Computational Anatomy for Multi-Organ Analysis in Medical Imaging: A Review

The medical image analysis field has traditionally been focused on the development of organ-, and disease-specific methods. Recently, the interest in the development of more 20 comprehensive computational anatomical models has grown, leading to the creation of multi-organ models. Multi-organ approaches, unlike traditional organ-specific strategies, incorporate inter-organ relations into the model, thus leading to a more accurate representation of the complex human anatomy. Inter-organ relations are not only spatial, but also functional and physiological. Over the years, the strategies 25 proposed to efficiently model multi-organ structures have evolved from the simple global modeling, to more sophisticated approaches such as sequential, hierarchical, or machine learning-based models. In this paper, we present a review of the state of the art on multi-organ analysis and associated computation anatomy methodology. The manuscript follows a methodology-based classification of the different techniques 30 available for the analysis of multi-organs and multi-anatomical structures, from techniques using point distribution models to the most recent deep learning-based approaches. With more than 300 papers included in this review, we reflect on the trends and challenges of the field of computational anatomy, the particularities of each anatomical region, and the potential of multi-organ analysis to increase the impact of 35 medical imaging applications on the future of healthcare.Comment: Paper under revie

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

The Translational Role of Diffusion Tensor Image Analysis in Animal Models of Developmental Pathologies

Diffusion Tensor Magnetic Resonance Imaging (DTI) has proven itself a powerful technique for clinical investigation of the neurobiological targets and mechanisms underlying developmental pathologies. The success of DTI in clinical studies has demonstrated its great potential for understanding translational animal models of clinical disorders, and preclinical animal researchers are beginning to embrace this new technology to study developmental pathologies. In animal models, genetics can be effectively controlled, drugs consistently administered, subject compliance ensured, and image acquisition times dramatically increased to reduce between-subject variability and improve image quality. When pairing these strengths with the many positive attributes of DTI, such as the ability to investigate microstructural brain organization and connectivity, it becomes possible to delve deeper into the study of both normal and abnormal development. The purpose of this review is to provide new preclinical investigators with an introductory source of information about the analysis of data resulting from small animal DTI studies to facilitate the translation of these studies to clinical data. In addition to an in depth review of translational analysis techniques, we present a number of relevant clinical and animal studies using DTI to investigate developmental insults in order to further illustrate techniques and to highlight where small animal DTI could potentially provide a wealth of translational data to inform clinical researchers

Developing advanced mathematical models for detecting abnormalities in 2D/3D medical structures.

Detecting abnormalities in two-dimensional (2D) and three-dimensional (3D) medical structures is among the most interesting and challenging research areas in the medical imaging field. Obtaining the desired accurate automated quantification of abnormalities in medical structures is still very challenging. This is due to a large and constantly growing number of different objects of interest and associated abnormalities, large variations of their appearances and shapes in images, different medical imaging modalities, and associated changes of signal homogeneity and noise for each object. The main objective of this dissertation is to address these problems and to provide proper mathematical models and techniques that are capable of analyzing low and high resolution medical data and providing an accurate, automated analysis of the abnormalities in medical structures in terms of their area/volume, shape, and associated abnormal functionality. This dissertation presents different preliminary mathematical models and techniques that are applied in three case studies: (i) detecting abnormal tissue in the left ventricle (LV) wall of the heart from delayed contrast-enhanced cardiac magnetic resonance images (MRI), (ii) detecting local cardiac diseases based on estimating the functional strain metric from cardiac cine MRI, and (iii) identifying the abnormalities in the corpus callosum (CC) brain structure—the largest fiber bundle that connects the two hemispheres in the brain—for subjects that suffer from developmental brain disorders. For detecting the abnormal tissue in the heart, a graph-cut mathematical optimization model with a cost function that accounts for the object’s visual appearance and shape is used to segment the the inner cavity. The model is further integrated with a geometric model (i.e., a fast marching level set model) to segment the outer border of the myocardial wall (the LV). Then the abnormal tissue in the myocardium wall (also called dead tissue, pathological tissue, or infarct area) is identified based on a joint Markov-Gibbs random field (MGRF) model of the image and its region (segmentation) map that accounts for the pixel intensities and the spatial interactions between the pixels. Experiments with real in-vivo data and comparative results with ground truth (identified by a radiologist) and other approaches showed that the proposed framework can accurately detect the pathological tissue and can provide useful metrics for radiologists and clinicians. To estimate the strain from cardiac cine MRI, a novel method based on tracking the LV wall geometry is proposed. To achieve this goal, a partial differential equation (PDE) method is applied 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. The main advantage of the proposed tracking method over traditional texture-based methods is its ability to track the movement and rotation of the LV wall based on tracking the geometric features of the inner, mid-, and outer walls of the LV. This overcomes noise sources that come from scanner and heart motion. To identify the abnormalities in the CC from brain MRI, the CCs are aligned using a rigid registration model and are segmented using a shape-appearance model. Then, they are mapped to a simple unified space for analysis. This work introduces a novel cylindrical mapping model, which is conformal (i.e., one to one transformation and bijective), that enables accurate 3D shape analysis of the CC in the cylindrical domain. The framework can detect abnormalities in all divisions of the CC (i.e., splenium, rostrum, genu and body). In addition, it offers a whole 3D analysis of the CC abnormalities instead of only area-based analysis as done by previous groups. The initial classification results based on the centerline length and CC thickness suggest that the proposed CC shape analysis is a promising supplement to the current techniques for diagnosing dyslexia. The proposed techniques in this dissertation have been successfully tested on complex synthetic and MR images and can be used to advantage in many of today’s clinical applications of computer-assisted medical diagnostics and intervention

