Basic design and simulation of a SPECT microscope for in vivo stem cell imaging

The need to understand the behavior of individual stem cells at the various stages of their differentiation and to assess the resulting reparative action in pre-clinical model systems, which typically involves laboratory animals, provides the motivation for imaging of stem cells in vivo at high resolution. Our initial focus is to image cells and cellular events at single cell resolution in vivo in shallow tissues (few mm of intervening tissue) in laboratory mice and rates. In order to accomplish this goal we are building a SPECT-based microscope. We based our design on earlier theoretical work with near-field coded apertures and have adjusted the components of the system to meet the real-world demands of instrument construction and of animal imaging. Our instrumental design possesses a reasonable trade-off between field-of-view, sensitivity, and contrast performance (photon penetration). A layered gold aperture containing 100 pinholes and intended for use in coded aperture imaging application has been designed and constructed. A silicon detector connected to a TimePix readout from the CERN collaborative group was selected for use in our prototype microscope because of its ultra-high spatial and energy resolution capabilities. The combination of the source, aperture, and detector has been modeled and the coded aperture reconstruction of simulated sources is presented in this work

Basic design and simulation of a SPECT microscope for in vivo stem cell imaging

The need to understand the behavior of individual stem cells at the various stages of their differentiation and to assess the resulting reparative action in pre-clinical model systems, which typically involves laboratory animals, provides the motivation for imaging of stem cells in vivo at high resolution. Our initial focus is to image cells and cellular events at single cell resolution in vivo in shallow tissues (few mm of intervening tissue) in laboratory mice and rates. In order to accomplish this goal we are building a SPECT-based microscope. We based our design on earlier theoretical work with near-field coded apertures and have adjusted the components of the system to meet the real-world demands of instrument construction and of animal imaging. Our instrumental design possesses a reasonable trade-off between field-of-view, sensitivity, and contrast performance (photon penetration). A layered gold aperture containing 100 pinholes and intended for use in coded aperture imaging application has been designed and constructed. A silicon detector connected to a TimePix readout from the CERN collaborative group was selected for use in our prototype microscope because of its ultra-high spatial and energy resolution capabilities. The combination of the source, aperture, and detector has been modeled and the coded aperture reconstruction of simulated sources is presented in this work

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

Comparison of k‐space sampling schemes for multidimensional MR spectroscopic imaging

For clinical 31P MR spectroscopic imaging (MRSI) studies, where signal averaging is necessary, some improvement of sensitivity and spatial response function may be achieved by acquiring data over a spherical k‐space volume and varying the number of averages acquired in proportion to the desired spatial filter. Eight different k‐space sampling schemes are compared through simulations that provide graphs of the spatial response functions (SRF), and tabulations of voxel volumes, relative signal‐to‐noise ratios (SNR), and relative data collection efficiencies (SNR per unit volume over the same time). All schemes were based on practical experiments, each of which could be implemented in the same length of time. The results show that in comparison with cubic k‐space sampling with the same number of signal averages at each point, spherical and acquisition‐weighted k‐space sampling can be used to achieve reduced Gibbs ringing along the principal axes directions, and thus reduced contamination from adjacent tissue in these directions, without degradation of voxel volume or SNR

Phosphorus-31 MR spectroscopic imaging (MRSI) of normal and pathological human brains

The goals of this study were to evaluate 31P MR spectroscopic imaging (MRSI) for clinical studies and to survey potentially significant spatial variations of 31P metabolite signals in normal and pathological human brains. In normal brains, chemical shifts and metabolite ratios corrected for saturation were similar to previous studies using single-volume localization techniques ( n = 10; pH = 7.01 ± 0.02; PCr Pi = 2.0 ± 0.4 ; PCr ATP = 1.4 ± 0.2 ; ATP Pi = 1.6 ± 0.2 ; PCr PDE = 0.52 ± 0.06 ; PCr PME = 1.3 ± 0.2 ; [Mg 2+] free = 0.26 ± 0.02 mM.) In 17 pathological case studies, ratios of 31P metabolite signals between the pathological regions and normal-appearing (usually homologous contralateral) regions were obtained. First, in subacute and chronic infarctions ( n = 9) decreased Pi (65 ± 12%), PCr (38 ± 6%), ATP (55 ± 6%), PDE (47 ± 9%), and total 31P metabolite signals (50 ± 8%) were observed. Second, regions of decreased total 31P metabolite signals were observed in normal pressure hydrocephalus (NPH, n = 2), glioblastoma ( n = 2), temporal lobe epilepsy ( n = 2), and transient ischemic attacks (TIAs, n = 2). Third, alkalosis was detected in the NPH periventricular tissue, glioblastoma, epilepsy ipsilateral ictal foci, and chronic infarction regions; acidosis was detected in subacute infarction regions. Fourth, in TIAs with no MRI-detected infarction, regions consistent with transient neurological deficits were detected with decreased Pi, ATP, and total 31P metabolite signals. These results demonstrate an advantage of 31P MRSI over single-volume 31P MRS techniques in that metabolite information is derived simultaneously from multiple regions of brain, including those outside the primary pathological region of interest. These preliminary findings also suggest that abnormal metabolite distributions may be detected in regions that appear normal on MR images

Elevated Lactate and Alkalosis in Chronic Human Brain Infarction Observed by 1H and 31P MR Spectroscopic Imaging

The goal of this study was to investigate lactate and pH distributions in subacutely and chronically infarcted human brains. Magnetic resonance spectroscopic imaging (MRSI) was used to map spatial distributions of 1H and 31P metabolites in 11 nonhemorrhagic subacute to chronic cerebral infarction patients and 11 controls. All six infarcts containing lactate were alkalotic (pHi = 7.20 ± 0.04 vs. 7.05 ± 0.01 contralateral, p < 0.01). This finding of elevated lactate and alkalosis in chronic infarctions does not support the presence of chronic ischemia; however, it is consistent with the presence of phagocytic cells, gliosis, altered buffering mechanisms, and/or luxury perfusion. Total 1H and 31P metabolites were markedly reduced (about 50% on average) in subacute and chronic brain infarctions ( p < 0.01), and N-acetyl aspartate (NAA) was reduced more (∼75%) than other metabolites ( p < 0.01). Because NAA is localized in neurons, selective NAA reduction is consistent with pathological findings of a greater loss of neurons than glial cells in chronic infarctions