Coded-aperture imaging in nuclear medicine

Coded-aperture imaging is a technique for imaging sources that emit high-energy radiation. This type of imaging involves shadow casting and not reflection or refraction. High-energy sources exist in x ray and gamma-ray astronomy, nuclear reactor fuel-rod imaging, and nuclear medicine. Of these three areas nuclear medicine is perhaps the most challenging because of the limited amount of radiation available and because a three-dimensional source distribution is to be determined. In nuclear medicine a radioactive pharmaceutical is administered to a patient. The pharmaceutical is designed to be taken up by a particular organ of interest, and its distribution provides clinical information about the function of the organ, or the presence of lesions within the organ. This distribution is determined from spatial measurements of the radiation emitted by the radiopharmaceutical. The principles of imaging radiopharmaceutical distributions with coded apertures are reviewed. Included is a discussion of linear shift-variant projection operators and the associated inverse problem. A system developed at the University of Arizona in Tucson consisting of small modular gamma-ray cameras fitted with coded apertures is described

Membrane-To-Nucleus Signaling Links Insulin-Like Growth Factor-1- and Stem Cell Factor-Activated Pathways

Stem cell factor (mouse: Kitl, human: KITLG) and insulin-like growth factor-1 (IGF1), acting via KIT and IGF1 receptor (IGF1R), respectively, are critical for the development and integrity of several tissues. Autocrine/paracrine KITLG-KIT and IGF1-IGF1R signaling are also activated in several cancers including gastrointestinal stromal tumors (GIST), the most common sarcoma. In murine gastric muscles, IGF1 promotes Kitl-dependent development of interstitial cells of Cajal (ICC), the non-neoplastic counterpart of GIST, suggesting cooperation between these pathways. Here, we report a novel mechanism linking IGF1-IGF1R and KITLG-KIT signaling in both normal and neoplastic cells. In murine gastric muscles, the microenvironment for ICC and GIST, human hepatic stellate cells (LX-2), a model for cancer niches, and GIST cells, IGF1 stimulated Kitl/KITLG protein and mRNA expression and promoter activity by activating several signaling pathways including AKT-mediated glycogen synthase kinase-3β inhibition (GSK3i). GSK3i alone also stimulated Kitl/KITLG expression without activating mitogenic pathways. Both IGF1 and GSK3i induced chromatin-level changes favoring transcriptional activation at the Kitl promoter including increased histone H3/H4 acetylation and H3 lysine (K) 4 methylation, reduced H3K9 and H3K27 methylation and reduced occupancy by the H3K27 methyltransferase EZH2. By pharmacological or RNA interference-mediated inhibition of chromatin modifiers we demonstrated that these changes have the predicted impact on KITLG expression. KITLG knock-down and immunoneutralization inhibited the proliferation of GIST cells expressing wild-type KIT, signifying oncogenic autocrine/paracrine KITLG-KIT signaling. We conclude that membrane-to-nucleus signaling involving GSK3i establishes a previously unrecognized link between the IGF1-IGF1R and KITLG-KIT pathways, which is active in both physiologic and oncogenic contexts and can be exploited for therapeutic purposes

Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model

Objective: This study investigates whether 99mTc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. Methods: High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat\u27s hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with 99mTc PYP. The radiotracer\u27s temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. Results: The washout kinetics of 99mTc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, 99mTc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered 99mTc PYP washout less than poloxamer-188 treatment. Conclusions: Behavior of 99mTc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of 99mTc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, 99mTc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury. © 2006 Elsevier Ltd and ISBI

Identification and quantification of transient receptor potential vanilloid 1 (TRPV1) in equine articular tissue

