Biomedical subjects

Simon R Cherry

Publications and source records attributed to Simon R Cherry.

11 recordsLinked to original sources

PubMed2003

MicroPET II: design, development and initial performance of an improved microPET scanner for small-animal imaging.

MicroPET II is a second-generation animal PET scanner designed for high-resolution imaging of small laboratory rodents. The system consists of 90 scintillation detector modules arranged in three contiguous axial rings with a ring diameter of 16.0 cm and an axial length of 4.9 cm. Each detector module consists of a 14 x 14 array of lutetium oxyorthosilicate (LSO) crystals coupled to a multi-channel photomultiplier tube (MC-PMT) through a coherent optical fibre bundle. Each LSO crystal element measures 0.975 mm x 0.975 mm in cross section by 12.5 mm in length. A barium sulphate reflector material was used between LSO elements leading to a detector pitch of 1.15 mm in both axial and transverse directions. Fused optical fibre bundles were made from 90 microm diameter glass fibres with a numerical aperture of 0.56. Interstitial extramural absorber was added between the fibres to reduce optical cross talk. A charge-division readout circuit was implemented on printed circuit boards to decode the 196 crystals in each array from the outputs of the 64 anode signals of the MC-PMT. Electronics from Concorde Microsystems Inc. (Knoxville, TN) were used for signal amplification, digitization, event qualification, coincidence processing and data capture. Coincidence data were passed to a host PC that recorded events in list mode. Following acquisition, data were sorted into sinograms and reconstructed using Fourier rebinning and filtered hackprojection algorithms. Basic evaluation of the system has been completed. The absolute sensitivity of the microPET II scanner was 2.26% at the centre of the field of view (CFOV) for an energy window of 250-750 keV and a timing window of 10 ns. The intrinsic spatial resolution of the detectors in the system averaged 1.21 mm full width at half maximum (FWHM) when measured with a 22Na point source 0.5 mm in diameter. Reconstructed image resolution ranged from 0.83 mm FWHM at the CFOV to 1.47 mm FWHM in the radial direction, 1.17 mm FWHM in the tangential direction and 1.42 mm FWHM in the axial direction at 1 cm offset from the CFOV. These values represent highly significant improvements over our earlier microPET scanner (approximately fourfold sensitivity increase and 25-35% improvement in linear spatial resolution under equivalent operating conditions) and are expected to be further improved when the system is fully optimized.

Animals↗

PubMed2003

High-resolution voxelation mapping of human and rodent brain gene expression.

Voxelation allows high-throughput acquisition of multiple volumetric images of brain gene expression, similar to those obtained from biomedical imaging systems. To obtain these images, the method employs analysis of spatially registered voxels (cubes). For creation of high-resolution maps using voxelation, relatively small voxel sizes are necessary and instruments will be required for semiautomated harvesting of such voxels. Here, we describe two devices that allow spatially registered harvesting of voxels from the human and rodent brain, giving linear resolutions of 3.3 and 1 mm, respectively. Gene expression patterns obtained using these devices showed good agreement with known expression patterns. The voxelation instruments and their future iterations represent a valuable approach to the genome scale acquisition of gene expression patterns in the human and rodent brain.

Animals↗

PubMed2002

Simultaneous molecular and anatomical imaging of the mouse in vivo.

Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice.

Animals↗

PubMed2002

Noninvasive measurement of myocardial activity concentrations and perfusion defect sizes in rats with a new small-animal positron emission tomograph.

