Rigid motion correction of dual opposed planar projections in single photon imaging.

Awake and/or freely moving small animal single photon emission imaging allows the continuous study of molecules exhibiting slow kinetics without the need to restrain or anaesthetise the animals. Estimating motion free projections in freely moving small animal planar imaging can be considered as a limited angle tomography problem, except that we wish to estimate the 2D planar projections rather than the 3D volume, where the angular sampling in all three axes depends on the rotational motion of the animal. In this study, we hypothesise that the motion corrected planar projections estimated by reconstructing an estimate of the 3D volume using an iterative motion compensating reconstruction algorithm and integrating it along the projection path, will closely match the true, motion-less, planar distribution regardless of the object motion. We tested this hypothesis for the case of rigid motion using Monte-Carlo simulations and experimental phantom data based on a dual opposed detector system, where object motion was modelled with 6 degrees of freedom. In addition, we investigated the quantitative accuracy of the regional activity extracted from the geometric mean of opposing motion corrected planar projections. Results showed that it is feasible to estimate qualitatively accurate motion-corrected projections for a wide range of motions around all 3 axes. Errors in the geometric mean estimates of regional activity were relatively small and within 10% of expected true values. In addition, quantitative regional errors were dependent on the observed motion, as well as on the surrounding activity of overlapping organs. We conclude that both qualitatively and quantitatively accurate motion-free projections of the tracer distribution in a rigidly moving object can be estimated from dual opposed detectors using a correction approach within an iterative reconstruction framework and we expect this approach can be extended to the case of non-rigid motion.

Determination of optimal collimation parameters for a rotating slat collimator system: a system matrix method using ML-EM.

Nowadays, Single Photon imaging has become an essential part of molecular imaging and nuclear medicine. Whether to establish a diagnosis or in the therapeutic monitoring, this modality presents performance that continues to improve. For over 50 years, several collimators have been proposed. Mainly governed by collimation parameters, the resolution-sensitivity trade-off is the factor determining the collimator the most suitable for an intended study. One alternative to the common approaches is the rotating slat collimator (RSC). In the present study, we are aiming at developing a preclinical system equipped with a RSC dedicated to mice and rats imaging, which requires both high sensitivity and spatial resolution. We investigated the resolution-sensitivity trade-offs obtained by varying different collimation parameters: (i) the slats height (H), and (ii) the gap between two consecutive slats (g), considering different intrinsic spatial resolutions. One system matrix was generated for each set of collimation parameters (H,g). Spatial resolutions, Signal-to-Noise Ratio (SNR) and sensitivity obtained for all the set of collimation parameters (H,g) were measured in the 2D projections reconstructed with ML-EM. According to our results, 20 mm high slats and a 1 mm gap were chosen as a good RSC candidate for a preclinical detection module. This collimator will ensure a sensitivity greater than 0.2% and a system spatial resolution below 1 mm, considering an intrinsic spatial resolution below 0.8 mm.

Assessment of a fast generated analytical matrix for rotating slat collimation iterative reconstruction: a possible method to optimize the collimation profile.

In SPECT imaging, improvement or deterioration of performance is mostly due to collimator design. Classical SPECT systems mainly use parallel hole or pinhole collimators. Rotating slat collimators (RSC) can be an interesting alternative to optimize the tradeoff between detection efficiency and spatial resolution. The present study was conducted using a RSC system for small animal imaging called CLiR. The CLiR system was used in planar mode only. In a previous study, planar 2D projections were reconstructed using the well-known filtered backprojection algorithm (FBP). In this paper, we investigated the use of the statistical reconstruction algorithm maximum likelihood expectation maximization (MLEM) to reconstruct 2D images with the CLiR system using a probability matrix calculated using an analytic approach. The primary objective was to propose a method to quickly generate a light system matrix, which facilitates its handling and storage, while providing accurate and reliable performance. Two other matrices were calculated using GATE Monte Carlo simulations to investigate the performance obtained using the matrix calculated analytically. The first matrix calculated using GATE took all the physics processes into account, where the second did not consider for the scattering, as the analytical matrix did not take this physics process into account either. 2D images were reconstructed using FBP and MLEM with the three different probability matrices. Both simulated and experimental data were used. A comparative study of these images was conducted using different metrics: the modulation transfert function, the signal-to-noise ratio and quantification measurement. All the results demonstrated the suitability of using a probability matrix calculated analytically. It provided similar results in terms of spatial resolution (about 0.6 mm with differences <5%), signal-to-noise ratio (differences <10%), or quality of image.

