Assessment of perfusion deficit with early phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol-amyloid-PET recordings.

PURPOSE: Characteristic features of amyloid-PET (A), tau-PET (T), and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of amyloid- or tau-PET recordings serve to detect cerebrometabolic deficits equally to FDG-PET, therefore providing a surrogate of neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism. Therefore, we undertook to compare [18F]flutemetamol-amyloid-PET and [18F]PI-2620 tau-PET as "one-stop shop" dual purpose tracers for the detection of neurodegenerative disease. METHODS: We obtained early-phase PET recordings with [18F]PI-2620 (0.5-2.5 min p.i.) and [18F]flutemetamol (0-10 min p.i.) in 64 patients with suspected neurodegenerative disease. We contrasted global mean normalized images (SUVr) in the patients with a normal cohort of 15 volunteers without evidence of increased pathology to ß-amyloid- and tau-PET examinations. Regional group differences of tracer uptake (z-scores) of 246 Brainnetome volumes of interest were calculated for both tracers, and the correlations of the z-scores were evaluated using Pearson's correlation coefficient. Lobar compartments, regions with significant neuronal injury (z-scores < - 3), and patients with different neurodegenerative disease entities (e.g., Alzheimer's disease or 4R-tauopathies) served for subgroup analysis. Additionally, we used partial regression to correlate regional perfusion alterations with clinical scores in cognition tests. RESULTS: The z-scores of perfusion-weighted images of both tracers showed high correlations across the brain, especially in the frontal and parietal lobes, which were the brain regions with pronounced perfusion deficit in the patient group (R = 0.83 ± 0.08; range, 0.61-0.95). Z-scores of individual patients correlated well by region (R = 0.57 ± 0.15; range, 0.16-0.90), notably when significant perfusion deficits were present (R = 0.66 ± 0.15; range, 0.28-0.90). CONCLUSION: The early perfusion phases of [18F]PI-2620 tau- and [18F]flutemetamol-amyloid-PET are roughly equivalent indices of perfusion defect indicative of regional and lobar neuronal injury in patients with various neurodegenerative diseases. As such, either tracer may serve for two diagnostic channels by assessment of amyloid/tau status and neuronal activity.

Assessment of cerebral dopamine D 2/3 formula-receptors in patients with bilateral vestibular failure.

BACKGROUND: Absence of peripheral vestibular input in bilateral vestibular failure (BVF) has been suggested to induce plastic reorganization in various brain regions. Among several neurotransmitters, dopamine is known to play a key role in cortico-striatal-sensorimotor processing. However, the role of dopamine in vestibular plasticity is scantly documented. OBJECTIVE: Assessment of D 2/3 formula-receptors in patients with BVF. METHODS: D 2/3 formula-receptor-PET using [18F]fallypride and MRI examinations were performed in 12 BVF-patients and 13 healthy controls. RESULTS: BVF-patients showed reduced D 2/3 formula-receptor availability (approximately 40%) in the temporo-parieto-occipital cortex bilaterally, including the multisensory vestibular cortex and visual motion-sensitive areas (MT/MST), as well as in the striatum and the right thalamus. Longer illness duration was associated with bilaterally lower D 2/3 formula-receptor availability in the middle/superior temporal gyrus (GTm/s). D 2/3 formula-receptor availability in the right GTm/s and bilateral insula decreased with severity of symptoms. BVF-patients with oscillopsia showed reduced D 2/3 formula-receptor availability in the right MT/MST and midbrain tectum. CONCLUSIONS: Reduced D 2/3 formula-receptor availability in multisensory vestibular cortical network areas and basal ganglia may indicate a receptor down-regulation due to the lack of peripheral vestibular input. The more pronounced decline in D 2/3 formula-receptor availability in the multisensory vestibular cortex in patients with prolonged illness suggests the occurrence of progressive changes in dopamine transmission.

Longitudinal assessment of cerebral ß-amyloid deposition in mice overexpressing Swedish mutant ß-amyloid precursor protein using 18F-florbetaben PET.

UNLABELLED: The progression of ß-amyloid deposition in the brains of mice overexpressing Swedish mutant ß-amyloid precursor protein (APP-Swe), a model of Alzheimer disease (AD), was investigated in a longitudinal PET study using the novel ß-amyloid tracer (18)F-florbetaben. METHODS: Groups of APP-Swe and age-matched wild-type (WT) mice (age range, 10-20 mo) were investigated. Dynamic emission recordings were acquired with a small-animal PET scanner during 90 min after the administration of (18)F-florbetaben (9 MBq, intravenously). After spatial normalization of individual PET recordings to common coordinates for mouse brain, binding potentials (BPND) and standardized uptake value ratios (SUVRs) were calculated relative to the cerebellum. Voxelwise analyses were performed using statistical parametric mapping (SPM). Histochemical analyses and ex vivo autoradiography were ultimately performed in a subset of animals as a gold standard assessment of ß-amyloid plaque load. RESULTS: SUVRs calculated from static recordings during the interval of 30-60 min after tracer injection correlated highly with estimates of BPND based on the entire dynamic emission recordings. (18)F-florbetaben binding did not significantly differ in APP-Swe mice and WT animals at 10 and 13 mo of age. At 16 mo of age, the APP-Swe mice had a significant 7.9% increase (P < 0.01) in cortical (18)F-florbetaben uptake above baseline and at 20 mo there was a 16.6% increase (P < 0.001), whereas WT mice did not show any temporal changes in tracer uptake during the interval of follow-up. Voxelwise SPM analyses revealed the first signs of increased cortical binding at 13 mo and confirmed progressive binding increases in both the frontal and the temporal cortices (P < 0.001 uncorrected) to 20 mo. The SUVR strongly correlated with percentage plaque load (R = 0.95, P < 0.001). CONCLUSION: In the first longitudinal PET study in an AD mouse model using the novel ß-amyloid tracer (18)F-florbetaben, the temporal and spatial progression of amyloidogenesis in the brain of APP-Swe mice were sensitively monitored. This method should afford the means for preclinical testing of novel therapeutic approaches to the treatment of AD.

