Automatic construction of subject-specific human airway geometry including trifurcations based on a CT-segmented airway skeleton and surface

We propose a method to construct three-dimensional airway geometric models based on airway skeletons, or centerlines (CLs). Given a CT-segmented airway skeleton and surface, the proposed CL-based method automatically constructs subject-specific models that contain anatomical information regarding branches, include bifurcations and trifurcations, and extend from the trachea to terminal bronchioles. The resulting model can be anatomically realistic with the assistance of an image-based surface; alternatively a model with an idealized skeleton and/or branch diameters is also possible. This method systematically identifies and classifies trifurcations to successfully construct the models, which also provides the number and type of trifurcations for the analysis of the airways from an anatomical point of view. We applied this method to 16 normal and 16 severe asthmatic subjects using their computed tomography images. The average distance between the surface of the model and the image-based surface was 11 % of the average voxel size of the image. The four most frequent locations of trifurcations were the left upper division bronchus, left lower lobar bronchus, right upper lobar bronchus, and right intermediate bronchus. The proposed method automatically constructed accurate subject-specific three-dimensional airway geometric models that contain anatomical information regarding branches using airway skeleton, diameters, and image-based surface geometry. The proposed method can construct (i) geometry automatically for population-based studies, (ii) trifurcations to retain the original airway topology, (iii) geometry that can be used for automatic generation of computational fluid dynamics meshes, and (iv) geometry based only on a skeleton and diameters for idealized branches.     

A model of the mechanics of airway narrowing

To examine the interaction between airway smooth muscle shortening and airway wall thickening on changes in pulmonary resistance, we have developed a model of the tracheobronchial tree that allows simulation of the mechanisms involved in airway narrowing. The model is based on the symmetrical dichotomous branching tracheobronchial tree as described by Weibel and uses fluid dynamic equations proposed by Pedley et al. to calculate inspiratory resistance during quiet tidal breathing. To allow for changes in lung volume, we used the airway pressure-area curves developed by Lambert et al. The model is easily implemented with a spreadsheet and personal computer that allows calculation of total and regional pulmonary resistance. At each airway generation in the model, provision is made for airway wall thickness, the maximal airway smooth muscle shortening achievable, and an S-shaped dose-response relationship to describe smooth muscle shortening. To test the validity of the model, we compared pressure-flow curves generated with the model with measurements of pulmonary resistance while normal subjects breathed air and 20% O2-80% He at a variety of lung volumes. By simulating progressive airway smooth muscle shortening, realistic pulmonary resistance vs. dose-response curves were produced. We conclude that this model provides realistic estimates of pulmonary resistance and shows potential for examining the various mechanisms that could produce excessive airway narrowing in disease.     

Comparison of dose conversion factors for radon progeny from the ICRP 66 regional model and an airway tube model of tracheo-bronchial tree

Current epidemiological approaches to radon dosimetry yield a dose conversion factor (DCF) of 4 mSv WLM⁻¹ while the dosimetric approaches give a value closer to 13 mSv WLM⁻¹. The present study investigated whether the application of compartment models for the bronchial (BB) and bronchiolar (bb) regions, rather than more anatomically realistic airway tube models, has brought the dosimetric DCF to the higher values. The airway tube model of the tracheo-bronchial tree was used to calculate the effective dose per unit radon exposure. All other elements of the human respiratory tract from the reports of the ICRP or NRC were adopted. A dosimetric derivation of the radon DCF using the airway tube model yielded a value of 14.2 mSv WLM⁻¹. This value is slightly larger than, but not significantly different from, the result obtained through the ICRP 66 approach. It is concluded that utilization of the airway tube model instead of the regional ICRP 66 compartmental model cannot reconcile the gap between dose conversion factors derived from epidemiological and dosimetric approaches.     

