Chasing quantitative biases in neutron imaging with scintillator-camera detectors: a practical method with black body grids.

We propose a method for improving the quantification of neutron imaging measurements with scintillator-camera based detectors by correcting for systematic biases introduced by scattered neutrons and other sources such as light reflections in the detector system. This method is fully experimental, using reference measurements with a grid of small black bodies (BB) to measure the bias contributions directly. Using two test samples, one made of lead alloy and having a moderate (20%) neutron transmission and one made of stainless-steel and having a very low (1%) transmission, we evaluated the improvement brought by this method in reducing both the average quantification bias and the uncertainty around this average bias after tomographic reconstruction. The results show that a reduction of the quantification bias of up to one order of magnitude can be obtained. For moderately transparent samples, little sensitivity is observed to the parameters used for the correction. For the more challenging sample with very low transmission, a correct placement of the BB grid is of utmost importance for a successful correction.

Analysis of the 148Gd and 154Dy Content in Proton-Irradiated Lead Targets.

This work presents the determination of the 148Gd and 154Dy content in Pb targets irradiated by 220-2600 MeV protons. It includes the chemical separation of lanthanides, followed by the preparation of proper samples, by molecular plating technique, for α-spectrometry measurements. The experimental cross section results were compared with theoretical predictions, calculated with the INCL++-ABLA07 code. The comparisons showed a satisfactory agreement for 148Gd (less than within a factor two), while measured 154Dy cross sections are higher than the theoretical values.

Dual spectrum neutron radiography: identification of phase transitions between frozen and liquid water.

In this Letter, a new approach to distinguish liquid water and ice based on dual spectrum neutron radiography is presented. The distinction is based on arising differences between the cross section of water and ice in the cold energy range. As a significant portion of the energy spectrum of the ICON beam line at Paul Scherrer Institut is in the thermal energy range, no differences can be observed with the entire beam. Introducing a polycrystalline neutron filter (beryllium) inside the beam, neutrons above its cutoff energy are filtered out and the cold energy region is emphasized. Finally, a contrast of about 1.6% is obtained with our imaging setup between liquid water and ice. Based on this measurement concept, the temporal evolution of the aggregate state of water can be investigated without any prior knowledge of its thickness. Using this technique, we could unambiguously prove the production of supercooled water inside fuel cells with a direct measurement method.

Imaging brain tumor proliferative activity with [124I]iododeoxyuridine.

Iododeoxyuridine (IUdR) uptake and retention was imaged by positron emission tomography (PET) at 0-48 min and 24 h after administration of 28.0-64.4 MBq (0.76-1.74 mCi) of [124I]IUdR in 20 patients with brain tumors, including meningiomas and gliomas. The PET images were directly compared with gadolinium contrast-enhanced or T2-weighted magnetic resonance images. Estimates for IUdR-DNA incorporation in tumor tissue (Ki) required pharmacokinetic modeling and fitting of the 0-48 min dynamically acquired data to correct the 24-h image data for residual, nonincorporated radioactivity that did not clear from the tissue during the 24-h period after IUdR injection. Standard uptake values (SUVs) and tumor:brain activity ratios (Tm:Br) were also calculated from the 24-h image data. The Ki, SUV, and Tm/Br values were related to tumor type and grade, tumor labeling index, and survival after the PET scan. The plasma half-life of [124I]IUdR was short (2-3 min), and the arterial plasma input function was similar between patients (48 +/- 12 SUV*min). Plasma clearance of the major radiolabeled metabolite ([124I]iodide) varied somewhat between patients and was markedly prolonged in one patient with renal insufficiency. It was apparent from our analysis that a sizable fraction (15-93%) of residual nonincorporated radioactivity (largely [124I]iodide) remained in the tumors after the 24-h washout period, and this fraction varied between the different tumor groups. Because the SUV and Tm:Br ratio values reflect both IUdR-DNA incorporated and exchangeable nonincorporated radioactivity, any residual nonincorporated radioactivity will amplify their values and distort their significance and interpretation. This was particularly apparent in the meningioma and glioblastoma multiforme groups of tumors. Mean tumor Ki values ranged between 0.5 +/- 0.9 (meningiomas) and 3.9 +/- 2.3 microl/min/g (peak value for glioblastoma multiforme, GBM). Comparable SUV and Tm:Br values at 24 h ranged from 0.13 +/- 0.03 to 0.29 +/- 0.19 and from 2.0 +/- 0.6 to 6.1 +/- 1.5 for meningiomas and peak GBMs, respectively. Thus, the range of values was much greater for Ki (approximately 8-fold) compared with that for SUV (approximately 2.2-fold) and Tm:Br (approximately 3-fold). The expected relationships between Ki, SUV, and Tm:Br and other measures of tumor proliferation (tumor type and grade, labeling index, and patient survival) were observed. However, greater image specificity and significance of the SUV and Tm:Br values would be obtained by achieving greater washout and clearance of the exchangeable fraction of residual (background) radioactivity in the tumors, i.e., by increased hydration and urinary clearance and possibly by imaging later than 24 h after [124I]IUdR administration.

