Relationship of amyloid beta and neurofibrillary tau deposition in Neurodegeneration in Aging Down Syndrome (NiAD) study at baseline.

IMPORTANCE: Adults with Down syndrome (DS) are at high-risk of revealing Alzheimer's disease (AD) pathology, in part due to the triplication of chromosome 21 encoding the amyloid precursor protein. Adults with DS are uniformly affected by AD pathology by their 30's and have a 70% to 80% chance of clinical dementia by their 60's. Our previous studies have assessed longitudinal changes in amyloid beta (Aß) accumulation in DS. OBJECTIVE: The goal of the present study was to assess the presence of brain tau using [18F]AV-1451 positron emission tomography (PET) in DS and to assess the relationship of brain tau pathology to Aß using Pittsburgh Compound B (PiB)-PET. DESIGN: Cohort study. SETTING: Multi-center study. PARTICIPANTS: Participants consisted of a sample of individuals with DS and sibling controls recruited from the community; exclusion criteria included contraindications for magnetic resonance imaging (MRI) and/or a medical or psychiatric condition that impaired cognitive functioning. EXPOSURES: PET brain scans to assess Aß ([11C]PiB) and tau ([18F]AV-1451) burden. MAIN OUTCOMES AND MEASURES: Multiple linear regression models (adjusted for chronological age, sex and performance site) were used to examine associations between regional [18F]AV-1451 standard uptake value ratio (SUVR) (based on regions associated with Braak stages 1-6) and global [11C]PiB SUVR (as both a continuous and dichotomous variable). RESULTS: A cohort of 156 participants (mean age = 39.05, SD(8.4)) were examined. These results revealed a significant relationship between in vivo Aß and tau pathology in DS. As a dichotomous variable, [18F]AV-1451 retention was higher in each Braak region in PiB(+) participants. We also found, based on our statistical models, starting with the Braak 3 region of interest (ROI), an acceleration of [18F]AV-1451 SUVR deposition with [11C]PiB SUVR increases.

Evaluation of a commercial radiochromatography module as an arterial blood activity monitor.

Input functions required for positron emission tomography (PET) tracer kinetic modeling are often obtained from arterial blood. In some situations, using short-lived radiotracers, e.g. [(15)O]water, rapid sample handling is required. A method used at several facilities is to pump blood through a detector system at a constant rate. We investigate the suitability of a commercial radiochromatography module (IN/US Posi-RAM) for this new use. The Posi-RAM consists of two 2.5 cm (length) x 2.5 cm (diameter) cylindrical bismuth germanate (BGO) detectors that can operate in coincidence mode. Arterial blood is transported through the system via a length of tubing with flow rate controlled by a peristalsis pump. A custom-counting loop and support frame were designed for the Posi-RAM for PET studies. System sensitivity was determined to be 1.1 x 10(4) cps/(MBq ml(-1)). Dead time as a function of count-rate was found to be less than 1% for concentrations below 3.5 MBq ml(-1), a range encompassing all human-study values. In a human study, the performance of the device was found to be similar to that of the facility's current blood monitor (Siemens Fluid Monitor). We conclude that the Posi-RAM has the necessary sensitivity and count-rate capabilities to be used as a real-time blood activity monitor.

Transmission scanning system for a gamma camera coincidence scanner.

UNLABELLED: The goal of this research was to develop and evaluate a practical transmission scanning system for attenuation correction on a 2-head gamma camera coincidence scanner. METHODS: The transmission system operates in singles mode and uses point sources of 137Cs that emit 662-keV gamma-radiation. Each point source is inserted between existing septa that are normally used to provide an approximately 2-dimensional emission acquisition geometry. The sources are placed along a line parallel to the axis of rotation near the edge of 1 camera. Data are acquired with the opposing camera. The septa provide axial collimation for the sources so that the transmission system operates in a 2-dimensional offset fanbeam geometry. Camera energy and spatial resolution were measured at 511 and 662 keV. Sensitivity was measured at 662 keV. The effects on axial resolution of adding supplemental collimation to the septa were shown. The system was calibrated and tested using a resolution (rod) phantom and a uniformity phantom. Torso phantom data were acquired. Patient transmission and emission scans were obtained. Postinjection transmission data were used to correct patient emission data. RESULTS: The camera resolution at postinjection counting rates was 11.7% full width at half maximum (FWHM) for 662-keV gamma-rays. Intrinsic spatial resolution was 2.7 mm (FWHM) at 662 keV. The sensitivity of the system was 280 Hz/MBq using five 74-MBq sources of 137Cs in the transmission geometry, with supplemental collimation added to the septa to improve axial resolution. The transaxial resolution of the system was such that the smallest rods (6-mm diameter and 12-mm spacing) were well resolved in a reconstructed resolution-phantom image. The corrected patient emission scans were free of attenuation-induced artifacts. CONCLUSION: An easily implemented transmission system for a 2-head gamma camera coincidence scanner that can be used for postinjection transmission scanning has been developed.