A Simple Geometrical Pattern for the Branching Distribution of the Bronchial Tree, Useful to Estimate Optimality Departures

The design of the bronchial tree has largely been proposed as a model of optimal design from a physical-functional perspective. However, the distributive function of the airway may be more related to a geometrical than a physical problem. The bronchial tree must distribute a three dimensional volume of inspired air on a two dimensional alveolar surface, included in a limited volume. It is thus valid to ask whether an optimal bronchial tree from a physical perspective is also optimum from a geometrical point of view. In this paper we generate a simple geometric model for the branching pattern of the bronchial tree, deducing relationships that permit estimation of the departures from the geometrical optimum of each bifurcation. We also, for comparative purposes, estimate the departures from the physical optimum. From the geometrical assumptions: i) a symmetrical dichotomic fractal design, ii) with minimum volume and iii) maximum dispersion of the terminal points; and several simulations we suggest that the optimality is characterized by a bifurcation angle theta approximately 60 degrees and a length reduction scale gamma = (1/2)(1/3) = 0.7937. We propose distances from the physical and geometrical optimality defined as Euclidean distances from the expected optima. We show how the advanced relationships and the distances can be used to estimate departures from the optimality in bronchographs of four species. We found lower physical and geometrical departures in the distal zone than those of the proximal zones, as well as lower physical than geometrical departures from optimality.     

Capillary-elastic instabilities of liquid-lined lung airways

To model the competition between capillary and elastic forces in controlling the shape of a small lung airway and its interior liquid lining, we compute the equilibrium configurations of a liquid-lined, externally pressurized, buckled elastic tube. We impose axial uniformity and assume that the liquid wets the tube wall with zero contact angle. Non-zero surface tension has a profound effect on the tube's quasi-steady inflation-deflation characteristics. At low liquid volumes, hysteresis arises through two distinct mechanisms, depending on the buckling wavenumber. Sufficient compression always leads to abrupt and irreversible collapse and flooding of the tube; flooding is promoted by increasing liquid volumes or surface tension. The model captures mechanisms whereby capillary-elastic instabilities can lead to airway closure.     

Genome-based phylogeny of dsDNA viruses by a novel alignment-free method

Sequence alignment is not directly applicable to whole genome phylogeny since several events such as rearrangements make full length alignments impossible. Here, a novel alignment-free method derived from the standpoint of information theory is proposed and used to construct the whole-genome phylogeny for a population of viruses from 13 viral families comprising 218 dsDNA viruses. The method is based on information correlation (IC) and partial information correlation (PIC). We observe that (i) the IC-PIC tree segregates the population into clades, the membership of each is remarkably consistent with biologist's systematics only with little exceptions; (ii) the IC-PIC tree reveals potential evolutionary relationships among some viral families; and (iii) the IC-PIC tree predicts the taxonomic positions of certain “unclassified” viruses. Our approach provides a new way for recovering the phylogeny of viruses, and has practical applications in developing alignment-free methods for sequence classification.     

Zero-stress state of intra- and extraparenchymal airways from human, pig, rabbit, and sheep lung.

Alterations in airway wall anatomic properties and the consequential effects on airway narrowing have been assessed by use of computational models. In these models, it is generally assumed that at zero transmural pressure the airway wall exists in a zero-stress state. Many studies have shown that this is often not the case, as evidenced by a nonzero opening angle. In this study, we measured the opening angle of airway rings at zero transmural pressure to test this assumption. The airway tree was dissected from human, pig, sheep, and rabbit lungs. Airways were excised from the tree, and the opening angle was measured. There were obvious species and regional differences in opening angle. Rabbit airways from both extraparenchymal and intraparenchymal sites exhibited marked opening angles (7-82 degrees). Extraparenchymal airways from sheep had large opening angles (up to 50 degrees), but ovine intraparenchymal airways had small opening angles. Measurable opening angles were rarely observed in human and porcine airways of any size. The assumption of a stable zero-stress state at zero transmural pressure is therefore valid for human and porcine, but not rabbit and sheep, airways.     

