Airway Segmentation and Centerline Extraction from Thoracic CT – Comparison of a New Method to State of the Art Commercialized Methods

Introduction

Our motivation is increased bronchoscopic diagnostic yield and optimized preparation, for navigated bronchoscopy. In navigated bronchoscopy, virtual 3D airway visualization is often used to guide a bronchoscopic tool to peripheral lesions, synchronized with the real time video bronchoscopy. Visualization during navigated bronchoscopy, the segmentation time and methods, differs. Time consumption and logistics are two essential aspects that need to be optimized when integrating such technologies in the interventional room. We compared three different approaches to obtain airway centerlines and surface.

Method

CT lung dataset of 17 patients were processed in Mimics (Materialize, Leuven, Belgium), which provides a Basic module and a Pulmonology module (beta version) (MPM), OsiriX (Pixmeo, Geneva, Switzerland) and our Tube Segmentation Framework (TSF) method. Both MPM and TSF were evaluated with reference segmentation. Automatic and manual settings allowed us to segment the airways and obtain 3D models as well as the centrelines in all datasets. We compared the different procedures by user interactions such as number of clicks needed to process the data and quantitative measures concerning the quality of the segmentation and centrelines such as total length of the branches, number of branches, number of generations, and volume of the 3D model.

Results

The TSF method was the most automatic, while the Mimics Pulmonology Module (MPM) and the Mimics Basic Module (MBM) resulted in the highest number of branches. MPM is the software which demands the least number of clicks to process the data. We found that the freely available OsiriX was less accurate compared to the other methods regarding segmentation results. However, the TSF method provided results fastest regarding number of clicks. The MPM was able to find the highest number of branches and generations. On the other hand, the TSF is fully automatic and it provides the user with both segmentation of the airways and the centerlines. Reference segmentation comparison averages and standard deviations for MPM and TSF correspond to literature.

Conclusion

The TSF is able to segment the airways and extract the centerlines in one single step. The number of branches found is lower for the TSF method than in Mimics. OsiriX demands the highest number of clicks to process the data, the segmentation is often sparse and extracting the centerline requires the use of another software system. Two of the software systems performed satisfactory with respect to be used in preprocessing CT images for navigated bronchoscopy, i.e. the TSF method and the MPM. According to reference segmentation both TSF and MPM are comparable with other segmentation methods. The level of automaticity and the resulting high number of branches plus the fact that both centerline and the surface of the airways were extracted, are requirements we considered particularly important. The in house method has the advantage of being an integrated part of a navigation platform for bronchoscopy, whilst the other methods can be considered preprocessing tools to a navigation system.     

An Efficient and Reliable Method of DNA Extraction from Meyna spinosa — A Traditional Medicinal Plant from North-East India

A simple, efficient and reliable CTAB method is standardized for genomic DNA isolation from fresh young leaves of a traditional medicinal plant Meyna spinosa. Key steps in the modified procedure include additional chloroform: isoamyl alcohol (24:1, v/v) extraction, addition of 4% PVP in the extraction buffer and an overnight isopropanol precipitation at room temperature. This procedure yields a high amount (46 μg DNA g^?1 fresh leaf tissue) of good quality DNA free from contaminants. The isolated DNA is suitable for digestion with EcoRI and HindIII restriction enzymes and can be used in other DNA manipulation techniques.     

Screening the Main Factors Affecting Extraction of the Antimicrobial Substance from Bacillus sp. fmbJ using the Plackett–Burman Method

Summary The Plackett–Burman screening method was utilized as a tool to evaluate the importance of the selected six factors, including methanol, ethanol, propanol, butanol, pH and time, which are relevant to the extraction of the antimicrobial substance produced by Bacillus sp. fmbJ. The main factors that affected the extraction of the antimicrobial substance were determined as methanol (P < 0.0001), ethanol (P < 0.0001), pH (P = 0.0032), and time (P < 0.0001) by using the JMP software. Within the test ranges, methanol, ethanol, and time showed a significant positive relativity to the total extracted amounts respectively; while pH had a significant negative effect. The maximum prediction profile indicated that the total extracted amounts for the antimicrobial substance would reach 50.21 mg/100 ml with 99.64% probability.     