Absorption of impinging water droplet in porous stones.

This paper presents an experimental investigation and numerical analysis of the absorption of water droplets impacting porous stones. The absorption process of an impinging droplet is here fully characterized from spreading to evaporation in terms of absorbed mass during droplet depletion and moisture content distribution in a time-resolved manner for three different natural stones. High-speed imaging and neutron radiography are used to quantify moisture absorption in porous stones of varying moisture properties from deposition until depletion. During impact and spreading, the droplet exhibits a dynamic non-wetting behavior. At maximum spreading, the droplet undergoes pinning, resulting into the contact radius remaining constant until droplet depletion. Absorption undergoes two phases: initially, absorption is hindered due a contact resistance attributed to entrapped air; afterwards, a more perfect capillary contact occurs and absorption goes on until depletion, concurrently with evaporation and further redistribution. A finite-element numerical model for isothermal unsaturated moisture transport in porous media captures the phases of mass absorption in good agreement with the experimental data. Droplet spreading and absorption are highly determined by the impact velocity of the droplet, while moisture content redistribution after depletion is much less dependent on impact conditions.

Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron emission tomography in patients with Parkinson's disease.

OBJECTIVE: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6-fluorine 18, an established imaging method for striatal dopaminergic neurons. METHODS: Twenty-three patients in different disease stages (Hoehm and Yahr stage 2.5-5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;4:427-42]; median duration, 12 years) were studied. PK-PD modeling followed a single oral dose of levodopa/benserazide. The sum score of the Columbia Rating Scale (CURSSigma) was used for clinical assessments. A nonparametric effect compartment approach assuming a sigmoidal E(max) model was applied to the PK-PD analysis of plasma levodopa concentrations and corresponding CURSSigma. Thereafter 6-[18F]levodopa PET was performed, and the influx rate constants (k(c)) for the putamen and the caudatus region were correlated with the median effective concentration (EC(50)) and the equilibrium half-life (T(eq)) of the PK-PD model. RESULTS: (1) A significant correlation was observed between PK-PD parameters or with k(c) putamen as the dependent variable and the duration of the disease as the independent variable, which explains 33% of the variability of the EC(50), 42% of the variability of T(eq), and 36% of the variability of k(c). (2) Significant correlations were observed between k(c) and either EC(50) or T(eq), yielding the closest correlation for the putamen region (r = -0.47, P <.05; and r = 0.55, P <.01; respectively). CONCLUSIONS: Our findings show that key parameters of a PK-PD model of levodopa were in fairly close agreement with imaging of dopaminergic neurons by 6-[18F]levodopa PET. However, although PK-PD modeling of levodopa has been proven as a useful investigation of approaches aimed to restore dopaminergic deficits or to monitor disease progression, this modeling cannot serve as a pathomorphologic surrogate for the loss of striatal dopaminergic neurons.

Complementary positron emission tomographic studies of the striatal dopaminergic system in Parkinson's disease.