NEMA NU 4-2008 validation and applications of the PET-SORTEO Monte Carlo simulations platform for the geometry of the Inveon PET preclinical scanner.

Monte Carlo-based simulation of positron emission tomography (PET) data plays a key role in the design and optimization of data correction and processing methods. Our first aim was to adapt and configure the PET-SORTEO Monte Carlo simulation program for the geometry of the widely distributed Inveon PET preclinical scanner manufactured by Siemens Preclinical Solutions. The validation was carried out against actual measurements performed on the Inveon PET scanner at the Australian Nuclear Science and Technology Organisation in Australia and at the Brain & Mind Research Institute and by strictly following the NEMA NU 4-2008 standard. The comparison of simulated and experimental performance measurements included spatial resolution, sensitivity, scatter fraction and count rates, image quality and Derenzo phantom studies. Results showed that PET-SORTEO reliably reproduces the performances of this Inveon preclinical system. In addition, imaging studies showed that the PET-SORTEO simulation program provides raw data for the Inveon scanner that can be fully corrected and reconstructed using the same programs as for the actual data. All correction techniques (attenuation, scatter, randoms, dead-time, and normalization) can be applied on the simulated data leading to fully quantitative reconstructed images. In the second part of the study, we demonstrated its ability to generate fast and realistic biological studies. PET-SORTEO is a workable and reliable tool that can be used, in a classical way, to validate and/or optimize a single PET data processing step such as a reconstruction method. However, we demonstrated that by combining a realistic simulated biological study ([(11)C]Raclopride here) involving different condition groups, simulation allows one also to assess and optimize the data correction, reconstruction and data processing line flow as a whole, specifically for each biological study, which is our ultimate intent.

Characterization of a rotating slat collimator system dedicated to small animal imaging.

Some current investigations based on small animal models are dedicated to functional cerebral imaging. They represent a fundamental tool to understand the mechanisms involved in neurodegenerative diseases. In the radiopharmaceutical development approach, the main challenge is to measure the radioactivity distribution in the brain of a subject with good temporal and spatial resolutions. Classical SPECT systems mainly use parallel hole or pinhole collimators. In this paper we investigate the use of a rotating slat collimator system for small animal brain imaging. The proposed prototype consists of a 64-channel multi-anode photomultiplier tube (H8804, Hamamatsu Corp.) coupled to a YAP:Ce crystal highly segmented into 32 strips of 0.575 × 18.4 × 10 mm(3). The parameters of the rotating slat collimator are optimized using GATE Monte Carlo simulations. The performance of the proposed prototype in terms of spatial resolution, detection efficiency and signal-to-noise ratio is compared to that obtained with a gamma camera equipped with a parallel hole collimator. Preliminary experimental results demonstrate that a spatial resolution of 1.54 mm can be achieved with a detection efficiency of 0.012% for a source located at 20 mm, corresponding to the position of the brain in the prototype field of view.

Relative importance of dissolved and food pathways for lead contamination in shrimp.

The relative importance of dissolved and food pathways and the influence of food type in the bioaccumulation and retention of lead in the shrimp Palaemonetes varians were examined using a radiotracer method. Shrimp were exposed to 210Pb-labelled seawater or fed two types of 210Pb-labelled food, viz. mussels or worms. The amount of radiotracer accumulated by shrimp was examined over a 7-day period, followed by a 1-month and a 7-day depuration period for the dissolved and food source, respectively. Steady state in the uptake was reached after 2 days exposure to dissolved lead, with a resultant estimated concentration factor of 98+/-3. Transfer factors following ingestion of contaminated mussels and worms were lower than unity for both food types, with lead transfer from worms being significantly higher than that from mussels. Accumulation of dissolved Pb by shrimp was found to occur mainly through adsorption on the exoskeleton with a minor accumulation in the internal tissues probably resulting from the intake of seawater for osmoregulation. In contrast, lead taken up from contaminated food was readily absorbed and bound in the internal tissues of P. varians. Although the transfer of lead to P. varians through the ingestion of contaminated food was low (TF<1%), it still represented 4 to 8% of the lead content in the prey which is a significant additional contribution of lead to the shrimp body burden. Independent of food type, following ingestion of contaminated food, approximately 23-27% of total lead accumulated in shrimp was located in the edible parts (e.g. muscle). Therefore, the food pathway is suggested to be a significant contributor to the lead transfer to humans through ingestion of contaminated shrimp. After exposure to contaminated food, lead loss kinetics were described by a two-component model, whereas Pb loss following direct uptake from seawater was best described by a three-component model. The additional compartment representing 64% of total Pb retained and characterized by a turnover<10 min, corresponded to lead weakly adsorbed on the exoskeleton and incorporated in the hepatopancreas. Nevertheless, a significant fraction of lead accumulated from the dissolved (2%) and food (52-57%) pathways remained irreversibly retained in the tissues, suggesting that this organism could also serve as an effective long-term bioindicator of lead contamination in marine waters.

