Collimation of a D-D Neutron Generator for Clinical Implementation of Neutron Stimulated Emission Computed Tomography: a Monte Carlo Study

This work is an investigation into collimator designs for a deuterium-deuterium (DD) neutron generator for an inexpensive and compact neutron imaging system that can be implemented in a hospital. The envisioned application is for a spectroscopic imaging technique called neutron stimulated emission computed tomography (NSECT).

Previous NSECT studies have been performed using a Van-de-Graaff accelerator at the Triangle Universities Nuclear Laboratory (TUNL) in Duke University. This facility has provided invaluable research into the development of NSECT. To transition the current imaging method into a clinically feasible system, there is a need for a high-intensity fast neutron source that can produce collimated beams. The DD neutron generator from Adelphi Technologies Inc. is being explored as a possible candidate to provide the uncollimated neutrons. This DD generator is a compact source that produces 2.5 MeV fast neutrons with intensities of 1012 n/s (4π). The neutron energy is sufficient to excite most isotopes of interest in the body with the exception of carbon and oxygen. However, a special collimator is needed to collimate the 4π neutron emission into a narrow beam. This work describes the development and evaluation of a series of collimator designs to collimate the DD generator for narrow beams suitable for NSECT imaging.

A neutron collimator made of high-density polyethylene (HDPE) and lead was modeled and simulated using the GEANT4 toolkit. The collimator was designed as a 52 x 52 x 52 cm3 HDPE block coupled with 1 cm lead shielding. Non-tapering (cylindrical) and tapering (conical) opening designs were modeled into the collimator to permit passage of neutrons. The shape, size, and geometry of the aperture were varied to assess the effects on the collimated neutron beam. Parameters varied were: inlet diameter (1-5 cm), outlet diameter (1-5 cm), aperture diameter (0.5-1.5 cm), and aperture placement (13-39 cm). For each combination of collimator parameters, the spatial and energy distributions of neutrons and gammas were tracked and analyzed to determine three performance parameters: neutron beam-width, primary neutron flux, and the output quality. To evaluate these parameters, the simulated neutron beams are then regenerated for a NSECT breast scan. Scan involved a realistic breast lesion implanted into an anthropomorphic female phantom.

This work indicates potential for collimating and shielding a DD neutron generator for use in a clinical NSECT system. The proposed collimator designs produced a well-collimated neutron beam that can be used for NSECT breast imaging. The aperture diameter showed a strong correlation to the beam-width, where the collimated neutron beam-width was about 10% larger than the physical aperture diameter. In addition, a collimator opening consisting of a tapering inlet and cylindrical outlet allowed greater neutron throughput when compared to a simple cylindrical opening. The tapering inlet design can allow additional neutron throughput when the neck is placed farther from the source. On the other hand, the tapering designs also decrease output quality (i.e. increase in stray neutrons outside the primary collimated beam). All collimators are cataloged in measures of beam-width, neutron flux, and output quality. For a particular NSECT application, an optimal choice should be based on the collimator specifications listed in this work.

High-fidelity, broadband stimulated-Brillouin-scattering-based slow light using fast noise modulation.

We demonstrate a 5-GHz-broadband tunable slow-light device based on stimulated Brillouin scattering in a standard highly-nonlinear optical fiber pumped by a noise-current-modulated laser beam. The noisemodulation waveform uses an optimized pseudo-random distribution of the laser drive voltage to obtain an optimal flat-topped gain profile, which minimizes the pulse distortion and maximizes pulse delay for a given pump power. In comparison with a previous slow-modulation method, eye-diagram and signal-to-noise ratio (SNR) analysis show that this broadband slow-light technique significantly increases the fidelity of a delayed data sequence, while maintaining the delay performance. A fractional delay of 0.81 with a SNR of 5.2 is achieved at the pump power of 350 mW using a 2-km-long highly nonlinear fiber with the fast noise-modulation method, demonstrating a 50% increase in eye-opening and a 36% increase in SNR in the comparison.

Measuring fast gene dynamics in single cells with time-lapse luminescence microscopy.

Time-lapse fluorescence microscopy is an important tool for measuring in vivo gene dynamics in single cells. However, fluorescent proteins are limited by slow chromophore maturation times and the cellular autofluorescence or phototoxicity that arises from light excitation. An alternative is luciferase, an enzyme that emits photons and is active upon folding. The photon flux per luciferase is significantly lower than that for fluorescent proteins. Thus time-lapse luminescence microscopy has been successfully used to track gene dynamics only in larger organisms and for slower processes, for which more total photons can be collected in one exposure. Here we tested green, yellow, and red beetle luciferases and optimized substrate conditions for in vivo luminescence. By combining time-lapse luminescence microscopy with a microfluidic device, we tracked the dynamics of cell cycle genes in single yeast with subminute exposure times over many generations. Our method was faster and in cells with much smaller volumes than previous work. Fluorescence of an optimized reporter (Venus) lagged luminescence by 15-20 min, which is consistent with its known rate of chromophore maturation in yeast. Our work demonstrates that luciferases are better than fluorescent proteins at faithfully tracking the underlying gene expression.

Can Genetics Predict Response to Complex Behavioral Interventions? Evidence from a Genetic Analysis of the Fast Track Randomized Control Trial.

Early interventions are a preferred method for addressing behavioral problems in high-risk children, but often have only modest effects. Identifying sources of variation in intervention effects can suggest means to improve efficiency. One potential source of such variation is the genome. We conducted a genetic analysis of the Fast Track randomized control trial, a 10-year-long intervention to prevent high-risk kindergarteners from developing adult externalizing problems including substance abuse and antisocial behavior. We tested whether variants of the glucocorticoid receptor gene NR3C1 were associated with differences in response to the Fast Track intervention. We found that in European-American children, a variant of NR3C1 identified by the single-nucleotide polymorphism rs10482672 was associated with increased risk for externalizing psychopathology in control group children and decreased risk for externalizing psychopathology in intervention group children. Variation in NR3C1 measured in this study was not associated with differential intervention response in African-American children. We discuss implications for efforts to prevent externalizing problems in high-risk children and for public policy in the genomic era.

Big or fast: two strategies in the developmental control of body size.

Adult body size is controlled by the mechanisms that stop growth when a species-characteristic size has been reached. The mechanisms by which size is sensed and by which this information is transduced to the growth regulating system are beginning to be understood in a few species of insects. Two rather different strategies for control have been discovered; one favors large body size and the other favors rapid development.