Measurement Of Density Changes Research Articles

Quantitative focused laser differential interferometry with hypersonic turbulent boundary layers.

The effect of turbulent wind-tunnel-wall boundary layers on density change measurements obtained with focused laser differential interferometry (FLDI) was studied using a detailed direct numerical simulation (DNS) of the wall from the Boeing/AFOSR Mach-6 Quiet Tunnel run in its noisy configuration. The DNS was probed with an FLDI model that is capable of reading in three-dimensional time-varying density fields and computing the FLDI response. Simulated FLDI measurements smooth the boundary-layer root-mean-square (RMS) profile relative to true values obtained by directly extracting the data from the DNS. The peak of the density change RMS measured by the FLDI falls within 20% of the true density change RMS. A relationship between local spatial density change and temporal density fluctuations was determined and successfully used to estimate density fluctuations from the FLDI measurements. FLDI measurements of the freestream fluctuations are found to be dominated by the off-axis tunnel-wall boundary layers for lower frequencies despite spatial suppression provided by the technique. However, low-amplitude (0.05%-5% of the mean density) target signals placed along the tunnel centerline were successfully measured over the noise of the boundary layers (which have RMS values of about 12% of the mean). Overall, FLDI was shown to be a useful technique for making quantitative turbulence measurements and to measure finite-width sinusoidal signals through turbulent boundary layers, but may not provide enough off-focus suppression to provide accurate freestream noise measurements, particularly at lower frequencies.

Spectroscopic Ellipsometry Investigation of a Sensing Functional Interface: DNA SAMs Hybridization

AbstractHere, a comprehensive study of a label‐free detection platform for the recognition of oligonucleotide sequences based on hybridization of thiol‐tethered DNA strands self‐assembled on flat gold films is presented. The study exploits in‐buffer spectroscopic ellipsometry (SE) measurements, a noninvasive method sensitive to monolayer films, supported by surface mass density change measurements (Quartz Crystal Microbalance with Dissipation, QCM‐D) obtained under comparable experimental conditions. SE and QCM‐D allow monitoring deposition of molecular precursors and DNA chain hybridization. Combining SE measurements with QCM‐D data paves the way for quantification of the assay through the possible calibration of SE data. Optical measurements also demonstrate the selectivity and recovery properties of the sensing platform. Broadband SE measurements are interpreted by means of an effective optical model. The model, complemented by information on film thickness (scanning probe nanolithography), and surface composition (monochromatic X‐ray Photoemission Spectroscopy, XPS), enables a clear spectral identification of UV DNA resonances and the formation of the thiolate interface with gold. Spectroscopic validation of the hybridization is complemented by employing labeled target strands. The influence of hybridization on UV resonances and optical thickness of the DNA film is discussed in the light of hypochromism, through comparison with QCM‐D data.

Muon radiography employing the DIRC principle for density change measurements under volcanoes and fluid reservoirs

Mapping the density distribution and monitoring density changes under volcanoes and geological reservoirs is a major challenge in geology and volcanology. Muon radiography has a high potential to advance this field, but often there are no inexpensive high-end detectors available that are suitable for field installations. A DIRC-type Cherenkov detector as a muon camera has a small dimension and is suited for such field applications (MagmaDIRC idea). In measuring directions and energies of the incoming muons one can turn the mass density integrals along the lines of flight into a radiography image, and by discarting low-energy muons with their blurred angular information one obtains sharper images. In particular one may detect the time variation of the mass density distributions situated above the horizon line in a volcanic edifice that occurs when magma is filling its plumbing system or when the level of a lava lake changes. Using numerical simulations, we discuss design aspects and the requirements of such a DIRC system. Two sites are identified for proof-of-principle field measurements. The required measurement times are estimated for the given site conditions and morphology based on the specifications of an operational DIRC system. The merits of DIRC sensors are contrasted to other muon radiography techniques.

Quantification of hepatic steatosis in histologic images by deep learning method.