BACKGROUND: We explored the feasibility of measuring regional tracer activity concentrations and flow defects in myocardium of rats with a high spatial resolution small-animal PET system (microPET). METHODS AND RESULTS: Myocardial images were obtained after intravenous (18)F-fluorodeoxyglucose (18FDG) in 11 normal rats (group 1) and assembled into polar maps. Regional 18F activity concentrations were measured in 9 regions of interest and compared with tissue activity concentrations measured by well counting. In another 9 rats (group 2), myocardial perfusion images were acquired with 13N-ammonia at baseline and during coronary occlusion. On the polar maps recorded during coronary occlusion, the size of perfusion defects was measured as the myocardium with <50% of maximum activity and expressed as percent total myocardium and was correlated with the area at risk defined by postmortem staining. The diagnostic quality of 18FDG and 13N-ammonia microPET images was good to excellent; the images were easily assembled into polar maps. In group 1, regional (18)F concentrations by microPET and postmortem were correlated linearly (r=0.99; P<0.01 for average and r=0.97; P<0.01 for regional concentrations). In group 2, perfusion defect sizes by microPET and postmortem were correlated linearly (P<0.01; r=0.93). CONCLUSIONS: The findings indicate the feasibility of noninvasive studies of the myocardium in rats with a dedicated small-animal PET-imaging device.

Animals↗

PubMed2002

Towards in vivo nuclear microscopy: iodine-125 imaging in mice using micro-pinholes.

Position-sensitive gamma-radiation detectors equipped with collimators have been used for in vivo imaging of the distribution of radiolabelled molecules in laboratory animals and humans for several decades. To date, the best image resolution achieved in a rodent is on the order of 1 mm. Here we demonstrate how a basic and compact gamma camera can be constructed for in vivo radionuclide imaging in small animals, at much higher spatial resolution. Resolution improvements were obtained by combining dense, shaped, micro-pinhole apertures with iodine-125, an isotope with low energy emissions, ease of incorporation into a wide range of molecules, and straightforward translation into the clinic via other isotopes of iodine that are suitable for nuclear medicine imaging. (125)I images of test distributions and a mouse thyroid have been obtained at a resolution of as high as 200 microm using this simple bench-top camera. Possible future applications and extension to ultra-high-resolution emission tomography are discussed.

Animals↗

PubMed2002

Cardiac myocyte-specific excision of the beta1 integrin gene results in myocardial fibrosis and cardiac failure.

Integrins link the extracellular matrix to the cellular cytoskeleton and serve important roles in cell growth, differentiation, migration, and survival. Ablation of beta1 integrin in all murine tissues results in peri-implantation embryonic lethality. To investigate the role of beta1 integrin in the myocardium, we used Cre-LoxP technology to inactivate the beta1 integrin gene exclusively in ventricular cardiac myocytes. Animals with homozygous ventricular myocyte beta1 integrin gene excision were born in appropriate numbers and grew into adulthood. These animals had 18% of control levels of beta1D integrin protein in the heart and displayed myocardial fibrosis. High-fidelity micromanometer-tipped catheterization of the intact 5-week-old beta1 integrin knockout mice showed depressed left ventricular basal and dobutamine-stimulated contractility and relaxation (LV dP/dt(max) and LV dP/dt(min)) as compared with control groups (n=8 to 10 of each, P<0.01). Hemodynamic loading imposed by 7 days of transverse aortic constriction showed that the beta1 integrin knockout mice were intolerant of this stress as they had 53% survival versus 88% in controls (n=15 each). By 6 months of age, mice with depressed ventricular expression of beta1 integrin developed a dilated cardiomyopathy that was not evident in any control animals and had patchy decrease in glucose metabolism as determined by positron emission tomography. Myocyte membrane integrity as determined via Evan's blue dye staining was disrupted in the beta1 integrin knockout mice. This model provides strong evidence for the importance of beta1 integrin in cardiac form and function and indicates that integrins can be linked to development of cardiomyopathies.

Animals↗

PubMed2002

Gene expression tomography.

Gene expression tomography, or GET, is a new method to increase the speed of three-dimensional (3-D) gene expression analysis in the brain. The name is evocative of the method's dual foundations in high-throughput gene expression analysis and computerized tomographic image reconstruction, familiar from techniques such as positron emission tomography (PET) and X-ray computerized tomography (CT). In GET, brain slices are taken using a cryostat in conjunction with axial rotation about independent axes to create a series of "views" of the brain. Gene expression information obtained from the axially rotated views can then be used to recreate 3-D gene expression patterns. GET was used to successfully reconstruct images of tyrosine hydroxylase gene expression in the mouse brain, using both RNase protection and real-time quantitative reverse transcription PCR (QRT-PCR). A Monte-Carlo analysis confirmed the good quality of the GET image reconstruction. By speeding acquisition of gene expression patterns, GET may help improve our understanding of the genomics of the brain in both health and disease.