Positron emission tomography in the assessment of left ventricular function in healthy rats: a comparison of four imaging methods.

OBJECTIVE: To measure left ventricular (LV) function parameters in heart of healthy rats by three different positron emission tomography (PET) imaging techniques and by magnetic resonance imaging (MRI). METHODS: ECG-gated microPET examinations were obtained in seven healthy rats with 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) for calculation of LV-function from the blood-pool phase of the dynamic recording (FDGBP), and also from the later myocardial uptake (FDGMyo). On subsequent days, we re-measured LV-function using the novel blood-pool tracer (68)Ga-albumin (AlbBP) and again by FDG (FDGMyo2) in one setting. Cine-MRI examination provided the reference standard measurement. RESULTS: The mean LV ejection fractions (LVEF) were 56 ± 3 (FDGBP), 55 ± 3 (FDGMyo), 56 ± 3 (FDGMyo2), 57 ± 3 (AlbBP), and 57 ± 2 (MRI). There were good to excellent correlations found between the LVEF-values as compared to MRI reference standard for FDGBP (r = 0.71), FDGMyo (r = 0.86) and AlbBP (r = 0.88). Both of the blood-pool methods significantly overestimated the magnitudes of end-diastolic-volume and end-systolic-volume, whereas FDGMyo matched closely to the MRI reference standard. There was no significant bias for both blood-pool methods and a minor negative bias for FDGMyo regarding the LV ejection fraction (LVEF) when compared to cine-MRI results. There was no significant difference between the means of FDGMyo and FDGMyo2 (P = .50). CONCLUSIONS: Relative to reference standard MRI measurements of LVEF, there was excellent agreement between PET-based measurements, notably for the novel blood-pool tracer (68)Ga-albumin.

Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy.

BACKGROUND: We performed an initial evaluation of non-invasive ECG-gated [18 F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study. METHODS: Mice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline. RESULTS: LV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis. CONCLUSIONS: LVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.

Assessment of α7 nicotinic acetylcholine receptor availability in juvenile pig brain with [¹8F]NS10743.

PURPOSE: To conduct a quantitative PET assessment of the specific binding sites in the brain of juvenile pigs for [(18)F]NS10743, a novel diazabicyclononane derivative targeting α7 nicotinic acetylcholine receptors (α7 nAChRs). METHODS: Dynamic PET recordings were made in isoflurane-anaesthetized juvenile pigs during 120 min after administration of [(18)F]NS10743 under baseline conditions (n = 3) and after blocking of the α7 nAChR with NS6740 (3 mg·kg(-1) bolus + 1 mg·kg(-1)·h(-1) continuous infusion; n = 3). Arterial plasma samples were collected for determining the input function of the unmetabolized tracer. Kinetic analysis of regional brain time-radioactivity curves was performed, and parametric maps were calculated relative to arterial input. RESULTS: Plasma [(18)F]NS10743 passed readily into the brain, with peak uptake occurring in α7 nAChR-expressing brain regions such as the colliculi, thalamus, temporal lobe and hippocampus. The highest SUV(max) was approximately 2.3, whereas the lowest uptake was in the olfactory bulb (SUV(max) 1.53 ± 0.32). Administration of NS6740 significantly decreased [(18)F]NS10743 binding late in the emission recording throughout the brain, except in the olfactory bulb, which was therefore chosen as reference region for calculation of BP(ND). The baseline BP(ND) ranged from 0.39 ± 0.08 in the cerebellum to 0.76 ± 0.07 in the temporal lobe. Pretreatment and constant infusion with NS6740 significantly reduced the BP(ND) in regions with high [(18)F]NS10743 binding (temporal lobe -29%, p = 0.01; midbrain: -35%, p = 0.02), without significantly altering the BP(ND) in low binding regions (cerebellum: -16%, p = 0.2). CONCLUSION: This study confirms the potential of [(18)F]NS10743 as a target-specific radiotracer for the molecular imaging of central α7 nAChRs by PET.

Computer-based blood donor screening: a status report.

There is a substantial literature suggesting that computer-assisted interviewing has advantages over face-to-face and written self-administration of interviews in venues eliciting sensitive information similar to that sought in blood donor history screening. We review some of the recent developments in blood donor history screening, the evidence suggesting that automated interviews should be useful, and the experience to date using computer interviews for blood donation. These data suggest that automated computer-assisted interviewing increases the elicitation of behaviors associated with the risk of transfusion-transmissible infection in donors, improves donor and staff satisfaction, and reduces errors and omissions that frequently accompany traditional interviewing methods. Food and Drug Administration-cleared systems for computer-assisted self-interview of blood donors are briefly described.