210Po and 210Pb cycling in a hydrothermal vent zone in the coastal Aegean sea.

To quantify the potential enhancement of naturally-occurring 210Po and 210Pb that may result from the high sulfur-reducing and sulfur-oxidizing regimes associated with hydrothermal vents, sinking particles from both inside and outside vent areas and benthic molluscs grazing on or living near bacterial mats in the vent zone were collected off Milos Island (Aegean Sea) and analyzed for their 210Po and 210Pb content. There was no significant difference in the range of 210Po specific activities measured in particulate material collected by sediment traps in a control area and in the vent area; the resultant 210Po levels were of the same order of magnitude as literature values reported for other Mediterranean coastal areas. 211Pb levels in sinking particles from the control site tended to be higher than those measured in the vent zone, as demonstrated by the lower 210Po/210Pb ratios observed in particles from the control site. Nevertheless, these 210Pb levels were also comparable with similar 210Pb data reported for the northwestern Mediterranean Sea. The 210Po and 210Pb vertical particulate fluxes were, on average, higher in the vent zone as a consequence of the higher particle flux. This observation indicates that vents can indirectly control the flux of these natural radionuclides by affecting the types and amount of particles produced in hydrothermal areas. The 210Po levels measured in a gastropod and a bivalve living on or near the microbial mat in the vent zone were higher than values reported for non-vent gastropods and bivalves from the NW Mediterranean Sea, an observation which suggests that an enhanced food chain transfer of 210Po may occur in the vicinity of vents off Milos Island. Nevertheless, the lack of a general enhancement of 210Po and 210Pb in the marine particulate samples collected indicates that any input of these radionuclides through venting activity may have a minimal effect in the surrounding environment.

The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10-methylenetetrahydrofolate reductase activity in healthy subjects.

We have studied the effect of common mutations (677C-->T and 1298A-->C) of the methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French subjects, aged 27-47 years. Serum folate, vitamin B12, and plasma total homocysteine were measured as well as the specific activity of MTHFR in lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18%, and that of those homozygous for the 1298CC genotype was 12.5%. The frequency of individuals heterozygous for both mutations was 23.5%. The 1298A-->C mutation was associated with decreased MTHFR specific activity in subjects with both 677CC and 677CT genotypes. This activity was 60% for the 677CC/1298AC genotype and 52% for the 677CC/1298CC genotype when compared with the MTHFR specific activity of the 677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype) had 36% of the reference specific activity. Although homocysteine levels in 677TT and 1298CC genotype subjects were higher than for other genotypes, no significant differences were observed among different genotypes. This may be due to high serum folate level in our samples, and suggests that folate therapy may be useful to prevent hyperhomocysteinaemia in homozygous mutant subjects.

5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort.

The 677cytosine mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C-->T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C-->T polymorphism (677TT genotype) in the present cohort was 16.8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT genotype. When segregated by gender, no differences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C-->T mutation. However, tHcy was significantly increased in men with the homozygous 677TT genotype. We also analysed the possible implication of a second new MTHFR polymorphism (1298A-->C) in subjects with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy >11.1 micromol/l). The polymorphism 1298A-->C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high frequency of the 677TT genotype in the French population. Women with this genotype did not show the same increase in tHcy observed in men. In the present study dietary folate intake was not measured. Thus, the interaction of dietary folate with the MTHFR genotype in the French population needs further study.

