Visualization of colorectal polyps with spiral CT colography: evaluation of processing parameters with perspective volume rendering

PURPOSE: To evaluate two key processing steps for detection of colon polyps with spiral computed tomographic (CT) colography with perspective volume rendering (PVR): image reconstruction and opacity assignment of the attenuation data. MATERIALS AND METHODS: Spiral CT was performed in 10 patients with known polyps confirmed at colonoscopy, and detailed quantitative analyses were performed of data obtained in four. First, anatomic fidelity of three-dimensional (3D) images generated from two-dimensional (2D) source images with equal voxel dimensions (87%-90% overlap) was compared with 3D images generated from 2D source images with unequal voxel dimensions (0%-80% overlap). Next, the relative dimensions of colorectal polyps to adjacent structures were evaluated for various opacity threshold settings. Then, step and sigmoidal opacity functions were compared with respect to image smoothness and edge sharpness. RESULTS: PVR images generated after interpolation of image data reconstructed with at least 60% overlap were equivalent in image quality to PVR images generated from source images with equal voxel dimensions. Relative polyp-to-haustral fold dimensions demonstrated substantial distortions with opacity thresholds below -700 HU. The 3D PVR images generated with the sigmoidal opacity function were significantly smoother than those generated with the step opacity function (paired t test, P < .02), with small differences noted in edge sharpness. CONCLUSION: Use of highly overlapping source images (87%-90%) was not necessary to generate 3D PVR images of colorectal polyps. Image artifacts were suppressed with use of an appropriate opacity threshold and a sigmoidal opacity function without substantial loss in edge sharpness.     

Activation of Notch3 in Renal Tubular Cells Leads to Progressive Cystic Kidney Disease

Background: Polycystic kidney disease (PKD) is a genetic disorder affecting millions of people worldwide that is characterized by fluid-filled cysts and leads to end-stage renal disease (ESRD). The hallmarks of PKD are proliferation and dedifferentiation of tubular epithelial cells, cellular processes known to be regulated by Notch signaling. Methods: We found increased Notch3 expression in human PKD and renal cell carcinoma biopsies. To obtain insight into the underlying mechanisms and the functional consequences of this abnormal expression, we developed a transgenic mouse model with conditional overexpression of the intracellular Notch3 (ICN3) domain specifically in renal tubules. We evaluated the alterations in renal function (creatininemia, BUN) and structure (cysts, fibrosis, inflammation) and measured the expression of several genes involved in Notch signaling and the mechanisms of inflammation, proliferation, dedifferentiation, fibrosis, injury, apoptosis and regeneration. Results: After one month of ICN3 overexpression, kidneys were larger with tubules grossly enlarged in diameter, with cell hypertrophy and hyperplasia, exclusively in the outer stripe of the outer medulla. After three months, mice developed numerous cysts in proximal and distal tubules. The cysts had variable sizes and were lined with a single- or multilayered, flattened, cuboid or columnar epithelium. This resulted in epithelial hyperplasia, which was observed as protrusions into the cystic lumen in some of the renal cysts. The pre-cystic and cystic epithelium showed increased expression of cytoskeletal filaments and markers of epithelial injury and dedifferentiation. Additionally, the epithelium showed increased proliferation with an aberrant orientation of the mitotic spindle. These phenotypic tubular alterations led to progressive interstitial inflammation and fibrosis. Conclusions: In summary, Notch3 signaling promoted tubular cell proliferation, the alignment of cell division, dedifferentiation and hyperplasia, leading to cystic kidney diseases and pre-neoplastic lesions.     

Partitioned optimization of complex queries

Performing complex analysis on top of massive data stores is essential to most modern enterprises and organizations and requires significant aggregation over different attribute sets (dimensions) of the participating relations. Such queries may take hours or days, a time period unacceptable in most cases. As a result, it is important to study these queries and identify special frequent cases that can be evaluated with specialized algorithms. Understanding complex aggregate queries leads to better execution plans and, consequently, performance.     

Visual language and software development environment for image processing

The Khoros system integrates multiple user interface modes, code generators, instructional aids, data visualization, and information processing to produce a comprehensive image processing research tool. This system can easily be tailored to other application domains because the tools of the system can modify themselves as well as the system. This attribute is important in a system that is designed to be extensible and portable. The Khoros infrastructure consists of three major components: a high-level user interface specification, methods of software development embedded in a code generation tool set, and an interoperable data exchange format and algorithm library. These basic facilities have been used to build a set of applications for performing image processing research, algorithm development, and data visualization. One of the most powerful features of the system is its high-level abstract visual language. Khoros is a successful demonstration of how development programming, end-user applications programming, information processing, data display, instruction, documentation, and maintenance can be integrated to build a state-of-the-art image/data processing and visualization software environment.     