Extraction of cartilage protein–polysaccharides with inorganic salt solutions

1. Bovine nasal cartilage was extracted with inorganic salt solutions of various ionic strengths. The efficiency of extraction of protein-polysaccharide from the tissue was determined for each extraction. The results confirm and enlarge earlier observations (Sajdera & Hascall, 1969). 2. The chloride salts of lanthanide metals extract high yields of protein-polysaccharide from the tissue at much lower concentrations than was achieved with univalent and bivalent salts. 3. The lanthanum salt of extracted protein-polysaccharide precipitates when the concentration of LaCl(3) is decreased. Precipitation is complete in the presence of 0.05m-LaCl(3). This finding is relevant to the interpretation of earlier observations on the effect of LaCl(3) on elastic recovery of articular cartilage after compression (Sokoloff, 1963). 4. A linear relationship was found between the concentration at which a particular salt is maximally effective in solubilizing protein-polysaccharide from the tissue and the enthalpy of hydration of the cation of the salt. On the basis of this relationship a hypothesis is proposed to explain the characteristic protein-polysaccharide-extraction profiles exhibited by inorganic salt solutions.     

Extraction of nuclear DNA from bone of skeletonized and fluid‐preserved museum specimens

Obtaining DNA sequences, particularly nuclear DNA, from museum specimens is challenging. We sequenced nuclear DNA from small bone fragments of skeletonized and fluid‐fixed museum specimens of squamate reptiles by using a forensic protocol developed for isolating DNA from human bones. The method yielded high quality nuclear DNA sequences from bones taken from 11 of 21 (52.4%) skeletonized or desiccated specimens, the oldest of which dated back to 1938, and 1 of 9 (11.1%) fluid‐preserved specimens, which was collected in 1957.     

Application of Oxathiaphospholane Method for the Synthesis of Oligodeoxyribonucleotide 5′-O-Conjugates

Abstract

2-Thiono-1,3,2-oxathiaphospholane derivatives of lipophilic alcohols including borneol, cholesterol, menthol and heptadecanol were synthesized and reacted with support-bound oligodeoxyribonucleotides containing free 5′-hydroxyl groups. The reaction is catalyzed by DBU and leads to oligodeoxyribonucleotide conjugates possessing a lipophilic alcohol residue bound at the 5′-end via a phosphorothioate linkage.     

Screening Plate Method for Detection of Bacterial β-Glucuronidase

For screening tests of bacterial beta-glucuronidase (EC 3.2.1.31) activity an agar plate (MUG plate) containing the enzyme substrate, 4-methylumbelliferyl-beta-D-glucuronide, was developed. In the presence of beta-glucuronidase, the strongly fluorescent 4-methylumbelliferone, which can be detected by ultraviolet light, was liberated. For tests of fastidious bacteria, the MUG-plate was enriched with supplements containing heat-labile growth factors without influencing the reaction. The plate was found to be suitable for screening tests. The sensitivity of the MUG-plate was determined by means of fluorimetric method. With the present method, beta-glucuronidase activities were demonstrated in some well-known beta-glucuronidae-producing microorganisms as well as in Bacteroides and Corynebacterium spp.     

FRACTURE OF THE METACARPAL SHAFT—A Method of Treatment

Anatomically, metacarpal fractures, when reduced, are not spontaneously stable. They require maintenance of this reduction because of the forces acting on the fragments. Closed methods of maintaining this reduction are ideal, but in selected cases, intramedullary fixation of the fracture, using the Kirschner wire, gives excellent results. The method under consideration does not disturb the fracture site itself, the Kirschner wire being introduced “blind.” Correct placement of the site of insertion of the wire, coupled with the rigid immobilization thus attained, gives excellent results in a high proportion of selected cases.     

DETERMINING DRUG SENSITIVITY—Use of the Gel Diffusion Method

A study was carried out to determine whether the double diffusion gel test when applied to the serum of patients with clear-cut penicillin reactions of various types, might be useful for demonstrating the presence of precipitating antibody. Results did not demonstrate the antibody.The difference in results with this test obtained by various workers was not explained by the observations in this study.Other approaches to determination of the mechanism of the penicillin reaction are discussed, and it is noted that the hemagglutination test, newly applied to the penicillin reaction problem, may be useful after further investigation.     

Novel Method for the Synthesis of 2′ -Phosphorylated Oligonucleotides

We have developed a new method for the preparation of oligodeoxyribonucleotides and oligo(2′-O-methylribonucleotides) that contain a 2′-phosphorylated ribonucleoside residue, and optimized it to avoid 2′ -3′ -isomerization and chain cleavage. Structures of the 2′ -phosphorylated oligonucleotides were confirmed by MALDI-TOF MS and enzymatic digestion, and the stability of their duplexes with DNA and RNA was investigated. 2′-Phosphorylated oligonucleotides may be useful intermediates for the introduction of various chemical groups for a wide range of applications.     

