FDG uptake heterogeneity in FIGO IIb cervical carcinoma does not predict pelvic lymph node involvement

TRANSLATIONAL RELEVANCE: Many types of cancer are located and assessed via positron emission tomography (PET) using the 18F-fluorodeoxyglucose (FDG) radiotracer of glucose uptake. There is rapidly increasing interest in exploiting the intra-tumor heterogeneity observed in these FDG-PET images as an indicator of disease outcome. If this image heterogeneity is of genuine prognostic value, then it either correlates to known prognostic factors, such as tumor stage, or it indicates some as yet unknown tumor quality. Therefore, the first step in demonstrating the clinical usefulness of image heterogeneity is to explore the dependence of image heterogeneity metrics upon established prognostic indicators and other clinically interesting factors. If it is shown that image heterogeneity is merely a surrogate for other important tumor properties or variations in patient populations, then the theoretical value of quantified biological heterogeneity may not yet translate into the clinic given current imaging technology. PURPOSE: We explore the relation between pelvic lymph node status at diagnosis and the visually evident uptake heterogeneity often observed in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images of cervical carcinomas. EXPERIMENTAL DESIGN: We retrospectively studied the FDG-PET images of 47 node negative and 38 node positive patients, each having FIGO stage IIb tumors with squamous cell histology. Imaged tumors were segmented using 40% of the maximum tumor uptake as the tumor-defining threshold and then converted into sets of three-dimensional coordinates. We employed the sphericity, extent, Shannon entropy (S) and the accrued deviation from smoothest gradients (ζ) as image heterogeneity metrics. We analyze these metrics within tumor volume strata via: the Kolmogorov-Smirnov test, principal component analysis and contingency tables. RESULTS: We found no statistically significant difference between the positive and negative lymph node groups for any one metric or plausible combinations thereof. Additionally, we observed that S is strongly dependent upon tumor volume and that ζ moderately correlates with mean FDG uptake. CONCLUSIONS: FDG uptake heterogeneity did not indicate patients with differing prognoses. Apparent heterogeneity differences between clinical groups may be an artifact arising from either the dependence of some image metrics upon other factors such as tumor volume or upon the underlying variations in the patient populations compared

Quantification of heterogeneity observed in medical images

BACKGROUND: There has been much recent interest in the quantification of visually evident heterogeneity within functional grayscale medical images, such as those obtained via magnetic resonance or positron emission tomography. In the case of images of cancerous tumors, variations in grayscale intensity imply variations in crucial tumor biology. Despite these considerable clinical implications, there is as yet no standardized method for measuring the heterogeneity observed via these imaging modalities. METHODS: In this work, we motivate and derive a statistical measure of image heterogeneity. This statistic measures the distance-dependent average deviation from the smoothest intensity gradation feasible. We show how this statistic may be used to automatically rank images of in vivo human tumors in order of increasing heterogeneity. We test this method against the current practice of ranking images via expert visual inspection. RESULTS: We find that this statistic provides a means of heterogeneity quantification beyond that given by other statistics traditionally used for the same purpose. We demonstrate the effect of tumor shape upon our ranking method and find the method applicable to a wide variety of clinically relevant tumor images. We find that the automated heterogeneity rankings agree very closely with those performed visually by experts. CONCLUSIONS: These results indicate that our automated method may be used reliably to rank, in order of increasing heterogeneity, tumor images whether or not object shape is considered to contribute to that heterogeneity. Automated heterogeneity ranking yields objective results which are more consistent than visual rankings. Reducing variability in image interpretation will enable more researchers to better study potential clinical implications of observed tumor heterogeneity

Development of fuel cell electrodes, Electrode improvement and life testing, tasks 1 and 3 Final report, 30 Jun. 1966 - 30 Apr. 1968

Volt-ampere characteristics improvement and life testing of electrodes for hydrogen oxygen fuel cell

Development Of Third Harmonic Generation As A Short Pulse Probe Of Shock Heated Material