OBJECTIVE: To assess the relationship between striatal dopa decarboxylase capacity, D2 dopamine receptor binding, and energy metabolism in Parkinson's disease (PD). DESIGN: Positron emission tomographic (PET) studies of glucose and dopa metabolism and D2 dopamine receptor binding in the caudate nucleus and putamen of patients with PD at different Hoehn and Yahr (HY) stages using PET and the tracers 18F-fluorodeoxyglucose (FDG), 6-18F-fluoro-L-dopa (FDOPA), and 11C-raclopride (RACLO). SETTING: Positron emission tomography research program at the Paul Scherrer Institute. SUBJECTS: Twenty patients with PD at different stages of the disease (HY stages I through IV; five patients for each stage) compared with separate groups of age-matched healthy subjects. MAIN OUTCOME MEASURES: Influx constant (Ki) for specific FDOPA uptake; uptake index ratio for RACLO binding to D2 dopamine receptors; normalized to global FDG metabolic rate for glucose consumption; and semiquantitative score for assessment of tremor, rigidity, and bradykinesia in PD. RESULTS: Patients with PD at HY stages I to II (hereafter HY-I-II PD) revealed reduced FDOPA metabolism, particularly in the putamen. The FDOPA uptake in the putamen and caudate nucleus declined with increasing HY staging and scoring for bradykinesia and rigidity. Putamen RACLO binding to D2 dopamine receptors was up-regulated in patients with HY-I-II PD but declined toward control values, with increasing disease severity. Putamen side-to-side asymmetries of FDOPA metabolism and RACLO binding revealed a significant correlation. Putamen FDG metabolism showed a relative increase in all patients with PD. CONCLUSIONS: Our results show that FDOPA, RACLO, and FDG PET measurements provide complementary information to characterize metabolic and receptor changes in the striatum of PD with different degrees of motor disability. The FDOPA uptake reflects the best motor-related pathologic features, as indicated by the significant correlation between Ki values and clinical scores. The significant association between RACLO and FDOPA in the putamen suggests that D2 dopamine receptor changes are related to the reduction of presynaptic dopaminergic nerve terminals. Putamen FDG increase is probably the result of more complex feedback mechanisms that are primarily induced by striatal dopamine deficiency.

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 x 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.

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.

Increased cerebral iron uptake in Wilson's disease: a 52Fe-citrate PET study.

UNLABELLED: Toxicity of abundant copper is the main cause of brain and liver tissue damage in patients with Wilson's disease (WD). However, there is also evidence of a disturbed iron metabolism in this genetically determined disorder. This PET study was undertaken to assess cerebral iron metabolism in WD patients. METHODS: We used 52Fe-citrate, which converts to 52Fe-transferrin in blood plasma, to study basic pharmacokinetic features of the cerebral iron transport in 6 WD patients and in 16 healthy volunteers (control subjects). A 2-tissue-compartment model and multiple time graphic plotting were used to calculate 52Fe-transferrin distribution volumes and transport rates. RESULTS: Net iron uptake (Ki) from plasma into brain tissue was significantly (P < 0.001) higher in WD patients (Ki [mean +/- SEM] = 15.1E-05 +/- 7.13E-05 [1/min]) than in healthy volunteers (Ki = 2.66E-05 +/- 0.351E-05 [1/min]). There was no difference of tracer iron distribution in the cerebral plasma volume between patients and healthy volunteers. Iron uptake values resulting from 2 methods to model PET data of patients and healthy volunteers were highly correlated (P < 0.001). CONCLUSION: An abnormally increased cerebral 52Fe-transferrin uptake was found in WD patients.

Dexamethasone treatment and plasma glucose levels: relevance for fluorine-18-fluorodeoxyglucose uptake measurements in gliomas.

UNLABELLED: Dexamethasone (DEX) is frequently used in brain tumor management. This study investigated the effect of DEX treatment and plasma glucose levels on 18F-fluorodeoxyglucose (FDG) uptake in patients with malignant gliomas (16 glioblastoma, 3 anaplastic astrocytoma). METHODS: Fifteen DEX-treated patients (mean relative dose 0.23 +/- 0.15 mg(-1) x kg(-1) x day(-1), range 0.07-0.53), four patients not treated with DEX and nine healthy subjects were studied using PET and FDG. PET data obtained from tumors and the contralateral cortex were fitted to a standard two-tissue compartment model. The FDG transport and phosphorylation rates, distribution volume (DV), steady-state accumulation (Ki), deoxyglucose metabolism (R), plasma volume as well as standardized uptake values (SUVs) and tumor-to-brain ratios were determined. In addition, the tumor size was estimated from the maximal area of contrast-enhancing tumor on computed cranial tomography (CCT) scans or MRI. RESULTS: FDG uptake was depressed in the contralateral cortex of patients and was related to tumor size. With increasing relative DEX dose, a decrease in the DV of tumors (linear regression p = 0.021) and in the DV (p = 0.109) and plasma volume (p = 0.010) of contralateral cortex was found. R, Ki and SUVs in tumors and contralateral cortex were not related to the relative DEX dose. With increasing plasma glucose levels, differential decreases in Ki and SUVs in tumors (p = 0.057 and p = 0.733, respectively) and contralateral cortex (p = 0.001 and p = 0.029, respectively) were observed. CONCLUSION: The data suggest that DEX affects FDG uptake in malignant gliomas through interaction with cerebral blood vessels and extracellular space, whereas FDG metabolism in tumors is not influenced substantially. This is of practical importance for patients having serial brain tumor imaging for treatment evaluation because patients may receive different DEX doses at different time points in the course of their disease. By contrast, the plasma glucose level must be considered a confounding variable when SUVs, tumor-to-brain ratios or Ki are used for treatment evaluation.

