Computer generative method on brain tumor segmentation in MRI images

Computer generative method has been used for a long time in brain tumor segmentation tasks on magnetic resonance images. The popularity of machine learning also prompts people to explore the use of generative methods to better train their segmentation models. At the early stage, brain tumor segmentation competitions like BraTS 2012 used computer synthetic MR images with tumor to solve the lack of enough data in the training set, and now, with the rise of computer generative models in deep learning, more researchers have started to work on this track to find a better solution for the task. This thesis addresses the implementation and analysis of some existing methods, specifically a tumor synthetic tool called TumorSim and a competition winning deep learning model that incorporates variational auto-encoder as a generative model. This thesis also reports on an experiment that uses imperfect segmented tumors from simple models as the input to a generative adversarial network to generate a better result.Ope

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

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low-and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource

Cancer diagnosis using deep learning: A bibliographic review

In this paper, we first describe the basics of the field of cancer diagnosis, which includes steps of cancer diagnosis followed by the typical classification methods used by doctors, providing a historical idea of cancer classification techniques to the readers. These methods include Asymmetry, Border, Color and Diameter (ABCD) method, seven-point detection method, Menzies method, and pattern analysis. They are used regularly by doctors for cancer diagnosis, although they are not considered very efficient for obtaining better performance. Moreover, considering all types of audience, the basic evaluation criteria are also discussed. The criteria include the receiver operating characteristic curve (ROC curve), Area under the ROC curve (AUC), F1 score, accuracy, specificity, sensitivity, precision, dice-coefficient, average accuracy, and Jaccard index. Previously used methods are considered inefficient, asking for better and smarter methods for cancer diagnosis. Artificial intelligence and cancer diagnosis are gaining attention as a way to define better diagnostic tools. In particular, deep neural networks can be successfully used for intelligent image analysis. The basic framework of how this machine learning works on medical imaging is provided in this study, i.e., pre-processing, image segmentation and post-processing. The second part of this manuscript describes the different deep learning techniques, such as convolutional neural networks (CNNs), generative adversarial models (GANs), deep autoencoders (DANs), restricted Boltzmann’s machine (RBM), stacked autoencoders (SAE), convolutional autoencoders (CAE), recurrent neural networks (RNNs), long short-term memory (LTSM), multi-scale convolutional neural network (M-CNN), multi-instance learning convolutional neural network (MIL-CNN). For each technique, we provide Python codes, to allow interested readers to experiment with the cited algorithms on their own diagnostic problems. The third part of this manuscript compiles the successfully applied deep learning models for different types of cancers. Considering the length of the manuscript, we restrict ourselves to the discussion of breast cancer, lung cancer, brain cancer, and skin cancer. The purpose of this bibliographic review is to provide researchers opting to work in implementing deep learning and artificial neural networks for cancer diagnosis a knowledge from scratch of the state-of-the-art achievements

Imaging Pain And Brain Plasticity: A Longitudinal Structural Imaging Study

Chronic musculoskeletal pain is a leading cause of disability worldwide yet the mechanisms of chronification and neural responses to effective treatment remain elusive. Non-invasive imaging techniques are useful for investigating brain alterations associated with health and disease. Thus the overall goal of this dissertation was to investigate the white (WM) and grey matter (GM) structural differences in patients with musculoskeletal pain before and after psychotherapeutic intervention: cognitive behavioral therapy (CBT). To aid in the interpretation of clinical findings, we used a novel porcine model of low back pain-like pathophysiology and developed a post-mortem, in situ, neuroimaging approach to facilitate translational investigation. The first objective of this dissertation (Chapter 2) was to identify structural brain alterations in chronic pain patients compared to healthy controls. To achieve this, we examined GM volume and diffusivity as well as WM metrics of complexity, density, and connectivity. Consistent with the literature, we observed robust differences in GM volume across a number of brain regions in chronic pain patients, however, findings of increased GM volume in several regions are in contrast to previous reports. We also identified WM changes, with pain patients exhibiting reduced WM density in tracts that project to descending pain modulatory regions as well as increased connectivity to default mode network structures, and bidirectional alterations in complexity. These findings may reflect network level dysfunction in patients with chronic pain. The second aim (Chapter 3) was to investigate reversibility or neuroplasticity of structural alterations in the chronic pain brain following CBT compared to an active control group. Longitudinal evaluation was carried out at baseline, following 11-week intervention, and a four-month follow-up. Similarly, we conducted structural brain assessments including GM morphometry and WM complexity and connectivity. We did not observe GM volumetric or WM connectivity changes, but we did discover differences in WM complexity after therapy and at follow-up visits. To facilitate mechanistic investigation of pain related brain changes, we used a novel porcine model of low back pain-like pathophysiology (Chapter 6). This model replicates hallmarks of chronic pain, such as soft tissue injury and movement alteration. We also developed a novel protocol to perform translational post-mortem, in situ, neuroimaging in our porcine model to reproduce WM and GM findings observed in humans, followed by a unique perfusion and immersion fixation protocol to enable histological assessment (Chapter 4). In conclusion, our clinical data suggest robust structural brain alterations in patients with chronic pain as compared to healthy individuals and in response to therapeutic intervention. However, the mechanism of these brain changes remains unknown. Therefore, we propose to use a porcine model of musculoskeletal pain with a novel neuroimaging protocol to promote mechanistic investigation and expand our interpretation of clinical findings

