Mapping genes for phosphorus utilization and correlated traits using a 4k SNP linkage map in Japanese quail (Coturnix japonica).

A large F2 cross with 920 Japanese quail was used to map QTL for phosphorus utilization, calcium utilization, feed per gain and body weight gain. In addition, four bone ash traits were included, because it is known that they are genetically correlated with the focal trait of phosphorus utilization. Trait recording was done at the juvenile stage of the birds. The individuals were genotyped genome-wide for about 4k SNPs and a linkage map constructed, which agreed well with the reference genome. QTL linkage mapping was performed using multimarker regression analysis in a line cross model. Single marker association mapping was done within the mapped QTL regions. The results revealed several genome-wide significant QTL. For the focal trait phosphorus utilization, a QTL on chromosome CJA3 could be detected by linkage mapping, which was substantiated by the results of the SNP association mapping. Four candidate genes were identified for this QTL, which should be investigated in future functional studies. Some overlap of QTL regions for different traits was detected, which is in agreement with the corresponding genetic correlations. It seems that all traits investigated are polygenic in nature with some significant QTL and probably many other small-effect QTL that were not detectable in this study.

Device for simultaneous positron emission tomography, laser speckle imaging and RGB reflectometry: validation and application to cortical spreading depression and brain ischemia in rats.

Brain function critically relies on the supply with energy substrates (oxygen and glucose) via blood flow. Alterations in energy demand as during neuronal activation induce dynamic changes in substrate fluxes and blood flow. To study the complex system that regulates cerebral metabolism requires the combination of methods for the simultaneous assessment of multiple parameters. We developed a multimodal imaging device to combine positron emission tomography (PET) with laser speckle imaging (LSI) and RGB reflectometry (RGBR). Depending on the radiotracer, PET provides 3-dimensional quantitative information of specific molecular processes, while LSI and RGBR measure cerebral blood flow (CBF) and hemoglobin oxygenation at high temporal and spatial resolution. We first tested the functional capability of each modality within our system and showed that interference between the modalities is negligible. We then cross-calibrated the system by simultaneously measuring absolute CBF using (15)O-H2O PET (CBF(PET)) and the inverse correlation time (ICT), the LSI surrogate for CBF. ICT and CBF(PET) correlated in multiple measurements in individuals as well as across different animals (R(2)=0.87, n=44 measurements) indicating that ICT can be used for absolute quantitative assessment of CBF. To demonstrate the potential of the combined system, we applied it to cortical spreading depression (CSD), a wave of transient cellular depolarization that served here as a model system for neurovascular and neurometabolic coupling. We analyzed time courses of hemoglobin oxygenation and CBF alterations coupled to CSD, and simultaneously measured regional uptake of (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) used as a radiotracer for regional glucose metabolism, in response to a single CSD and to a cluster of CSD waves. With this unique combination, we characterized the changes in cerebral metabolic rate of oxygen (CMRO2) in real-time and showed a correlation between (18)F-FDG uptake and the number of CSD waves that passed the local tissue. Finally, we examined CSD spontaneously occurring during focal ischemia also referred to as peri-infarct depolarization (PID). In the vicinity of the ischemic territory, we observed PIDs that were characterized by reduced CMRO2 and increased oxygen extraction fraction (OEF), indicating a limitation of oxygen supply. Simultaneously measured PET showed an increased (18)F-FDG uptake in these regions. Our combined system proved to be a novel tool for the simultaneous study of dynamic spatiotemporal alterations of cortical blood flow, oxygen metabolism and glucose consumption under normal and pathologic conditions.

Feedback effect during ultrafast demagnetization dynamics in ferromagnets.

