To analyze brightness, contrast, and color balance of digital versus film retinal images in a multicenter clinical trial, to propose a model image from exemplars, and to optimize both image types for ...evaluation of age-related macular degeneration (AMD).
The Age-Related Eye Disease Study 2 (AREDS2) is enrolling subjects from 90 clinics, with three quarters of them using digital and one quarter using film cameras. Image brightness (B), contrast (C), and color balance (CB) were measured with three-color luminance histograms. First, the exemplars (film and digital) from expert groups were analyzed, and an AMD-oriented model was constructed. Second, the impact of B/C/CB on the appearance of typical AMD abnormalities was analyzed. Third, B/C/CB in AREDS2 images were compared between film (156 eyes) and digital (605 eyes), and against the model. Fourth, suboptimal images were enhanced by adjusting B/C/CB to bring them into accord with model parameters.
Exemplar images had similar brightness, contrast, and color balance, supporting an image model. Varying a specimen image through a wide range of B/C/CB revealed greatest contrast of drusen and pigment abnormalities against normal retinal pigment epithelium with the model parameters. AREDS2 digital images were more variable than film, with lower correspondence to our model. Ten percent of digital were too dim and 19% too bright (oversaturated), versus 1% and 4% of film, respectively. On average, digital had lower green channel contrast (giving less retinal detail) than film. Overly red color balance (weaker green) was observed in 23% of digital versus 8% of film. About half of digital (but fewer film) images required enhancement before AMD grading. After optimization of both image types, AREDS2 image quality was judged as good as that in AREDS (all film).
A histogram-based model, derived from exemplars, provides a pragmatic guide for image analysis and enhancement. In AREDS2, the best digital images matched the best film. Overall, however, digital provided lower contrast of retinal detail. Digital images taken with higher G-to-R ratio showed better brightness and contrast management. Optimization of images in the multicenter study helps standardize documentation of AMD (ClinicalTrials.gov NCT00345176).
Changes in retinal vascular caliber measured from digital color fundus photographs have been independently associated with systemic outcomes in epidemiologic studies, but the effect of image ...resolution and compression on vascular measurements has not been previously evaluated.
To explore image compression, 40 natively digital fundus images were selected with good photo quality, high spatial resolution, and no previous image compression. Using Adobe Photoshop, these images were compressed at progressively higher levels up to 147:1, and then retinal vascular caliber was measured at each level using semiautomated software. To examine resolution, 40 fundus photographs acquired on high-resolution film were scanned with settings corresponding to 10, 7, 5, 3, and 1 megapixel fundus cameras. After adjusting for scale factor, vascular caliber was measured at each level of resolution. Data were analyzed by comparing the calculated central retinal arteriole equivalent (CRAE) and the central retinal venular equivalent (CRVE) of the original and altered images, using repeated measures ANOVA.
CRAE became significantly wider with increasing levels of compression at the 25:1 threshold (~1 μm wider, P < 0.001) and was ~5 μm wider with 147:1 compression. CRVE also increased, but less than CRAE. Using 7 (megapixel)-MP resolution as the standard, CRVE was significantly narrower at the 5-MP simulation (~2 μm, P < 0.001) and was ~12 μm narrower at the 1-MP simulation. CRAE also decreased, but less than CRVE.
Increasing digital image file compression and decreasing fundus image spatial resolution led to skewed measurements of the retinal vascular caliber.
Studies have used central retinal arteriolar (CRAE) and central retinal venular (CRVE) calibers, measured from images produced with computerized image analysis, to detect risk factors for systemic ...diseases. The authors explored suboptimal image focus as a possible contributing factor to artificially larger vascular caliber measurements.
From the reading center image collections, 30 digital retinal images were selected for optimum quality. Image analysis software was used to derive nine progressively blurred versions of the originals. IVAN measurement software was used to measure CRAE and CRVE in the original and the blurred series derived from them. To check the adequacy of the simulation, progressively defocused series of images were taken of several volunteers.
For CRAE, each level of simulated blurring produced a statically significant increase in apparent vessel caliber from the original (P<0.01, Wilcoxon signed rank test). For an average CRAE of 160 μm, mean broadening with minimal/moderate/severe blurring was 3 μm/12 μm/33 μm. For CRVE, every blurring level beyond the first was found to be significant (P<0.01). From an average CRVE of 200 μm, mean broadening ranged from 0 to 11 μm with minimal to severe blurring. Analysis of the progressively defocused series taken of volunteers yielded similar results overall.
Suboptimal focus can result in erroneously larger vessel caliber measurements. Slight blurring has a minimal effect, but more severe blurring has a progressively greater effect.