BONE LOSS IN RELATION TO HYPOTHALAMIC ATROPHY IN ALZHEIMER'S DISEASE

Epidemiologic projections indicate that the incidence of Alzheimer's disease (AD) will increase dramatically in the coming decades due largely to the demographics of the disease and our aging population. Associated cognitive and physical decline greatly contributes to disability in older adults and places considerable burden on the health system, patients, and caregivers. Bone loss and increased risk of fractures are associated with AD, however little is known about mechanisms of this association. The body of presented work extends the literature on a relationship between bone loss and AD. Overall, the presented work provides initial evidence that accelerated bone loss observed in individuals in the early stages of AD may be partially due to distortion of central regulatory mechanisms by neurodegeneration. This is the first work to demonstrate that hypothalamic atrophy is related to bone loss and this relationship may be mediated by leptin-dependent mechanisms in humans in the early stages of AD. The work in Chapter 2 assessed bone health in the earliest clinical stages of AD in comparison to non-demented aging and examined the relationship of bone mineral density (BMD) with cognitive performance and brain atrophy, both of which are used as surrogate markers of neurodegeneration. We tested the hypothesis that bone density would be lower in early AD and associated with brain atrophy and cognitive decline. The results of this cross-sectional study supported our hypothesis and found that BMD is reduced in men and women in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early Alzheimer's disease. AD is associated with pathological changes in the hypothalamus, a key regulatory structure of bone remodeling. The aim of Chapter 3 was to extend previous findings of the association between BMD and neuroimaging markers of neurodegeneration by looking at global and regional, hypothalamus specifically, measures of brain volume in early AD and non-demented aging. The results demonstrated that in early AD, low BMD was associated with low volume of gray matter in brain structures predominantly affected by AD early in the disease, including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional gray matter volume was found in non-demented controls. These results suggest that central mechanisms of bone remodeling may be disrupted by neurodegeneration. There is very limited guidance in the literature regarding useful and reliable techniques for studying hypothalamic anatomy using neuroimaging. In Chapter 4, we compared an automated neuroimaging technique - voxel-based morphometry (VBM) - to a "gold standard" manual method assessing volumetry of the hypothalamus. The atlas-based VBM volumetry showed promise as a useful tool for regional volumetry of the hypothalamus and has advantages over manual tracing as it is currently used. The results of this study provided guidance for method selection in future work. In Chapter 5, we further examined the hypothesis that AD may influence bone density in cortical skeletal sites directly through atrophy of the hypothalamus, the major central regulatory structure of bone remodeling. We previously reported in cross-section that BMD was lower in those with early AD and suggested that brain atrophy, specifically of the hypothalamus, was associated with lower BMD in AD. We now examined if similar results were apparent in a two year longitudinal study to extend our previous finding of an association between hypothalamic atrophy and bone density. We also explore predictors of bone loss in AD and healthy aging. Our results demonstrate that bone loss may be accelerated in AD compared with non-demented controls. For AD participants, bone loss was associated with hypothalamic atrophy over two years. Additionally, bone loss was associated with baseline levels of the vitamin D. For non-demented participants, bone loss was associated with age, female gender and decline in physical activity. Different predictors of bone loss may suggest that mechanisms of bone loss may differ in aging and AD and that neurodegeneration may contribute to bone loss in early AD. These results extend and strengthen the cross-sectional observations in Chapters 2&3. The purpose of the work presented in Chapter 6 was to further extend previous observations by assessing the roles of leptin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) , two important regulators of hypothalamic control of bone remodeling, in mediating relationship between hypothalamic structural changes and bone loss in AD. We used a hypothetical model with statistical structural equation or path modeling to examine if leptin, GH, and IGF-I may mediate the relationship between hypothalamic structural changes. The model demonstrated that hypothalamic atrophy had a direct relationship with bone loss. There was no apparent association between baseline IGF-1 and leptin with bone loss but we observed changes in both leptin and IGF-1 over two years that were associated with hypothalamic atrophy. Leptin increased over two years in AD and increase in leptin was associated with hypothalamic atrophy. On the other hand, IGF-1 declined over two year and this decrease was associated with increase in leptin. These results suggest that it is conceivable that central regulatory mechanisms of bone mass may be disturbed by neurodegeneration leading to bone loss in participants in the early stages of AD. In summary, this body of work demonstrates that bone density is reduced in women and men with early stages of AD and continues to decline over time, exceeding bone loss in non-demented older adults. While the causes of bone loss in AD remain unclear, the observed association of hypothalamic atrophy with bone loss suggests neurodegeneration may play a role in bone loss observed in AD and highlights a need for further studies. This work also corroborates other studies on the importance of vitamin D and physical activity for bone health. The findings of this body of work are important because evidence that bone loss in AD is associated with the atrophy in regions involved in the central regulation of bone mass may be relevant to therapeutic strategies to prevent or treat bone loss in AD and neurodegenerative diseases

Self-injurious behaviours are associated with alterations in the somatosensory system in children with autism spectrum disorder.