Effects of (S)-ketamine on striatal dopamine: a [11C]raclopride PET study of a model psychosis in humans.

Administration of the N-methyl-D-aspartate (NMDA) antagonist S-ketamine in normals produces a psychosis-like syndrome including several positive and negative symptoms of schizophrenic disorders (Abi-Saab WM, D'Souza DC, Moghaddam B, Krystal JH. The NMDA antagonist model for schizophrenia: promise and pitfalls. Pharmacopsychiatry 1998;31:104-109). Given the clinical efficacy of dopamine (DA) D2 receptor antagonists in the treatment of positive symptoms, it is conceivable that S-ketamine-induced psychotic symptoms are partially due to a secondary activation of dopaminergic systems. To date, animal and human studies of the effects of NMDA antagonists on striatal DA levels have been inconsistent. The present study used positron emission tomography (PET) to determine whether a psychotomimetic dose of S-ketamine decreases the in vivo binding of [11C]raclopride to striatal DA D2 receptors in humans (n = 8). S-ketamine elicited a psychosis-like syndrome, including alterations in mood, cognitive disturbances, hallucinations and ego-disorders. S-ketamine decreased [11C]raclopride binding potential (BP) significantly in the ventral striatum (-17.5%) followed by the caudate nucleus (-14.3%) and putamen (-13.6%), indicating an increase in striatal DA concentration. The change in raclopride BP in the ventral striatum correlated with heightened mood ranging from euphoria to grandiosity. These results provide evidence that the glutamatergic NMDA receptor may contribute to psychotic symptom formation via modulation of the DA system.

Cerebral 6-[18F]fluoro-L-DOPA uptake in rhesus monkey: pharmacological influence of aromatic amino acid decarboxylase (AAAD) and catechol-O-methyltransferase (COMT) inhibition.

FDOPA/PET scans were performed in one rhesus monkey to study the influence of three catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on FDOPA pharmacokinetics. COMT inhibitors were administered in combination with carbidopa, a peripherally acting inhibitor of the aromatic amino acid decarboxylase (AAAD). FDOPA was administered intravenously and its metabolic fate in plasma was determined using an HPLC system with an on-line gamma-gamma coincidence detector. Cerebral tracer uptake was assessed in the striatum and in a non-dopaminergic brain region (occipital cortex). In the periphery, the pharmacokinetic efficiency of FDOPA was increased due to the combined inhibition of COMT and AAAD activity. All three COMT inhibitors reduced the FDOPA methylation rate constant in plasma, with complete suppression obtained in the case of Ro 40-7592. In the brain, specific 18F radioactivity (striatal minus brain reference radioactivity) increased as a result of the increase in FDOPA plasma availability following the administration of COMT and AAAD inhibitors. We established a significant linear correlation between striatal radioactivity and FDOPA plasma levels (r = 0.924 +/- 0.048, P < 0.0001 for total striatal and r = 0.948 +/- 0.054, P < 0.0001 for specific striatal radioactivity). Using plasma FDOPA radioactivity as input, we found that the striatal FDOPA uptake rate constant KiFD was not changed by any of the inhibitors. Thus, the enhancement of striatal radioactivity after application of enzyme inhibitors is a consequence of the increase in plasma FDOPA that becomes available for conversion to fluorodopamine in the striatal dopaminergic nerve terminals. By contrast, using the radioactivity in a non-dopaminergic region (cortex) as input, we found that the striatal FDOPA uptake rate constant Ki(ref) was significantly (P < 0.0001) increased following pretreatment with COMT inhibitors. Our analysis demonstrated that Ki(ref) and the 3-OMFD contribution to the cerebral radioactivity were inversely correlated.

Positron emission tomography in drug evaluation: influence of three different catechol-O-methyltransferase inhibitors on metabolism of [NCA] 6-[18F]fluoro-L-dopa in rhesus monkey.

We compared the influence of three different catechol-O-methyltransferase (COMT) inhibitors (CGP 28014, OR-611 and Ro 40-7592) on the metabolism of no-carrier-added (NCA) 6-[18F]fluoro-L-dopa (6-FDOPA) in one Rhesus monkey. All three COMT inhibitors improved 6-FDOPA availability in plasma, increased the specific uptake in the brain and thus improved 6-FDOPA uptake measurements using positron emission tomography (PET). Best results were obtained with Ro 40-7592.

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.

[76Br]Bromodeoxyuridine PET in tumor-bearing animals.

