Absolute quantitative total-body small-animal SPECT with focusing pinholes

Purpose: In pinhole SPECT, attenuation of the photon flux on trajectories between source and pinholes affects quantitative accuracy of reconstructed images. Previously we introduced iterative methods that compensate for image degrading effects of detector and pinhole blurring, pinhole sensitivity and scatter for multi-pinhole SPECT. The aim of this paper is (1) to investigate the accuracy of the Chang algorithm in rodents and (2) to present a practical Changbased method using body outline contours obtained with optical cameras. Methods: Here we develop and experimentally validate a practical method for attenuation correction based on a Chang first-order method. This approach has the advantage that it is employed after, and therefore independently from, iterative reconstruction. Therefore, no new system matrix has to be calculated for each specific animal. Experiments with phantoms and animals were performed with a highresolution focusing multi-pinhole SPECT system (USPECT-II, MILabs, The Netherlands). This SPECT system provides three additional optical camera images of the animal for each SPECT scan from which the animal contour can be estimated. Results: Phantom experiments demonstrated that an average quantification error of –18.7% was reduced to –1.7% when both window-based scatter correction and Chang correction based on the body outline from optical images were applied. Without scatter and attenuation correction, quantification errors in a sacrificed rat containing sources with known activity ranged from –23.6 to –9.3%. These errors were reduced to values between –6.3 and +4.3% (with an average magnitude of 2.1%) after applying scatter and Chang attenuation correction. Conclusion: We conclude that the modified Chang correction based on body contour combined with window-based scatter correction is a practical method for obtaining small-animal SPECT images with high quantitative accuracy.Radiation, Radionuclides and ReactorsApplied Science

Small-animal SPECT and SPECT/CT: application in cardiovascular research

Preclinical cardiovascular research using noninvasive radionuclide and hybrid imaging systems has been extensively developed in recent years. Single photon emission computed tomography (SPECT) is based on the molecular tracer principle and is an established tool in noninvasive imaging. SPECT uses gamma cameras and collimators to form projection data that are used to estimate (dynamic) 3-D tracer distributions in vivo. Recent developments in multipinhole collimation and advanced image reconstruction have led to sub-millimetre and sub-half-millimetre resolution SPECT in rats and mice, respectively. In this article we review applications of microSPECT in cardiovascular research in which information about the function and pathology of the myocardium, vessels and neurons is obtained. We give examples on how diagnostic tracers, new therapeutic interventions, pre- and postcardiovascular event prognosis, and functional and pathophysiological heart conditions can be explored by microSPECT, using small-animal models of cardiovascular disease

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Patterns in Soil-Vegetation-Atmosphere Systems: Monitoring, Modeling, and Data Assimilation

In this special issue, we present recent scientific work that analyzes the role of patterns in soil-vegetation-atmosphere (SVA) systems over a wide range of scales ranging from the pore scale up to mesoscale catchments. Specific attention is given to the development of novel data assimilation methods, noninvasive measurement techniques that allow mapping spatial patterns of state variables and fluxes, and two-way coupling of models in a scale-consistent way. "Patterns in Soil-Vegetation-Atmosphere Systems" is also the research topic of a collaborative research center (TR32) between the universities of Aachen, Bonn, and Cologne and the Forschungszentrum Julich. In this center, which is funded by the Deutsche Forschungsgemeinschaft, on the basis of an international evaluation, scientists covering a broad range of earth science disciplines are working together. During June 11-12, 2010 the center organized its first international workshop in Aachen. The contributions presented in this special issue of Vadose Zone Journal include contributions from the collaborative research center and external contributions, both from Germany and worldwide

Pharmacogenetic Analysis of Dopamine and Glutamate Receptor Gene Polymorphisms and Clinical Response to Clozapine in Patients wtih Schizophrenia

