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PURPOSE: Even though [(123)I]FP-CIT SPECT provides high accuracy in detecting nigrostriatal cell loss in neurodegenerative parkinsonian syndromes (PS), some patients with an inconclusive diagnosis remain. We investigated whether the diagnostic accuracy in patients with clinically uncertain PS with previously inconclusive findings can be improved by the use of iterative reconstruction algorithms and an improved semiquantitative evaluation which additionally implemented a correction algorithm for patient age and gamma camera dependency (EARL-BRASS; Hermes Medical Solutions, Sweden). METHODS: We identified 101 patients with inconclusive findings who underwent an [(123)I]FP-CIT SPECT between 2003 and 2010 as part of the diagnostic process of suspected PS at the University of Munich, and re-evaluated these scans using iterative reconstruction algorithms and the new corrected EARL-BRASS. Clinical follow-up was obtained in 62 out of the 101 patients and constituted the gold standard for the re-evaluation to assess the possible improvement in diagnostic accuracy. RESULTS: Clinical follow-up confirmed the diagnosis of PS in 11 of the 62 patients. In patients in whom both visual and semiquantitative analysis showed concordant findings (48 patients), a high negative predictive value (93 %), positive predictive value (100 %) and accuracy (94 %) were found, and thus a correct diagnosis was obtained in 45 of the 48 patients. Among the 14 patients with discordant findings, the additional semiquantitative analysis correctly identified all five of nine patients patients without PS by nonpathological semiquantitative findings in visually pathological or inconclusive scans. In contrast, four of the remaining five patients with decreased semiquantitative values but visually normal scans did not show a PS during follow-up. CONCLUSION: The age-corrected and camera-corrected mode of evaluation using EARL-BRASS provided a notable improvement in the diagnostic accuracy of [(123)I]FP-CIT SPE

Whereas positron emission tomography (PET) with the antagonist ligand [18F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patientswith the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [18F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d.), and again at a later date, afterwithholding pramipexole 48–72 h (OFF-Sifrol); in that condition the serumpramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01) occupancy at [18F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.

The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glucose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadolescence. However, the impact of post-natal brain development on the vulnerability of CMRglc to the onset of BS has not been documented. Therefore, cerebral blood flow and metabolism were measured using a variant of the Kety–Schmidt method, in conjunction with quantitative regional estimation of brain glucose uptake by FDG-PET in groups of neonate and juvenile pigs, under a condition of light sedation or after induction of deep anaesthesia with thiopental. Quantification of simultaneous ECoG recordings was used to establish the correlation between anaesthesia-related changes in brain electrical activity and the observed cerebrometabolic changes. In the condition of light sedation the magnitude of CMRglc was approximately 20% higher in the older pigs, with the greatest developmental increase evident in the cerebral cortex and basal ganglia (P < 0.05). Onset of BS was associated with 20–40% declines in CMRglc. Subtraction of the mean parametric maps for CMRglc showed the absolute reductions in CMRglc evoked by thiopental anaesthesia to be two-fold greater in the pre-adolescent pigs than in the neonates (P < 0.05). Thus, the lesser suppression of brain energy demand of neonate brain during deep anaesthesia represents a reduced part of thiopental suppressing brain metabolism in neonates.

Positron emission tomography (PET) with the high affinity dopamine D2/3 receptor ligand [18F]-fallypride affords estimates of the binding potential (BPND) in extra-striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [18F]-fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [18F]-fallypride predicts flow-dependence of tracer delivery to brain, which may be a source of variance of the apparent BPND in regions of high binding. To test this prediction, we conducted a retrospective analysis of [18F]-fallypride PET data from a group of 50 healthy volunteers (age 18-58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120-s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BPND calculated by the simplified reference tissue model (SRTM) and the individual VC-AUC. The magnitude of BPND in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC-AUC, suggesting that approximately 9% of the variance in the [18F]-fallypride BPND in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BPND in putamen of the present healthy control group.

We present the results of a wavelet-based approach to the study of the chaotic dynamics of a one dimensional model that shows a direct transition to spatiotemporal chaos. We find that the dynamics of this model in the spatiotemporally chaotic regime may be understood in terms of localized dynamics in both space and scale (wavenumber). A projection onto a Daubechies basis yields a good separation of scales, as shown by an examination of the contribution of different wavelet levels to the power spectrum. At most scales, including the most energetic ones, we find essentially Gaussian dynamics. We also show that removal of certain wavelet modes can be made without altering the dynamics of the system as described by the Lyapunov spectrum.