Purpose: Specific activating mutations within the epidermal growth factor receptor ( EGFR ) identify a subset of non–small cell lung cancers with dramatic sensitivity to the specific tyrosine kinase ...inhibitors (TKI),
gefitinib and erlotinib. Despite the abundant expression of EGFR protein in a broad range of epithelial cancers, EGFR mutations have not been reported in a substantial fraction of other cancers. Given recent reports of TKI-responsive cases
of esophageal and pancreatic cancer, this study was designed to determine the prevalence of EGFR mutations in these gastrointestinal cancers.
Experimental Design: We sequenced exons 18 to 21 of EGFR from 21 cases of Barrett's esophagus, 5 cases of high-grade esophageal dysplasia, 17 cases of esophageal adenocarcinoma,
and 55 cases of pancreatic adenocarcinoma. Subsets of esophageal ( n = 7) and pancreatic cancer cases ( n = 5) were obtained from patients who were subsequently treated with gefitinib or erlotinib-capecitabine, respectively.
Results: Mutations of EGFR were identified in two esophageal cancers (11.7%), three cases of Barrett's esophagus (14.2%), and two pancreatic cancers
(3.6%). The mutations consisted of the recurrent missense L858R and in-frame deletion delE746-A750, previously characterized
as activating EGFR mutations in non–small cell lung cancer. We also identified the TKI drug resistance–associated EGFR T790M mutation in an untreated case of Barrett's esophagus and the corresponding adenocarcinoma.
Conclusion: The presence of activating mutations within EGFR in both esophageal and pancreatic adenocarcinomas defines a previously unrecognized subset of gastrointestinal tumors in
which EGFR signaling may play an important biological role. EGFR mutations in premalignant lesions of Barrett's esophagus also point to these as an early event in transformation of the esophageal
epithelium. The role of genotype-directed TKI therapy should be tested in prospective clinical trials.
The secretion of placental lactogen begins early in pregnancy. Previous studies indicate that rat placental lactogen (rPL) is secreted from Day 8 of pregnancy and that it is luteolytic as well as ...luteotrophic. This study establishes the onset of both the luteotrophic and the luteolytic effects of placental lactogen in pregnant rats subject to timed hypophysectomy. Pregnancy was preserved in all groups with the administration of dydrogesterone (9 beta, 10 alpha-pregna4,6-diene-3, 20 dione), a progesterone analog, and diethylstilbestrol, an estrogen analog. Plasma progesterone and 20 alpha-hydroxypregn-4-ene-3-one (20-OHP) were measured in serial serum samples by RIA. The data indicate that rPL is secreted as early in pregnancy as the seventh day. Rats hypophysectomized on Day 6 of pregnancy or later had ovaries that contained corpora lutea that secreted increasing quantities of progesterone during pregnancy. On Day 16 serum progesterone values were lowest in animals operated on Days 4 and 5 compared to animals operated on Days 6 or 8. The 20-OHP serum values from animals operated on Days 4 and 5 declined steadily from Day 8 to Day 16. These findings indicate progestational incompetency, which was confirmed morphologically. Thus, rPL secretion begins by Day 7 and it is both luteotrophic and luteolytic.
The ARIES-RS tokamak is a conceptual, D–T-burning 1000 MWe power plant. As with earlier ARIES design studies, the final design of ARIES-RS was obtained in a self-consistent manner using the best ...available physics and engineering models. Detailed analyses of individual systems together with system interfaces and interactions were incorporated into the ARIES systems code in order to assure self-consistency and to optimize towards the lowest cost system. The ARIES-RS design operates with a reversed-shear plasma and employs a moderate aspect ratio (
A=4.0). The plasma current is relatively low (
I
p=11.32 MA) and bootstrap current fraction is high (
f
BC=0.88). Consequently, the auxiliary power required for RF current drive is relatively low (∼80 MW). At the same time, the average toroidal beta is high (
β=5%), providing power densities near practical engineering limits (the peak neutron wall loading is 5.7 MW m
−2). The toroidal-field (TF) coil system is designed with relatively `conventional' materials (Nb
3Sn and NbTi conductor with 316SS structures), and is operated at a design limit of ∼16 T at the coil in order to optimize the design point. The ARIES-RS design uses a self-cooled lithium blanket with vanadium alloy as the structural material. The V-alloy has low activation, low afterheat, high temperature capability and can handle high heat flux. A self-cooled liquid lithium blanket is simple, and with the development of an insulating coating, has low operating pressure. Also, this blanket gives excellent neutronics performance. Detailed analysis has been performed to minimize the cost and maximize the performance of the blanket and shield. One of the distinctive features of this design is the integration of the first wall, blanket, parts of the shield, divertor and stability shells into an integral unit within each sector. The maintenance scheme consists of horizontal removal of entire sectors. Prior to the initiation of the ARIES-RS study, a set of top-level requirements and goals for fusion demonstration and commercial power plants was evolved in collaboration with representatives from US electric utilities and from industry. The degree to which ARIES-RS reached these requirements and goals and the necessary trade-offs are described and the high-leverage areas and key R&D items are presented.
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