Interpatient variability in clinical response to antipsychotics (AP) is observed in the treatment of schizophrenia (SCZ) with evidence to support a genetic basis for this phenomenon. Dysfunction in the dopaminergic (DA) system as well as the glutamatergic (GLU) system have both been implicated in the formation of SCZ symptoms. Therefore, we explored the role of DA and GLU receptor variation on clinical response to CLZ, an AP of last resort. We focused on DA receptor genes DRD3, DRD4, and DRD5 having already previously published on DRD1 and DRD2 in this sample. N-methyl-D-aspartate receptor (NMDAR) subunit gene variants and epistatic effects between and among these variants and DA receptor gene variants were also studied. For DRD3, we extended a statistically significant meta-analysis on single nucleotide polymorphism (SNP) rs6280 (Ser9Gly) previously performed by Jonsson et al. (2003). We observed a consistent trend for the serine allele and poor CLZ response (six of seven studies with the same direction of effect). Eight other tagged DRD3 SNPs were also tested with two identified for future replication. For DRD4, associations were observed between the 4-repeat allele of the exon III variable number tandem repeat (VNTR) polymorphism and better CLZ response in Caucasians with a non-significant but same direction of effect in African-Americans; the 142/140-base pair (bp) genotype of the intron 1 guanine mononucleotide repeat ((G)n) polymorphism with poor CLZ response in the whole sample; and the 1-copy allele of the 5’-flanking region 120-bp tandem repeat polymorphism in African-Americans. Three other tagged SNPs across DRD4 and five across DRD5 were negative. Our investigation of GLU receptor gene variants focused on NMDAR subunit genes GRIN1, GRIN2A, and GRIN2B with negative findings. Examining gene-gene epistatic effects among and between NMDAR subunit and DA receptor gene polymorphisms identified several interactions with the strongest result being between the DRD1 rs686 G carrier/DRD3 Ser9Gly G non-carrier group with good response. Overall, our results suggest possible minor roles for DA receptor gene variants on CLZ response. Integrating this data with exciting new advances in technologies and bioinformatics will surely bring us closer to personalized medicine in psychiatry.Ph

Excitation of an electrostatic wave by a cold electron current sheet of finite thickness

Electrostatic waves excited by a field-aligned electron current sheet of finite thickness are investigated. The finite width of the current sheet gives rise to boundary conditions to be satisfied at the sheet edge. This results in a restriction to the number of modes which may be driven unstable. Ducted and evanescent mode solutions are obtained. It is shown that the finite thickness of the current sheet partially stabilizes the system and contributes to the coherence of the excited waves.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25284/1/0000727.pd

The Rice Endosperm ADP-Glucose Pyrophosphorylase Large Subunit is Essential for Optimal Catalysis and Allosteric Regulation of the Heterotetrameric Enzyme

Although an alternative pathway has been suggested, the prevailing view is that starch synthesis in cereal endosperm is controlled by the activity of the cytosolic isoform of ADPglucose pyrophosphorylase (AGPase). In rice, the cytosolic AGPase isoform is encoded by the OsAGPS2b and OsAGPL2 genes, which code for the small (S2b) and large (L2) subunits of the heterotetrameric enzyme, respectively. In this study, we isolated several allelic missense and nonsense OsAGPL2 mutants by N-methyl-N-nitrosourea (MNU) treatment of fertilized egg cells and by TILLING (Targeting Induced Local Lesions in Genomes). Interestingly, seeds from three of the missense mutants (two containing T139I and A171V) were severely shriveled and had seed weight and starch content comparable with the shriveled seeds from OsAGPL2 null mutants. Results from kinetic analysis of the purified recombinant enzymes revealed that the catalytic and allosteric regulatory properties of these mutant enzymes were significantly impaired. The missense heterotetramer enzymes and the S2b homotetramer had lower specific (catalytic) activities and affinities for the activator 3-phosphoglycerate (3-PGA). The missense heterotetramer enzymes showed more sensitivity to inhibition by the inhibitor inorganic phosphate (Pi) than the wild-type AGPase, while the S2b homotetramer was profoundly tolerant to Pi inhibition. Thus, our results provide definitive evidence that starch biosynthesis during rice endosperm development is controlled predominantly by the catalytic activity of the cytoplasmic AGPase and its allosteric regulation by the effectors. Moreover, our results show that the L2 subunit is essential for both catalysis and allosteric regulatory properties of the heterotetramer enzyme