Dynamic measurement of pennation angle of gastrocnemius muscles during contractions based on ultrasound imaging

ABSTRACT: BACKGROUND: Muscle fascicle pennation angle (PA) is an important parameter related to musculoskeletal functions, and ultrasound imaging has been widely used for measuring PA, but manually and frame by frame in most cases. We have earlier reported an automatic method to estimate aponeurosis orientation based on Gabor transform and Revoting Hough Transform (RVHT). METHODS: In this paper, we proposed a method to estimate the overall orientation of muscle fascicles in a region of interest, in order to complete computing the orientation of the other side of the pennation angle, but the side found by RVHT. The measurements for orientations of both fascicles and aponeurosis were conducted in each frame of ultrasound images, and then the dynamic change of pennation angle during muscle contraction was obtained automatically. The method for fascicle orientation estimation was evaluated using synthetic images with different noise levels and later on 500 ultrasound images of human gastrocnemius muscles during isometric plantarflexion. RESULTS: The muscle fascicle orientations were also estimated manually by two operators. From the results it's found that the proposed automatic method demonstrated a comparable performance to the manual method. CONCLUSIONS: With the proposed methods, ultrasound measurement for muscle pennation angles can be more widely used for functional assessment of muscles.     

Airway smooth muscle orientation in intraparenchymal airways

Lei, M., H. Ghezzo, M. F. Chen, and D. H. Eidelman.Airway smooth muscle orientation in intraparenchymal airways.J. Appl. Physiol. 82(1): 70-77, 1997.Airway smooth muscle (ASM) shortening is the central eventleading to bronchoconstriction. The degree to which airway narrowingoccurs as a consequence of shortening is a function of both themechanical properties of the airway wall as well as the orientation ofthe muscle fibers. Although the latter is theoretically important, ithas not been systematically measured to date. The purpose of this studywas to determine the angle of orientation of ASM () in normal lungs by using a morphometric approach. We analyzed the airway tree of theleft lower lobes of four cats and one human. All material was fixedwith 10% buffered Formalin at a pressure of 25 cmH₂O for 48 h. The fixed materialwas dissected along the airway tree to permit isolation ofgenerations 4-18 in the cats andgenerations 5-22 in the humanspecimen. Each airway generation was individually embedded in paraffin.Five-micrometer-thick serial sections were cut parallel to the airwaylong axis and stained with hematoxylin-phloxine-saffron. Each blockyielded three to five sections containing ASM. To determine , wemeasured the orientation of ASM nuclei relative to the transverse axisof the airway by using a digitizing tablet and a light microscope (×250) equipped with a drawing tube attachment. Inspection of thesections revealed extensive ASM crisscrossing without a homogeneous orientation. The  was clustered between 20° and 20°in all airway generations and did not vary much between generations inany of the cats or in the human specimen. When  was expressedwithout regard to sign, the mean values were 13.2° in the cats and13.1° in the human. This magnitude of obliquity is not likely toresult in physiologically important changes in airway length duringbronchoconstriction.

     

A three-dimensional model of the human airway tree.

A three-dimensional (3D) model of the human airway tree is proposed using a deterministic algorithm that can generate a branching duct system in an organ. The algorithm is based on two principles: 1) the amount of fluid delivery through a branch is proportional to the volume of the region it supplies; and 2) the terminal branches are arranged homogeneously within the organ. These principles define the basic process of branching: generation of the dimensions and directionality of two daughter branches is governed by the properties of the parent branch and the region the parent supplies. The algorithm is composed of nine basic rules and four complementary rules. When the contour of an organ and the position of the trunk are specified, branches are successively generated by the algorithm. Applied to the human lung, the algorithm generates an airway tree that consists of approximately 54,000 branches. Its morphometric characteristics are in good agreement with those reported in the literature. The algorithm and the 3D airway model are useful for studying the structure-function relationship in the lung.     

The influence of seat configuration on maximal average crank power during pedaling: a simulation study

Manipulating seat configuration (i.e., seat tube angle, seat height and pelvic orientation) alters the bicycle-rider geometry, which influences lower extremity muscle kinematics and ultimately muscle force and power generation during pedaling. Previous studies have sought to identify the optimal configuration, but isolating the effects of specific variables on rider performance from the confounding effect of rider adaptation makes such studies challenging. Of particular interest is the influence of seat tube angle on rider performance, as seat tube angle varies across riding disciplines (e.g., road racers vs. triathletes). The goals of the current study were to use muscle-actuated forward dynamics simulations of pedaling to 1) identify the overall optimal seat configuration that produces maximum crank power and 2) systematically vary seat tube angle to assess how it influences maximum crank power. The simulations showed that a seat height of 0.76 m (or 102% greater than trochanter height), seat tube angle of 85.1 deg, and pelvic orientation of 20.5 deg placed the major power-producing muscles on more favorable regions of the intrinsic force-length-velocity relationships to generate a maximum average crank power of 981 W. However, seat tube angle had little influence on crank power, with maximal values varying at most by 1% across a wide range of seat tube angles (65 to 110 deg). The similar power values across the wide range of seat tube angles were the result of nearly identical joint kinematics, which occurred using a similar optimal seat height and pelvic orientation while systematically shifting the pedal angle with increasing seat tube angles.     

