Test-retest reproducibility of 18F-MPPF PET in healthy humans: a reliability study.

The aim of this study was to assess the reliability of 2'-methoxyphenyl-(N-2'-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine (18F-MPPF) PET binding parameter's quantification via a test-retest study over a long-term period. METHODS: Ten healthy volunteers underwent 2 dynamic 18F-MPPF PET scans in an interval of 6 mo. As a methodologic control, 10 simulated datasets, including interindividual functional and anatomic variabilities, were also used to assess the measurement variations in the absence of intraindividual variability. Indices of tracer binding were computed using 2 different models: (a) the simplified reference tissue model (SRTM) and (b) the Logan graphical model. The SRTM allows computing the binding potential (BP) index and plasma-to-brain transport constants (R1, k2). The Logan model evaluates the distribution volume (DV). For both methods, cerebellum was taken as the reference region. From both models, binding indices were calculated with time-activity curves extracted from regions of interest, on one hand, and for each voxel to perform parametric images on the other hand. RESULTS: Reliability indices--that is, bias, variability, and intraclass correlation (ICC)--indicated a good reproducibility: the BP percentage change in mean between test and retest is close to 1% in rich regions and 2% in poor regions. The typical error is around 7%. Mean ICC is over 0.70. The DV percentage change in the mean is +/-2.5%, with a typical error close to 6% and an ICC over 0.60. CONCLUSION: Our results show a good reliability, with a reasonable level of intraindividual biologic variability that allows crossover studies with 18F-MPPF in which small percentage changes are expected between test and retest measurements, in group studies and for single subject assessment.     

Dynamic spin labeling angiography in extracranial carotid artery stenosis

BACKGROUND AND PURPOSE: Similar to digital subtraction angiography, dynamic spin labeling angiography (DSLA) provides time-resolved measurements of the influx of blood into the cerebral vascular tree. We determined whether DSLA may help in assessing the degree of stenosis and whether it provides information about intracerebral collateralization and allows us to monitor the hemodynamic effects of vascular interventions. METHODS: We developed a segmented DSLA sequence that allowed the formation of images representing inflow delays in 41-ms increments. Thirty patients with unilateral carotid artery stenosis and 10 control subjects underwent DSLA. Arrival times of the labeled arterial blood bolus were measured in the carotid siphon (CS) and the middle cerebral artery (MCA) on both sides, and the corresponding side-to-side arrival time differences (ATDs) were calculated. ATDs before and after carotid endarterectomy or percutaneous angioplasty were studied in 10 patients. RESULTS: The degree of stenosis was significantly correlated with ATD in the cerebral vessels. Receiver operating characteristic analysis yielded a cutoff CS ATD of 110 ms to separate stenoses <70% from those > or =70%, with a sensitivity of 90% and a specificity of 67%. In one third of patients, ATD was higher in the MCA than in the CS; this finding suggested an absence of collateralization. Most patients had reduced ATD in the MCA. The degree of ATD reduction was regarded as a quantitative measure of collateralization. Successful intervention resulted in normalized ATDs. CONCLUSION: DSLA is a promising method that allowed us to noninvasively quantify the hemodynamic effect of extracranial carotid stenosis and the resulting intracranial collateralization.     

Electrophysiological correlates of visual adaptation to faces and body parts in humans

The existence of facial aftereffects suggests that shape-selective mechanisms at the higher stages of visual object coding -- similarly to the early processing of low-level visual features -- are adaptively recalibrated. Our goal was to uncover the ERP correlates of shape-selective adaptation and to test whether it is also involved in the visual processing of human body parts. We found that prolonged adaptation to female hands -- similarly to adaptation to female faces -- biased the judgements about the subsequently presented hand test stimuli: they were perceived more masculine than in the control conditions. We also showed that these hand aftereffects are size and orientation invariant. However, no aftereffects were found when the adaptor and test stimuli belonged to different categories (i.e. face adaptor and hand test, or vice versa), suggesting that the underlying adaptation mechanisms are category-specific. In accordance with the behavioral results, both adaptation to faces and hands resulted in a strong and category-specific modulation -- reduced amplitude and increased latency -- of the N170 component of ERP responses. Our findings suggest that shape-selective adaptation is a general mechanism of visual object processing and its neural effects are primarily reflected in the N170 component of the ERP responses.     

Profound midbrain atrophy in patients with Wilson’s disease and neurological symptoms?

Wilson’s disease (WD) is characterized by impaired hepatic copper secretion and subsequent copper accumulation in many organs predominantly liver and brain, secondary to loss of function mutations in the copper transport protein ATP7B. If the disease is recognized too late or treatment is not adequate, brain copper accumulation leads to progressive neurodegeneration with a variety of clinical symptoms. The nigrostriatal dopaminergic system seems rather vulnerable. Midbrain atrophy, however, has not been recognized as one of the prime features of patients with WD. Here we report quantification of midbrain diameter in 41 patients with WD. Data were correlated to the severity of neurological symptoms and the integrity of dopaminergic neurons measured via dopamine transporter binding. For control, we measured midbrain diameter in 18 patients with no evidence for brainstem dysfunction and 5 patients with progressive supranuclear palsy (PSP). Patients with WD had a reduced midbrain diameter (15.5 ± 0.4 mm) compared to controls (18.5 ± 0.2 mm). WD patients without neurological symptoms had midbrain diameter that were not different from controls (18.0 ± 0.3 mm), while patients with neurological symptoms showed midbrain atrophy similar to patients with PSP (14.4 ± 0.3 mm versus 14.1 ± 0.3). There was a strong and significant correlation between midbrain atrophy and the severity of neurological symptoms (r= −0.68, p < 0.001) while midbrain atrophy and dopamine transporter binding correlated significantly but was less pronounced (r=0.46, p < 0.001). In summary, we were able to show, that midbrain diameter is an easy to perform quantification of neurodegeneration induced by brain copper accumulation and that other structures than substantia nigra dopaminergic neurons seem to contribute to midbrain atrophy in WD.