Calculation of attenuation factors from combined singles and coincidence emission projections.

We have developed a simple method for determining coincidence attenuation-correction factors C (the inverse of the total attenuation factors) from collimated singles (SPECT) and coincidence [positron emission tomography (PET)] projections without transmission data. Attenuation-correction factor estimates are determined for individual lines of response (LOR's) independently. The required data can be acquired using a gamma-camera system with coincidence capabilities. A first-order approximation (R) of C for an LOR is given by the product of the singles count rates, taken at each end of the LOR divided by the square of the coincidence count rate. The method was tested using simulated singles and coincidence projections starting with emission and attenuation maps from patient PET scans. Noise and resolution effects were modeled in separate studies. In the noise-free, high-resolution simulations, a scatter plot of the C values versus the corresponding R values for all LOR's produces a well-defined trajectory with little variance. Values of lnR were reconstructed into good quality attenuation maps that compare favorably with the originals. We conclude that the method works well on ideal data. The introduction of noise results in degraded images. In a simulated patient study, lung and outer body boundaries were visible in images produced with 3.2 x 10(4) coincidence counts.

Registration-based method for determining relative PET/MR left-right image orientation.

A quality control method is described for verifying that the coordinate systems of a PET and MR image from the same subject have the same relative left-right orientation. Such ambiguities can arise, for example, at the coordinating center receiving data from many institutions in large multisite studies. In this study, image registration was performed on the PET/MR image pair. The MR image was then reflected (left/right reversed) and the image registration was performed again. A comparison of the values of the cost function describing the accuracy of the registration was used to identify the correct relative orientation. In 122 studies using data with known orientations, 100% accuracy of the method was observed.

FDG imaging of lung nodules: a phantom study comparing SPECT, camera-based PET, and dedicated PET.

PURPOSE: To evaluate 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) imaging of simulated lung nodules in a realistic chest phantom by using attenuation-corrected and non-attenuation-corrected 511-keV single photon emission computed tomography (SPECT), camera-based positron emission tomography (PET), and dedicated PET imaging. MATERIALS AND METHODS: Spheres with diameters of 6, 10, 13, and 22 mm were placed in the lungs of an anthropomorphic chest phantom to simulate nodules. The lungs, nodules, chest wall, and mediastinum were filled with fluorine-18 activities based on the average radionuclide concentrations in those structures from analysis of attenuation-corrected dedicated FDG PET scans. The image sets were evaluated visually and quantitatively by using contrast and signal-to-noise ratios. RESULTS: Attenuation correction reduced the artificially high apparent uptake in the lungs, restored the spherical shape to the nodules, and provided an accurate outer body contour with appropriate intensity. Dedicated PET depicted all four nodules, camera-based PET depicted the three largest nodules, and SPECT depicted the two largest nodules. Lesion contrast was better on the attenuation-corrected images than on the non-attenuation-corrected images. The signal-to-noise ratio generally was improved with attenuation correction. CONCLUSION: Attenuation correction results in many changes in the images and improves lesion detection.

Detection of Recurrent Brain Tumor. Comparison of MR Registered Camera-Based and Dedicated PET Images.

The purpose of this study is to compare the quality of images and the results of camera-based and dedicated position emission tomography (PET) in the same patients with suspected recurrent or persistent brain tumor after therapy. Both PET studies were interpreted using registration with contrast-enhanced magnetic resonance imaging (MRI) studies. Twenty-three patients with 24 contrast-enhancing lesions by MRI were included. Camera-based PET images were more difficult to register and resulted in less accurate automated determination of the edge because of image noise. Dedicated PET images demonstrated better gray matter to white matter discrimination in every patient. Camera-based PET identified tumor in 17 of 19 lesions that were abnormal for tumor by dedicated PET. Camera-based PET identified absence of tumor in 4 of 5 lesions considered negative for tumor by dedicated PET. Thus, despite the limitations related to camera-based PET, the overall concordance of interpretation using MRI registered images is good.