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Biomedical subjects

David Gur

Publications and source records attributed to David Gur.

At least 55 records · Page 3Linked to original sources
PubMed2004

Generation of Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel vaccine candidates.

In a search for novel attenuated vaccine candidates for use against Yersinia pestis, the causative agent of plague, a signature-tagged mutagenesis strategy was used and optimized for a subcutaneously infected mouse model. A library of tagged mutants of the virulent Y. pestis Kimberley53 strain was generated. Screening of 300 mutants through two consecutive cycles resulted in selection of 16 mutant strains that were undetectable in spleens 48 h postinfection. Each of these mutants was evaluated in vivo by assays for competition against the wild-type strain and for virulence following inoculation of 100 CFU (equivalent to 100 50% lethal doses [LD50] of the wild type). A wide spectrum of attenuation was obtained, ranging from avirulent mutants exhibiting competition indices of 10(-5) to 10(-7) to virulent mutants exhibiting a delay in the mean time to death or mutants indistinguishable from the wild type in the two assays. Characterization of the phenotypes and genotypes of the selected mutants led to identification of virulence-associated genes coding for factors involved in global bacterial physiology (e.g., purH, purK, dnaE, and greA) or for hypothetical polypeptides, as well as for the virulence regulator gene lcrF. One of the avirulent mutant strains (LD50, >10(7) CFU) was found to be disrupted in the pcm locus, which is presumably involved in the bacterial response to environmental stress. This Kimberley53pcm mutant was superior to the EV76 live vaccine strain because it induced 10- to 100-fold-higher antibody titers to the protective V and F1 antigens and because it conferred efficacious protective immunity.

Animals↗
PubMed2004

Computer-aided detection schemes: the effect of limiting the number of cued regions in each case.

OBJECTIVE: We assessed performance changes of a mammographic computer-aided detection scheme when we restricted the maximum number of regions that could be identified (cued) as showing positive findings in each case. MATERIALS AND METHODS: A computer-aided detection scheme was applied to 500 cases (or 2,000 images), including 300 cases in which mammograms showed verified malignant masses. We evaluated the overall case-based performance of the scheme using a free-response receiver operating characteristic approach, and we measured detection sensitivity at a fixed false-positive detection rate of 0.4 per image after gradually reducing the maximum number of cued regions allowed for each case from seven to one. RESULTS: The original computer-aided detection scheme achieved a maximum case-based sensitivity of 97% at 3.3 false-positive detected regions per image. For a detection decision score set at 0.565, the scheme had a 79% (237/300) case-based sensitivity, with 0.4 false-positive detected regions per image. After limiting the number of maximum allowed cued regions per case, the false-positive rates decreased faster than the true-positive rates. At a maximum of two cued regions per case, the false-positive rate decreased from 0.4 to 0.21 per image, whereas detection sensitivity decreased from 237 to 220 masses. To maintain sensitivity at 79%, we reduced the detection decision score to as low as 0.36, which resulted in a reduction of false-positive detected regions from 0.4 to 0.3 per image and a reduction in region-based sensitivity from 66.1% to 61.4%. CONCLUSION: Limiting the maximum number of cued regions per case can improve the overall case-based performance of computer-aided detection schemes in mammography.

Breast Neoplasms↗
PubMed2004

Size and morphology of the trachea before and after lung volume reduction surgery.