To develop and test a novel method for automatic quantification of hepatic steatosis in histologic images based on the deep learning scheme designed to predict the fat ratio directly, which aims to improve accuracy in diagnosis of non-alcoholic fatty liver disease (NAFLD) with objective assessment of the severity of hepatic steatosis instead of subjective visual estimation. Thirty-six 8-week old New Zealand white rabbits of both sexes were fed with high-cholesterol, high-fat diet and sacrificed under deep anesthesia at various time points to obtain the pathological specimen. All rabbits were performed by multislice computed tomography for surveillance to measure density changes of liver parenchyma. A deep learning scheme using a convolutional neural network was developed to directly predict the liver fat ratio based on the pathological images. The average error value, standard deviation, and accuracy (error <5%) were evaluated and compared between the deep learning scheme and manual segmentation results. The Pearson's correlation coefficient was also calculated in this study. The deep learning scheme performs successfully on rabbit liver histologic data, showing a high degree of accuracy and stability. The average error value, standard deviation, and accuracy (error <5%) were 3.21%, 4.02%, and 79.10% for the cropped images, 2.22%, 1.92%, and 88.34% for the original images, respectively. The strong positive correlation was also observed for cropped images (R = 0.9227) and original images (R = 0.9255) in comparison to labeled fat ratio. This new deep learning scheme may aid in the quantification of steatosis in the liver and facilitate its treatment by providing an earlier clinical diagnosis.

133P - Evaluating lung ct density changes among patients with extensive stage small cell lung cancer (ES-SCLC) treated with thoracic radiotherapy (TRT) alone or TRT followed by combined ipilimumab (IPI) and nivolumab (NIVO)

BackgroundRadiation induced CT changes may be apparent following completion of TRT. We sought to quantify differences in radiation-associated densities on serial CT scans of patients with ES-SCLC treated with TRT alone versus TRT followed by combined IPI and NIVO. MethodsBetween 2016 and 2018, patients at a single institution with ES-SCLC who achieved stable disease or better following initial treatment with platinum doublet chemotherapy were offered TRT and prescribed a total dose of 30Gy in 10 fractions targeting initially involved thoracic tumor sites. Combined IPI 3mg/kg and NIVO 1mg/kg was administered every 3 weeks for up to 4 doses. We evaluated an irradiated region of interest (ROI) within the lungs and a volume of lung (outside the Planning Target Volume) receiving > 20Gy. Within the ROI, we calculated the Hounsfield unit (HU) mean for each patient prior to therapy and at subsequent follow-up CT thorax at least 60 days and closest to 120 days after commencing TRT. To quantify CT density change, we measured the difference in HU mean within the irradiated ROI before and after treatment. ResultsSeventeen patients enrolled on NCT03043599 received TRT followed by combined IPI/NIVO. Two additional patients received the same treatment off protocol. Eleven patients received TRT alone (no IPI/NIVO). The average increase in HU mean within 20Gy irradiated ROI before and after treatment was 9% (max 59%, min -19%) across the study cohort (n=30). CTCAE grade 3 or higher pulmonary toxicity (N=8 of 30) was significantly associated with increased CT density change within the ROI (mean 28% vs 2%, p=0.001). Treatment with TRT and IPI/NIVO (N=19 of 30) demonstrated a trend towards increased mean CT density change within the ROI compared to patients treated with TRT alone (mean 13% vs. 0%, p=0.1). ConclusionsQuantifying CT density change within irradiated lung parenchyma may offer a novel approach to predict radiation associated pulmonary toxicities. Measuring density changes across patient cohorts receiving TRT with novel systemic therapies may help to identify combined treatment strategies likely to be associated with diminished risk of toxicity. Legal entity responsible for the studyThe authors. FundingBristol-Myers Squibb. DisclosureS. Kim: Research grant / Funding (institution): Bristol-Myers Squibb. S.A. Rosenberg: Advisory / Consultancy: Novocure. J.E. Gray: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Genentech; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Triptych Health Partners. S.J. Antonia: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck; Advisory / Consultancy: CBMG; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: AstraZeneca/MedImmune; Advisory / Consultancy: Memgen; Advisory / Consultancy: FLX Bio; Advisory / Consultancy: Nektar; Advisory / Consultancy: Venn. B. Perez: Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: AstraZeneca. All other authors have declared no conflicts of interest.

