Feasibility of direct digital sampling for diffuse optical frequency domain spectroscopy in tissue

Frequency domain optical spectroscopy in the diffusive regime is currently being investigated for biomedical applications including tumor detection, therapy monitoring, exercise metabolism, and others. Analog homodyne or heterodyne detection of sinusoidally modulated signals have been the predominant method for measuring phase and amplitude of photon density waves that have traversed through tissue. Here we demonstrate the feasibility of utilizing direct digital sampling of modulated signals using a 3.6 Gigasample/second 12 bit Analog to Digital Converter. Digitally synthesized modulated signals between 50MHz and 400MHz were measured on tissue simulating phantoms at six near-infrared wavelengths. An amplitude and phase precision of 1% and 0.6 degrees were achieved during drift tests. Amplitude, phase, scattering and absorption values were compared with a well-characterized network analyzer based diffuse optical device. Measured optical properties measured with both systems were within 3.6% for absorption and 2.8% for scattering over a range of biologically relevant values. Direct digital sampling represents a viable method for frequency domain diffuse optical spectroscopy and has the potential to reduce system complexity, size, and cost

Spatio-Temporal Patterns of Barmah Forest Virus Disease in Queensland, Australia

Background Barmah Forest virus (BFV) disease is a common and wide-spread mosquito-borne disease in Australia. This study investigated the spatio-temporal patterns of BFV disease in Queensland, Australia using geographical information system (GIS) tools and geostatistical analysis. Methods/Principal Findings We calculated the incidence rates and standardised incidence rates of BFV disease. Moran's I statistic was used to assess the spatial autocorrelation of BFV incidences. Spatial dynamics of BFV disease was examined using semi-variogram analysis. Interpolation techniques were applied to visualise and display the spatial distribution of BFV disease in statistical local areas (SLAs) throughout Queensland. Mapping of BFV disease by SLAs reveals the presence of substantial spatio-temporal variation over time. Statistically significant differences in BFV incidence rates were identified among age groups (χ2 = 7587, df = 7327,p<0.01). There was a significant positive spatial autocorrelation of BFV incidence for all four periods, with the Moran's I statistic ranging from 0.1506 to 0.2901 (p<0.01). Semi-variogram analysis and smoothed maps created from interpolation techniques indicate that the pattern of spatial autocorrelation was not homogeneous across the state. Conclusions/Significance This is the first study to examine spatial and temporal variation in the incidence rates of BFV disease across Queensland using GIS and geostatistics. The BFV transmission varied with age and gender, which may be due to exposure rates or behavioural risk factors. There are differences in the spatio-temporal patterns of BFV disease which may be related to local socio-ecological and environmental factors. These research findings may have implications in the BFV disease control and prevention programs in Queensland

Longitudinal Tracking of Human Fetal Cells Labeled with Super Paramagnetic Iron Oxide Nanoparticles in the Brain of Mice with Motor Neuron Disease

Stem Cell (SC) therapy is one of the most promising approaches for the treatment of Amyotrophic Lateral Sclerosis (ALS). Here we employed Super Paramagnetic Iron Oxide nanoparticles (SPIOn) and Hoechst 33258 to track human Amniotic Fluid Cells (hAFCs) after transplantation in the lateral ventricles of wobbler (a murine model of ALS) and healthy mice. By in vitro, in vivo and ex vivo approaches we found that: 1) the main physical parameters of SPIOn were maintained over time; 2) hAFCs efficiently internalized SPIOn into the cytoplasm while Hoechst 33258 labeled nuclei; 3) SPIOn internalization did not alter survival, cell cycle, proliferation, metabolism and phenotype of hAFCs; 4) after transplantation hAFCs rapidly spread to the whole ventricular system, but did not migrate into the brain parenchyma; 5) hAFCs survived for a long time in the ventricles of both wobbler and healthy mice; 6) the transplantation of double-labeled hAFCs did not influence mice survival

3D Visualisation of Navigation Catheters for Endovascular Procedures Using a 3D Hub and Fiber Optic RealShape Technology: Phantom Study Results

Objective: Fiber Optic RealShape (FORS) is a new technology that visualises the full three dimensional (3D) shape of guidewires using an optical fibre embedded in the device. Co-registering FORS guidewires with anatomical images, such as a digital subtraction angiography (DSA), provides anatomical context for navigating these devices during endovascular procedures. The objective of this study was to demonstrate the feasibility and usability of visualising compatible conventional navigation catheters, together with the FORS guidewire, in phantom with a new 3D Hub technology and to understand potential clinical benefits. Methods: The accuracy of localising the 3D Hub and catheter in relation to the FORS guidewire, was evaluated using a translation stage test setup and a retrospective analysis of prior clinical data. Catheter visualisation accuracy and navigation success was assessed in a phantom study where 15 interventionists navigated devices to three pre-defined targets in an abdominal aortic phantom using an Xray or computed tomography angiography (CTA) roadmap. Additionally, the interventionists were surveyed about the usability and potential benefits of the 3D Hub. Results: The location of the 3D Hub and catheter along the FORS guidewire was detected correctly 96.59% of the time. During the phantom study, all 15 interventionists successfully reached the target locations 100% of the time and the error in catheter visualisation was 0.69 mm. The interventionists agreed or strongly agreed that the 3D Hub was easy to use and the greatest potential clinical benefit over FORS is in offering interventionists choice over which catheter they used. Conclusion: This set of studies has shown that FORS guided catheter visualisation, enabled by a 3D Hub, is accurate and easy to use in a phantom setting. Further evaluation is needed to understand the benefits and limitations of the 3D Hub technology during endovascular procedures

Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy

Background: To determine if infectious disease events in HIV-infected patients treated with highly active antiretroviral therapy (HAART) are a consequence of the restoration of pathogen-specific immune responses, a single-centre retrospective study of all HIV-infected patients commencing HAART prior to 1 July 1997 was undertaken to determine the incidence, characteristics and time of onset of disease episodes in HAART responders (decrease in plasma HIV RNA of > 1 log10 copies/mL). Methods: Baseline and post-therapy changes in CD4 T-cell counts and HIV RNA were compared in patients with and without disease and delayed-type hypersensitivity responses to mycobacterial antigens were measured in selected patients. Results: Thirty-three of 132 HAART responders (25%) exhibited one or more disease episodes after HAART, related to a pre-existent or subclinical infection by an opportunistic pathogen. Disease episodes were most often related to infections by mycobacteria or herpesviruses but hepatitis C virus (HCV), molluscum contagiosum virus and human papilloma virus were also implicated. They were most common in patients with a baseline CD4 T-cell count of < 50/uL and occurred most often during the first 2 months of therapy and when CD4 T-cell counts were increasing. Mycobacteria- and HCV-related diseases were associated with restoration of pathogen-specific immune responses. Conclusions: We conclude that improved immune function in immunodeficient patients treated with HAART may restore pathogen-specific immune responses and cause inflammation in tissues infected by those pathogens