the extraction process. Secondly, the brain tissues are segmented based on shape priors, built using a subset of co-aligned training images, that is adapted during the segmentation process using first- and second-order visual appearance features of infant MRIs. The accuracy of the presented segmentation approach has been tested on 300 infant subjects and evaluated blindly on 15 adult subjects. The experimental results have been evaluated by the MICCAI MR Brain Image Segmentation (MRBrainS13) challenge organizers using three metrics: Dice coefficient, 95-percentile Hausdorff distance, and absolute volume difference. The proposed method has been ranked the first in terms of performance and speed

A novel diffusion tensor imaging-based computer-aided diagnostic system for early diagnosis of autism.

Autism spectrum disorders (ASDs) denote a significant growing public health concern. Currently, one in 68 children has been diagnosed with ASDs in the United States, and most children are diagnosed after the age of four, despite the fact that ASDs can be identified as early as age two. The ultimate goal of this thesis is to develop a computer-aided diagnosis (CAD) system for the accurate and early diagnosis of ASDs using diffusion tensor imaging (DTI). This CAD system consists of three main steps. First, the brain tissues are segmented based on three image descriptors: a visual appearance model that has the ability to model a large dimensional feature space, a shape model that is adapted during the segmentation process using first- and second-order visual appearance features, and a spatially invariant second-order homogeneity descriptor. Secondly, discriminatory features are extracted from the segmented brains. Cortex shape variability is assessed using shape construction methods, and white matter integrity is further examined through connectivity analysis. Finally, the diagnostic capabilities of these extracted features are investigated. The accuracy of the presented CAD system has been tested on 25 infants with a high risk of developing ASDs. The preliminary diagnostic results are promising in identifying autistic from control patients

A CAD system for early diagnosis of autism using different imaging modalities.

The term “autism spectrum disorder” (ASD) refers to a collection of neuro-developmental disorders that affect linguistic, behavioral, and social skills. Autism has many symptoms, most prominently, social impairment and repetitive behaviors. It is crucial to diagnose autism at an early stage for better assessment and investigation of this complex syndrome. There have been a lot of efforts to diagnose ASD using different techniques, such as imaging modalities, genetic techniques, and behavior reports. Imaging modalities have been extensively exploited for ASD diagnosis, and one of the most successful ones is Magnetic resonance imaging(MRI),where it has shown promise for the early diagnosis of the ASD related abnormalities in particular. Magnetic resonance imaging (MRI) modalities have emerged as powerful means that facilitate non-invasive clinical diagnostics of various diseases and abnormalities since their inception in the 1980s. After the advent in the nineteen eighties, MRI soon became one of the most promising non- invasive modalities for visualization and diagnostics of ASD-related abnormalities. Along with its main advantage of no exposure to radiation, high contrast, and spatial resolution, the recent advances to MRI modalities have notably increased diagnostic certainty. Multiple MRI modalities, such as different types of structural MRI (sMRI) that examines anatomical changes, and functional MRI (fMRI) that examines brain activity by monitoring blood flow changes,have been employed to investigate facets of ASD in order to better understand this complex syndrome. This work aims at developing a new computer-aided diagnostic (CAD) system for autism diagnosis using different imaging modalities. It mainly relies on making use of structural magnetic resonance images for extracting notable shape features from parts of the brainthat proved to correlate with ASD from previous neuropathological studies. Shape features from both the cerebral cortex (Cx) and cerebral white matter(CWM)are extracted. Fusion of features from these two structures is conducted based on the recent findings suggesting that Cx changes in autism are related to CWM abnormalities. Also, when fusing features from more than one structure, this would increase the robustness of the CAD system. Moreover, fMRI experiments are done and analyzed to find areas of activation in the brains of autistic and typically developing individuals that are related to a specific task. All sMRI findings are fused with those of fMRI to better understand ASD in terms of both anatomy and functionality,and thus better classify the two groups. This is one aspect of the novelty of this CAD system, where sMRI and fMRI studies are both applied on subjects from different ages to diagnose ASD. In order to build such a CAD system, three main blocks are required. First, 3D brain segmentation is applied using a novel hybrid model that combines shape, intensity, and spatial information. Second, shape features from both Cx and CWM are extracted and anf MRI reward experiment is conducted from which areas of activation that are related to the task of this experiment are identified. Those features were extracted from local areas of the brain to provide an accurate analysis of ASD and correlate it with certain anatomical areas. Third and last, fusion of all the extracted features is done using a deep-fusion classification network to perform classification and obtain the diagnosis report. Fusing features from all modalities achieved a classification accuracy of 94.7%, which emphasizes the significance of combining structures/modalities for ASD diagnosis. To conclude, this work could pave the pathway for better understanding of the autism spectrum by finding local areas that correlate to the disease. The idea of personalized medicine is emphasized in this work, where the proposed CAD system holds the promise to resolve autism endophenotypes and help clinicians deliver personalized treatment to individuals affected with this complex syndrome

A novel NMF-based DWI CAD framework for prostate cancer.

In this thesis, a computer aided diagnostic (CAD) framework for detecting prostate cancer in DWI data is proposed. The proposed CAD method consists of two frameworks that use nonnegative matrix factorization (NMF) to learn meaningful features from sets of high-dimensional data. The first technique, is a three dimensional (3D) level-set DWI prostate segmentation algorithm guided by a novel probabilistic speed function. This speed function is driven by the features learned by NMF from 3D appearance, shape, and spatial data. The second technique, is a probabilistic classifier that seeks to label a prostate segmented from DWI data as either alignat, contain cancer, or benign, containing no cancer. This approach uses a NMF-based feature fusion to create a feature space where data classes are clustered. In addition, using DWI data acquired at a wide range of b-values (i.e. magnetic field strengths) is investigated. Experimental analysis indicates that for both of these frameworks, using NMF producing more accurate segmentation and classification results, respectively, and that combining the information from DWI data at several b-values can assist in detecting prostate cancer