We are studying high-pressure laser produced shock waves in silicon (100). To examine the material dynamics, we are performing pump-probe style experiments utilizing 600 ps and 40 fs laser pulses from a Ti:sapphire laser. Two-dimensional interferometry reveals information about the shock breakout, while third harmonic light generated at the rear surface is used to infer the crystalline state of the material as a function of time. Sustained third harmonic generation (THG) during a similar to 100 kbar shock breakout indicate that the rear surface remains crystalline for at least 3 ns. However, a decrease in THG during a similar to 300 kbar shock breakout suggests a different behavior, which could include a change in crystalline structure.Mechanical Engineerin

Laser-Induced Spall Of Aluminum And Aluminum Alloys At High Strain Rates

We conducted laser-induced spall experiments aimed at studying how a material's microstructure affects the tensile fracture characteristics at high strain rates (> 10(6) s(-1)). We used the Z-Beamlet Laser at Sandia National Laboratory to drive shocks and to measure the spall strength of aluminum targets with various microstructures. The targets were recrystallized, high-purity aluminum (Al-HP RX), recrystallized aluminum + 3 wt.% magnesium (Al-3Mg RX), and cold-worked aluminum + 3 wt.% magnesium (Al-3Mg CW). The Al-3Mg RX and Al-3Mg CW are used to explore the roles that solid-solution alloying and cold-work strengthening play in the spall process. Using a line-VISAR (Velocity Interferometer System for Any Reflector) and analysis of recovered samples, we were able to measure spall strength and determine failure morphology in these targets. We find that the spall strength is highest for Al-HP RX. Analysis reveals that material grain size plays a vital role in the fracture morphology and spall strength results.Mechanical Engineerin

Activation of miR-9 by human papillomavirus in cervical cancer

Cervical cancer is the third most common cancer in women worldwide, leading to about 300,000 deaths each year. Most cervical cancers are caused by human papillomavirus (HPV) infection. However, persistent transcriptional activity of HPV oncogenes, which indicates active roles of HPV in cervical cancer maintenance and progression, has not been well characterized. Using our recently developed assays for comprehensive profiling of HPV E6/E7 transcripts, we have detected transcriptional activities of 10 high-risk HPV strains from 87 of the 101 cervical tumors included in the analysis. These HPV-positive patients had significantly better survival outcome compared with HPV-negative patients, indicating HPV transcriptional activity as a favorable prognostic marker for cervical cancer. Furthermore, we have determined microRNA (miRNA) expression changes that were correlated with tumor HPV status. Our profiling and functional analyses identified miR-9 as the most activated miRNA by HPV E6 in a p53-independent manner. Further target validation and functional studies showed that HPV-induced miR-9 activation led to significantly increased cell motility by downregulating multiple gene targets involved in cell migration. Thus, our work helps to understand the molecular mechanisms as well as identify potential therapeutic targets for cervical cancer and other HPV-induced cancers

Defining spatial housing submarkets: Exploring the case for expert delineated boundaries

Although there are numerous reasons for real estate analysts to construct spatial housing submarkets, there is little clarity about how this might best be done in practice. The existing literature offers a variety of techniques including those based on principal components analysis, cluster analysis and a range of other statistical procedures. This paper asks whether, given their market expertise and their role in disseminating information, shaping search patterns and informing bid formation, real estate agents might offer an effective but less data intensive method of submarket construction. The empirical research is based on an experiment that compares the predictive of different sets of submarket boundaries constructed by using either standard statistical methods or through consultation with real estate agents and other market analysts. The analysis draws on housing transactions data from Istanbul, Turkey. While the results do not demonstrate the outright superiority of any single method, they do suggest that expert-defined boundaries tend to perform at least as well as alternative construction techniques. Importantly, the results suggest that agent-based methods for delineating submarket boundaries might be used with a degree of confidence by real estate analysts and planners in market contexts where rich micro-datasets are not readily available. This has been one of the constraints internationally on wider adoption of submarket boundaries as an analytical tool