Distribution coefficients (Kd's) for use in risk assessment models of the Kara Sea.

As a prerequisite for most evaluations of radionuclide transport pathways in marine systems, it is necessary to obtain basic information on the sorption potential of contaminants onto particulate matter. Kd values for use in modeling radionuclide dispersion in the Kara Sea have been determined as part of several international programs addressing the problem of radioactive debris residing in Arctic Seas. Field and laboratory Kd experiments were conducted for the following radionuclides associated with nuclear waste: americium, europium, plutonium, cobalt, cesium and strontium. Emphasis has been placed on two regions in the Kara Sea: (i) the Novaya Zemlya Trough (NZT) and (ii) the mixing zones of the Ob and Yenisey Rivers (RMZ). Short-term batch Kd experiments were performed at-sea on ambient water column samples and on samples prepared both at-sea and in the laboratory by mixing filtered bottom water with small amounts of surficial bottom sediments (particle concentrations in samples = 1-30 mg/l). Within both regions, Kd values for individual radionuclides vary over two to three orders of magnitude. The relative particle affinities for radionuclides in the two regions are americium approximately equal to europium > plutonium > cobalt > cesium > strontium. The values determined in this study agree with minimum values given in the IAEA Technical Report [IAEA, 1985. Sediment Kd's and Concentration Factors for Radionuclides in the Marine Environment. Technical Report No. 247. International Atomic Energy Agency, Vienna.]. Given the importance of Kd's in assessments of critical transport pathways for radionuclide contaminants, we recommend that Kd ranges of values for specific elements rather than single mean values be incorporated into model simulations of radionuclide dispersion.

Human haptocorrin in hepatocellular carcinoma.

This study aimed to determine whether haptocorrin (HC), a vitamin B12 binder, is stored in hepatic cells and whether this storage is modified by hepatic carcinogenesis. It was carried out using immunohistochemistry on different liver tissues (normal liver and steatosis, N = 22; cirrhosis, N = 13; and hepatocellular carcinoma, N = 31). No significant immunostaining of HC was detected in noncancerous biopsies with the exception of in one case of cirrhosis. Hepatocellular carcinoma (HCC) sections showed a weak to moderate cytoplasmic staining of cancerous cells (93% of cases) and of noncancerous hepatocytes surrounding the tumor (95%) of cases. Sections with pseudoglandular structures showed a moderate to strong staining of their secretion products. These results and previous studies would seem to confirm the hypothesis that the raised HC serum level observed in HCC is due both to the increased hepatic synthesis of HC and to a decreased uptake by the liver of the particular isoform of this glycoprotein present in the serum of HCC patients.

Bioaccumulation and retention of lead in the mussel Mytilus galloprovincialis following uptake from seawater.

Bioaccumulation of lead in the mussel Mytilus galloprovincialis from 210Pb-labeled bulk seawater (dissolved and particulate pathways combined) was examined over 21 days. The lead bioaccumulation factor (BAF) at equilibrium was estimated to be 211 +/- 10 ml g-1. This value was two orders of magnitude lower than BAFs reported in the literature for other trace metals in this bivalve indicating that lead is not efficiently accumulated by mussels from bulk seawater. The resultant lead distribution in mussels was 49 +/- 10% in soft tissues and 46 +/- 16% in the shell suggesting similar uptake rates (Bq day-1) in both compartments throughout the exposure. Total elimination for lead in mussels was adequately described by a short-term compartment with a biological half-life for loss of 1.4 +/- 0.3 days and a long-term compartment which released lead only very slowly (Tb1/2 = 2.5 +/- 0.7 months). No difference was noted for lead elimination rates in shell and in soft parts. When experimentally exposed to lead under conditions representative of natural environmental lead levels in water, including both that in the dissolved phase and in the food, the shell compartment was shown to contain the major fraction of the total lead accumulated by mussels. Therefore mussels may be considered as good bioindicators of lead contamination accumulated from the dissolved rather than from the particulate source. Furthermore, the relatively slow uptake and the long depuration half-life of lead will limit the ability of mussels to accurately record short-term variations in lead concentrations in the surrounding waters, a fact which should be taken into consideration in order to define the appropriate sampling frequency for mussels used in biomonitoring programs involving lead.