Peter Vontobel

PROPERTIES OF THE RADIOGRAPHY FACILITY NEUTRA AT SINQ AND ITS POTENTIAL FOR USE AS EUROPEAN REFERENCE FACILITY

Abstract At December 3rd 1996, the spallation neutron source SINQ had its first proton beam onthe target. With a steady-state proton beam of 850 IlA this facility is now the strongest of its kind in the world. One of the first experimental facilities in operation was theradiography station NEUTRA (for NEUtron Transmission Radiography). The designwas described at earlier meetings [1,2] and the first validation measurements werereported [3]. There are some advantages in comparison to other radiography stations atresearch reactors. This will be demonstrated in detail by means of the measured valuesand examples of practical applications. The use as reference facility will be envisagedwithin an European project (COST-524).

5-HT Modulation of Dopamine Release in Basal Ganglia in Psilocybin-Induced Psychosis in Man—A PET Study with [11C]raclopride

The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent indoleamine hallucinogen and a mixed 5-HT2A and 5-HT1A receptor agonist. Psilocybin administration (0.25 mg/kg p.o.) produced changes in mood, disturbances in thinking, illusions, elementary and complex visual hallucinations and impaired ego-functioning. Psilocybin significantly decreased [11C]raclopride receptor binding potential (BP) bilaterally in the caudate nucleus (19%) and putamen (20%) consistent with an increase in endogenous dopamine. Changes in [11C]raclopride BP in the ventral striatum correlated with depersonalization associated with euphoria. Together with previous reports of 5-HT receptor involvement in striatal dopamine release, it is concluded that stimulation of both 5-HT2A and 5-HT1A receptors may be important for the modulation of striatal dopamine release in acute psychoses. The present results indirectly support the hypothesis of a serotonin-dopamine dysbalance in schizophrenia and suggest that psilocybin is a valuable tool in the analysis of serotonin-dopamine interactions in acute psychotic states.

Three‐dimensional visualization and quantification of water content in the rhizosphere

• Despite the importance of rhizosphere properties for water flow from soil to roots, there is limited quantitative information on the distribution of water in the rhizosphere of plants. • Here, we used neutron tomography to quantify and visualize the water content in the rhizosphere of the plant species chickpea (Cicer arietinum), white lupin (Lupinus albus), and maize (Zea mays) 12 d after planting. • We clearly observed increasing soil water contents (θ) towards the root surface for all three plant species, as opposed to the usual assumption of decreasing water content. This was true for tap roots and lateral roots of both upper and lower parts of the root system. Furthermore, water gradients around the lower part of the roots were smaller and extended further into bulk soil compared with the upper part, where the gradients in water content were steeper. • Incorporating the hydraulic conductivity and water retention parameters of the rhizosphere into our model, we could simulate the gradual changes of θ towards the root surface, in agreement with the observations. The modelling result suggests that roots in their rhizosphere may modify the hydraulic properties of soil in a way that improves uptake under dry conditions.

Bradykinesia in early Huntington’s disease

Background: Huntington’s disease (HD) is generally considered a hyperkinetic disorder, although hypokinetic features are part of the motor syndrome. Moreover, the striatum is considered to play a key role in initiating and executing motor programs and achieving optimal scheduling in response generation. Controversial results regarding the association between clinical features and markers of progression of the disease might be the result of inadequate restriction of clinical signs to the choreatic syndrome. Objective: To determine the relationship of neurologic motor and cognitive indices in patients with HD with intrinsic neuronal loss in the striatum, as measured using raclopride C11 and PET. Patients and Methods: A cross-sectional study was performed on 11 patients with mild HD (stages 0–2). Motor (Unified Huntington’s Disease Rating Scale [UHDRS], saccadic and tapping speed) and cognitive (verbal fluency, Trail Making Test, Stroop Test, Symbol Digit Modalities Test, Conditioned Associative Learning Test, and silhouette identification and object decision of the Visual Object and Space Perception battery) scores were correlated with raclopride C11 binding. Results: Bradykinesia (a summation of five items of the UHDRS motor scale) was the best predictor for stage, that is, functional capacity, and showed a highly significant relationship with putaminous D2 binding (r = −0.94) and with CAG expansion length × years of age (r = 0.96). The exclusion of two patients with a rigid-akinetic HD variant did not alter these coefficients. Chorea was less well correlated than bradykinesia with D2 binding in all striatal regions. Performance on different cognitive tests, especially in timed tasks, was highly correlated with raclopride C11 binding in caudate nucleus and ventral striatum. Conclusion: Loss of D2 binding in the striatum is highly correlated with the deficit in fast motor and cognitive processing in patients with early Huntington’s Disease. Thus, impairment of rapid execution of adequate responses to environmental changes seems to be a common manifestation of striatal disorders.