OBJECTIVE: The purpose of this investigation was to determine the effect of lung volume reduction surgery on measured tracheal features. MATERIALS AND METHODS: Twenty-four male and 19 female patients with emphysema underwent lung volume reduction surgery, pulmonary function testing, and repeated CT. The tracheal air column was segmented from axial images. The sagittal and coronal dimensions of the intrathoracic trachea were determined. Tracheal morphology was quantified using the tracheal (coronal and sagittal dimensions) and circularity indexes. The results were compared with pulmonary function test results. RESULTS: Morphologic appearance of the intrathoracic trachea was consistent before and 3 months after surgery. The group means of the tracheal length, mean area, and volume were 78.60 mm (+/- 16.88 mm), 283.84 mm(2) (+/- 61.47 mm(2)), and 22.59 cm(3) (+/- 7.69 cm(3)), respectively, before surgery and 67.53 mm (+/- 15.78 mm), 309.12 mm(2) (+/- 79.83 mm(2)), and 20.99 cm(3) (+/- 7.27 cm(3)), respectively, after surgery (p < 0.05). Mean tracheal indexes were 0.85 (+/- 0.11) before surgery and 0.82 (+/- 0.04) after surgery (p < 0.01). Mean circularity indexes were 0.91 (+/- 0.03) before surgery and 0.90 (+/- 0.04) after surgery (p < 0.05). The size of the trachea was significantly correlated with lung volume before and after surgery (p < 0.05). The changes in tracheal features and changes in pulmonary function were not correlated (p > 0.05), except for tracheal area (p < 0.05). CONCLUSION: Our data suggest that tracheal dimensions reflect the severity of emphysema as reflected by increased lung volumes. Tracheal features were poor predictors of changes in postsurgical pulmonary function parameters evaluated in this preliminary study.

Female↗
PubMed2003

Automated lung segmentation in X-ray computed tomography: development and evaluation of a heuristic threshold-based scheme.

RATIONALE AND OBJECTIVES: To develop and evaluate a reliable, fully-automated lung segmentation scheme for application in X-ray computed tomography. MATERIALS AND METHODS: The automated scheme was heuristically developed using a slice-based, pixel-value threshold and two sets of classification rules. Features used in the rules include size, circularity, and location. The segmentation scheme operates slice-by-slice and performs three key operations: (1) image preprocessing to remove background pixels, (2) computation and application of a pixel-value threshold to identify lung tissue, and (3) refinement of the initial segmented regions to prune incorrectly detected airways and separate fused right and left lungs. RESULTS: The performance of the automated segmentation scheme was evaluated using 101 computed tomography cases (91 thick slice, 10 thin slice scans). The 91 thick cases were pre- and post-surgery from 50 patients and were not independent. The automated scheme successfully segmented 94.0% of the 2,969 thick slice images and 97.6% of the 1,161 thin slice images. The mean difference of the total lung volumes calculated by the automated scheme and functional residual capacity plus 60% inspiratory capacity was -24.7 +/- 508.1 mL. The mean differences of the total lung volumes calculated by the automated scheme and an established, commonly used semi-automated scheme were 95.2 +/- 52.5 mL and -27.7 +/- 66.9 mL for the thick and thin slice cases, respectively. CONCLUSION: This simple, fully-automated lung segmentation scheme provides an objective tool to facilitate lung segmentation from computed tomography scans.

Image Processing, Computer-Assisted↗
PubMed2003

Performance change of mammographic CAD schemes optimized with most-recent and prior image databases.

RATIONALE AND OBJECTIVES: The authors evaluated performance changes in the detection of masses on "current" (latest) and "prior" images by computer-aided diagnosis (CAD) schemes that had been optimized with databases of current and prior mammograms. MATERIALS AND METHODS: The authors selected 260 pairs of matched consecutive mammograms. Each current image depicted one or two verified masses. All prior images had been interpreted originally as negative or probably benign. A CAD scheme initially detected 261 mass regions and 465 false-positive regions on the current images, and 252 corresponding mass regions (early signs) and 471 false-positive regions on prior images. These regions were divided into two training and two testing databases. The current and prior training databases were used to optimize two CAD schemes with a genetic algorithm. These schemes were evaluated with two independent testing databases. RESULTS: The scheme optimized with current images produced areas under the receiver operating characteristic curve of (0.89 +/- 0.01 and 0.65 +/- 0.02 when tested with current images and prior images, respectively. The scheme optimized with prior images produced areas under the receiver operating characteristic curve of 0.81 +/- 0.02 and 0.71 +/- 0.02 when tested with current images and prior images, respectively. Performance changes for both current and prior testing databases were significant (P < .01) for the two schemes. CONCLUSION: CAD schemes trained with current images do not perform optimally in detecting masses depicted on prior images. To optimize CAD schemes for early detection, it may be important to include in the training database a large fraction of prior images originally reported as negative and later proven to be positive.

Algorithms↗
PubMed2003

Integrated density of a lesion: a quantitative, mammographically derived, invariable measure.

A method for quantitatively estimating lesion "size" from mammographic images was developed and evaluated. The main idea behind the measure, termed "integrated density" (ID), is that the total x-ray attenuation attributable to an object is theoretically invariant with respect to the projected view and object deformation. Because it is possible to estimate x-ray attenuation of a lesion from relative film densities, after appropriate corrections for background, the invariant property of the measure is expected to result in an objective method for evaluating the "sizes" of breast lesions. ID was calculated as the integral of the estimated image density attributable to a lesion, relative to surrounding background, over the area of the lesion and after corrections for the nonlinearity of the film characteristic curve. This effectively provides a measure proportional to lesion volume. We computed ID and more traditional measures of size (such as "mass diameter" and "effective size") for 100 pairs of ipsilateral mammographic views, each containing a lesion that was relatively visible in both views. The correlation between values calculated for each measure from corresponding pairs of ipsilateral views were computed and compared. All three size-related measures (mass diameter, effective size, and ID) exhibited reasonable linear relationship between paired views (r2>0.7, P<0.001). Specifically, the ID measures for the 100 masses were found to be highly correlated (r2=0.9, P<0.001) between ipsilateral views of the same mass. The correlation increased substantially (r2=0.95), when a measure with linear dimensions of length was defined as the cube root of ID. There is a high degree of correlation between ID-based measures obtained from different views of the same mass. ID-based measures showed a higher degree of invariance than mass diameter or effective size.

Absorptiometry, Photon↗
PubMed2003

Development of an improved selective agar medium for isolation of Yersinia pestis.

Existing media designed for selective isolation of clinically important members of the genus Yersinia were found to be unsatisfactory for the growth and isolation of Yersinia pestis. We report the development of a new selective agar medium (termed BIN) that supports the growth of Y. pestis. The development of the formulation of this medium was based on a fluorescence screening system designed for monitoring bacterial growth on semisolid media, using a green fluorescent protein-expressing strain. High-throughput combinatorial experiments can be conducted for the quantitative evaluation of the effect of different medium components on growth. Generation of fluorescence plots in this system, using microplates, allowed the quantitative evaluation of the growth rate of Y. pestis EV76 cultures in different agar compositions. The final BIN formulation is based on brain heart infusion agar, to which the selective agents irgasan, cholate salts, crystal violet, and nystatin were introduced. It was found that BIN agar is more efficient in supporting colony formation and recovery of Y. pestis than are the conventional semisolid media MacConkey agar and Yersinia-selective agar (cefsulodin-irgasan-novobiocin agar). The advantage of BIN over other media has been also demonstrated in recovering virulent Y. pestis from the mixed bacterial populations found in decaying carcasses of infected mice. The BIN medium is suggested as a selective medium for isolation and recovery of Y. pestis from various backgrounds.

Agar↗
PubMed2003

Prevalence effect in a laboratory environment.

