Mitigation of artifacts due to isolated acoustic heterogeneities in photoacoustic computed tomography using a variable data truncation-based reconstruction method

Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the absorbed optical energy density within tissue. If the object possesses spatially variant acoustic properties that are unaccounted for by the reconstruction method, the estimated image can contain distortions. While reconstruction methods have recently been developed to compensate for this effect, they generally require the object's acoustic properties to be known a priori. To circumvent the need for detailed information regarding an object's acoustic properties, we previously proposed a half-time reconstruction method for PACT. A half-time reconstruction method estimates the PACT image from a data set that has been temporally truncated to exclude the data components that have been strongly aberrated. However, this method can be improved upon when the approximate sizes and locations of isolated heterogeneous structures, such as bones or gas pockets, are known. To address this, we investigate PACT reconstruction methods that are based on a variable data truncation (VDT) approach. The VDT approach represents a generalization of the half-time approach, in which the degree of temporal truncation for each measurement is determined by the distance between the corresponding ultrasonic transducer location and the nearest known bone or gas void location. Computer-simulated and experimental data are employed to demonstrate the effectiveness of the approach in mitigating artifacts due to acoustic heterogeneities

Compensation for acoustic heterogeneities in photoacoustic computed tomography using a variable temporal data truncation reconstruction method

Photoacoustic computed tomography (PACT) is an emerging computed imaging modality that exploits optical contrast and ultrasonic detection principles to form images of the absorbed optical energy density within tissue. If the object possesses spatially variant acoustic properties that are unaccounted for by the reconstruction algorithm, the estimated image can contain distortions. While reconstruction algorithms have recently been developed for compensating for this effect, they generally require the objects acoustic properties to be known a priori. To circumvent the need for detailed information regarding an objects acoustic properties, we have previously proposed a half-time reconstruction method for PACT. A half-time reconstruction method estimates the PACT image from a data set that has been temporally truncated to exclude the data components that have been strongly aberrated. In this approach, the degree of temporal truncation is the same for all measurements. However, this strategy can be improved upon it when the approximate sizes and locations of strongly heterogeneous structures such as gas voids or bones are known. In this work, we investigate PACT reconstruction algorithms that are based on a variable temporal data truncation (VTDT) approach that represents a generalization of the half-time reconstruction approach. In the VTDT approach, the degree of temporal truncation for each measurement is determined by the distance between the corresponding transducer location and the nearest known bone or gas void location. Reconstructed images from a numerical phantom is employed to demonstrate the feasibility and effectiveness of the approach

Compensation for air voids in photoacoustic computed tomography image reconstruction

Most image reconstruction methods in photoacoustic computed tomography (PACT) assume that the acoustic properties of the object and the surrounding medium are homogeneous. This can lead to strong artifacts in the reconstructed images when there are significant variations in sound speed or density. Air voids represent a particular challenge due to the severity of the differences between the acoustic properties of air and water. In whole-body small animal imaging, the presence of air voids in the lungs, stomach, and gastrointestinal system can limit image quality over large regions of the object. Iterative reconstruction methods based on the photoacoustic wave equation can account for these acoustic variations, leading to improved resolution, improved contrast, and a reduction in the number of imaging artifacts. However, the strong acoustic heterogeneities can lead to instability or errors in the numerical wave solver. Here, the impact of air voids on PACT image reconstruction is investigated, and procedures for their compensation are proposed. The contributions of sound speed and density variations to the numerical stability of the wave solver are considered, and a novel approach for mitigating the impact of air voids while reducing the computational burden of image reconstruction is identified. These results are verified by application to an experimental phantom

Detection of ultra-high energy cosmic ray showers with a single-pixel fluorescence telescope

We present a concept for large-area, low-cost detection of ultra-high energy cosmic rays (UHECRs) with a Fluorescence detector Array of Single-pixel Telescopes (FAST), addressing the requirements for the next generation of UHECR experiments. In the FAST design, a large field of view is covered by a few pixels at the focal plane of a mirror or Fresnel lens. We report first results of a FAST prototype installed at the Telescope Array site, consisting of a single 200 mm photomultiplier tube at the focal plane of a 1 m$^2$ Fresnel lens system taken from the prototype of the JEM-EUSO experiment. The FAST prototype took data for 19 nights, demonstrating remarkable operational stability. We detected laser shots at distances of several kilometres as well as 16 highly significant UHECR shower candidates.Comment: Accepted for publication in Astroparticle Physic

Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection.

BackgroundWe reported previously on the emergence and clinical implications of simian immunodeficiency virus (SIVmac251) mutants with a K65R mutation in reverse transcriptase (RT), and the role of CD8+ cell-mediated immune responses in suppressing viremia during tenofovir therapy. Because of significant sequence differences between SIV and HIV-1 RT that affect drug susceptibilities and mutational patterns, it is unclear to what extent findings with SIV can be extrapolated to HIV-1 RT. Accordingly, to model HIV-1 RT responses, 12 macaques were inoculated with RT-SHIV, a chimeric SIV containing HIV-1 RT, and started on prolonged tenofovir therapy 5 months later.ResultsThe early virologic response to tenofovir correlated with baseline viral RNA levels and expression of the MHC class I allele Mamu-A*01. For all animals, sensitive real-time PCR assays detected the transient emergence of K70E RT mutants within 4 weeks of therapy, which were then replaced by K65R mutants within 12 weeks of therapy. For most animals, the occurrence of these mutations preceded a partial rebound of plasma viremia to levels that remained on average 10-fold below baseline values. One animal eventually suppressed K65R viremia to undetectable levels for more than 4 years; sequential experiments using CD8+ cell depletion and tenofovir interruption demonstrated that both CD8+ cells and continued tenofovir therapy were required for sustained suppression of viremia.ConclusionThis is the first evidence that tenofovir therapy can select directly for K70E viral mutants in vivo. The observations on the clinical implications of the K65R RT-SHIV mutants were consistent with those of SIVmac251, and suggest that for persons infected with K65R HIV-1 both immune-mediated and drug-dependent antiviral activities play a role in controlling viremia. These findings suggest also that even in the presence of K65R virus, continuation of tenofovir treatment as part of HAART may be beneficial, particularly when assisted by antiviral immune responses