3D neutron computed tomography: requirements and applications

Abstract In contrast to X-rays, neutrons can penetrate most metals easily. Neutron attenuation is strongly isotope dependent, and a high contrast is possible for many light-weight elements. Especially their high sensitivity for hydrogen makes them a valuable tool for the detection of organic materials like lubricants, plastics or sealants within metal housings. Neutron radiography and tomography complement the application of X-rays for the inspection of complex and critical components like in automotive and aerospace applications. However, the requirements for beam geometry are much higher for tomography than for simple radiography because the sample cannot be close to the detector, as the sample has to be rotated in the beam, usually by 180°. This paper gives an overview on tomography requirements and limitations, applications and future prospects.

New features in cold neutron radiography and tomography Part II: applied energy-selective neutron radiography and tomography

Abstract The neutron attenuation coefficient drops for many solid materials quite drastically at a defined cold neutron energy known as a Bragg-cut-off in the cross-section diagrams. In many cases, the drop in attenuation for the corresponding elements is significant and this behavior can be exploited to change the material contrast in radiography and tomography images by modifying the spectrum of the applied neutron beam. The energy-dependent experiments were performed at the Prompt Gamma-ray Activation beam line where the irradiation position is at the end of a curved neutron guide, which delivers cold neutrons from the spallation source SINQ (PSI, Switzerland). This beam position gave the opportunity to perform radiography and tomography at low neutron energies. An effective monochromatization of the primary neutron beam was obtained by using a neutron velocity selector. The intensity of the modified beam was still reasonable for radiography images at different neutron energies and the experiments were performed in relatively short measuring times. A variety of samples were studied to illustrate possible applications of energy-selective radiography and tomography. This new neutron imaging technique provided encouraging results and projects of developing permanent facilities for such investigations at PSI and FRM II are under study.

Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography.

We used positron emission tomography and [11C]flumazenil to analyze the benzodiazepine receptor binding in symptomatic and asymptomatic carriers of the Huntingtons disease gene. We found an inverse relationship between [11C]flumazenil and [11C]raclopride binding in the putamen of symptomatic patients, and interpret this result as GABA receptor upregulation.

Impaired somatosensory discrimination of shape in Parkinson's disease: Association with caudate nucleus dopaminergic function

Tactile discrimination of macrogeometric objects in a two‐alternative forced‐choice procedure represents a demanding task involving somatosensory pathways and higher cognitive processing. The objects for somatosensory discrimination, i.e., rectangular parallelepipeds differing only in oblongness, were presented in sequential pairs to normal volunteers and 12 parkinsonian patients. The performance of patients was significantly impaired compared to normal volunteers. From a biochemical point of view, the patients were characterized by a severely reduced 6‐[18F]‐fluoro‐L‐dopa (FDOPA) tracer metabolism in the basal ganglia, as measured using positron emission tomography (PET). Furthermore, reduced specific FDOPA metabolism in the putamen was consistent with the impaired motor capacities of the patients. The reduced specific FDOPA‐uptake within the caudate nucleus was associated with additionally diminished somatosensory discrimination. This association, of low perception during task performance and decreased FDOPA‐uptake, provides direct evidence for the role of the caudate nucleus in the cognitive part of the task. We suggest that directed attention and working memory were critically involved as a result of disturbed interactions between the head of the caudate nucleus and the dorsolateral prefrontal cortex. Furthermore, there were indications of an additional involvement of the mesolimbic system, which might be of importance during challenging situations such as forced choice. We conclude that differential effects on parts of the basal ganglia, during evolution of the degenerative process characteristic of Parkinsons disease, have profound consequences on the performance of skills, as shown here for a somatosensory discrimination task. Hum. Brain Mapping 8:1–12, 1999.