Motivated by the recent controversy about the importance of spin-flip scattering for ultrafast demagnetization in ferromagnets, we study the spin-dependent electron dynamics based on a dynamical Elliott-Yafet mechanism. The key improvement to earlier approaches is the use of a modified Stoner model with a dynamic exchange splitting between majority and minority bands. In the framework of our microscopic model, we find a novel feedback effect between the time-dependent exchange splitting and the spin-flip scattering. This feedback effect allows us to reproduce important properties of the demagnetization dynamics quantitatively. Our results demonstrate that in general Elliott-Yafet spin-flip scattering needs to be taken into account to obtain a microscopic picture of demagnetization dynamics.

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with (99m)Tc- and (123)I-labelled probes.

PURPOSE: The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake. METHODS: A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor. RESULTS: In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight. CONCLUSION: Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers.

Multi-modality imaging of uveal melanomas using combined PET/CT, high-resolution PET and MR imaging.

UNLABELLED: We investigated the efficacy of combined FDG-PET/CT imaging for the diagnosis of small-size uveal melanomas and the feasibility of combining separate, high-resolution (HR) FDG-PET with MRI for its improved localization and detection. PATIENTS, METHODS: 3 patients with small-size uveal melanomas (0.2-1.5 ml) were imaged on a combined whole-body PET/CT, a HR brain-PET, and a 1.5 T MRI. Static, contrast-enhanced FDG-PET/CT imaging was performed of head and torso with CT contrast enhancement. HR PET imaging was performed in dynamic mode 0-180 min post-injection of FDG. MRI imaging was performed using a high-resolution small-loop-coil placed over the eye in question with T2-3D-TSE and T1-3D-SE with 18 ml Gd-contrast. Patients had their eyes shaded during the scans. Lesion visibility on high-resolution FDG-PET images was graded for confidence: 1: none, 2: suggestive, 3: clear. Mean tumour activity was calculated for summed image frames that resulted in confidence grades 2 and 3. Whole-body FDG-PET/CT images were reviewed for lesions. PET-MRI and PET/CT-MRI images of the head were co-registered for potentially improved lesion delineation. RESULTS: Whole-body FDG-PET/CT images of 3/3 patients were positive for uveal melanomas and negative for disseminated disease. HR FDG-PET was positive already in the early time frames. One patient exhibited rising tumour activity with increasing uptake time on FDG-PET. MRI images of the eye were co-registered successfully to FDG-PET/CT using a manual alignment approach. CONCLUSIONS: Small-size uveal melanomas can be detected with whole-body FDG-PET/CT. This feasibility study suggests the exploration of HR FDG-PET in order to provide additional diagnostic information on patients with uveal melanomas. First results support extended uptake times and high-sensitivity PET for improved tumour visibility. MRI/PET co-registration is feasible and provides correlated functional and anatomical information that may support alternative therapy regimens.

Molecular and functional imaging technology for the development of efficient treatment strategies for gliomas.

Gliomas are the most common types of brain tumors, which invariably lead to death over months or years. Before new and potentially more effective treatment strategies, such as gene therapy, can be effectively introduced into clinical application the following goals must be reached: (1) the determination of localization, extent and metabolic activity of the glioma; (2) the assessment of functional changes within the surrounding brain tissue; (3) the identification of genetic changes on the molecular level leading to disease; and in addition (4) a detailed non-invasive analysis of both endogenous and exogenous gene expression in animal models and in the clinical setting. Non-invasive imaging of endogenous gene expression by means of positron emission tomography (PET) may reveal insight into the molecular basis of pathogenesis and metabolic activity of the glioma and the extent of treatment response. When exogenous genes are introduced to serve for a therapeutic function, PET imaging techniques may reveal the assessment of the location, magnitude and duration of therapeutic gene expression and its relation to the therapeutic effect. Here, we review the main principles of PET imaging and its key roles in neurooncology research.

HeinzelCluster: accelerated reconstruction for FORE and OSEM3D.