Muon Borehole Detector Design for Use in 4-D Density Overburden Monitoring

The increase in atmospheric CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> concentrations has initiated research into carbon sequestration methods. One possibility is to store CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> in subsurface porous reservoirs. Monitoring the injected CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> plume is vital because escaping CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> poses health and environmental risks. Typically, seismic reflection methods are used to determine the change in density due to the replacement of brine by CO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> in the reservoir but this is expensive and not continuous. A potential alternative is to use cosmic muon tomography to measure density changes in the reservoir as a function of time. This paper describes the development of a muon detector that will be capable of being deployed in boreholes. The detector will be designed to have the required dimensions, an angular resolution of approximately 2°, and be mechanically robust. The prototype design is based on alternating layers of scintillating rods, which can provide 4-D reconstruction of the overburden to detect small changes in density at depths up to approximately 2 km. Geant4, a Monte Carlo simulation code, is being used to develop models to guide the design of the physical configuration. Preliminary testing and measurements have been performed to validate the simulation predictions and optimize physical performance parameters. The simulated and preliminary experimental results are presented here.

A comprehensive tool for measuring mammographic density changes over time

BackgroundMammographic density is a marker of breast cancer risk and diagnostics accuracy. Density change over time is a strong proxy for response to endocrine treatment and potentially a stronger predictor of breast cancer incidence. We developed STRATUS to analyse digital and analogue images and enable automated measurements of density changes over time.MethodRaw and processed images from the same mammogram were randomly sampled from 41,353 healthy women. Measurements from raw images (using FDA approved software iCAD) were used as templates for STRATUS to measure density on processed images through machine learning. A similar two-step design was used to train density measures in analogue images. Relative risks of breast cancer were estimated in three unique datasets. An alignment protocol was developed using images from 11,409 women to reduce non-biological variability in density change. The protocol was evaluated in 55,073 women having two regular mammography screens. Differences and variances in densities were compared before and after image alignment.ResultsThe average relative risk of breast cancer in the three datasets was 1.6 [95% confidence interval (CI) 1.3–1.8] per standard deviation of percent mammographic density. The discrimination was AUC 0.62 (CI 0.60–0.64). The type of image did not significantly influence the risk associations. Alignment decreased the non-biological variability in density change and re-estimated the yearly overall percent density decrease from 1.5 to 0.9%, p < 0.001.ConclusionsThe quality of STRATUS density measures was not influenced by mammogram type. The alignment protocol reduced the non-biological variability between images over time. STRATUS has the potential to become a useful tool for epidemiological studies and clinical follow-up.

Microstructural characterization and density change of 304 stainless steel reflector blocks after long-term irradiation in EBR-II

While thin reactor structural components such as cladding and ducts do not experience significant gradients in dpa rate, gamma heating rate, temperature or stress, thick components can develop strong local variations in void swelling and irradiation creep in response to gradients in these variables. In this study we conducted microstructural investigations by transmission electron microscopy of two 52 mm thick 304-type stainless steel hex-blocks irradiated for 12 years in the EBR-II reactor with accumulated doses ranging from ∼0.4 to 33 dpa. Spatial variations in the populations of voids, precipitates, Frank loops and dislocation lines have been determined for 304 stainless steel sections exposed to different temperatures, different dpa levels and at different dpa rates, demonstrating the existence of spatial gradients in the resulting void swelling. The microstructural measurements compare very well with complementary density change measurements regarding void swelling gradients in the 304 stainless steel hex-block components.The TEM studies revealed that the original cold-worked-state microstructure of the unirradiated blocks was completely erased by irradiation, replaced by high densities of interstitial Frank loops, voids and carbide precipitates at both the lowest and highest doses. At large dose levels the amount of volumetric void swelling correlated directly with the gamma heating gradient-related temperature increase (e.g. for 28 dpa, ∼2% swelling at 418 °C and ∼2.9% swelling at 448 °C). Under approximately iso-thermal local conditions, volumetric void swelling was found to increase with dose level (e.g. ∼0.2% swelling at 0.4 dpa, ∼0.5% swelling at 4 dpa and ∼2% swelling at 28 dpa). Carbide precipitate formation levels were found to be relatively independent of both dpa level and temperature and induced a measurable densification. Void swelling was dominant at the higher dose levels and caused measurable decreases in density. Void swelling at the lowest doses was larger than might be expected based on the dpa level, an observation in agreement with earlier studies showing that the onset of void swelling is accelerated by decreasing dpa rates.

