Volumetric segmentation of multiple basal ganglia structures

We present a new active contour-based, statistical method for simultaneous volumetric segmentation of multiple subcortical structures in the brain. Neighboring anatomical structures in the human brain exhibit co-dependencies which can aid in segmentation, if properly analyzed and modeled. Motivated by this observation, we formulate the segmentation problem as a maximum a posteriori estimation problem, in which we incorporate statistical prior models on the shapes and inter-shape (relative) poses of the structures of interest. This provides a principled mechanism to bring high level information about the shapes and the relationships of anatomical structures into the segmentation problem. For learning the prior densities based on training data, we use a nonparametric multivariate kernel density estimation framework. We combine these priors with data in a variational framework, and develop an active contour-based iterative segmentation algorithm. We test our method on the problem of volumetric segmentation of basal ganglia structures in magnetic resonance (MR) images. We compare our technique with existing methods and demonstrate the improvements it provides in terms of segmentation accuracy

Coupled non-parametric shape and moment-based inter-shape pose priors for multiple basal ganglia structure segmentation

This paper presents a new active contour-based, statistical method for simultaneous volumetric segmentation of multiple subcortical structures in the brain. In biological tissues, such as the human brain, neighboring structures exhibit co-dependencies which can aid in segmentation, if properly analyzed and modeled. Motivated by this observation, we formulate the segmentation problem as a maximum a posteriori estimation problem, in which we incorporate statistical prior models on the shapes and inter-shape (relative) poses of the structures of interest. This provides a principled mechanism to bring high level information about the shapes and the relationships of anatomical structures into the segmentation problem. For learning the prior densities we use a nonparametric multivariate kernel density estimation framework. We combine these priors with data in a variational framework and develop an active contour-based iterative segmentation algorithm. We test our method on the problem of volumetric segmentation of basal ganglia structures in magnetic resonance (MR) images. We present a set of 2D and 3D experiments as well as a quantitative performance analysis. In addition, we perform a comparison to several existent segmentation methods and demonstrate the improvements provided by our approach in terms of segmentation accuracy

Coupled non-parametric shape and moment-based inter-shape pose priors for multiple basal ganglia structure segmentation

Brain tissue and structure segmentation in magnetic resonance (MR) images is a fundamental problem in clinical studies of brain structure and function. Due to limitations such as low contrast, partial volume effects, and field inhomogeneities, the delineation of subcortical (basal ganglia) structures such as caudate nucleus, putamen, and thalamus from white matter, gray matter and cerebrospinal fluid (CSF) is a very challenging problem. This thesis presents a new method for simultaneous segmentation of multiple brain structures. We formulate the segmentation problem as a maximum a posteriori estimation problem, in which we incorporate statistical prior models on the shapes and relative poses of the structures of interest. Our method is motivated by the observation that neighboring or coupling structures in medical images generate configurations and co-dependencies which could potentially aid in segmentation if properly exploited. Our coupled shape priors are learned through nonparametric multivariate kernel density estimation based on training data. Relative pose priors are modeled via standard moments. Given this framework, the segmentation problems turns into an optimization problem, which we solve using active contours. We present experimental results on synthetic data as well as on a rich set of real MR images demonstrating the effectiveness of the proposed method in segmenting basal ganglia structures as well as improvements it provides over existing approaches

Nonparametric joint shape learning for customized shape modeling

We present a shape optimization approach to compute patient-specific models in customized prototyping applications. We design a coupled shape prior to model the transformation between a related pair of surfaces, using a nonparametric joint probability density estimation. The coupled shape prior forces with the help of application-specific data forces and smoothness forces drive a surface deformation towards a desired output surface. We demonstrate the usefulness of the method for generating customized shape models in applications of hearing aid design and pre-operative to intra-operative anatomic surface estimation

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

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

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

Quantitative MRI correlates of hippocampal and neocortical pathology in intractable temporal lobe epilepsy

Intractable or drug-resistant epilepsy occurs in over 30% of epilepsy patients, with many of these patients undergoing surgical excision of the affected brain region to achieve seizure control. Advances in MRI have the potential to improve surgical treatment of epilepsy through improved identification and delineation of lesions. However, validation is currently needed to investigate histopathological correlates of these new imaging techniques. The purpose of this work is to investigate histopathological correlates of quantitative relaxometry and DTI from hippocampal and neocortical specimens of intractable TLE patients. To achieve this goal I developed and evaluated a pipeline for histology to in-vivo MRI image registration, which finds dense spatial correspondence between both modalities. This protocol was divided in two steps whereby sparsely sectioned histology from temporal lobe specimens was first registered to the intermediate ex-vivo MRI which is then registered to the in-vivo MRI, completing a pipeline for histology to in-vivo MRI registration. When correlating relaxometry and DTI with neuronal density and morphology in the temporal lobe neocortex, I found T1 to be a predictor of neuronal density in the neocortical GM and demonstrated that employing multi-parametric MRI (combining T1 and FA together) provided a significantly better fit than each parameter alone in predicting density of neurons. This work was the first to relate in-vivo T1 and FA values to the proportion of neurons in GM. When investigating these quantitative multimodal parameters with histological features within the hippocampal subfields, I demonstrated that MD correlates with neuronal density and size, and can act as a marker for neuron integrity within the hippocampus. More importantly, this work was the first to highlight the potential of subfield relaxometry and diffusion parameters (mainly T2 and MD) as well as volumetry in predicting the extent of cell loss per subfield pre-operatively, with a precision so far unachievable. These results suggest that high-resolution quantitative MRI sequences could impact clinical practice for pre-operative evaluation and prediction of surgical outcomes of intractable epilepsy

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

腹部CT像上の複数オブジェクトのセグメンテーションのための統計的手法に関する研究

Computer aided diagnosis (CAD) is the use of a computer-generated output as an auxiliary tool for the assistance of efficient interpretation and accurate diagnosis. Medical image segmentation has an essential role in CAD in clinical applications. Generally, the task of medical image segmentation involves multiple objects, such as organs or diffused tumor regions. Moreover, it is very unfavorable to segment these regions from abdominal Computed Tomography (CT) images because of the overlap in intensity and variability in position and shape of soft tissues. In this thesis, a progressive segmentation framework is proposed to extract liver and tumor regions from CT images more efficiently, which includes the steps of multiple organs coarse segmentation, fine segmentation, and liver tumors segmentation. Benefit from the previous knowledge of the shape and its deformation, the Statistical shape model (SSM) method is firstly utilized to segment multiple organs regions robustly. In the process of building an SSM, the correspondence of landmarks is crucial to the quality of the model. To generate a more representative prototype of organ surface, a k-mean clustering method is proposed. The quality of the SSMs, which is measured by generalization ability, specificity, and compactness, was improved. We furtherly extend the shapes correspondence to multiple objects. A non-rigid iterative closest point surface registration process is proposed to seek more properly corresponded landmarks across the multi-organ surfaces. The accuracy of surface registration was improved as well as the model quality. Moreover, to localize the abdominal organs simultaneously, we proposed a random forest regressor cooperating intensity features to predict the position of multiple organs in the CT image. The regions of the organs are substantially restrained using the trained shape models. The accuracy of coarse segmentation using SSMs was increased by the initial information of organ positions.Consequently, a pixel-wise segmentation using the classification of supervoxels is applied for the fine segmentation of multiple organs. The intensity and spatial features are extracted from each supervoxels and classified by a trained random forest. The boundary of the supervoxels is closer to the real organs than the previous coarse segmentation. Finally, we developed a hybrid framework for liver tumor segmentation in multiphase images. To deal with these issues of distinguishing and delineating tumor regions and peripheral tissues, this task is accomplished in two steps: a cascade region-based convolutional neural network (R-CNN) with a refined head is trained to locate the bounding boxes that contain tumors, and a phase-sensitive noise filtering is introduced to refine the following segmentation of tumor regions conducted by a level-set-based framework. The results of tumor detection show the adjacent tumors are successfully separated by the improved cascaded R-CNN. The accuracy of tumor segmentation is also improved by our proposed method. 26 cases of multi-phase CT images were used to validate our proposed method for the segmentation of liver tumors. The average precision and recall rates for tumor detection are 76.8% and 84.4%, respectively. The intersection over union, true positive rate, and false positive rate for tumor segmentation are 72.7%, 76.2%, and 4.75%, respectively.九州工業大学博士学位論文 学位記番号: 工博甲第546号 学位授与年月日: 令和4年3月25日1 Introduction|2 Literature Review|3 Statistical Shape Model Building|4 Multi-organ Segmentation|5 Liver Tumors Segmentation|6 Summary and Outlook九州工業大学令和3年