Medical image analysis methods in MR/CT-imaged acute-subacute ischemic stroke lesion:Segmentation, prediction and insights into dynamic evolution simulation models. A critical appraisal

AbstractOver the last 15years, basic thresholding techniques in combination with standard statistical correlation-based data analysis tools have been widely used to investigate different aspects of evolution of acute or subacute to late stage ischemic stroke in both human and animal data. Yet, a wave of biology-dependent and imaging-dependent issues is still untackled pointing towards the key question: “how does an ischemic stroke evolve?” Paving the way for potential answers to this question, both magnetic resonance (MRI) and CT (computed tomography) images have been used to visualize the lesion extent, either with or without spatial distinction between dead and salvageable tissue. Combining diffusion and perfusion imaging modalities may provide the possibility of predicting further tissue recovery or eventual necrosis. Going beyond these basic thresholding techniques, in this critical appraisal, we explore different semi-automatic or fully automatic 2D/3D medical image analysis methods and mathematical models applied to human, animal (rats/rodents) and/or synthetic ischemic stroke to tackle one of the following three problems: (1) segmentation of infarcted and/or salvageable (also called penumbral) tissue, (2) prediction of final ischemic tissue fate (death or recovery) and (3) dynamic simulation of the lesion core and/or penumbra evolution. To highlight the key features in the reviewed segmentation and prediction methods, we propose a common categorization pattern. We also emphasize some key aspects of the methods such as the imaging modalities required to build and test the presented approach, the number of patients/animals or synthetic samples, the use of external user interaction and the methods of assessment (clinical or imaging-based). Furthermore, we investigate how any key difficulties, posed by the evolution of stroke such as swelling or reperfusion, were detected (or not) by each method. In the absence of any imaging-based macroscopic dynamic model applied to ischemic stroke, we have insights into relevant microscopic dynamic models simulating the evolution of brain ischemia in the hope to further promising and challenging 4D imaging-based dynamic models. By depicting the major pitfalls and the advanced aspects of the different reviewed methods, we present an overall critique of their performances and concluded our discussion by suggesting some recommendations for future research work focusing on one or more of the three addressed problems

Automated detection of brain abnormalities in neonatal hypoxia ischemic injury from MR images.

We compared the efficacy of three automated brain injury detection methods, namely symmetry-integrated region growing (SIRG), hierarchical region splitting (HRS) and modified watershed segmentation (MWS) in human and animal magnetic resonance imaging (MRI) datasets for the detection of hypoxic ischemic injuries (HIIs). Diffusion weighted imaging (DWI, 1.5T) data from neonatal arterial ischemic stroke (AIS) patients, as well as T2-weighted imaging (T2WI, 11.7T, 4.7T) at seven different time-points (1, 4, 7, 10, 17, 24 and 31 days post HII) in rat-pup model of hypoxic ischemic injury were used to assess the temporal efficacy of our computational approaches. Sensitivity, specificity, and similarity were used as performance metrics based on manual ('gold standard') injury detection to quantify comparisons. When compared to the manual gold standard, automated injury location results from SIRG performed the best in 62% of the data, while 29% for HRS and 9% for MWS. Injury severity detection revealed that SIRG performed the best in 67% cases while 33% for HRS. Prior information is required by HRS and MWS, but not by SIRG. However, SIRG is sensitive to parameter-tuning, while HRS and MWS are not. Among these methods, SIRG performs the best in detecting lesion volumes; HRS is the most robust, while MWS lags behind in both respects

Asymmetry Analysis in Rodent Cerebral Ischemia Models

Rationale and Objectives: An automated method for identification and segmentation of acute/subacute ischemic stroke, using the inherent bi-fold symmetry in brain images, is presented. An accurate and automated method for localization of acute ischemic stroke could provide physicians with a mechanism for early detection and potentially faster delivery of effective stroke therapy. Materials and Methods: Segmentation of ischemic stroke was performed on magnetic resonance (MR) images of subacute rodent cerebral ischemia. Eight adult male Wistar rats weighing 225–300 g were anesthetized with halothane in a mix of 70% nitrous oxide/30% oxygen. Animal core temperature was maintained at 37°C during the entire surgical procedure, including occlusion of the middle cerebral artery (MCA) and the 90-minute post-reperfusion period. To confirm cerebral ischemia, transcranial measurements of cerebral blood flow were performed with laser-Doppler flowmetry, using 15-mm flexible fiberoptic Doppler probes attached to the skull over the MCA territory. Animal MR scans were performed at 1.5 T using a knee coil. Three experts performed manual tracing of the stroke regions for each rat, using the histologic-stained slices to guide delineation of stroke regions. A strict tracing protocol was followed that included multiple (three) tracings of each stroke region. The volumetric MR image data were processed for each rat by computing the axis of symmetry and extracting statistical dissimilarities. A nonparametric Wilcoxon rank sum test operating on paired windows in opposing hemispheres identified seeds in the pixels exhibiting statistically significant bi-fold mirror asymmetry. Two brain reference maps were used for analysis: an absolute difference map (ADM) and a statistical difference map (SDM). Although an ADM simply displays the absolute difference by subtracting one brain hemisphere from its reflection, SDM highlights regions by labeling pixels exhibiting statistically significant asymmetry. Results: To assess the accuracy of the proposed segmentation method, the surrogate ground truth (the stroke tracing data) was compared to the results of our proposed automated segmentation algorithm. Three accuracy segmentation metrics were utilized: true-positive volume fraction (TPVF), false-positive volume fraction (FPVF), and false-negative volume fraction (FNVF). The mean value of the TPVF for our segmentation method was 0.8877; 95% CI 0.7254 to 1.0500; the mean FPVF was 0.3370, 95% CI –0.0893 to 0.7633; the mean FNVF was 0.1122, 95% CI –0.0502 to 0.2747. Conclusions: Unlike most segmentation methods that require some degree of manual intervention, our segmentation algorithm is fully automated and highly accurate in identifying regions of brain asymmetry. This approach is attractive for numerous neurologic applications where the operator's intervention should be minimal or null