Using iterative three-dimensional (3D) reconstruction techniques for reconstruction of positron emission tomography (PET) is not feasible on most single-processor machines due to the excessive computing time needed, especially so for the large sinogram sizes of our high-resolution research tomograph (HRRT). In our first approach to speed up reconstruction time we transform the 3D scan into the format of a two-dimensional (2D) scan with sinograms that can be reconstructed independently using Fourier rebinning (FORE) and a fast 2D reconstruction method. On our dedicated reconstruction cluster (seven four-processor systems, Intel PIII@700 MHz, switched fast ethernet and Myrinet, Windows NT Server), we process these 2D sinograms in parallel. We have achieved a speedup > 23 using 26 processors and also compared results for different communication methods (RPC, Syngo, Myrinet GM). The other approach is to parallelize OSEM3D (implementation of C Michel), which has produced the best results for HRRT data so far and is more suitable for an adequate treatment of the sinogram gaps that result from the detector geometry of the HRRT. We have implemented two levels of parallelization for four dedicated cluster (a shared memory fine-grain level on each node utilizing all four processors and a coarse-grain level allowing for 15 nodes) reducing the time for one core iteration from over 7 h to about 35 min.

Novel neuroimaging findings in a patient with cerebral Whipple's disease: a magnetic resonance imaging and positron emission tomography study.

The authors report a 43-year-old patient with histopathologically proven cerebral Whipple's disease. Magnetic resonance imaging (MRI) revealed a multilayered left frontal lesion without mass effect, no perifocal brain edema, no contrast enhancement, and a thin shell of fluid signal that presented as an incomplete, open ring. An [11C]methionine positron emission tomography (PET) study showed low uptake below the threshold that is characteristic for brain tumors. In precise co-registration to the MR images, the PET data showed that increased uptake was mainly located in the direct adjacent part of the MRI lesion. The fluid signal on MRI corresponded to the extensive outflow of fluid from the lesion, which was observed during neurosurgical resection, and also to the neuropathological findings. The authors conclude that this cerebral manifestation of Whipple's disease made a unique and hitherto undescribed appearance on MRI; uptake pattern of PET amino acid tracer may help in the preoperative distinction of inflammatory from neoplastic lesions.

Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo.

OBJECTIVE: Although Parkinson disease with dementia (PDD) and dementia with Lewy bodies (DLB) show a wide clinical and neuropathologic overlap, they are differentiated according to the order and latency of cognitive and motor symptom appearance. Whether both are distinct disease entities is an ongoing controversy. Therefore, we directly compared patients with DLB and PDD with multitracer PET. METHODS: PET with (18)fluorodopa (FDOPA), N-(11)C-methyl-4-piperidyl acetate (MP4A), and (18)fluorodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest-based statistics. RESULTS: We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls. CONCLUSIONS: Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.

Reduction of dose to the female breast as a result of spectral optimisation for high-contrast thoracic CT imaging: a phantom study.

Various approaches to reduce dose to the female breast in thoracic CT have been investigated. We evaluated the potential for reduction of dose to the breast by optimal choice of the X-ray spectra. The effect of X-ray energy variation on dose to the female breast in thoracic CT was examined by simulations and measurements of image contrast, image noise and radiation dose. A standard thorax phantom was used with various extension rings and breasts added and the following contrast inserts: iodine, calcium hydroxyapatite and a pure soft-tissue density difference. Three-dimensional dose distributions were determined by a validated Monte Carlo tool. The contrast-to-noise ratio per unit dose (CNRD) was determined for tube voltages of 40-200 kV by simulations and for 60-140 kV by measurements on a clinical CT scanner. CNRD curves did not show significant variations in soft-tissue density contrast, but considerable optimisation potential for iodine and skeletal imaging at reduced energies. Exact values depend on the patient's cross-section and X-ray spectrum. For example, reducing the tube voltage from 120 kV to 80 kV on the scanner reduced dose to the female breast typically by 50% without deterioration of the CNR. This method exceeds the dose reduction potential of other measures. We conclude that tube voltages in thoracic CT can be lowered for contrast medium and skeletal imaging without affecting the CNR but with a significant decrease in dose to the female breast.

PET-based molecular imaging in neuroscience.

Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and "phenotyping" of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed.