Eric A. Hoffman

Intrathoracic airway trees: segmentation and airway morphology analysis from low-dose CT scans

The segmentation of the human airway tree from volumetric computed tomography (CT) images builds an important step for many clinical applications and for physiological studies. Previously proposed algorithms suffer from one or several problems: leaking into the surrounding lung parenchyma, the need for the user to manually adjust parameters, excessive runtime. Low-dose CT scans are increasingly utilized in lung screening studies, but segmenting them with traditional airway segmentation algorithms often yields less than satisfying results. In this paper, a new airway segmentation method based on fuzzy connectivity is presented. Small adaptive regions of interest are used that follow the airway branches as they are segmented. This has several advantages. It makes it possible to detect leaks early and avoid them, the segmentation algorithm can automatically adapt to changing image parameters, and the computing time is kept within moderate values. The new method is robust in the sense that it works on various types of scans (low-dose and regular dose, normal subjects and diseased subjects) without the need for the user to manually adjust any parameters. Comparison with a commonly used region-grow segmentation algorithm shows that the newly proposed method retrieves a significantly higher count of airway branches. A method that conducts accurate cross-sectional airway measurements on airways is presented as an additional processing step. Measurements are conducted in the original gray-level volume. Validation on a phantom shows that subvoxel accuracy is achieved for all airway sizes and airway orientations.

MDCT-based 3-D texture classification of emphysema and early smoking related lung pathologies

Our goal is to enhance the ability to differentiate normal lung from subtle pathologies via multidetector row CT (MDCT) by extending a two-dimensional (2-D) texturebased tissue classification [adaptive multiple feature method (AMFM)] to use three-dimensional (3-D) texture features. We performed MDCT on 34 humans and classified volumes of interest (VOIs) in the MDCT images into five categories: EC, emphysema in severe chronic obstructive pulmonary disease (COPD); MC, mild emphysema in mild COPD; NC, normal appearing lung in mild COPD; NN, normal appearing lung in normal nonsmokers; and NS, normal appearing lung in normal smokers. COPD severity was based upon pulmonary function tests (PFTs). Airways and vessels were excluded from VOIs; 24 3-D texture features were calculated; and a Bayesian classifier was used for discrimination. A leave-one-out method was employed for validation. Sensitivity of the four-class classification in the form of 3-D/2-D was: EC: 85%/71%, MC: 90%/82%; NC: 88%/50%; NN: 100%/60%. Sensitivity and specificity for NN using a two-class classification of NN and NS in the form of 3-D/2-D were: 99%/72% and 100%/75%, respectively. We conclude that 3-D AMFM analysis of lung parenchyma improves discrimination compared to 2-D AMFM of the same VOIs. Furthermore, our results suggest that the 3-D AMFM may provide a means of discriminating subtle differences between smokers and nonsmokers both with normal PFTs.

Characterization of the interstitial lung diseases via density-based and texture-based analysis of computed tomography images of lung structure and function1 ☆

RATIONALE AND OBJECTIVES Efforts to establish a quantitative approach to the computed tomography (CT)-based character ization of the lung parenchyma in interstitial lung disease (including emphysema) has been sought. The accuracy of these tools must be site independent. Multi-detector row CT has remained the gold standard for imaging the lung, and it provides the ability to image both lung structure as well as lung function. MATERIAL AND METHODS Imaging is via multi-detector row CT and protocols include careful control of lung volume during scanning. Characterization includes not only anatomic-based measures but also functional measures including regional parameters derived from measures of pulmonary blood flow and ventilation. Image processing includes the automated detection of the lungs, lobes, and airways. The airways provide the road map to the lung parenchyma. Software automatically detects the airways, the airway centerlines, and the branch points, and then automatically labels the airway tree segments with a standardized set of labels, allowing for intersubject as well intrasubject comparisons across time. By warping all lungs to a common atlas, the atlas provides the range of normality for the various parameters provided by CT imaging. RESULTS Imaged density and textural changes mark underlying structural changes at the most peripheral regions of the lung. Additionally, texture-based alterations in the parameters of blood flow may provide early evidence of pathologic processes. Imaging of stable xenon gas provides a regional measure of ventilation which, when coupled with measures of flow, provide for a textural analysis regional of ventilation-perfusion matching. CONCLUSION With the improved resolution and speed of CT imaging, the patchy nature of regional parenchymal pathology can be imaged as texture of structure and function. With careful control of imaging protocols and the use of objective image analysis methods it is possible to provide site-independent tools for the assessment of interstitial lung disease. There remains a need to validate these methods, which requires interdisciplinary and cross-institutional efforts to gather appropriate data bases of images along with a consensus on appropriate ground truths associated with the images. Furthermore, there is the growing need for scanner manufacturers to focus on not just visually pleasing images, but on quantitatifiably accurate images.

Original ResearchAsthmaAirway Remodeling Measured by Multidetector CT Is Increased in Severe Asthma and Correlates With Pathology

BACKGROUND To prospectively apply an automated, quantitative three-dimensional approach to imaging and airway analysis to assess airway remodeling in asthma patients. METHODS Using quantitative software (Pulmonary Workstation, version 0.139; VIDA Diagnostics; Iowa City, IA) that enables quantitative airway segment measurements of low-dose, thin-section (0.625 to 1.25 mm), multidetector-row CT (MDCT) scans, we compared airway wall thickness (WT) and wall area (WA) in 123 subjects participating in a prospective multicenter cohort study, the National Institutes of Health Severe Asthma Research Program (patients with severe asthma, n = 63; patients with mild-to-moderate asthma, n = 35); and healthy subjects, n = 25). A subset of these subjects underwent fiberoptic bronchoscopy and endobronchial biopsies (n = 32). WT and WA measurements were corrected for total airway diameter and area: WT and WA, respectively. RESULTS Subjects with severe asthma had a significantly greater WT% than patients with mild-to-moderate asthma and healthy subjects (17.2 +/- 1.5 vs 16.5 +/- 1.6 [p = 0.014] and 16.3 +/- 1.2 [p = 0.031], respectively) and a greater WA percentage (WA%) compared to patients with mild-to-moderate asthma and healthy subjects (56.6 +/- 2.9 vs 54.7 +/- 3.3 [p = 0.005] and 54.6 +/- 2.4 [p = 0.003], respectively). Both WT% and WA% were inversely correlated with baseline FEV(1) percent predicted (r = -0.39, p < 0.0001 and r = -0.40, p < 0.0001, respectively) and positively correlated with response to a bronchodilator (r = 0.28, p = 0.002 and r = 0.35, p < 0.0001, respectively). The airway epithelial thickness measure on the biopsy sample correlated with WT% (r = 0.47; p = 0.007) and WA% (r = 0.52; p = 0.003). In the same individual, there is considerable regional heterogeneity in airway WT. CONCLUSION Patients with severe asthma have thicker airway walls as measured on MDCT scan than do patients with mild asthma or healthy subjects, which correlates with pathologic measures of remodeling and the degree of airflow obstruction. MDCT scanning may be a useful technique for assessing airway remodeling in asthma patients, but overlap among the groups limits the diagnostic value in individual subjects.

Pathogen transmission as a selective force against cannibalism

Cannibalism is uncommon in most species despite being taxonomically widespread. This rarity is surprising, because cannibalism can confer important nutritional and competitive advantages to the cannibal. A general, but untested, explanation for why cannibalism is rare is that cannibals may be especially likely to acquire pathogens from conspecifics, owing to greater genetic similarity among conspecifics and selection for host specificity and resistance to host immune defences among pathogens. We tested this hypothesis by contrasting the fitness consequences of intra- versus interspecific predation of diseased and non-diseased prey. We fed cannibalistic tiger salamander (Ambystoma tigrinum) larvae diseased conspecifics, healthy conspecifics, diseased heterospecifics (a sympatric congener, small-mouthed salamanders, A. texanum), or healthy heterospecifics. Cannibals that ate diseased conspecifics were significantly less likely to survive to metamorphosis and grew significantly less than those that ate diseased heterospecifics, but none of the other groups differed. Tiger salamander larvae also preferentially preyed on heterospecifics when given a choice between healthy conspecifics and heterospecifics. These results suggest that pathogen transmission is an important cost of cannibalism and provide a general explanation for why cannibalism is infrequent in most species. Copyright 1998 The Association for the Study of Animal Behaviour Copyright 1998 The Association for the Study of Animal Behaviour.

Subclinical Atherosclerosis, Airflow Obstruction and Emphysema: the MESA Lung Study

Airflow obstruction is an independent risk factor for cardiovascular events in the general population. The affected vascular bed and contribution of emphysema to cardiovascular risk are unclear. We examined whether an obstructive pattern of spirometry and quantitatively defined emphysema were associated with subclinical atherosclerosis in the carotid, peripheral and coronary circulations. The Multi-Ethnic Study of Atherosclerosis recruited participants aged 45–84 yrs without clinical cardiovascular disease. Spirometry, carotid intima-media thickness (IMT), ankle-brachial index (ABI) and coronary artery calcium (CAC) were measured using standard protocols. Percentage of emphysema-like lung was measured in the lung windows of cardiac computed tomography scans among 3,642 participants. Multiple linear regression was used to adjust for cardiac risk factors, including C-reactive protein. Decrements in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity ratio were associated with greater internal carotid IMT, particularly among smokers (p=0.03 and p<0.001, respectively) whereas percentage emphysema was associated with reduced ABI regardless of smoking history (p=0.004). CAC was associated with neither lung function (prevalence ratio for the presence of CAC in severe airflow obstruction 0.99, 95% CI 0.91–1.07) nor percentage emphysema. An obstructive pattern of spirometry and emphysema were associated distinctly and independently with subclinical atherosclerosis in the carotid arteries and peripheral circulation, respectively, and were not independently related to CAC.

EVOLUTIONARY HISTORY OF THE NORTHERN LEOPARD FROG: RECONSTRUCTION OF PHYLOGENY, PHYLOGEOGRAPHY, AND HISTORICAL CHANGES IN POPULATION DEMOGRAPHY FROM MITOCHONDRIAL DNA

Abstract This study uses a combined methodological approach including phylogenetic, phylogeographic, and demographic analyses to understand the evolutionary history of the northern leopard frog, Rana pipiens. We tested hypotheses concerning how (or if) known geological events and key features of the species biology influenced the contemporary geographic and genetic distribution of R. pipiens. We assayed mitochondrial DNA variation from 389 individuals within 35 populations located throughout the species range. Our a priori expectations for patterns and processes influencing the current genetic structure of R. pipiens were supported by the data. However, our analyses revealed specific aspects of R. pipiens evolutionary history that were unexpected. The phylogenetic analysis indicated that R. pipiens is split into populations containing discrete eastern or western haplotypes, with the Mississippi River and Great Lakes region dividing the geographic ranges. Nested clade analysis indicated that the biological process most often invoked to explain the pattern of haplotype position is restricted gene flow with isolation by distance. Demographic analyses showed evidence of both historical bottlenecks and population expansions. Surprisingly, the genetic evidence indicated that the western haplotypes had significantly reduced levels of genetic diversity relative to the eastern haplotypes and that major range expansions occurred in both regions well before the most recent glacial retreat. This study provides a detailed history of how a widespread terrestrial vertebrate responded to episodic Pleistocene glacial events in North America. Moreover, this study illustrates how complementary methods of data analysis can be used to disentangle recent and ancient effects on the genetic structure of a species.