Computer Vision Techniques for Transcatheter Intervention

Minimally invasive transcatheter technologies have demonstrated substantial promise for the diagnosis and treatment of cardiovascular diseases. For example, TAVI is an alternative to AVR for the treatment of severe aortic stenosis and TAFA is widely used for the treatment and cure of atrial fibrillation. In addition, catheter-based IVUS and OCT imaging of coronary arteries provides important information about the coronary lumen, wall and plaque characteristics. Qualitative and quantitative analysis of these cross-sectional image data will be beneficial for the evaluation and treatment of coronary artery diseases such as atherosclerosis. In all the phases (preoperative, intraoperative, and postoperative) during the transcatheter intervention procedure, computer vision techniques (e.g., image segmentation, motion tracking) have been largely applied in the field to accomplish tasks like annulus measurement, valve selection, catheter placement control, and vessel centerline extraction. This provides beneficial guidance for the clinicians in surgical planning, disease diagnosis, and treatment assessment. In this paper, we present a systematical review on these state-of-the-art methods.We aim to give a comprehensive overview for researchers in the area of computer vision on the subject of transcatheter intervention. Research in medical computing is multi-disciplinary due to its nature, and hence it is important to understand the application domain, clinical background, and imaging modality so that methods and quantitative measurements derived from analyzing the imaging data are appropriate and meaningful. We thus provide an overview on background information of transcatheter intervention procedures, as well as a review of the computer vision techniques and methodologies applied in this area

Novel mathematical modeling approaches to assess ischemic stroke lesion evolution on medical imaging

Stroke is a major cause of disability and death worldwide. Although different clinical studies and trials used Magnetic Resonance Imaging (MRI) to examine patterns of change in different imaging modalities (eg: perfusion and diffusion), we still lack a clear and definite answer to the question: “How does an acute ischemic stroke lesion grow?” The inability to distinguish viable and dead tissue in abnormal MR regions in stroke patients weakens the evidence accumulated to answer this question, and relying on static snapshots of patient scans to fill in the spatio-temporal gaps by “thinking/guessing” make it even harder to tackle. Different opposing observations undermine our understanding of ischemic stroke evolution, especially at the acute stage: viable tissue transiting into dead tissue may be clear and intuitive, however, “visibly” dead tissue restoring to full recovery is still unclear. In this thesis, we search for potential answers to these raised questions from a novel dynamic modelling perspective that would fill in some of the missing gaps in the mechanisms of stroke evolution. We divided our thesis into five parts. In the first part, we give a clinical and imaging background on stroke and state the objectives of this thesis. In the second part, we summarize and review the literature in stroke and medical imaging. We specifically spot gaps in the literature mainly related to medical image analysis methods applied to acute-subacute ischemic stroke. We emphasize studies that progressed the field and point out what major problems remain. Noticeably, we have discovered that macroscopic (imaging-based) dynamic models that simulate how stroke lesion evolves in space and time were completely overlooked: an untapped potential that may alter and hone our understanding of stroke evolution. Progress in the dynamic simulation of stroke was absent –if not inexistent. In the third part, we answer this new call and apply a novel current-based dynamic model âpreviously applied to compare the evolution of facial characteristics between Chimpanzees and Bonobos [Durrleman 2010] – to ischemic stroke. This sets a robust numerical framework and provides us with mathematical tools to fill in the missing gaps between MR acquisition time points and estimate a four-dimensional evolution scenario of perfusion and diffusion lesion surfaces. We then detect two characteristics of patterns of abnormal tissue boundary change: spatial, describing the direction of change –outward as tissue boundary expands or inward as it contracts–; and kinetic, describing the intensity (norm) of the speed of contracting and expanding ischemic regions. Then, we compare intra- and inter-patients estimated patterns of change in diffusion and perfusion data. Nevertheless, topology change limits this approach: it cannot handle shapes with different parts that vary in number over time (eg: fragmented stroke lesions, especially in diffusion scans, which are common). In the fourth part, we suggest a new mathematical dynamic model to increase rigor in the imaging-based dynamic modeling field as a whole by overcoming the topology-change hurdle. Metamorphosis. It morphs one source image into a target one [Trouvé 2005]. In this manuscript, we extend it into dealing with more than two time-indexed images. We propose a novel extension of image-to-image metamorphosis into longitudinal metamorphosis for estimating an evolution scenario of both scattered and solitary ischemic lesions visible on serial MR. It is worth noting that the spatio-temporal metamorphosis we developed is a generic model that can be used to examine intensity and shape changes in time-series imaging and study different brain diseases or disorders. In the fifth part, we discuss our main findings and investigate future directions to explore to sharpen our understanding of ischemia evolution patterns

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LITS) organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2016 and International Conference On Medical Image Computing Computer Assisted Intervention (MICCAI) 2017. Twenty four valid state-of-the-art liver and liver tumor segmentation algorithms were applied to a set of 131 computed tomography (CT) volumes with different types of tumor contrast levels (hyper-/hypo-intense), abnormalities in tissues (metastasectomie) size and varying amount of lesions. The submitted algorithms have been tested on 70 undisclosed volumes. The dataset is created in collaboration with seven hospitals and research institutions and manually reviewed by independent three radiologists. We found that not a single algorithm performed best for liver and tumors. The best liver segmentation algorithm achieved a Dice score of 0.96(MICCAI) whereas for tumor segmentation the best algorithm evaluated at 0.67(ISBI) and 0.70(MICCAI). The LITS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.Comment: conferenc

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