Joint pain and osteoarthritis (OA) are some of the most common causes of lameness in horses, and most of the available treatments focus on symptomatic relief without a disease-modifying effect. TRPV1 is a potential target for treating joint diseases, including OA, and the present study aims to investigate if the TRPV1 receptor is present in equine articular tissue and determine whether the number of receptors is upregulated in joint inflammation. Metacarpo/metatarsophalangeal (MCP/MTP) joints from 15 horses euthanised for reasons unrelated to this study were included. Based on synovial fluid analysis, macroscopic evaluation, and magnetic resonance imaging (MRI), joints were divided into two groups: healthy joints and joints with pathology. ELISA analysis was performed on synovial tissue harvested from all joints. TPRV1 was found in all joints. The mean concentration of TRPV1 compared to total protein in healthy joints (8.4 × 10−7 ng/mL) and joints with pathology (12.9 × 10−7 ng/mL) differed significantly (p = 0.01, t-test with Welch correction). Quantitative real-time reverse transcriptase PCR analysis was performed on RNA isolates from synovial tissue from all joints. TRPV1 mRNA expression ratio normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in healthy joints (0.16 (SD: 0.19)) and joints with pathology (0.24 (SD: 0.14)) did not differ significantly (p = 0.43, t-test with Welch correction). mRNA expression of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) was very low for both groups. In conclusion, TRPV1 was detected both on mRNA and the protein level, with a higher expression of TRPV1 in samples from joints with pathology. Future studies will determine the clinical potential of equine TRPV1 as a target in the management of joint pain and inflammation

Multiple-pinhole transaxial tomography: A model and analysis.

Multiple-pinhole transaxial tomography, a form of single-photon emission computed tomography (SPECT), is performed using novel imagers that have arrays of pinholes for image formation rather than collimators. Some such imagers, the University of Arizona (UA) transaxial systems, consist of coded apertures and modular gamma cameras and acquire data without system motion. They are the only such SPECT systems. This dissertation presents results from studies in which tomography using the UA imagers was simulated and studies in which the singular-value decompositions (SVDs) of multiple-pinhole imagers were calculated. The studies were performed to assess system configurations and to begin characterization of multiple-pinhole tomographs in terms of their SVDs. Our initial study involved simulation of systems consisting of arrays with uniformly spaced pinholes that produce multiplexed data and polygonal detectors comprising sixteen UA modules. This study shows that useful images can be obtained from static systems that have apertures that produce duplexed data and that significantly more useful images can be obtained using detectors that have resolution that is twice as fine as that of the UA modules. Numerical computation of the SVDs of several imagers including a single-pinhole imager and an orthogonal-pinhole imager produced visual displays of the object-space singular vectors of the systems. These displays demonstrate that the SVDs of multiple-pinhole systems can be expressed in terms of the SVDs of single-pinhole systems. The symmetries of all single-slice systems are rotational or reflective. The associated symmetry groups are cyclic groups or dihedral groups. The object-space singular vectors of these systems exhibit the same symmetries as the systems and exhibit multiplicities consistent with the irreducible representations of the associated groups. Results of analysis of the calculated SVDs demonstrate relationships among system symmetries, singular-vector symmetries, and irreducible representations. The results of our final study, a comparison of a system that has 64 pinholes spaced uniformly with one that has 64 pinholes spaced as a dilute uniformly redundant array, show that systems that have pinholes that are not uniformly spaced may prove the most useful

Online learning motivation

The popularity and interest in online learning is progressing rapidly. Public schools are facing funding and budget cuts and the possibility that online courses could provide instruction at minimal or lower cost is of interest in my school district. This action research project includes a review of sources that explain how children learn to read and how they learn from technology. The study includes classroom observations of a small group of middle school students in a reading intervention program. The focus of the study is whether or not interactive online learning activities can motivate some unmotivated learners. The major implications of this study indicate that students of this age are motivated by classroom online and face-to-face activities that provide them with independence, choice, flexibility, and supports their individual needs

The value of the read-aloud

As a classroom reading teacher I often ask myself, How can I help my students develop a love of reading? I decided the best opportunity I have to share my love of reading with students is through read-alouds. For this reason the focus of my research is the read-aloud and what effect, if any, it has on students\u27 reading. I interviewed the parents of my student subjects to see how much their children read in the home. I also administered a survey to the students to get an idea of their attitudes toward reading. I observed and documented students\u27 engagement levels in various read-aloud settings. I read students\u27 journals after they\u27d written their reactions to read-alouds and how much time they were spending in their free-reads . The knowledge and insight I gained by the capstone process proved positive and helpful in my classroom teaching