Comparison of Two Methods for Automatic Brain Morphometry Analysis

The methods of computational neuroanatomy are widely used; the data on their individual strengths and limitations from direct comparisons are, however, scarce. The aim of the present study was direct comparison of DBM based on high-resolution spatial transforms with widely used VBM analysis based on segmented high-resolution images. We performed DBM and VBM analyses on simulated volume changes in a set of 20 3-D MR images, compared to 30 MR images, where only random spatial transforms were introduced. The ability of the two methods to detect regions with the simulated volume changes was determined using overlay index together with the ground truth regions of the simulations; the precision of the detection in space was determined using the distance measures between the centers of detected and simulated regions. DBM was able to detect all the regions with simulated local volume changes with high spatial precision. On the other hand, VBM detected only changes in vicinity of the largest simulated change, with a poor overlap of the detected changes and the ground truth. Taken together we suggest that the analysis of high-resolution deformation fields is more convenient, sensitive, and precise than voxel-wise analysis of tissue-segmented images

Wavelet Features for Recognition of First Episode of Schizophrenia from MRI Brain Images

Machine learning methods are increasingly used in various fields of medicine, contributing to early diagnosis and better quality of care. These outputs are particularly desirable in case of neuropsychiatric disorders, such as schizophrenia, due to the inherent potential for creating a new gold standard in the diagnosis and differentiation of particular disorders. This paper presents a scheme for automated classification from magnetic resonance images based on multiresolution representation in the wavelet domain. Implementation of the proposed algorithm, utilizing support vector machines classifier, is introduced and tested on a dataset containing 104 patients with first episode schizophrenia and healthy volunteers. Optimal parameters of different phases of the algorithm are sought and the quality of classification is estimated by robust cross validation techniques. Values of accuracy, sensitivity and specificity over 71% are achieved

REGISTRATION AND SEGMENTATION OF BRAIN MR IMAGES FROM ELDERLY INDIVIDUALS

Quantitative analysis of the MRI structural and functional images is a fundamental component in the assessment of brain anatomical abnormalities, in mapping functional activation onto human anatomy, in longitudinal evaluation of disease progression, and in computer-assisted neurosurgery or surgical planning. Image registration and segmentation is central in analyzing structural and functional MR brain images. However, due to increased variability in brain morphology and age-related atrophy, traditional methods for image registration and segmentation are not suitable for analyzing MR brain images from elderly individuals. The overall goal of this dissertation is to develop algorithms to improve the registration and segmentation accuracy in the geriatric population. The specific aims of this work includes 1) to implement a fully deformable registration pipeline to allow a higher degree of spatial deformation and produce more accurate deformation field, 2) to propose and validate an optimum template selection method for atlas-based segmentation, 3) to propose and validate a multi-template strategy for image normalization, which characterizes brain structural variations in the elderly, 4) to develop an automated segmentation and localization method to access white matter integrity (WMH) in the elderly population, and finally 5) to study the default-mode network (DMN) connectivity and white matter hyperintensity in late-life depression (LLD) with the developed registration and segmentation methods. Through a series of experiments, we have shown that the deformable registration pipeline and the template selection strategies lead to improved accuracy in the brain MR image registration and segmentation, and the automated WMH segmentation and localization method provides more specific and more accurate information about volume and spatial distribution of WMH than traditional visual grading methods. Using the developed methods, our clinical study provides evidence for altered DMN connectivity in LLD. The correlation between WMH volume and DMN connectivity emphasizes the role of vascular changes in LLD's etiopathogenesis

A Comprehensive Corpus Callosum Segmentation Tool for Detecting Callosal Abnormalities and Genetic Associations from Multi Contrast MRIs

Structural alterations of the midsagittal corpus callosum (midCC) have been associated with a wide range of brain disorders. The midCC is visible on most MRI contrasts and in many acquisitions with a limited field-of-view. Here, we present an automated tool for segmenting and assessing the shape of the midCC from T1w, T2w, and FLAIR images. We train a UNet on images from multiple public datasets to obtain midCC segmentations. A quality control algorithm is also built-in, trained on the midCC shape features. We calculate intraclass correlations (ICC) and average Dice scores in a test-retest dataset to assess segmentation reliability. We test our segmentation on poor quality and partial brain scans. We highlight the biological significance of our extracted features using data from over 40,000 individuals from the UK Biobank; we classify clinically defined shape abnormalities and perform genetic analyses

