Improved Modeling of System Response in List Mode EM Reconstruction of Compton Scatter Camera Images

An improved List Mode EM method for reconstructing Compton scattering camera images has been developed. First, an approximate method for computation of the spatial variation in the detector sensitivity has been derived and validated by Monte Carlo computation. A technique for estimating the relative weight of system matrix coefficients for each gamma in the list has also been employed, as has a method for determining the relative probabilities of emission having some from pixels tallied in each list-mode back-projection. Finally, a technique has been developed for modeling the effects of Doppler broadening and finite detector energy resolution on the relative weights for pixels neighbor to those intersected by the back-projection, based on values for the FWHM of the spread in the cone angle computed by Monte Carlo. Memory issues typically associated with list mode reconstruction are circumvented by storing only a list of the pixels intersected by the back-projections, and computing the weights of the neighboring pixels at each iteration step. Simulated projection data has been generated for a representative Compton camera system (CSPRINT) for several source distributions and reconstructions performed. Reconstructions have also been performed for experimental data for distributed sources.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86027/1/Fessler157.pd

List-Mode Maximum Likelihood Reconstruction of Compton Scatter Camera Images in Nuclear Medicine

A Maximum Likelihood (ML) image reconstruction technique using list-mode data has been applied to Compton scattering camera imaging. List-mode methods are appealing in Compton camera image reconstruction because the total number of data elements in the list (the number of detected photons) is significantly smaller than the number of possible combinations of position and energy measurements, leading to a much smaller problem than that faced by traditional iterative reconstruction techniques. For a realistic size device, the number of possible detector bins can be as large as 10 billion per pixel of the image space, while the number of counted photons would typically be a very small fraction of that. The primary difficulty in applying the list-mode technique is in determining the parameters which describe the response of the imaging system. In this work, a simple method for determining the required system matrix coefficients is employed, in which a back-projection is performed in list-mode, and response coefficients determined for only tallied pixels. Projection data has been generated for a representative Compton camera system by Monte Carlo simulation for disk sources with hot and cold spots and energies of 141, 364, and 511 keV, and reconstructions performed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85815/1/Fessler155.pd

Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

Copy Number Variation of CCL3-like Genes Affects Rate of Progression to Simian-AIDS in Rhesus Macaques (Macaca mulatta)

Variation in genes underlying host immunity can lead to marked differences in susceptibility to HIV infection among humans. Despite heavy reliance on non-human primates as models for HIV/AIDS, little is known about which host factors are shared and which are unique to a given primate lineage. Here, we investigate whether copy number variation (CNV) at CCL3-like genes (CCL3L), a key genetic host factor for HIV/AIDS susceptibility and cell-mediated immune response in humans, is also a determinant of time until onset of simian-AIDS in rhesus macaques. Using a retrospective study of 57 rhesus macaques experimentally infected with SIVmac, we find that CCL3L CNV explains approximately 18% of the variance in time to simian-AIDS (p<0.001) with lower CCL3L copy number associating with more rapid disease course. We also find that CCL3L copy number varies significantly (p<10−6) among rhesus subpopulations, with Indian-origin macaques having, on average, half as many CCL3L gene copies as Chinese-origin macaques. Lastly, we confirm that CCL3L shows variable copy number in humans and chimpanzees and report on CCL3L CNV within and among three additional primate species. On the basis of our findings we suggest that (1) the difference in population level copy number may explain previously reported observations of longer post-infection survivorship of Chinese-origin rhesus macaques, (2) stratification by CCL3L copy number in rhesus SIV vaccine trials will increase power and reduce noise due to non-vaccine-related differences in survival, and (3) CCL3L CNV is an ancestral component of the primate immune response and, therefore, copy number variation has not been driven by HIV or SIV per se

Taxonomy based on science is necessary for global conservation

Peer reviewe