Recovering Root System Traits Using Image Analysis Exemplified by Two-Dimensional Neutron Radiography Images of Lupine

Image-based parameterization of root architectural models is advanced by a new approach for the analysis of image sequences of plant root systems. Root system traits are important in view of current challenges such as sustainable crop production with reduced fertilizer input or in resource-limited environments. We present a novel approach for recovering root architectural parameters based on image-analysis techniques. It is based on a graph representation of the segmented and skeletonized image of the root system, where individual roots are tracked in a fully automated way. Using a dynamic root architecture model for deciding whether a specific path in the graph is likely to represent a root helps to distinguish root overlaps from branches and favors the analysis of root development over a sequence of images. After the root tracking step, global traits such as topological characteristics as well as root architectural parameters are computed. Analysis of neutron radiographic root system images of lupine (Lupinus albus) grown in mesocosms filled with sandy soil results in a set of root architectural parameters. They are used to simulate the dynamic development of the root system and to compute the corresponding root length densities in the mesocosm. The graph representation of the root system provides global information about connectivity inside the graph. The underlying root growth model helps to determine which path inside the graph is most likely for a given root. This facilitates the systematic investigation of root architectural traits, in particular with respect to the parameterization of dynamic root architecture models.

Electrophysiological study, biodistribution in mice, and preliminary PET evaluation in a rhesus monkey of 1-amino-3-[18F]fluoromethyl-5-methyl-adamantane (18F-MEM): a potential radioligand for mapping the NMDA-receptor complex.

The effect of the fluorinated memantine derivative and NMDA receptor antagonist, 1-amino-3-fluoromethyl-5-methyl-adamantane (19F-MEM), at the NMDA receptor ion channel was studied by patch clamp recording. The results showed that 19F-MEM is a moderate NMDA receptor channel blocker. A procedure for the routine preparation of the 18F-labelled analog 18F-MEM has been developed using a two-step reaction sequence. This involves the no-carrier-added nucleophilic radiofluorination of 1-[N-(tert-butyloxy)carbamoyl]-3-(toluenesulfonyloxy)methyl- 5-methyl-adamantane and the subsequent cleavage of the BOC-protecting group using aqueous HCI. The 18F-MEM was obtained in 22 +/- 7% radiochemical yield (decay-corrected to EOB) in a total synthesis time including HPLC purification of 90 min. A biodistribution study after i.v. injection of 18F-MEM in mice showed a fast clearance of radioactivity from blood and relatively high initial uptake in the kidney and in the lung, which gradually decreased with time. The brain uptake was high (up to 3.6% ID/g, 60 min postinjection) with increasing brain-blood ratios: 2.40, 5.10, 6.33, and 9.27 at 5, 30, 60, and 120 min, respectively. The regional accumulation of the radioactivity in the mouse brain was consistent with the known distribution of the PCP recognition site. Preliminary PET evaluation of the radiotracer in a rhesus monkey demonstrated good uptake and prolonged retention in the brain, with a plateau from 35 min onwards p.i. in the NMDA receptor-rich regions (frontal cortex, striata, and temporal cortex). Delineation of the hippocampus, a region known to contain a high density of NMDA receptors, was not possible owing to the resolution of the PET tomograph. The regional brain uptake of 18F-MEM was changed by memantine and by a pharmacological dose of (+)-MK-801, indicating competition for the same binding sites. In a preliminary experiment, haloperidol, a dopamine D2 and sigma receptor antagonist, decreased the binding of 18F-MEM from the brain regions examined, suggesting that binding was also occurring to the sigma recognition sites.