Nitric oxide inhibition induces early activation of type I collagen gene in renal resistance vessels and glomeruli in transgenic mice. Role of endothelin

Hypertension is often associated with the development of nephroangio- and glomerulo-sclerosis. This pathophysiological process is due to increased extracellular matrix protein, particularly type I collagen, accumulation. This study investigated whether nitric oxide (NO) synthesis is involved in the mechanism(s) regulating activation of the collagen I gene in afferent arterioles and glomeruli. Experiments were performed on transgenic mice harboring the luciferase gene under the control of the collagen I-alpha2 chain promoter [procolalpha2(I)]. Measurements of luciferase activity provide highly sensitive estimates of collagen I gene activation. NO synthesis was inhibited by NG-nitro-L-arginine methyl ester (L-NAME) (20 mg/kg per day) for a period of up to 14 wk. Systolic blood pressure was increased after 6 wk of treatment (117+/-2 versus 129+/-2 mmHg, P < 0.01) and reached a plateau after 10 wk (around 160 mmHg). Luciferase activity was increased in freshly isolated afferent arterioles and glomeruli as early as week 4 of L-NAME treatment (150 and 200% of baseline, P < 0.01, respectively). The activation of procolalpha2(I) became more pronounced with time, and at 14 wk increased four- and tenfold compared with controls in afferent arterioles and glomeruli, respectively (P < 0.001). In contrast, luciferase activity remained unchanged in aorta and heart up to 8 wk and was increased thereafter. Increased histochemical staining for extracellular matrix deposition, and particularly of collagen I, was detected in afferent arterioles and glomeruli after 10 wk of L-NAME treatment. This fibrogenic process was accompanied by an increased urinary excretion rate of endothelin. In separate experiments, the stimulatory effect of L-NAME on collagen I gene activation was abolished when animals were treated with bosentan, an endothelin receptor antagonist. Similarly, bosentan reduced the increased extracellular matrix deposition in afferent arterioles and glomeruli during NO inhibition. Interestingly, bosentan had no effect on the L-NAME- induced increase of systolic pressure. These data indicate that NO inhibition induces an early activation of the collagen I gene in afferent arterioles and glomeruli. This activation in the kidney precedes the increase in blood pressure and the procolalpha2(I) activation in heart and aorta, suggesting a specific renal effect of NO blockade on collagen I gene expression that is independent of increased blood pressure and, at least partly, mediated through stimulation of the endothelin receptor. Use of procolalpha2(I) transgenic mice provides a novel and efficient model to study the pathophysiological mechanism(s) regulating renal fibrosis.     

Clarion cochlear implant: short-term effects on voice parameters

The effect of acetylcholine on the neurointermediate lobe beta-endorphin secretion was studied in the neonatal and in the adult rat in vitro. Acetylcholine stimulated beta-endorphin secretion from the 2-day- and 5-day-old neurointermediate lobe, the effect was dose dependent and more pronounced in the presence of the cholinesterase inhibitor eserine. The 10-day-, the 21-day-old and the adult rat neurointermediate lobes did not respond to acetylcholine, even in the presence of eserine. Basal beta-endorphin secretion was elevated by the D2 receptor antagonist sulpiride, but acetylcholine was without effect in the 10-day-old and in the adult neurointermediate lobe even after dopamine receptor blockade. The beta-endorphin stimulatory response to acetylcholine was diminished by the M1 muscarinic receptor antagonist pirenzepine and blocked by the M3 > M1 antagonist 4-diamino-phenyl-piperidine (4-DAMP). The selective M2 antagonist methoctramine and nicotine had no effect. These data indicate that the neurointermediate lobe beta-endorphin secretion is under special muscarinic cholinergic regulation for a relatively short time after birth. The disappearance of this stimulatory cholinergic effect in later life might be due to changes in the intracellular secretory machinery in the IL and/or to the uncoupling of the cholinergic receptors from the intracellular signal transduction system(s) responsible for the stimulated secretion in the rat melanotrope cells.