Neuroanatomical pattern classification in a population-based sample of first-episode schizophrenia

AbstractRecent neuroanatomical pattern classification studies have attempted to individually classify cases with psychotic disorders using morphometric MRI data in an automated fashion. However, this approach has not been tested in population-based samples, in which variable patterns of comorbidity and disease course are typically found. We aimed to evaluate the diagnostic accuracy (DA) of the above technique to discriminate between incident cases of first-episode schizophrenia identified in a circumscribed geographical region over a limited period of time, in comparison with next-door healthy controls. Sixty-two cases of first-episode schizophrenia or schizophreniform disorder and 62 age, gender and educationally-matched controls underwent 1.5T MRI scanning at baseline, and were naturalistically followed-up over 1year. T1-weighted images were used to train a high-dimensional multivariate classifier, and to generate both spatial maps of the discriminative morphological patterns between groups and ROC curves. The spatial map discriminating first-episode schizophrenia patients from healthy controls revealed a complex pattern of regional volumetric abnormalities in the former group, affecting fronto-temporal-occipital gray and white matter regions bilaterally, including the inferior fronto-occipital fasciculus, as well as the third and lateral ventricles. However, an overall modest DA (73.4%) was observed for the individual discrimination between first-episode schizophrenia patients and controls, and the classifier failed to predict 1-year prognosis (remitting versus non-remitting course) of first-episode schizophrenia (DA=58.3%). In conclusion, using a “real world” sample recruited with epidemiological methods, the application of a neuroanatomical pattern classifier afforded only modest DA to classify first-episode schizophrenia subjects and next-door healthy controls, and poor discriminative power to predict the 1-year prognosis of first-episode schizophrenia

A four-dimensional probabilistic atlas of the human brain

The authors describe the development of a four-dimensional atlas and reference system that includes both macroscopic and microscopic information on structure and function of the human brain in persons between the ages of 18 and 90 years. Given the presumed large but previously unquantified degree of structural and functional variance among normal persons in the human population, the basis for this atlas and reference system is probabilistic. Through the efforts of the International Consortium for Brain Mapping (ICBM), 7,000 subjects will be included in the initial phase of database and atlas development. For each subject, detailed demographic, clinical, behavioral, and imaging information is being collected. In addition, 5,800 subjects will contribute DNA for the purpose of determining genotype-phenotype-behavioral correlations. The process of developing the strategies, algorithms, data collection methods, validation approaches, database structures, and distribution of results is described in this report. Examples of applications of the approach are described for the normal brain in both adults and children as well as in patients with schizophrenia. This project should provide new insights into the relationship between microscopic and macroscopic structure and function in the human brain and should have important implications in basic neuroscience, clinical diagnostics, and cerebral disorders

Converting Neuroimaging Big Data to information: Statistical Frameworks for interpretation of Image Driven Biomarkers and Image Driven Disease Subtyping

Large scale clinical trials and population based research studies collect huge amounts of neuroimaging data. Machine learning classifiers can potentially use these data to train models that diagnose brain related diseases from individual brain scans. In this dissertation we address two distinct challenges that beset a wider adoption of these tools for diagnostic purposes. The first challenge that besets the neuroimaging based disease classification is the lack of a statistical inference machinery for highlighting brain regions that contribute significantly to the classifier decisions. In this dissertation, we address this challenge by developing an analytic framework for interpreting support vector machine (SVM) models used for neuroimaging based diagnosis of psychiatric disease. To do this we first note that permutation testing using SVM model components provides a reliable inference mechanism for model interpretation. Then we derive our analysis framework by showing that under certain assumptions, the permutation based null distributions associated with SVM model components can be approximated analytically using the data themselves. Inference based on these analytic null distributions is validated on real and simulated data. p-Values computed from our analysis can accurately identify anatomical features that differentiate groups used for classifier training. Since the majority of clinical and research communities are trained in understanding statistical p-values rather than machine learning techniques like the SVM, we hope that this work will lead to a better understanding SVM classifiers and motivate a wider adoption of SVM models for image based diagnosis of psychiatric disease. A second deficiency of learning based neuroimaging diagnostics is that they implicitly assume that, `a single homogeneous pattern of brain changes drives population wide phenotypic differences\u27. In reality it is more likely that multiple patterns of brain deficits drive the complexities observed in the clinical presentation of most diseases. Understanding this heterogeneity may allow us to build better classifiers for identifying such diseases from individual brain scans. However, analytic tools to explore this heterogeneity are missing. With this in view, we present in this dissertation, a framework for exploring disease heterogeneity using population neuroimaging data. The approach we present first computes difference images by comparing matched cases and controls and then clusters these differences. The cluster centers define a set of deficit patterns that differentiates the two groups. By allowing for more than one pattern of difference between two populations, our framework makes a radical departure from traditional tools used for neuroimaging group analyses. We hope that this leads to a better understanding of the processes that lead to disease and also that it ultimately leads to improved image based disease classifiers

