Development of Anatomical and Functional Magnetic Resonance Imaging Measures of Alzheimer Disease

Alzheimer disease is considered to be a progressive neurodegenerative condition, clinically characterized by cognitive dysfunction and memory impairments. Incorporating imaging biomarkers in the early diagnosis and monitoring of disease progression is increasingly important in the evaluation of novel treatments. The purpose of the work in this thesis was to develop and evaluate novel structural and functional biomarkers of disease to improve Alzheimer disease diagnosis and treatment monitoring. Our overarching hypothesis is that magnetic resonance imaging methods that sensitively measure brain structure and functional impairment have the potential to identify people with Alzheimer’s disease prior to the onset of cognitive decline. Since the hippocampus is considered to be one of the first brain structures affected by Alzheimer disease, in our first study a reliable and fully automated approach was developed to quantify medial temporal lobe atrophy using magnetic resonance imaging. This measurement of medial temporal lobe atrophy showed differences (pnovel biomarker of brain activity was developed based on a first-order textural feature of the resting state functional magnetic resonance imagining signal. The mean brain activity metric was shown to be significantly lower (pp18F labeled fluorodeoxyglucose positron emission tomography. In the final study, we examine whether combined measures of gait and cognition could predict medial temporal lobe atrophy over 18 months in a small cohort of people (N=22) with mild cognitive impairment. The results showed that measures of gait impairment can help to predict medial temporal lobe atrophy in people with mild cognitive impairment. The work in this thesis contributes to the growing evidence the specific magnetic resonance imaging measures of brain structure and function can be used to identify and monitor the progression of Alzheimer’s disease. Continued refinement of these methods, and larger longitudinal studies will be needed to establish whether the specific metrics of brain dysfunction developed in this thesis can be of clinical benefit and aid in drug development

Accurate Real Time Localization Tracking in A Clinical Environment using Bluetooth Low Energy and Deep Learning

Deep learning has started to revolutionize several different industries, and the applications of these methods in medicine are now becoming more commonplace. This study focuses on investigating the feasibility of tracking patients and clinical staff wearing Bluetooth Low Energy (BLE) tags in a radiation oncology clinic using artificial neural networks (ANNs) and convolutional neural networks (CNNs). The performance of these networks was compared to relative received signal strength indicator (RSSI) thresholding and triangulation. By utilizing temporal information, a combined CNN+ANN network was capable of correctly identifying the location of the BLE tag with an accuracy of 99.9%. It outperformed a CNN model (accuracy = 94%), a thresholding model employing majority voting (accuracy = 95%), and a triangulation classifier utilizing majority voting (accuracy = 95%). Future studies will seek to deploy this affordable real time location system in hospitals to improve clinical workflow, efficiency, and patient safety

Spontaneous low frequency BOLD signal variations from resting-state fMRI are decreased in Alzheimer disease

Previous studies have demonstrated altered brain activity in Alzheimer\u27s disease using task based functional MRI (fMRI), network based resting-state fMRI, and glucose metabolism from 18 F fluorodeoxyglucose-PET (FDG-PET). Our goal was to define a novel indicator of neuronal activity based on a first-order textural feature of the resting state functional MRI (RS-fMRI) signal. Furthermore, we examined the association between this neuronal activity metric and glucose metabolism from F-18 FDG-PET. We studied 15 normal elderly controls (NEC) and 15 probable Alzheimer disease (AD) subjects from the AD Neuroimaging Initiative. An independent component analysis was applied to the RS-fMRI, followed by template matching to identify neuronal components (NC). A regional brain activity measurement was constructed based on the variation of the RS-fMRI signal of these NC. The standardized glucose uptake values of several brain regions relative to the cerebellum (SUVR) were measured from partial volume corrected FDG-PET images. Comparing the AD and NEC groups, the mean brain activity metric was significantly lower in the accumbens, while the glucose SUVR was significantly lower in the amygdala and hippocampus. The RS-fMRI brain activity metric was positively correlated with cognitive measures and amyloid beta 1-42 cerebral spinal fluid levels; however, these did not remain significant following Bonferroni correction. There was a significant linear correlation between the brain activity metric and the glucose SUVR measurements. This proof of concept study demonstrates that this novel and easy to implement RS-fMRI brain activity metric can differentiate a group of healthy elderly controls from a group of people with AD