Vision-Based On-Loom Measurement of Yarn Densities in Woven Fabrics

A vision-based measurement system to quantify the yarn density of woven fabrics during production is presented. As an extension to an earlier developed fabric flaw detection system, the proposed framework consists of a combination of basic and custom-made image-processing techniques that allow to precisely track single wefts and warps within fabric images—in real-time. Several adaptations facilitate the measurement of density changes for plain, satin, and twill weaves. In this paper, the algorithmic framework has been evaluated in several comprehensive on-line experiments on a real-world air-jet loom and is additionally compared with three alternative methods for fabric density measurement. It proved to be precise, robust, and applicable for industrial use as it overcomes many of the existing shortcomings of current methods.

Measure bone volume and density changes of sites grafted with bone allografts and a titanium mesh on cone-beam computed tomography: a technique.

The aim of this study was to introduce a novel method to evaluate volumetric and density changes of the augmented sites. A ridge augmentation procedure, using particulate bone allografts and a titanium mesh, was performed on the posterior edentulous mandible of 3 participants. Cone-beam computed tomography was taken preoperatively (1st scan), immediately (2nd scan), and 5 months (3rd scan) after the surgery. The grafted area was segmented on the 2nd and 3rd scans, using the 1st scan as the reference. The volume of the grafted area and the newly formed bone-graft complex that is defined by a preselected threshold was then determined. The bone mineral density (BMD) of the grafted area was determined by comparing gray-scale histograms of the grafted area for the 2nd and 3rd scans using the cortical bone adjacent to the grafted area as the reference. The mean volumetric shrinkage was 13.5%. The BMD increase was 4.65%. The mean error in determining cortical bone density between the scans was 1.69%. A novel technique to measure bone volume and density changes after bone augmentation was described. The low measurement/scanning error suggested that this technique is reliable and reproducible.

Cavity optomechanics on a microfluidic resonator with water and viscous liquids

Currently, optical or mechanical resonances are commonly used in microfluidic research. However, optomechanical oscillations by light pressure were not shown with liquids. This is because replacing the surrounding air with water inherently increases the acoustical impedance and hence, the associated acoustical radiation losses. Here, we bridge between microfluidics and optomechanics by fabricating a hollow-bubble resonator with liquid inside and optically exciting vibrations with 100 MHz rates using only mW optical-input power. This constitutes the first time that any microfluidic system is optomechanically actuated. We further prove the feasibility of microfluidic optomechanics on liquids by demonstrating vibrations on organic fluids with viscous dissipation higher than blood viscosity while measuring density changes in the liquid via the vibration frequency shift. Our device will enable using cavity optomechanics for studying non-solid phases of matter, while light is easily coupled from the outer dry side of the capillary and fluid is provided using a standard syringe pump. Scientists in the USA have successfully used optomechanics to probe a microfluidic system. Kyu Hyun Kim and co-workers at the University of Michigan and the University of Illinois at Urbana-Champaign fabricated a bulbous hollow-glass capillary and filled it with sugar-water solution. They then used a tapered optical fibre to couple light evanescently in the perimeter of the capillary and thus excite optical whispering gallery modes. This optical mode excites a vibrational mode of the liquid-filled glass structure via the centrifugal radiation pressure that light applies while circumferentially circulating, which in turn modulated the light at a particular frequency. The frequency of the induced vibrations varied with the sugar concentration of the liquid, thus indicating the potential of the structure to function as a sensor. The researchers found that input optical powers as small as 1 mW were sufficient to induce vibrations.

Shifts in the Distribution of Mass Densities Is a Signature of Caloric Restriction in Caenorhabditis elegans

Although the starvation response of the model multicellular organism Caenorhabditis elegans is a subject of much research, there is no convenient phenotypic readout of caloric restriction that can be applicable to large numbers of worms. This paper describes the distribution of mass densities of populations of C. elegans, from larval stages up to day one of adulthood, using isopycnic centrifugation, and finds that density is a convenient, if complex, phenotypic readout in C. elegans. The density of worms in synchronized populations of wildtype N2 C. elegans grown under standard solid-phase culture conditions was normally distributed, with distributions peaked sharply at a mean of 1.091 g/cm3 for L1, L2 and L3 larvae, 1.087 g/cm3 for L4 larvae, 1.081 g/cm3 for newly molted adults, and 1.074 g/cm3 at 24 hours of adulthood. The density of adult worms under starvation stress fell well outside this range, falling to a mean value of 1.054 g/cm3 after eight hours of starvation. This decrease in density correlated with the consumption of stored glycogen in the food-deprived worms. The density of the worms increased when deprived of food for longer durations, corresponding to a shift in the response of the worms: worms sacrifice their bodies by retaining larvae, which consume the adults from within. Density-based screens with the drug Ivermectin on worms cultured on single plates resulted in a clear bimodal (double-peaked) distribution of densities corresponding to drug exposed and non-exposed worms. Thus, measurements of changes in density could be used to conduct screens on the effects of drugs on several populations of worms cultured on single plates.

Abstract A116: Inter-scan reproducibility of mammographic density measurements

Abstract Introduction: A decrease in mammographic density is increasingly used as an intermediate marker to evaluate the effect of interventions for reducing breast cancer risk. Technical aspects, such as a different amount of compression, could influence density measurements. We investigated the inter-scan reproducibility of mammographic density measurements to see whether this may influence measurements of true changes in density. Methods: We included women with two mammograms made closely after one another (median 12 days), with no true changes in breast density expected to happen: 106 had two Full-Field Digital Mammograms (FFDM), 12 had two Film-Screen Mammograms (FSM) and 52 had one FFDM and one FSM. We estimated intraclass correlation coefficients, and mean absolute density differences between both mammograms. Results: The intraclass correlation between percent density measurements on two FFDMs was 0.93 (95%CI 0.91-0.95), between two FSMs 0.94 (95%CI 0.84-0.98), and between FFDM and FSM 0.72 (95%CI 0.61-0.80). The mean absolute difference in percent density between two FFDMs was 4.3% (95%CI 3.8-4.9) and between two FSMs 6.5% (95%CI 3.4-9.6). On average, percent density in the same woman was higher on FFDM than on FSM (difference 12.9% (95%CI 11.0-14.8)). Conclusion: When studying changes in mammographic density, it is important to compare two mammograms of the same type (FSM or FFDM). Even then, although intraclass correlation coefficients are high, the absolute differences in percent density are still of a magnitude that may influence detectability of true changes in mammographic density. Citation Format: Mariëtte Lokate, Marleen Emaus, Michiel Kallenberg, Marije Bakker, Nico Karssemeijer, Wouter Veldhuis, Petra Peeters, Carla van Gils. Inter-scan reproducibility of mammographic density measurements. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A116.

Application of Light Refractive Tomography for Reconstructing Ultrasound Fields in Various Media

Abstract This paper describes an optical measurement technique, referred to as light refractive tomography (LRT), which enables noninvasive measurement of ultrasound pressure fields in water. The pressure field arising from a cylindrically focused ultrasound transducer is measured separately by means of LRT and hydrophone. Good agreement is achieved between the results obtained by these two different methods. After that, LRT is extended and applied to the reconstruction of density variations in a PMMA block induced by ultrasound. The results appear plausible, however, a quantitative verification is currently still missing, since we know of no other published methods succeeding so far in the measurement of density change in solids induced by ultrasound.

Electrical resistivity method for the measurement of density changes near a probe

In order to investigate changes in porosity in saturated silica sand, an electrical resistivity probe for physical model testing was developed. For non-conducting particles, electrical resistivity measurements in porous media actually measure the resistivity of the pore water, changes of which are directly related to porosity change. The sensor has been integrated in a measurement probe and a model pile to measure density changes continuously during penetration. This first implementation used in the geotechnical centrifuge shows the feasibility of the method, although the initial results also show some systematic errors resulting from the construction of the probe and the measurement method itself.

Rapid species displacement during the invasion of Florida by the tropical house gecko Hemidactylus mabouia