CT-measured regional specific volume change reflects regional ventilation in supine sheep

Computer tomography (CT) imaging techniques permit the noninvasive measurement of regional lung function. Regional specific volume change (sVol), determined from the change in lung density over a tidal breath, should correlate with regional ventilation and regional lung expansion measured with other techniques. sVol was validated against xenon (Xe)-CT-specific ventilation (sV) in four anesthetized, intubated, mechanically ventilated sheep. Xe-CT used expiratory gated axial scanning during the washin and washout of 55% Xe. sVol was measured from the tidal changes in tissue density (H, houndsfield units) of lung regions using the relationship sVol = [1,000(Hi - He)]/[He(1,000 + Hi)], where He and Hi are expiratory and inspiratory regional density. Distinct anatomical markings were used to define corresponding lung regions of interest between inspiratory, expiratory, and Xe-CT images, with an average region of interest size of 1.6 +/- 0.7 ml. In addition, sVol was compared with regional volume changes measured directly from the positions of implanted metal markers in an additional animal. A linear relationship between sVol and sV was demonstrated over a wide range of regional sV found in the normal supine lung, with an overall correlation coefficient (R(2)) of 0.66. There was a tight correlation (R(2) = 0.97) between marker-measured volume changes and sVol. Regional sVol, which involves significantly reduced exposure to radiation and Xe gas compared with the Xe-CT method, represents a safe and efficient surrogate for measuring regional ventilation in experimental studies and patients.

Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.

Recent evidence suggests that endothelial dysfunction and pathology of pulmonary vascular responses may serve as a precursor to smoking-associated emphysema. Although it is known that emphysematous destruction leads to vasculature changes, less is known about early regional vascular dysfunction which may contribute to and precede emphysematous changes. We sought to test the hypothesis, via multidetector row CT (MDCT) perfusion imaging, that smokers showing early signs of emphysema susceptibility have a greater heterogeneity in regional perfusion parameters than emphysema-free smokers and persons who had never smoked (NS). Assuming that all smokers have a consistent inflammatory response, increased perfusion heterogeneity in emphysema-susceptible smokers would be consistent with the notion that these subjects may have the inability to block hypoxic vasoconstriction in patchy, small regions of inflammation. Dynamic ECG-gated MDCT perfusion scans with a central bolus injection of contrast were acquired in 17 NS, 12 smokers with normal CT imaging studies (SNI), and 12 smokers with subtle CT findings of centrilobular emphysema (SCE). All subjects had normal spirometry. Quantitative image analysis determined regional perfusion parameters, pulmonary blood flow (PBF), and mean transit time (MTT). Mean and coefficient of variation were calculated, and statistical differences were assessed with one-way ANOVA. MDCT-based MTT and PBF measurements demonstrate globally increased heterogeneity in SCE subjects compared with NS and SNI subjects but demonstrate similarity between NS and SNI subjects. These findings demonstrate a functional lung-imaging measure that provides a more mechanistically oriented phenotype that differentiates smokers with and without evidence of emphysema susceptibility.

PROXIMATE CAUSES OF CANNIBALISTIC POLYPHENISM IN LARVAL TIGER SALAMANDERS

Larval tiger salamanders, Ambystoma tigrinum, exist as small-headed “typical” morphs that feed mainly on aquatic invertebrates and as large-headed “cannibal” morphs that often prey on conspecifics. Previous experiments have demonstrated that cannibals are induced facultatively when crowded with conspecific larvae. We asked: (1) What sensory cues trigger expression of cannibals? (2) Does larval age influence expression of cannibals? (3) Are cannibals also induced by crowding with heterospecifics? (4) Do cannibals suppress others from developing into cannibals? We found that tactile cues from other salamander larvae were necessary to elicit cannibals. Cannibals were produced when tiger salamander larvae were crowded with congeneric larvae, and these heterospecific-induced cannibals were expressed at an earlier age than those induced by conspecifics. Furthermore, younger larvae were more likely to develop into cannibals. Finally, visual and chemical cues from cannibals did not suppress other larvae from deve...