Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

INTRODUCTION: Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. METHODS: We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. RESULTS: Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. DISCUSSION: Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.

Cerebral microbleed incidence, relationship to amyloid burden: The Mayo Clinic Study of Aging.

OBJECTIVE: To determine the incidence of cerebral microbleeds (CMBs) and the association of amyloid PET burden with incident CMBs. METHODS: A total of 651 participants, age ≥50 years (55% male), underwent 3T MRI scans with ≥2 separate T2*-weighted gradient recalled echo sequences from October 2011 to August 2017. Eighty-seven percent underwent 11C Pittsburgh compound B (PiB) PET scans. Age-specific CMB incidence rates were calculated by using the piecewise exponential model. Using structural equation models (SEMs), we assessed the effect of amyloid load and baseline CMBs on future CMBs after considering the direct and indirect age, sex, vascular risk factors, and APOE effects. RESULTS: Participants' mean age (SD) was 69.8 (10.0) years at baseline MRI, and 111 participants (17%) had ≥1 baseline CMB. The mean (SD) of the time interval between scans was 2.7 (1.0) years. The overall population incidence rate for CMBs was 3.6/100 person-years and increased with age: from 1.5/100 new CMBs at age 50 to 11.6/100 person-years at age 90. Using the piecewise exponential model regression, the incidence rates increased with age and the presence of baseline CMBs. The SEMs showed that (1) increasing age at MRI or carrying an APOE4 allele was associated with more amyloid at baseline, and higher amyloid, particularly occipital amyloid load, in turn increased the risk of a new lobar CMB; and (2) the presence of CMBs at baseline increased the risk of a lobar CMB and had a larger effect size than amyloid load. CONCLUSIONS: Age and APOE4 carrier status act through amyloid load to increase the risk of subsequent lobar CMBs, but the presence of baseline CMBs is the most important risk factor for future CMBs.

Out-of-hospital cardiac arrest in denver, colorado: epidemiology and outcomes.

OBJECTIVES: The annual incidence of out-of-hospital cardiac arrest (OOHCA) in the United States is approximately 6 per 10,000 population and survival remains low. Relatively little is known about the performance characteristics of a two-tiered emergency medical services (EMS) system split between fire-based basic life support (BLS) dispersed from fixed locations and hospital-based advanced life support (ALS) dispersed from nonfixed locations. The objectives of this study were to describe the incidence of OOHCA in Denver, Colorado, and to define the prevalence of survival with good neurologic function in the context of this particular EMS system. METHODS: This was a retrospective cohort study using standardized abstraction methodology. A two-tiered hospital-based EMS system for the County of Denver and 10 receiving hospitals were studied. Consecutive adult patients who experienced nontraumatic OOHCA from January 1, 2003, through December 31, 2004, were enrolled. Demographic, prehospital arrest characteristics, treatment data, and survival data using the Utstein template were collected. Good neurologic survival was defined by a Cerebral Performance Categories (CPC) score of 1 or 2. RESULTS: During the study period, 1,985 arrests occurred. Of these, 715 (36%) had attempted resuscitation by paramedics and constitute our study sample. The median age was 65 years (interquartile range = 52-78 years), 69% were male, 41% had witnessed arrest, 25% had bystander cardiopulmonary resuscitation (CPR) performed, and 30% had ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as their initial rhythm. Of the 715 patients, 545 (76%) were transported to a hospital, 223 (31%) had return of spontaneous circulation (ROSC), 175 (25%) survived to hospital admission, 58 (8%) survived to hospital discharge, and 42 (6%, 95% confidence interval [CI] = 4% to 8%) had a good neurologic outcome. CONCLUSIONS: Out-of-hospital cardiac arrest survival in Denver, Colorado, is similar to that of other United States communities. This finding provides the basis for future epidemiologic and health services research in the out-of-hospital and ED settings in our community.

Intensity non-uniformity correction using N3 on 3-T scanners with multichannel phased array coils.

Measures of structural brain change based on longitudinal MR imaging are increasingly important but can be degraded by intensity non-uniformity. This non-uniformity can be more pronounced at higher field strengths, or when using multichannel receiver coils. We assessed the ability of the non-parametric non-uniform intensity normalization (N3) technique to correct non-uniformity in 72 volumetric brain MR scans from the preparatory phase of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Normal elderly subjects (n=18) were scanned on different 3-T scanners with a multichannel phased array receiver coil at baseline, using magnetization prepared rapid gradient echo (MP-RAGE) and spoiled gradient echo (SPGR) pulse sequences, and again 2 weeks later. When applying N3, we used five brain masks of varying accuracy and four spline smoothing distances (d=50, 100, 150 and 200 mm) to ascertain which combination of parameters optimally reduces the non-uniformity. We used the normalized white matter intensity variance (standard deviation/mean) to ascertain quantitatively the correction for a single scan; we used the variance of the normalized difference image to assess quantitatively the consistency of the correction over time from registered scan pairs. Our results showed statistically significant (p<0.01) improvement in uniformity for individual scans and reduction in the normalized difference image variance when using masks that identified distinct brain tissue classes, and when using smaller spline smoothing distances (e.g., 50-100 mm) for both MP-RAGE and SPGR pulse sequences. These optimized settings may assist future large-scale studies where 3-T scanners and phased array receiver coils are used, such as ADNI, so that intensity non-uniformity does not influence the power of MR imaging to detect disease progression and the factors that influence it.

Common MRI acquisition non-idealities significantly impact the output of the boundary shift integral method of measuring brain atrophy on serial MRI.

Measuring rates of brain atrophy from serial magnetic resonance imaging (MRI) studies is an attractive way to assess disease progression in neurodegenerative disorders, particularly Alzheimer's disease (AD). A widely recognized approach is the boundary shift integral (BSI). The objective of this study was to evaluate how several common scan non-idealities affect the output of the BSI algorithm. We created three types of image non-idealities between the image volumes in a serial pair used to measure between-scan change: inconsistent image contrast between serial scans, head motion, and poor signal-to-noise (SNR). In theory the BSI volume difference measured between each pair of images should be zero and any deviation from zero should represent corruption of the BSI measurement by some non-ideality intentionally introduced into the second scan in the pair. Two different BSI measures were evaluated, whole brain and ventricle. As the severity of motion, noise, and non-congruent image contrast increased in the second scan, the calculated BSI values deviated progressively more from the expected value of zero. This study illustrates the magnitude of the error in measures of change in brain and ventricle volume across serial MRI scans that can result from commonly encountered deviations from ideal image quality. The magnitudes of some of the measurement errors seen in this study exceed the disease effect in AD shown in various publications, which range from 1% to 2.78% per year for whole brain atrophy and 5.4% to 13.8% per year for ventricle expansion (Table 1). For example, measurement error may exceed 100% if image contrast properties dramatically differ between the two scans in a measurement pair. Methods to maximize consistency of image quality over time are an essential component of any quantitative serial MRI study.