Image databases in medical applications

The number of medical images acquired yearly in hospitals increases all the time. These imaging data contain lots of information on the characteristics of anatomical structures and on their variations. This information can be utilized in numerous medical applications. In deformable model-based segmentation and registration methods, the information in the image databases can be used to give a priori information on the shape of the object studied and the gray-level values in the image, and on their variations. On the other hand, by studying the variations of the object of interest in different populations, the effects of, for example, aging, gender, and diseases on anatomical structures can be detected. In the work described in this Thesis, methods that utilize image databases in medical applications were studied. Methods were developed and compared for deformable model-based segmentation and registration. Model selection procedure, mean models, and combination of classifiers were studied for the construction of a good a priori model. Statistical and probabilistic shape models were generated to constrain the deformations in segmentation and registration so that only the shapes typical to the object studied were accepted. In the shape analysis of the striatum, both volume and local shape changes were studied. The effects of aging and gender, and also the asymmetries were examined. The results proved that the segmentation and registration accuracy of deformable model-based methods can be improved by utilizing the information in image databases. The databases used were relatively small. Therefore, the statistical and probabilistic methods were not able to model all the population-specific variation. On the other hand, the simpler methods, the model selection procedure, mean models, and combination of classifiers, gave good results also with the small image databases. Two main applications were the reconstruction of 3-D geometry from incomplete data and the segmentation of heart ventricles and atria from short- and long-axis magnetic resonance images. In both applications, the methods studied provided promising results. The shape analysis of the striatum showed that the volume of the striatum decreases in aging. Also, the shape of the striatum changes locally. Asymmetries in the shape were found, too, but any gender-related local shape differences were not found.reviewe

FreeSurfer-initiated fully-automated subcortical brain segmentation in MRI using Large Deformation Diffeomorphic Metric Mapping.

Fully-automated brain segmentation methods have not been widely adopted for clinical use because of issues related to reliability, accuracy, and limitations of delineation protocol. By combining the probabilistic-based FreeSurfer (FS) method with the Large Deformation Diffeomorphic Metric Mapping (LDDMM)-based label-propagation method, we are able to increase reliability and accuracy, and allow for flexibility in template choice. Our method uses the automated FreeSurfer subcortical labeling to provide a coarse-to-fine introduction of information in the LDDMM template-based segmentation resulting in a fully-automated subcortical brain segmentation method (FS+LDDMM). One major advantage of the FS+LDDMM-based approach is that the automatically generated segmentations generated are inherently smooth, thus subsequent steps in shape analysis can directly follow without manual post-processing or loss of detail. We have evaluated our new FS+LDDMM method on several databases containing a total of 50 subjects with different pathologies, scan sequences and manual delineation protocols for labeling the basal ganglia, thalamus, and hippocampus. In healthy controls we report Dice overlap measures of 0.81, 0.83, 0.74, 0.86 and 0.75 for the right caudate nucleus, putamen, pallidum, thalamus and hippocampus respectively. We also find statistically significant improvement of accuracy in FS+LDDMM over FreeSurfer for the caudate nucleus and putamen of Huntington\u27s disease and Tourette\u27s syndrome subjects, and the right hippocampus of Schizophrenia subjects