Children with autism spectrum disorder (ASD) frequently engage in self-injurious behaviours, often in the absence of reporting pain. Previous research suggests that altered pain sensitivity and repeated exposure to noxious stimuli are associated with morphological changes in somatosensory and limbic cortices. Further evidence from postmortem studies with self-injurious adults has indicated alterations in the structure and organization of the temporal lobes; however, the effect of self-injurious behaviour on cortical development in children with ASD has not yet been determined. Thirty children and adolescents (mean age = 10.6 ± 2.5 years; range 7-15 years; 29 males) with a clinical diagnosis of ASD and 30 typically developing children (N = 30, mean age = 10.7 ± 2.5 years; range 7-15 years, 26 males) underwent T1-weighted magnetic resonance and diffusion tensor imaging. No between-group differences were seen in cerebral volume, surface area or cortical thickness. Within the ASD group, self-injury scores negatively correlated with thickness in the right superior parietal lobule t = 6.3, p \u3c 0.0001, bilateral primary somatosensory cortices (SI) (right: t = 4.4, p = 0.02; left: t = 4.48, p = 0.004) and the volume of the left ventroposterior (VP) nucleus of the thalamus (r = -0.52, p = 0.008). Based on these findings, we performed an atlas-based region-of-interest diffusion tensor imaging analysis between SI and the VP nucleus and found that children who engaged in self-injury had significantly lower fractional anisotropy (r = -0.4, p = 0.04) and higher mean diffusivity (r = 0.5, p = 0.03) values in the territory of the left posterior limb of the internal capsule. Additionally, greater incidence of self-injury was associated with increased radial diffusivity values in bilateral posterior limbs of the internal capsule (left: r = 0.5, p = 0.02; right: r = 0.5, p = 0.009) and corona radiata (left: r = 0.6, p = 0.005; right: r = 0.5, p = 0.009). Results indicate that self-injury is related to alterations in somatosensory cortical and subcortical regions and their supporting white-matter pathways. Findings could reflect use-dependent plasticity in the somatosensory system or disrupted brain development that could serve as a risk marker for self-injury

Imaging Neuroinflammation in Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system CNS), where inflammation and neurodegeneration lead to irreversible neuronal damage. In MS, a dysfunctional immune system causes auto‐reactive lymphocytes to migrate into CNS where they initiate an inflammatory cascade leading to focal demyelination, axonal degeneration and neuronal loss. One of the hallmarks of neuronal injury and neuroinflammation is the activation of microglia. Activated microglia are found not only in the focal inflammatory lesions, but also diffusely in the normal‐appearing white matter (NAWM), especially in progressive MS. The purine base, adenosine is a ubiquitous neuromodulator in the CNS and also participates in the regulation of inflammation. The effect of adenosine mediated via adenosine A2A receptors has been linked to microglial activation, whereas modulating A2A receptors may exert neuroprotective effects. In the majority of patients, MS presents with a relapsing disease course, later advancing to a progressive phase characterised by a worsening, irreversible disability. Disease modifying treatments can reduce the severity and progression in relapsing MS, but no efficient treatment exists for progressive MS. The aim of this research was to investigate the prevalence of adenosine A2A receptors and activated microglia in progressive MS by using in vivo positron emission tomography (PET) imaging and [11C]TMSX and [11C](R)‐PK11195 radioligands. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed to evaluate structural brain damage. Non‐invasive input function methods were also developed for the analyses of [11C]TMSX PET data. Finally, histopathological correlates of [11C](R)‐PK11195 radioligand binding related to chronic MS lesions were investigated in post‐mortem samples of progressive MS brain using autoradiography and immunohistochemistry. [11C]TMSX binding to A2A receptors was increased in NAWM of secondary progressive MS (SPMS) patients when compared to healthy controls, and this correlated to more severe atrophy in MRI and white matter disintegration (reduced fractional anisotropy, FA) in DTI. The non‐invasive input function methods appeared as feasible options for brain [11C]TMSX images obviating arterial blood sampling. [11C](R)‐PK11195 uptake was increased in the NAWM of SPMS patients when compared to patients with relapsing MS and healthy controls. Higher [11C](R)‐PK11195 binding in NAWM and total perilesional area of T1 hypointense lesions was associated with more severe clinical disability, increased brain atrophy, higher lesion load and reduced FA in NAWM in the MS patients. In autoradiography, increased perilesional [11C](R)‐PK11195 uptake was associated with increased microglial activation identified using immunohistochemistry. In conclusion, brain [11C]TMSX PET imaging holds promise in the evaluation of diffuse neuroinflammation in progressive MS. Being a marker of microglial activation, [11C](R)‐ PK11195 PET imaging could possibly be used as a surrogate biomarker in the evaluation of the neuroinflammatory burden and clinical disease severity in progressive MS.Siirretty Doriast