A review of intrinsic optical imaging serial blockface histology (ICI-SBH) for whole rodent brain imaging

In recent years, multiple serial histology techniques were developed to enable whole rodent brain imaging in 3-D. The main driving forces behind the emergence of these imaging techniques were the genome-wide atlas of gene expression in the mouse brain, the pursuit of the mouse brain connectome, and the BigBrain project. These projects rely on the use of optical imaging to target neuronal structures with histological stains or fluorescent dyes that are either expressed by transgenic mice or injected at specific locations in the brain. Efforts to adapt the serial histology acquisition scheme to use intrinsic contrast imaging (ICI) were also put forward, thus leveraging the natural contrast of neuronal tissue. This review focuses on these efforts. First, the origin of optical contrast in brain tissue is discussed with emphasis on the various imaging modalities exploiting these contrast mechanisms. Serial blockface histology (SBH) systems using ICI modalities are then reported, followed by a review of some of their applications. These include validation studies and the creation of multimodal brain atlases at a micrometer resolution. The paper concludes with a perspective of future developments, calling for a consolidation of the SBH research and development efforts around the world. The goal would be to offer the neuroscience community a single standardized open-source SBH solution, including optical design, acquisition automation, reconstruction algorithms, and analysis pipelines

Restauration d'images en IRM anatomique pour l'étude préclinique des marqueurs du vieillissement cérébral

Les maladies neurovasculaires et neurodégénératives liées à l'âge sont en forte augmentation. Alors que ces changements pathologiques montrent des effets sur le cerveau avant l'apparition de symptômes cliniques, une meilleure compréhension du processus de vieillissement normal du cerveau aidera à distinguer l'impact des pathologies connues sur la structure régionale du cerveau. En outre, la connaissance des schémas de rétrécissement du cerveau dans le vieillissement normal pourrait conduire à une meilleure compréhension de ses causes et peut-être à des interventions réduisant la perte de fonctions cérébrales associée à l'atrophie cérébrale. Par conséquent, ce projet de thèse vise à détecter les biomarqueurs du vieillissement normal et pathologique du cerveau dans un modèle de primate non humain, le singe marmouset (Callithrix Jacchus), qui possède des caractéristiques anatomiques plus proches de celles des humains que de celles des rongeurs. Cependant, les changements structurels (par exemple, de volumes, d'épaisseur corticale) qui peuvent se produire au cours de leur vie adulte peuvent être minimes à l'échelle de l'observation. Dans ce contexte, il est essentiel de disposer de techniques d'observation offrant un contraste et une résolution spatiale suffisamment élevés et permettant des évaluations détaillées des changements morphométriques du cerveau associé au vieillissement. Cependant, l'imagerie de petits cerveaux dans une plateforme IRM 3T dédiée à l'homme est une tâche difficile car la résolution spatiale et le contraste obtenus sont insuffisants par rapport à la taille des structures anatomiques observées et à l'échelle des modifications attendues. Cette thèse vise à développer des méthodes de restauration d'image pour les images IRM précliniques qui amélioreront la robustesse des algorithmes de segmentation. L'amélioration de la résolution spatiale des images à un rapport signal/bruit constant limitera les effets de volume partiel dans les voxels situés à la frontière entre deux structures et permettra une meilleure segmentation tout en augmentant la reproductibilité des résultats. Cette étape d'imagerie computationnelle est cruciale pour une analyse morphométrique longitudinale fiable basée sur les voxels et l'identification de marqueurs anatomiques du vieillissement cérébral en suivant les changements de volume dans la matière grise, la matière blanche et le liquide cérébral.Age-related neurovascular and neurodegenerative diseases are increasing significantly. While such pathological changes show effects on the brain before clinical symptoms appear, a better understanding of the normal aging brain process will help distinguish known pathologies' impact on regional brain structure. Furthermore, knowledge of the patterns of brain shrinkage in normal aging could lead to a better understanding of its causes and perhaps to interventions reducing the loss of brain functions. Therefore, this thesis project aims to detect normal and pathological brain aging biomarkers in a non-human primate model, the marmoset monkey (Callithrix Jacchus) which possesses anatomical characteristics more similar to humans than rodents. However, structural changes (e.g., volumes, cortical thickness) that may occur during their adult life may be minimal with respect to the scale of observation. In this context, it is essential to have observation techniques that offer sufficiently high contrast and spatial resolution and allow detailed assessments of the morphometric brain changes associated with aging. However, imaging small brains in a 3T MRI platform dedicated to humans is a challenging task because the spatial resolution and the contrast obtained are insufficient compared to the size of the anatomical structures observed and the scale of the xpected changes with age. This thesis aims to develop image restoration methods for preclinical MR images that will improve the robustness of the segmentation algorithms. Improving the resolution of the images at a constant signal-to-noise ratio will limit the effects of partial volume in voxels located at the border between two structures and allow a better segmentation while increasing the results' reproducibility. This computational imaging step is crucial for a reliable longitudinal voxel-based morphometric analysis and for the identification of anatomical markers of brain aging by following the volume changes in gray matter, white matter and cerebrospinal fluid

