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INTRODUCTION Blood tests have the potential to improve the accuracy of Alzheimer's disease (AD) clinical diagnosis, which will enable greater access to AD‐specific treatments. This study compared leading commercial blood tests for amyloid pathology and other AD‐related outcomes. METHODS Plasma samples from the Alzheimer's Disease Neuroimaging Initiative were assayed with AD blood tests from C2N Diagnostics, Fujirebio Diagnostics, ALZPath, Janssen, Roche Diagnostics, and Quanterix. Outcomes measures were amyloid positron emission tomography (PET), tau PET, cortical thickness, and dementia severity. Logistic regression models assessed the classification accuracies of individual or combined plasma biomarkers for binarized outcomes, and Spearman correlations evaluated continuous relationships between individual plasma biomarkers and continuous outcomes. RESULTS Measures of plasma p‐tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with all AD outcomes. DISCUSSION This study identified the plasma biomarker analytes and assays that most accurately classified amyloid pathology and other AD‐related outcomes. Highlights Plasma p‐tau217 measures most accurately classified amyloid and tau status. Plasma Aβ42/Aβ40 had relatively low accuracy in classification of amyloid status. Plasma p‐tau217 measures had higher correlations with cortical thickness than NfL. Correlations of plasma biomarkers with dementia symptoms were relatively low.

Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined.

The purpose of this study was to determine if in vivo high resolution 3D MRI and localized 1H MR spectroscopy (MRS) can detect brain findings resembling Alzheimer's disease in a transgenic mouse model of Tau pathology. Seven double transgenic rTg4510 female mice and 7 age-matched wild-type (wt) female mice were evaluated at 5months of age. To confirm the usefulness and consistency of in vivo MRI/S, we also scanned the brains of 14 male mice (7 rTg4510 and 7 age-matched wt) at 8months of age. Mean hippocampal and cerebral cortex volumes in the female rTg4510 mice were 26.7% and 20.6% smaller than that in the wt controls (p<0.0001), respectively. Mean hippocampal and cerebral cortex volumes in the male rTg4510 mice were 18.4% and 16.9% smaller than that in the wt controls (p<0.00005), respectively. The mean volumes of the cerebellum were not statistically different between the rTg4510 and the wt groups. MRS assessment revealed that the myo-inositol to total creatine ratios (mIns/tCr), a measure of gliosis, were significantly higher in the hippocampus of rTg4510 mice relative to wt mice (p=0.03 for the females; p=0.005 for the males). Immunohistochemistry and histology in the same animals verified previously published data showing elevation of hyperphosphorylated Tau, glial activation and cortical and hippocampal neuronal loss. This study demonstrates that in vivo MRI/S can be a non-invasive biomarker to assess brain atrophy and related biochemical changes in the rTg4510 mouse model. ► Application of in vivo MRI/S to tauopathy mouse model- rTg4510. ► High resolution 3D MRI can sensitively assess brain atrophy of rTg4510 mice. ► Myo-inositol can be a sensitive biomarker for glial activation. ► The MRI/S findings were verified by histology and immunohistochemistry.

While neurodegenerative diseases are characterized by steady degeneration over relatively long timelines, it is widely believed that the early stages are the most promising for therapeutic intervention, before irreversible neuronal loss occurs. Developing a therapeutic response requires a precise measure of disease progression. However, since the early stages are for the most part asymptomatic, obtaining accurate measures of disease progression is difficult. Longitudinal databases of hundreds of subjects observed during several years with tens of validated biomarkers are becoming available, allowing the use of computational methods. We propose a widely applicable statistical methodology for creating a disease progression score (DPS), using multiple biomarkers, for subjects with a neurodegenerative disease. The proposed methodology was evaluated for Alzheimer's disease (AD) using the publicly available AD Neuroimaging Initiative (ADNI) database, yielding an Alzheimer's DPS or ADPS score for each subject and each time-point in the database. In addition, a common description of biomarker changes was produced allowing for an ordering of the biomarkers. The Rey Auditory Verbal Learning Test delayed recall was found to be the earliest biomarker to become abnormal. The group of biomarkers comprising the volume of the hippocampus and the protein concentration amyloid beta and Tau were next in the timeline, and these were followed by three cognitive biomarkers. The proposed methodology thus has potential to stage individuals according to their state of disease progression relative to a population and to deduce common behaviors of biomarkers in the disease itself. [Display omitted] ► A computational neurodegenerative disease progression score (DPS) is proposed ► The DPS combines measurements from multiple biomarkers ► Validation with the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort ► An Alzheimer's DPS (ADPS) is computed for each subject and time-point in ADNI ► Evidence for a common Alzheimer's disease progression within ADNI subjects

The traditional means of analysis of tumor growth and morphology is to excise the tumor and study thin, histopathology slices under the microscope. This method requires a different subject for each time Estpoint and runs the real risk of missing some aspect of the tumor not collected in the slice. Ultrasound provide a means to study the tumor in vivo but the images can be hard to interpret. In this research, pixel intensity and contrast and entropy measurements of texture, derived from a cooccurrence function of the image, are used in a robust multivariate image segmentation algorithm to classify the tumor into viable and necrotic cells, reducing misclassification of tissue in the absence of reliable a priori information while allowing for a variable cost function for the type of misclassification. A nude mouse with an Hras tumor was used to establish the model and four nude mice with B16-F10 tumors were used to study the tumor growth over 14 days post cell injection. Histopathology images, one for the Hras tumor and one from mouse 3 of the B16-F10 tumors, were used to validate the segmented image. The multivariate method identified 73% of the necrosis using the mean pixel intensity and texture information while the intensity-alone method identified only 39% of the necrotic-associated pixels.

Leading figures in the Deleuzean philosophy of art criticism field contribute chapters that explore the extensive writings on art, art history, and aesthetics in the realm of contemporary art, of Deleuze and Guattari.