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Alzheimer's disease (AD) dementia is a consequence of heterogeneous and complex interactions of age-related neurodegeneration and vascular-associated pathologies. Evidence has accumulated that there is increased atherosclerosis/arteriosclerosis of the intracranial arteries in AD and that this may be additive or synergistic with respect to the generation of hypoxia/ischemia and cognitive dysfunction. The effectiveness of pharmacologic therapies and lifestyle modification in reducing cardiovascular disease has prompted a reconsideration of the roles that cardiovascular disease and cerebrovascular function play in the pathogenesis of dementia. Using two-dimensional phase-contrast magnetic resonance imaging, we quantified cerebral blood flow within the internal carotid, basilar, and middle cerebral arteries in a group of individuals with mild to moderate AD (n = 8) and compared the results with those from a group of age-matched nondemented control (NDC) subjects (n = 9). Clinical and psychometric testing was performed on all individuals, as well as obtaining their magnetic resonance imaging-based hippocampal volumes. Our experiments reveal that total cerebral blood flow was 20% lower in the AD group than in the NDC group, and that these values were directly correlated with pulse pressure and cognitive measures. The AD group had a significantly lower pulse pressure (mean AD 48, mean NDC 71; P = 0.0004). A significant group difference was also observed in their hippocampal volumes. Composite z-scores for clinical, psychometric, hippocampal volume, and hemodynamic data differed between the AD and NDC subjects, with values in the former being significantly lower (t = 12.00, df = 1, P = 0.001) than in the latter. These results indicate an association between brain hypoperfusion and the dementia of AD. Cardiovascular disease combined with brain hypoperfusion may participate in the pathogenesis/pathophysiology of neurodegenerative diseases. Future longitudinal and larger-scale confirmatory investigations measuring multidomain parameters are warranted.

Chapter 2 discusses radiation safety and risks. For anyone involved with medical imaging, it is essential to be on familiar terms with radiation terminology.Those who are not will find themselves on unsteady ground either when reading the literature or discussing the particulars of a computed tomography (CT) scan with patients. The numerous terms used to describe radiation dose contribute substantially to the confusion, and the first step to a solid understanding is to use only two or three terms for dose measurement. Otherwise, using the full range of units e.g. Roentgen, rad, rem, Gray, Sievert, and their respective conversion factors will cause confusion. In this book, the terminology of radiation dose will be limited to the most commonly used measurements.

Background Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data. Objective To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial. Methods Using data from a clinical trial in progressive multiple sclerosis, we explored how major changes in imaging hardware affected data. We analyzed the extent to which these changes affected imaging biomarkers and the estimated treatment effects by including such changes as a time-dependent covariate. Results Significant differences whole brain atrophy (brain parenchymal fraction, BPF) and microstructure (transverse diffusivity, TD) between scans with and without changes were found and depended on the type of hardware change. A switch from GE HDxt to Siemens Skyra led to significant shifts in BPF (p < 0.04) and TD (p < 0.0001). However, we could not detect the influence of hardware changes on overall trial outcomes– differences between placebo and treatment arms in change over time of BPF and TD (p > 0.5). Conclusions The results suggest that differences among hardware types should be considered when planning and analyzing brain atrophy and diffusivity in a longitudinal clinical trial.