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

Deformation-invariant sparse coding

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 87-91).Sparse coding represents input signals each as a sparse linear combination of a set of basis or dictionary elements where sparsity encourages representing each input signal with a few of the most indicative dictionary elements. In this thesis, we extend sparse coding to allow dictionary elements to undergo deformations, resulting in a general probabilistic model and accompanying inference algorithm for estimating sparse linear combination weights, dictionary elements, and deformations. We apply our proposed method on functional magnetic resonance imaging (fMRI) data, where the locations of functional regions in the brain evoked by a specific cognitive task may vary across individuals relative to anatomy. For a language fMRI study, our method identifies activation regions that agree with known literature on language processing. Furthermore, the deformations learned by our inference algorithm produce more robust group-level effects than anatomical alignment alone.by George H. Chen.S.M

An image segmentation and registration approach to cardiac function analysis using MRI

Cardiovascular diseases (CVDs) are one of the major causes of death in the world. In recent years, significant progress has been made in the care and treatment of patients with such diseases. A crucial factor for this progress has been the development of magnetic resonance (MR) imaging which makes it possible to diagnose and assess the cardiovascular function of the patient. The ability to obtain high-resolution, cine volume images easily and safely has made it the preferred method for diagnosis of CVDs. MRI is also unique in its ability to introduce noninvasive markers directly into the tissue being imaged(MR tagging) during the image acquisition process. With the development of advanced MR imaging acquisition technologies, 3D MR imaging is more and more clinically feasible. This recent development has allowed new potentially 3D image analysis technologies to be deployed. However, quantitative analysis of cardiovascular system from the images remains a challenging topic. The work presented in this thesis describes the development of segmentation and motion analysis techniques for the study of the cardiac anatomy and function in cardiac magnetic resonance (CMR) images. The first main contribution of the thesis is the development of a fully automatic cardiac segmentation technique that integrates and combines a series of state-of-the-art techniques. The proposed segmentation technique is capable of generating an accurate 3D segmentation from multiple image sequences. The proposed segmentation technique is robust even in the presence of pathological changes, large anatomical shape variations and locally varying contrast in the images. Another main contribution of this thesis is the development of motion tracking techniques that can integrate motion information from different sources. For example, the radial motion of the myocardium can be tracked easily in untagged MR imaging since the epi- and endocardial surfaces are clearly visible. On the other hand, tagged MR imaging allows easy tracking of both longitudinal and circumferential motion. We propose a novel technique based on non-rigid image registration for the myocardial motion estimation using both untagged and 3D tagged MR images. The novel aspect of our technique is its simultaneous use of complementary information from both untagged and 3D tagged MR imaging. The similarity measure is spatially weighted to maximise the utility of information from both images. The thesis also proposes a sparse representation for free-form deformations (FFDs) using the principles of compressed sensing. The sparse free-form deformation (SFFD) model can capture fine local details such as motion discontinuities without sacrificing robustness. We demonstrate the capabilities of the proposed framework to accurately estimate smooth as well as discontinuous deformations in 2D and 3D CMR image sequences. Compared to the standard FFD approach, a significant increase in registration accuracy can be observed in datasets with discontinuous motion patterns. Both the segmentation and motion tracking techniques presented in this thesis have been applied to clinical studies. We focus on two important clinical applications that can be addressed by the techniques proposed in this thesis. The first clinical application aims at measuring longitudinal changes in cardiac morphology and function during the cardiac remodelling process. The second clinical application aims at selecting patients that positively respond to cardiac resynchronization therapy (CRT). The final chapter of this thesis summarises the main conclusions that can be drawn from the work presented here and also discusses possible avenues for future research

Registration of histology and magnetic resonance imaging of the brain

Combining histology and non-invasive imaging has been attracting the attention of the medical imaging community for a long time, due to its potential to correlate macroscopic information with the underlying microscopic properties of tissues. Histology is an invasive procedure that disrupts the spatial arrangement of the tissue components but enables visualisation and characterisation at a cellular level. In contrast, macroscopic imaging allows non-invasive acquisition of volumetric information but does not provide any microscopic details. Through the establishment of spatial correspondences obtained via image registration, it is possible to compare micro- and macroscopic information and to recover the original histological arrangement in three dimensions. In this thesis, I present: (i) a survey of the literature relative to methods for histology reconstruction with and without the help of 3D medical imaging; (ii) a graph-theoretic method for histology volume reconstruction from sets of 2D sections, without external information; (iii) a method for multimodal 2D linear registration between histology and MRI based on partial matching of shape-informative boundaries