There is considerable interest in understanding how invasive species disperse across landscapes, and how they affect resident species. However, quantifying these processes using mark recapture or manipulative experiments can be time consuming and costly. A different approach is to study density changes across a broader landscape, and take advantage of naturally existing replicate locations that are imperfect, but plentiful. We documented sites of recent colonization and measured density changes in the invasive gecko Hemidactylus mabouia and the prior resident gecko Hemidactylus garnotii in Florida. We surveyed geckos at 398 locations from 19 regional sites distributed across central and southern Florida. We documented changes in abundance through repeated censuses of 56 locations in areas of sympatry between 2001 and 2009. Complete displacement occurred in 10% increase in H. mabouia per year. There was evidence that H. mabouia reaches a higher carrying capacity than H. garnotii, which likely contributes to its competitive dominance. Changes in relative abundance within patches were consistent with a density dependent mechanism of displacement, suggesting the decline of H. garnotii is functionally linked to increases in H. mabouia abundance, which allows us to rule out coincidental factors not directly associated with H. mabouia. However, simulations showed that even highly asymmetric differences in carrying capacity and competitive ability were not sufficient to account for the rapid displacement we observed. We conclude that mechanisms other than resource competition must be at work to drive species displacement in this system.

Influence of thermal and radiation effects on microstructural and mechanical properties of Nb–1Zr

The microstructural changes and corresponding effects on mechanical properties, electrical resistivity and density of Nb–1Zr were examined following neutron irradiation up to 1.8 dpa at temperatures of 1073, 1223 and 1373 K and compared with material thermally aged for similar exposure times of ∼1100 h. Thermally driven changes in the development of intragranular and grain boundary precipitate phases showed a greater influence on mechanical and physical properties compared to irradiation-induced defects for the examined conditions. Initial formation of the zirconium oxide precipitates was identified as cubic structured plates following a Baker–Nutting orientation relationship to the β-Nb matrix, with particles developing a monoclinic structure on further growth. Tensile properties of the Nb–1Zr samples showed increased strength and reduced elongation following aging and irradiation below 1373 K, with the largest tensile and hardness increases following aging at 1098 K. Tensile properties at 1373 K for the aged and irradiated samples were similar to that of the as-annealed material. Total elongation was lower in the aged material due to a strain hardening response, rather than a weak strain softening observed in the irradiated materials due in part to an irregular distribution of the precipitates in the irradiated materials. Though intergranular fracture surfaces were observed on the 1248 K aged tensile specimens, the aged and irradiated material showed uniform elongations >3% and total elongation >12% for all conditions tested. Cavity formation was observed in material irradiated to 0.9 dpa at 1073 and 1223 K. However, since void densities were estimated to be below 3 × 10 17 m −3 these voids contributed little to either mechanical strengthening of the material or measured density changes.

Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine

Backgrounds and purposeThe main objectives of the present study were (i) to measure density changes of activated microglia and the peripheral benzodiazepine receptor/translocator protein (TSPO) system during normal ageing in the human brain with positron emission tomography (PET) using the TSPO molecular imaging biomarker [11C]vinpocetine and (ii) to compare the level and pattern of TSPO in Alzheimer (AD) patients with age matched healthy subjects, in order to assess the biomarker's usefulness as a diagnostic imaging marker in normal (ageing) and pathological (AD) up-regulation of microglia. Methods and subjectsPET measurements were made in healthy volunteers, aged between 25 and 78years, and AD patients, aged between 67 and 82years, using [11C]vinpocetine as the tracer. Global and regional quantitative parameters of tracer uptake and binding, including time activity curves (TAC) of standard uptake values (%SUV), binding affinity parameters, intensity spectrum and homogeneity of the uptake distribution were measured and analysed. ResultsBoth %SUV and binding values increased with age linearly in the whole brain and in all brain regions. There were no significant differences between the %SUV values of the AD patients and age matched control subjects. There were, however, significant differences in %SUV values in a large number of brain regions between young subjects and old subjects, as well as young subjects and AD patients. The intensity spectrum analysis and homogeneity analysis of the voxel data show that the homogeneity of the %SUV values decreases with ageing and during the disease, whereas the centre of the intensity spectrum is shifted to higher %SUV values. These data indicate an inhomogeneous up-regulation of the TSPO system during ageing and AD. These changes were significant between the group of young subjects and old subjects, as well as young subjects and AD patients, but not between old subjects and AD patients. ConclusionsThe present data indicate that [11C]vinpocetine may serve as a molecular imaging biomarker of the activity of the TSPO system and, consequently, of the up-regulation of microglia during ageing and in neuroinflammatory diseases. However, the global and regional brain %SUV values between AD patients and age matched controls are not different from each other. The disease specific changes, measured with [11C]vinpocetine in AD, are significantly different from those measured in age matched controls only if the inhomogeneities in the uptake pattern are explored with advanced mathematical techniques. For this reason, PET studies using [11C]vinpocetine, as molecular imaging biomarker, can efficiently visualise the activation of microglia and the up-regulation of TSPO during ageing and in diseased brains with the help of an appropriate inhomogeneity analysis of the radioligand's brain uptake pattern.

Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1.

Abstract Abstract #61 Background:&amp;#x2028; Numerous studies have documented the importance of mammographic breast density as a risk factor for breast cancer. It has the highest attributable risk of all currently known risk factors, and is modifiable. For mammographic density to be considered a biomarker, however, one would have to demonstrate that the risk reduction induced by a preventive intervention can be predicted by change in density, and that those who experience the largest change are most likely to have benefited. In the IBIS-1 study, tamoxifen reduced the risk of breast cancer by about 40% (Cuzick, et al JNCI 2007). Here we focus on whether the change in breast density after 12-18 months of prophylactic treatment predicts the subsequent impact of tamoxifen on the development of breast cancer.&amp;#x2028; Material and Methods:&amp;#x2028; The entry and 12-18 month mammograms for 120 UK breast cancer cases and 943 controls (women who had not developed breast cancer) who were participants in IBIS-1 were retrieved and mammographic density visually assessed (as a percentage of the total breast area) by a consultant radiologist (RW) using a semi-continuous 21-point categorical scale (0,5, 10,…, 100). Using logistic regression we assessed the univariate and multivariate effects of treatment, mammographic density (change over the first 12-18 months on treatment and at entry), anthropometric, hormonal and familial factors on the risk of developing breast cancer. All analyses were unmatched but adjusted for age at entry to the study. Sub-analyses were performed on the placebo and tamoxifen arms separately.&amp;#x2028; Results:&amp;#x2028; Mammographic density at entry, BMI, breast cancer risk (from the Cuzick-Tyrer model) and change in density during the first 12-18 months of treatment were all significant in the multivariate model. In the tamoxifen arm (N=504, 48 cases and 456 controls), only change in mammographic density was significant (P = 0.05). For the 46% of women in the tamoxifen arm whose density reduced by 10% or more, the risk of breast cancer was reduced by 52% relative to the control group (P = 0.01) while for the 54% of women whose density was not reduced by 10 % there was only a non-significant 8% reduction in breast cancer risk.&amp;#x2028; Discussion:&amp;#x2028; Our findings suggest that the impact of tamoxifen on risk reduction is predictable by the changes it induces on breast density after 12-18 months of treatment. Changes in breast density may therefore constitute an early indicator of treatment efficacy, which would be useful for the evaluation of new chemoprevention therapies. Furthermore, by measuring density changes between baseline and initial follow up mammograms in high risk women receiving tamoxifen, it may be possible to determine which women are actually benefiting from the intervention (and should therefore continue treatment), and those who might benefit more from alternative risk reducing strategies. These findings need confirmation in an independent study. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 61.

Systematics of compression of hard materials

Hard materials have the remarkable property that relatively little internal energy of shock compression is deposited as temperature and associated thermal pressure. As a result, the Hugoniot curve is nearly coincident with the 0-K isotherm. Since the isentrope is intermediate between isotherm and Hugoniot, all three curves of a given hard material are nearly coincident. Published data for diamond and Gd3Ga5O12 (GGG) show this to be the case up to 600 GPa and 80 GPa, respectively. Above 100 GPa on the Hugoniot the incompressibilities, defined to be the derivative of pressure with respect to compression, of GGG, other oxides and even CaF2 are significantly greater than that of diamond. In fact, above 100 GPa CaF2 might well be the least compressible of any known material. Little EOS data of weakly compressible materials have been measured in a diamond anvil cell (DAC) above a few tens of GPa at 300 K because these materials often become amorphous, which means density in a DAC cannot be measured by X-ray diffraction. Amorphization suggests the onset of a sluggish phase transition. On the other hand, Hugoniot experiments readily measure density changes caused by compression and phase transitions independent of material structure. Hugoniots of weakly compressible materials suggest experiments to determine structures and compressibilities in laser-heated DACs at 100 GPa pressures, as has been done with TiO2 and perovskite, and Hugoniot data might provide estimates of compressions of oxides representative of the deep interiors of rocky planets in other solar systems.