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

The introduction of capillary structures in 4D simulated vascular tree for ART 3.5D algorithm further validation

open6openBarra, Beatrice; El Hadji, Sara; De Momi, Elena; Ferrigno, Giancarlo; Cardinale, Francesco; Baselli, GiuseppeBarra, Beatrice; EL HADJI, Sara; DE MOMI, Elena; Ferrigno, Giancarlo; Cardinale, Francesco; Baselli, Giusepp

Spatio-Temporal U-Net for Cerebral Artery and Vein Segmentation in Digital Subtraction Angiography

X-ray digital subtraction angiography (DSA) is widely used for vessel and/or flow visualization and interventional guidance during endovascular treatment of patients with a stroke or aneurysm. To assist in peri-operative decision making as well as post-operative prognosis, automatic DSA analysis algorithms are being developed to obtain relevant image-based information. Such analyses include detection of vascular disease, evaluation of perfusion based on time intensity curves (TIC), and quantitative biomarker extraction for automated treatment evaluation in endovascular thrombectomy. Methodologically, such vessel-based analysis tasks may be facilitated by automatic and accurate artery-vein segmentation algorithms. The present work describes to the best of our knowledge the first study that addresses automatic artery-vein segmentation in DSA using deep learning. We propose a novel spatio-temporal U-Net (ST U-Net) architecture which integrates convolutional gated recurrent units (ConvGRU) in the contracting branch of U-Net. The network encodes a 2D+t DSA series of variable length and decodes it into a 2D segmentation image. On a multi-center routinely acquired dataset, the proposed method significantly outperformed U-Net (P<0.001) and traditional Frangi-based K-means clustering (P$<$0.001). Particularly in artery-vein segmentation, ST U-Net achieved a Dice coefficient of 0.794, surpassing the existing state-of-the-art methods by a margin of 12\%-20\%. Code will be made publicly available upon acceptance

Numerical algorithm to recover contrast dynamics in 3D digital subtraction angiography data-sets: a preliminary clinical validation

Several neurosurgical procedures, such as ArteroVenous Malformations (AVMs) and StereoElectroEncephaloGraphy (SEEG) require accurate reconstruction of the cerebral vascular tree, as well as the classification of arteries and veins, to increase the safety of the intervention. We propose ART-3.5D, a novel approach to recover the dynamic information from standard Cone Beam Computed Tomography Angiography scans based on the post- processing of both the segmented angiogram and the raw data-set

ART 3.5D: an algorithm to label arteries and veins from three-dimensional angiography

Preoperative three-dimensional (3-D) visualization of brain vasculature by digital subtraction angiography from computerized tomography (CT) in neurosurgery is gaining more and more importance, since vessels are the primary landmarks both for organs at risk and for navigation. Surgical embolization of cerebral aneurysms and arteriovenous malformations, epilepsy surgery, and stereoelectroencephalography are a few examples. Contrast-enhanced cone-beam computed tomography (CE-CBCT) represents a powerful facility, since it is capable of acquiring images in the operation room, shortly before surgery. However, standard 3-D reconstructions do not provide a direct distinction between arteries and veins, which is of utmost importance and is left to the surgeon's inference so far. Pioneering attempts by true four-dimensional (4-D) CT perfusion scans were already described, though at the expense of longer acquisition protocols, higher dosages, and sensible resolution losses. Hence, space is open to approaches attempting to recover the contrast dynamics from standard CE-CBCT, on the basis of anomalies overlooked in the standard 3-D approach. This paper aims at presenting algebraic reconstruction technique (ART) 3.5D, a method that overcomes the clinical limitations of 4-D CT, from standard 3-D CE-CBCT scans. The strategy works on the 3-D angiography, previously segmented in the standard way, and reprocesses the dynamics hidden in the raw data to recover an approximate dynamics in each segmented voxel. Next, a classification algorithm labels the angiographic voxels and artery or vein. Numerical simulations were performed on a digital phantom of a simplified 3-D vasculature with contrast transit. CE-CBCT projections were simulated and used for ART 3.5D testing. We achieved up to 90% classification accuracy in simulations, proving the feasibility of the presented approach for dynamic information recovery for arteries and veins segmentation

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

Human Treelike Tubular Structure Segmentation: A Comprehensive Review and Future Perspectives

Various structures in human physiology follow a treelike morphology, which often expresses complexity at very fine scales. Examples of such structures are intrathoracic airways, retinal blood vessels, and hepatic blood vessels. Large collections of 2D and 3D images have been made available by medical imaging modalities such as magnetic resonance imaging (MRI), computed tomography (CT), Optical coherence tomography (OCT) and ultrasound in which the spatial arrangement can be observed. Segmentation of these structures in medical imaging is of great importance since the analysis of the structure provides insights into disease diagnosis, treatment planning, and prognosis. Manually labelling extensive data by radiologists is often time-consuming and error-prone. As a result, automated or semi-automated computational models have become a popular research field of medical imaging in the past two decades, and many have been developed to date. In this survey, we aim to provide a comprehensive review of currently publicly available datasets, segmentation algorithms, and evaluation metrics. In addition, current challenges and future research directions are discussed.Comment: 30 pages, 19 figures, submitted to CBM journa

Automatic Pancreas Segmentation and 3D Reconstruction for Morphological Feature Extraction in Medical Image Analysis

The development of highly accurate, quantitative automatic medical image segmentation techniques, in comparison to manual techniques, remains a constant challenge for medical image analysis. In particular, segmenting the pancreas from an abdominal scan presents additional difficulties: this particular organ has very high anatomical variability, and a full inspection is problematic due to the location of the pancreas behind the stomach. Therefore, accurate, automatic pancreas segmentation can consequently yield quantitative morphological measures such as volume and curvature, supporting biomedical research to establish the severity and progression of a condition, such as type 2 diabetes mellitus. Furthermore, it can also guide subject stratification after diagnosis or before clinical trials, and help shed additional light on detecting early signs of pancreatic cancer. This PhD thesis delivers a novel approach for automatic, accurate quantitative pancreas segmentation in mostly but not exclusively Magnetic Resonance Imaging (MRI), by harnessing the advantages of machine learning and classical image processing in computer vision. The proposed approach is evaluated on two MRI datasets containing 216 and 132 image volumes, achieving a mean Dice similarity coefficient (DSC) of 84:1 4:6% and 85:7 2:3% respectively. In order to demonstrate the universality of the approach, a dataset containing 82 Computer Tomography (CT) image volumes is also evaluated and achieves mean DSC of 83:1 5:3%. The proposed approach delivers a contribution to computer science (computer vision) in medical image analysis, reporting better quantitative pancreas segmentation results in comparison to other state-of-the-art techniques, and also captures detailed pancreas boundaries as verified by two independent experts in radiology and radiography. The contributions’ impact can support the usage of computational methods in biomedical research with a clinical translation; for example, the pancreas volume provides a prognostic biomarker about the severity of type 2 diabetes mellitus. Furthermore, a generalisation of the proposed segmentation approach successfully extends to other anatomical structures, including the kidneys, liver and iliopsoas muscles using different MRI sequences. Thus, the proposed approach can incorporate into the development of a computational tool to support radiological interpretations of MRI scans obtained using different sequences by providing a “second opinion”, help reduce possible misdiagnosis, and consequently, provide enhanced guidance towards targeted treatment planning

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