PURPOSE: To measure observer performance at various levels of prevalence. MATERIALS AND METHODS: A multiobserver multiabnormality receiver operating characteristic (ROC) study to assess the effect of prevalence on observer performance was conducted. Fourteen observers, including eight faculty members, two fellows, and four residents, interpreted 1,632 posteroanterior chest images with five prevalence levels by using a nested study design. Performance comparisons were accomplished by using a multireader multicase approach to assess the effect of prevalence from 28% (69 of 249) to 2% (31 of 1,577) on diagnostic accuracy. The mean times required to review and report a case were analyzed and compared for different levels of prevalence and readers' experience. RESULTS: Area under the ROC curve demonstrated that, with the study experimental conditions, no significant effect could be measured as a function of prevalence (P >.05) for any abnormality, group of cases, or readers. There were no significant differences (P >.05) in the mean times required to review and report cases at different prevalence levels and with different groups of readers. CONCLUSION: The consistency in the results and the size of this study suggest that with laboratory conditions, if a prevalence effect exists, it is quite small in magnitude; hence, it will not likely alter conclusions derived from such studies.

Laboratories↗
PubMed2003

Prescreening mammography by technologists: a preliminary assessment.

OBJECTIVE: We assessed the ability of technologists to accurately classify screening mammograms as either showing negative findings or requiring follow-up. SUBJECTS AND METHODS: In a prospective study, 33 technologists at a central facility and five satellite breast imaging facilities recorded whether mammograms obtained during 3019 examinations showed negative findings or findings that indicated that additional procedures were required. The technologists were not specifically trained for the experiment. The technologists' interpretations were compared with radiologists' interpretations. RESULTS: Technologists and radiologists agreed in 82% of the cases (77% negative findings and 5% requiring follow-up). Of the 175 cases recommended for follow-up by only the radiologists, 17 were ultimately biopsied and two were found to be malignant. CONCLUSION: Even without undergoing additional training, technologists can perform at reasonable levels of accuracy in classifying screening mammograms. The possibility of using technologists to group cases after the technologists have undergone training is an interesting concept that should be explored further.

Allied Health Personnel↗
PubMed2003

Optimal reference mammography: a comparison of mammograms obtained 1 and 2 years before the present examination.

OBJECTIVE: We assessed and compared the benefit of using images acquired 1 year or 2 years previously during mammography interpretations. MATERIALS AND METHODS: Eleven radiologists and one resident reviewed 128 cases three times: once without prior mammograms for comparison, once with mammograms from the most recent (1 year) examination, and once with mammograms acquired 2 years previously. They were asked to determine whether the patient should be recalled for additional procedures. Performances under the three conditions were compared. RESULTS: Radiologists were significantly more accurate (p < 0.001) when comparison mammograms (obtained 1 or 2 years previously) were available. Although sensitivity was not significantly affected between the availability of mammograms from 1 or 2 years earlier (p > 0.10), the specificity was. Specificity using mammograms from the latest examination (obtained 1 year previously) as a reference was significantly better (p = 0.03) than specificity using mammograms obtained 2 years previously. CONCLUSION: Comparison mammograms are important for accurate diagnosis-in particular, for increasing specificity. The latest prior examination seems to be the optimal one for this purpose.

Breast Neoplasms↗
PubMed2002

Computerized assessment of tissue composition on digitized mammograms.

RATIONALE AND OBJECTIVES: The authors developed a computerized method for the quantitative assessment of breast tissue composition on digitized mammograms. MATERIALS AND METHODS: Three radiologists were asked to review 200 digitized mammograms and independently provide a Breast Imaging Reporting and Data System-like rating for breast tissue composition on a scale of 0 to 4. These values were incorporated into a "consensus" rating that was used as a reference point in the development and evaluation of a computerized method. After tissue segmentation that excluded nontissue areas, a set of quantitative features was computed. A computerized summary index that attempts to reproduce the radiologists' ratings was developed. Correlation coefficients (Pearson r) were used to compare the computerized index with the consensus ratings. RESULTS: Some individual features computed for the relatively dense breast areas showed good correlation (r > 0.8) with the radiologists' subjective ratings. The summary index of tissue composition demonstrated a significant correlation (r = 0.87), as well. CONCLUSION: Computerized methods that show good correlation with radiologists' ratings of breast tissue composition can be developed.

Breast↗