Diverging volumetric trajectories following pediatric traumatic brain injury.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2-5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8-18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2-5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory

Structural Abnormalities in Gambling Disorder Using Voxel-Based Morphometry

Gambling is a recreational activity popular across the globe, but maladaptive gambling behavior can pose serious, negative consequences to the gambler. Gambling disorder (GD) is a psychiatric disorder that focuses on these dysfunctional behaviors. In order to investigate the structural brain abnormalities in GD, a whole-brain exploratory analysis was carried out using voxel-based morphometry (VBM8). VBM8 was selected to enable direct comparison to an earlier study. There were no significant differences in global- or regional- gray and white matter volumes between GD patients and healthy controls (HC). These findings suggest that GD is not associated with macroscopic brain anatomical abnormalities or that anatomical abnormalities are too small compared to the individual variance to be detected with VBM8

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

Grey and white matter correlates of recent and remote autobiographical memory retrieval:Insights from the dementias

The capacity to remember self-referential past events relies on the integrity of a distributed neural network. Controversy exists, however, regarding the involvement of specific brain structures for the retrieval of recently experienced versus more distant events. Here, we explored how characteristic patterns of atrophy in neurodegenerative disorders differentially disrupt remote versus recent autobiographical memory. Eleven behavioural-variant frontotemporal dementia, 10 semantic dementia, 15 Alzheimer's disease patients and 14 healthy older Controls completed the Autobiographical Interview. All patient groups displayed significant remote memory impairments relative to Controls. Similarly, recent period retrieval was significantly compromised in behavioural-variant frontotemporal dementia and Alzheimer's disease, yet semantic dementia patients scored in line with Controls. Voxel-based morphometry and diffusion tensor imaging analyses, for all participants combined, were conducted to investigate grey and white matter correlates of remote and recent autobiographical memory retrieval. Neural correlates common to both recent and remote time periods were identified, including the hippocampus, medial prefrontal, and frontopolar cortices, and the forceps minor and left hippocampal portion of the cingulum bundle. Regions exclusively implicated in each time period were also identified. The integrity of the anterior temporal cortices was related to the retrieval of remote memories, whereas the posterior cingulate cortex emerged as a structure significantly associated with recent autobiographical memory retrieval. This study represents the first investigation of the grey and white matter correlates of remote and recent autobiographical memory retrieval in neurodegenerative disorders. Our findings demonstrate the importance of core brain structures, including the medial prefrontal cortex and hippocampus, irrespective of time period, and point towards the contribution of discrete regions in mediating successful retrieval of distant versus recently experienced events

Influence of Analytic Techniques on Comparing Dti-Derived Measurements in Early Stage Parkinson\u27s Disease

Diffusion tensor imaging (DTI) studies in early Parkinson\u27s disease (PD) to understand pathologic changes in white matter (WM) organization are variable in their findings. Evaluation of different analytic techniques frequently employed to understand the DTI-derived change in WM organization in a multisite, well-characterized, early stage PD cohort should aid the identification of the most robust analytic techniques to be used to investigate WM pathology in this disease, an important unmet need in the field. Thus, region of interest (ROI)-based analysis, voxel-based morphometry (VBM) analysis with varying spatial smoothing, and the two most widely used skeletonwise approaches (tract-based spatial statistics, TBSS, and tensor-based registration, DTI-TK) were evaluated in a DTI dataset of early PD and Healthy Controls (HC) from the Parkinson\u27s Progression Markers Initiative (PPMI) cohort. Statistical tests on the DTI-derived metrics were conducted using a nonparametric approach from this cohort of early PD, after rigorously controlling for motion and signal artifacts during DTI scan which are frequent confounds in this disease population. Both TBSS and DTI-TK revealed a significantly negative correlation of fractional anisotropy (FA) with disease duration. However, only DTI-TK revealed radial diffusivity (RD) to be driving this FA correlation with disease duration. HC had a significantly positive correlation of MD with cumulative DaT score in the right middle-frontal cortex after a minimum smoothing level (at least 13mm) was attained. The present study found that scalar DTI-derived measures such as FA, MD, and RD should be used as imaging biomarkers with caution in early PD as the conclusions derived from them are heavily dependent on the choice of the analysis used. This study further demonstrated DTI-TK may be used to understand changes in DTI-derived measures with disease progression as it was found to be more accurate than TBSS. In addition, no singular region was identified that could explain both disease duration and severity in early PD. The results of this study should help standardize the utilization of DTI-derived measures in PD in an effort to improve comparability across studies and time, and to minimize variability in reported results due to variation in techniques

Machine Learning Based Autism Detection Using Brain Imaging

Autism Spectrum Disorder (ASD) is a group of heterogeneous developmental disabilities that manifest in early childhood. Currently, ASD is primarily diagnosed by assessing the behavioral and intellectual abilities of a child. This behavioral diagnosis can be subjective, time consuming, inconclusive, does not provide insight on the underlying etiology, and is not suitable for early detection. Diagnosis based on brain magnetic resonance imaging (MRI)—a widely used non- invasive tool—can be objective, can help understand the brain alterations in ASD, and can be suitable for early diagnosis. However, the brain morphological findings in ASD from MRI studies have been inconsistent. Moreover, there has been limited success in machine learning based ASD detection using MRI derived brain features. In this thesis, we begin by demonstrating that the low success in ASD detection and the inconsistent findings are likely attributable to the heterogeneity of brain alterations in ASD. We then show that ASD detection can be significantly improved by mitigating the heterogeneity with the help of behavioral and demographics information. Here we demonstrate that finding brain markers in well-defined sub-groups of ASD is easier and more insightful than identifying markers across the whole spectrum. Finally, our study focused on brain MRI of a pediatric cohort (3 to 4 years) and achieved a high classification success (AUC of 95%). Results of this study indicate three main alterations in early ASD brains: 1) abnormally large ventricles, 2) highly folded cortices, and 3) low image intensity in white matter regions suggesting myelination deficits indicative of decreased structural connectivity. Results of this thesis demonstrate that the meaningful brain markers of ASD can be extracted by applying machine learning techniques on brain MRI data. This data-driven technique can be a powerful tool for early detection and understanding brain anatomical underpinnings of ASD