Animals↗

PubMed2002

Statistical analysis of multiplex brain gene expression images.

Analysis of variance (ANOVA) was employed to investigate 9,000 gene expression patterns from brains of both normal mice and mice with a pharmacological model of Parkinson's disease (PD). The data set was obtained using voxelation, a method that allows high-throughput acquisition of 3D gene expression patterns through analysis of spatially registered voxels (cubes). This method produces multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. The ANOVA model was compared to the results from singular value decomposition (SVD) by using the first 42 singular vectors of the data matrix, a number equal to the rank of the ANOVA model. The ANOVA was also compared to the results from non-parametric statistics. Lastly, images were obtained for a subset of genes that emerged from the ANOVA as significant. The results suggest that ANOVA will be a valuable framework for insights into the large number of gene expression patterns obtained from voxelation.

Analysis of Variance↗

PubMed2002

High-throughput imaging of brain gene expression.

Voxelation is a new method for acquisition of three dimensional (3D) gene expression patterns in the brain. It employs high-throughput analysis of spatially registered voxels (cubes) to produce multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. Using microarrays, 24 voxel images of coronal hemisections at the level of the hippocampus of both the normal human brain and Alzheimer's disease brain were acquired for 2000 genes. The analysis revealed a common network of coregulated genes, and allowed identification of putative control regions. In addition, singular value decomposition (SVD), a mathematical method used to provide economical explanations of complex data sets, produced images that distinguished between brain structures, including cortex, caudate, and hippocampus. The results suggest that voxelation will be a useful approach for understanding how the genome constructs the brain.

Adult↗

PubMed2002

Multiplex three-dimensional brain gene expression mapping in a mouse model of Parkinson's disease.

To facilitate high-throughput 3D imaging of brain gene expression, a new method called voxelation has been developed. Spatially registered voxels (cubes) are analyzed, resulting in multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. Using microarrays, 40 voxel images for 9000 genes were acquired from brains of both normal mice and mice in which a pharmacological model of Parkinson's disease (PD) had been induced by methamphetamine. Quality-control analyses established the reproducibility of the voxelation procedure. The investigation revealed a common network of coregulated genes shared between the normal and PD brain, and allowed identification of putative control regions responsible for these networks. In addition, genes involved in cell/cell interactions were found to be prominently regulated in the PD brains. Finally, singular value decomposition (SVD), a mathematical method used to provide parsimonious explanations of complex data sets, identified gene vectors and their corresponding images that distinguished between normal and PD brain structures, most pertinently the striatum.

Animals↗

PubMed2002

Effect of phantom voxelization in CT simulations.

In computer simulations of x-ray CT systems one can either use continuous geometrical descriptions for phantoms or a voxelized representation. The voxelized approach allows arbitrary phantoms to be defined without being confined to geometrical shapes. The disadvantage of the voxelized approach is that inherent errors are introduced due to the phantom voxelization. To study effects of phantom discretization, analytical CT simulations were run for a fan-beam geometry with phantom voxel sizes ranging from 0.0625 to 2 times the reconstructed pixel size and noise levels corresponding to 10(3) - 10(7) photons per detector pixel prior to attenuation. The number of rays traced per detector element was varied from 1 to 16. Differences in the filtered backprojection images caused by changing the phantom matrix sizes and number of rays traced were assessed by calculating the difference between reconstructions based on the finest matrix and coarser matrix simulations. In noise free simulations, all phantom matrix sizes produced a measurable difference in comparison with the finest phantom matrix used. When even a small amount of noise was added to the projection data, the differences due to the phantom discretization were masked by the noise, and in all cases there was almost no improvement by using a phantom matrix that was more than twice as fine as the reconstruction matrix. No substantial improvement was achieved by tracing more than 4 rays per detector pixel.

Algorithms↗