Semiautomated Assessment of the Anterior Cingulate Cortex in Alzheimer\u27s Disease

© 2019 by the American Society of Neuroimaging BACKGROUND AND PURPOSE: The anterior cingulate cortex (ACC) is involved in several cognitive processes including executive function. Degenerative changes of ACC are consistently seen in Alzheimer\u27s disease (AD). However, volumetric changes specific to the ACC in AD are not clear because of the difficulty in segmenting this region. The objectives of the current study were to develop a precise and high-throughput approach for measuring ACC volumes and to correlate the relationship between ACC volume and cognitive function in AD. METHODS: Structural T 1 -weighted magnetic resonance images of AD patients (n = 47) and age-matched controls (n = 47) at baseline and at 24 months were obtained from the Alzheimer\u27s disease neuroimaging initiative (ADNI) database and studied using a custom-designed semiautomated segmentation protocol. RESULTS: ACC volumes obtained using the semiautomated protocol were highly correlated to values obtained from manual segmentation (r =.98) and the semiautomated protocol was considerably faster. When comparing AD and control subjects, no significant differences were observed in baseline ACC volumes or in change in ACC volumes over 24 months using the two segmentation methods. However, a change in ACC volume over 24 months did not correlate with a change in mini-mental state examination scores. CONCLUSIONS: Our results indicate that the proposed semiautomated segmentation protocol is reliable for determining ACC volume in neurodegenerative conditions including AD

Dosimetric evaluation of synthetic CT generated with GANs for MRI-only proton therapy treatment planning of brain tumors

PURPOSE: The purpose of this study was to address the dosimetric accuracy of synthetic computed tomography (sCT) images of patients with brain tumor generated using a modified generative adversarial network (GAN) method, for their use in magnetic resonance imaging (MRI)-only treatment planning for proton therapy. METHODS: Dose volume histogram (DVH) analysis was performed on CT and sCT images of patients with brain tumor for plans generated for intensity-modulated proton therapy (IMPT). All plans were robustly optimized using a commercially available treatment planning system (RayStation, from RaySearch Laboratories) and standard robust parameters reported in the literature. The IMPT plan was then used to compute the dose on CT and sCT images for dosimetric comparison, using RayStation analytical (pencil beam) dose algorithm. We used a second, independent Monte Carlo dose calculation engine to recompute the dose on both CT and sCT images to ensure a proper analysis of the dosimetric accuracy of the sCT images. RESULTS: The results extracted from RayStation showed excellent agreement for most DVH metrics computed on the CT and sCT for the nominal case, with a mean absolute difference below 0.5% (0.3 Gy) of the prescription dose for the clinical target volume (CTV) and below 2% (1.2 Gy) for the organs at risk (OARs) considered. This demonstrates a high dosimetric accuracy for the generated sCT images, especially in the target volume. The metrics obtained from the Monte Carlo doses mostly agreed with the values extracted from RayStation for the nominal and worst-case scenarios (mean difference below 3%). CONCLUSIONS: This work demonstrated the feasibility of using sCT generated with a GAN-based deep learning method for MRI-only treatment planning of patients with brain tumor in intensity-modulated proton therapy

Classification results for RS-fMRI brain activity, glucose metabolism measured by FDG-PET SUVR, and normalized volume measured using MRI.

<p>The 95% confidence interval (CI) is provided in parentheses.</p

Relationship between mean brain activity measured using RS-fMRI and CSF derived Amyloid Beta_1-42.

<p>The 95% confidence intervals for the regressions are shown as dotted lines. Association between the brain activity and Aβ_1–42 in the cerebellum (r = 0.40, <i>p</i> = 0.03, A), amygdala (r = 0.51, <i>p</i> = 0.004, B), accumbens (r = 0.37, <i>p</i> = 0.04, C), pallidum (r = 0.41, <i>p</i> = 0.02, D), and putamen (r = 0.41, <i>p</i> = 0.02, E). These correlations were not significant following Bonferroni correction for multiple comparisons.</p