5-bromodeoxyuridine (BUdR) provides in vitro measures of tumor cell proliferation. We used positron emission tomography to study tissue and plasma kinetics of [76Br]BUdR in tumor-bearing animals. In order to account for the slow washout of the major plasma metabolite, [76Br]bromide, a mathematical correction for the distribution volume of [76Br]bromide was applied. However, following correction specific tumor tracer retention was low or even zero and did not correlate with independent measures of proliferation. The kinetic characteristics of [76Br]BUdR make this tracer unsuitable for proliferation imaging.

Long-term intracerebral infusion of fibroblast growth factors restores motility and enhances F-DOPA uptake in parkinsonian monkeys.

Fibroblast growth factors (FGFs) are important for dopamine neurons in health and disease. Acidic (aFGF) and basic (bFGF) fibroblast growth factors increase the survival and growth of dopamine cells. Nigrostriatal dopamine neurons, the target cells for degeneration in Parkinson's disease, display receptors for basic fibroblast growth factor and these receptors are decreased in the brain of parkinsonian patients. We have investigated the effects of long-term intrastriatal infusion of FGFs in hemiparkinsonian monkeys. All animals were lesioned with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 0.4mgkg(-1), into the left internal carotid artery. The monkeys that had persistent asymmetric akinesia and contralateral rotation induced by apomorphine, were selected for chronic, unilateral, intracerebral infusion of neurotrophic factors or vehicle into the striatum ipsilateral to the lesion. Two animals received intrastriatal aFGF or bFGF, 2mugweek(-1), for 6 months. The controls received intrastriatal saline or intraventricular epidermal growth factor (EGF). F-DOPA positron emission tomography scans were performed in each animal before and after the intracerebral infusion of neurotrophic factors. We measured the tyrosine hydroxylase (TH) immunoreactive neurons in the substantia nigra and terminals in the striatum and evaluated the pathological complications related to the treatment or the delivery system. All four animals had, after the lesion with MPTP, a transient but incomplete recovery of akinesia. This period of spontaneous improvement was followed by a progressive deterioration of motor behaviour during the following months. The monkeys treated with FGFs, however, recovered quickly and persistently during the intracerebral infusion. F-DOPA uptake, prior to the intracerebral infusion, was greatly reduced in the lesioned striatum. The post-infusion F-DOPA scans revealed a 60% reduction respect to baseline in the lesioned striatum of the saline and EGF-infused animals. In the animals infused with FGFs, the post-infusion F-DOPA uptake increased more than 400% in the lesioned (and infused) striatum and around 200-300% in the contralateral side, with respect to the pre-infusion scan. The number of TH-positive cells in the substantia nigra correlated well with the uptake of F-DOPA in the post-infusion scan. No severe side-effects were present. Intrastriatal infusion of FGFs restores motor behaviour and increases F-DOPA striatal uptake in hemiparkinsonian monkeys.

The use of amorphous silicon flat panels as detector in neutron imaging.

A first test for neutron detection with a flat panel device based on the amorphous silicon technology is described in this report. The most important parameters defining the performance for neutron imaging are described. The first findings are encouraging for further improvements.

Hydrogen distribution measurements by neutrons.

The paper describes how hydrogenous materials can be investigated with state-of-the-art neutron radiography detection methods. The methodical problems for a precise quantification and steps towards their solution are demonstrated. Based on several practical examples, the diversity of problems to be solved by neutron imaging is illustrated.

Study of material changes of SINQ target rods after long-term exposure by neutron radiography methods.

This paper describes the results of non-destructive investigations by indirect neutron radiography methods obtained at the facility NEUTRA [Nondestruct. Testing Eval. 16 (2000b) 203], spallation neutron source SINQ [Operating experience and development projects at SINQ, PSI Report 98-04, ISSN 1019-0643]. Target rods from the second SINQ metal target were removed after 6 Ah of proton beam exposure and studied under well-shielded conditions. No real damage was found at one of the 11 observed rods and one tube. However, hydrogen accumulation could be identified inside the zircaloy rods and the steel rods as well. Whereas the hydrogen has a homogenous distribution in Zr (with the peak value near the centre of the applied beam), the steel samples show clusters of hydrogen near the edge of the Zr cladding. Lead (in steel cladding) was found modified by accumulations of spallation products, mainly mercury. In the radiography images, a depression of the neutron field was observed due to the absorption by mercury. The applied method with Dy and In as neutron converters and imaging plates [Nucl. Instrum. Methods 377 (1996) 119] as secondary detectors seems to be optimal for such kind of investigations, especially when quantitative considerations have to be made.