An Algorithm for Cladistics—Method of Minimal Parallel Evolution

The paper presented here is Concerned with the numerical cladisties. In consideration of the fact that the parallel evolution has close relation to the length of evolution graph, a new method of reconstructing evolutionary tree has been developed for the application and practice of cladistics. The procedure of the algorithm of the new method presented in Table I is similar to the method described in paper "An algorithm for cladistics method of maximal same step length". An essential step of the algorithm is how to decide the coefficient between two cladistic units (CTUs). A coefficient called parallel evolutionary coefficient between CTUp and CTUq is defined as follows: where the j is code of CTU and the i is code of character; E(p, q, i, j) is a function given by following expression: min (X_ij, Xpj)+(X_ij, Xqj)-2min(Xpj, Xqj) as Xij>min (Xpj, Xqj) E(p,q, i,j ) = 0 otherwise. where the X_ij is the ith row (CTU) jth colunm (Character) element of the data matrix. Because the method of minimal parallel evolution is closely related to the length of evolutionary graph, it is superior to the method of maximal same step length. A simple datum as an example for comparison shows that the method of minimal parallel evolution can arrive at a better result. But in some cases, we may combine one method with another and thus the coefficient should take following form: S(S_ij)=M·S (C) _ij-N·S(P) _ij in which S (C) _ij and S (P) _ij are the same step coefficients and the parallel evolution coefficient respectively, and the M and N are positive integers as a weightnumber being given in advance.     

Effect of α-Tocopherol and Culture Method on Reproduction of Turbatrix aceti

The effect of α-tocopherol on the reproductive capacity of the free-living nematode Turbatrix aceti was determined using three different culture methods: mass culture, pair culture. and single culture. Significant differences were observed between control and α-tocopherol cultured nematodes for all reproductive parameters measured. The reproductive period started at a significantly earlier time and the length of the reproductive period was significantly longer in α-tocopherol cultured nematodes. The average number of offspring was 34 in control cultures as compared to 55 in α-tocopherol cultures. The eggs of α-tocopherol cultured females showed a more regular outline and uniform distribution of yolk than did eggs from control females.     

Extraction and Characterization of α-Chitin and Chitosan from Six Different Aquatic Invertebrates

Chitin and chitosan were extracted from six different aquatic invertebrate species. Species dry weights varied between 5 % and 20 % chitin, and the chitosan productivity of these chitins varied between 66 % and 74 %. Chitin and chitosan structures were characterized by FTIR, TGA, XRD, and SEM. FTIR results showed that the chitins obtained from the organisms were observed in α form. Chitin thermal stabilities were in the order Ranatra linearis?>?Anax imperator?>?Hydrophilus piceus?>?Notonecta glauca?>?Agabus bipustulatus?>?Asellus aquaticus, and chitosan thermal stabilities in the order N. glauca?>?A. bipustulatus?>?A. imperator?>?R. linearis?>?H. piceus?>?A. aquaticus. The crystalline index values of chitins varied between 76.4 % and 90.6 %. Their surface morphology was examined by SEM, revealing nanofibre structures. These six aquatic invertebrate species with characterized chitin and chitosan structures may be used as alternative chitin and chitosan sources for various technological purposes.     

Application of a High Throughput Method of Biomarker Discovery to Improvement of the EarlyCDT?-Lung Test

Background

The National Lung Screening Trial showed that CT screening for lung cancer led to a 20% reduction in mortality. However, CT screening has a number of disadvantages including low specificity. A validated autoantibody assay is available commercially (EarlyCDT®-Lung) to aid in the early detection of lung cancer and risk stratification in patients with pulmonary nodules detected by CT.Recent advances in high throughput (HTP) cloning and expression methods have been developed into a discovery pipeline to identify biomarkers that detect autoantibodies. The aim of this study was to demonstrate the successful clinical application of this strategy to add to the EarlyCDT-Lung panel in order to improve its sensitivity and specificity (and hence positive predictive value, (PPV)).

Methods and Findings

Serum from two matched independent cohorts of lung cancer patients were used (n = 100 and n = 165). Sixty nine proteins were initially screened on an abridged HTP version of the autoantibody ELISA using protein prepared on small scale by a HTP expression and purification screen. Promising leads were produced in shake flask culture and tested on the full assay. These results were analyzed in combination with those from the EarlyCDT-Lung panel in order to provide a set of re-optimized cut-offs. Five proteins that still displayed cancer/normal differentiation were tested for reproducibility and validation on a second batch of protein and a separate patient cohort. Addition of these proteins resulted in an improvement in the sensitivity and specificity of the test from 38% and 86% to 49% and 93% respectively (PPV improvement from 1 in 16 to 1 in 7).

Conclusion

This is a practical example of the value of investing resources to develop a HTP technology. Such technology may lead to improvement in the clinical utility of the EarlyCDT­-Lung test, and so further aid the early detection of lung cancer.