Statistical growth modeling of longitudinal DT-MRI for regional characterization of early brain development

pre-printA population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI

Automated Extraction of Biomarkers for Alzheimer's Disease from Brain Magnetic Resonance Images

In this work, different techniques for the automated extraction of biomarkers for Alzheimer's disease (AD) from brain magnetic resonance imaging (MRI) are proposed. The described work forms part of PredictAD (www.predictad.eu), a joined European research project aiming at the identification of a unified biomarker for AD combining different clinical and imaging measurements. Two different approaches are followed in this thesis towards the extraction of MRI-based biomarkers: (I) the extraction of traditional morphological biomarkers based on neuronatomical structures and (II) the extraction of data-driven biomarkers applying machine-learning techniques. A novel method for a unified and automated estimation of structural volumes and volume changes is proposed. Furthermore, a new technique that allows the low-dimensional representation of a high-dimensional image population for data analysis and visualization is described. All presented methods are evaluated on images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), providing a large and diverse clinical database. A rigorous evaluation of the power of all identified biomarkers to discriminate between clinical subject groups is presented. In addition, the agreement of automatically derived volumes with reference labels as well as the power of the proposed method to measure changes in a subject's atrophy rate are assessed. The proposed methods compare favorably to state-of-the art techniques in neuroimaging in terms of accuracy, robustness and run-time

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

Doctor of Philosophy

dissertationMagnetic Resonance (MR) is a relatively risk-free and flexible imaging modality that is widely used for studying the brain. Biophysical and chemical properties of brain tissue are captured by intensity measurements in T1W (T1-Weighted) and T2W (T2-Weighted) MR scans. Rapid maturational processes taking place in the infant brain manifest as changes in co{\tiny }ntrast between white matter and gray matter tissue classes in these scans. However, studies based on MR image appearance face severe limitations due to the uncalibrated nature of MR intensity and its variability with respect to changing conditions of scan. In this work, we develop a method for studying the intensity variations between brain white matter and gray matter that are observed during infant brain development. This method is referred to by the acronym WIVID (White-gray Intensity Variation in Infant Development). WIVID is computed by measuring the Hellinger Distance of separation between intensity distributions of WM (White Matter) and GM (Gray Matter) tissue classes. The WIVID measure is shown to be relatively stable to interscan variations compared with raw signal intensity and does not require intensity normalization. In addition to quantification of tissue appearance changes using the WIVID measure, we test and implement a statistical framework for modeling temporal changes in this measure. WIVID contrast values are extracted from MR scans belonging to large-scale, longitudinal, infant brain imaging studies and modeled using the NLME (Nonlinear Mixed Effects) method. This framework generates a normative model of WIVID contrast changes with time, which captures brain appearance changes during neurodevelopment. Parameters from the estimated trajectories of WIVID contrast change are analyzed across brain lobes and image modalities. Parameters associated with the normative model of WIVID contrast change reflect established patterns of region-specific and modality-specific maturational sequences. We also detect differences in WIVID contrast change trajectories between distinct population groups. These groups are categorized based on sex and risk/diagnosis for ASD (Autism Spectrum Disorder). As a result of this work, the usage of the proposed WIVID contrast measure as a novel neuroimaging biomarker for characterizing tissue appearance is validated, and the clinical potential of the developed framework is demonstrated

Connectomics across development:towards mapping brain structure from birth to childhood

The brain is probably the most complex system of the human body, composed of numerous neural units interconnected at dierent scales. This highly structured architecture provides the ability to communicate, synthesize information and perform the analytical tasks of human beings. Its development starts during the transition between the embryonic and fetal periods, from a simple tubular to a highly complex folded structure. It is globally organized as early as birth. This developing process is highly vulnerable to antenatal adverse conditions. Indeed, extreme prematurity and intra uterine growth restriction are major risk factors for long-term morbidities, including developmental ailments such as cerebral palsy, mental retardation and a wide spectrum of learning disabilities and behavior disorders. In this context, the characterization of the brainâs normative wiring pattern is crucial for our understanding of its architecture and workings, as the origin of many neurological and neurobehavioral disorders is found in early structural brain development. Diusion magnetic resonance imaging (dMRI) allows the in vivo assessment of biological tissues at the microstructural level. It has emerged as a powerful tool to study brain connectivity and analyse the underlying substrate of the human brain, comprising its structurally integrated and functionally specialized architecture. dMRI has been widely used in adult studies. Nevertheless, due to technical constraints, this mapping at earlier stages of development has not yet been accomplished. Yet, this time period is of extreme importance to comprehend the structural and functional integrity of the brain. This thesis is motivated by this shortfall, and intends to fill the gap between the clinical and neuroscience demands and the methodological developments needed to fulfill them. In our work, we comprehensibly study the brain structural connectivity of children born extremely prematurely and/or with additional prenatal restriction at school-age. We provide evidence that brain systems that mature early in development are the most vulnerable to antenatal insults. Interestingly, the alterations highlighted in these systems correlate with the neurobehavioral and cognitive impairments seen in these children at school-age. The overall brain organization appear also altered after preterm birth and prenatal restriction. Indeed, these children show dierent brain network modular topology, with a reduction in the overall network capacity. What remains unclear is whether the alterations seen at school age are already present at birth and, if yes, to what extent. In this thesis we set the technical basis to enable the connectome analysis as early as at birth. This task is challenging when dealing with neonatal data. Indeed, most of the assumptions used in adult data processing methods do not hold, due to the inverted image contrast and other MRI artefacts such as motion, partial volume and intensity inhomogeneities. Here, we propose a novel technique for surface reconstruction, and provide a fully-automatic procedure to delineate the newborn cortical surface, opening the way to establish the newborn connectome

Shape analysis of the human brain.

Autism is a complex developmental disability that has dramatically increased in prevalence, having a decisive impact on the health and behavior of children. Methods used to detect and recommend therapies have been much debated in the medical community because of the subjective nature of diagnosing autism. In order to provide an alternative method for understanding autism, the current work has developed a 3-dimensional state-of-the-art shape based analysis of the human brain to aid in creating more accurate diagnostic assessments and guided risk analyses for individuals with neurological conditions, such as autism. Methods: The aim of this work was to assess whether the shape of the human brain can be used as a reliable source of information for determining whether an individual will be diagnosed with autism. The study was conducted using multi-center databases of magnetic resonance images of the human brain. The subjects in the databases were analyzed using a series of algorithms consisting of bias correction, skull stripping, multi-label brain segmentation, 3-dimensional mesh construction, spherical harmonic decomposition, registration, and classification. The software algorithms were developed as an original contribution of this dissertation in collaboration with the BioImaging Laboratory at the University of Louisville Speed School of Engineering. The classification of each subject was used to construct diagnoses and therapeutic risk assessments for each patient. Results: A reliable metric for making neurological diagnoses and constructing therapeutic risk assessment for individuals has been identified. The metric was explored in populations of individuals having autism spectrum disorders, dyslexia, Alzheimers disease, and lung cancer. Conclusion: Currently, the clinical applicability and benefits of the proposed software approach are being discussed by the broader community of doctors, therapists, and parents for use in improving current methods by which autism spectrum disorders are diagnosed and understood