Growth of the ferret tracheobronchial tree

Because the ferret is being used increasingly in inhalation toxicology and lung physiology studies, it is necessary to better understand the airway structure of its tracheobronchial tree. Previously published information does not include dimensions of bronchi and bronchioles in either adult or growing ferrets. The airway structure of interest for calculating inhaled particle deposition patterns includes airway lengths, diameters and branching angles in each generation. Measurements of these dimensions were obtained for several selected airway paths on replica casts. Casts were made in-situ in four male litter mates age 14 hours, 9.5 days, 16.5 days and 56 days. These data demonstrate, that as with human lung growth, body length at a given age is a good predictor of airway lengths and diameters. Airway branch angles do not appear to change significantly during growth. Sufficient measurements were made to provide dimensions of a typical tracheobronchial pathway for this species. This pathway begins with the trachea and ends at the terminal bronchiole. The morphometric data were not sufficient to determine whether or not the number of tracheobronchial generations increase or decrease postnatally.     

Dual assessment of airway area profile and respiratory input impedance from a single transient wave.

This report concerns the inference of geometric and mechanical airway characteristics based on information derived from a single transient planar wave recorded at the airway opening. We describe a new method to simultaneously measure upper airway area and respiratory input impedance by performing dual analysis of a single pressure wave. The algorithms required to reconstruct airway dimensions and mechanical characteristics were developed, implemented, and tested with reference to known physical models. Our method appears suitable to estimate, even under severe intensive care unit conditions, the respiratory system frequency response (above 10 Hz) in intubated patients and the patency of the endotracheal tube used to connect the patients to the ventilator.     

Orientation and location of the finite helical axis of the equine forelimb joints

To reduce anatomically unrealistic limb postures in a virtual musculoskeletal model of a horse's forelimb, accurate knowledge on forelimb joint constraints is essential. The aim of this cadaver study is to report all orientation and position changes of the finite helical axes (FHA) as a function of joint angle for different equine forelimb joints. Five horse cadaver forelimbs with standardized cuts at the midlevel of each segment were used. Bone pins with reflective marker triads were drilled into the forelimb bones. Unless joint angles were anatomically coupled, each joint was manually moved independently in all three rotational degrees of freedom (flexion–extension, abduction–adduction, internal–external rotation). The 3D coordinates of the marker triads were recorded using a six infra-red camera system. The FHA and its orientational and positional properties were calculated and expressed against joint angle over the entire range of motion using a finite helical axis method. When coupled, joint angles and FHA were expressed in function of flexion–extension angle. Flexion–extension movement was substantial in all forelimb joints, the shoulder allowed additional considerable motion in all three rotational degrees of freedoms. The position of the FHA was constant in the fetlock and elbow and a constant orientation of the FHA was found in the shoulder. Orientation and position changes of the FHA over the entire range of motion were observed in the carpus and the interphalangeal joints. We report FHA position and orientation changes as a function of flexion–extension angle to allow for inclusion in a musculoskeletal model of a horse to minimize calculation errors caused by incorrect location of the FHA.     

A model of muscular control of upper airway geometry

Some disorders of the upper airway in humans are marked by decreased cross-sectional area and increased airway wall compliance. Based on our observations from studies performed in the isolated upper airway of dogs, we hypothesized that the size, and perhaps the geometry, of the airway was altered by changes in the relative activation levels of various muscle pairs. This could be accomplished either by altering the intensity of the neuromuscular input, or by activating muscle pairs which have different geometric orientation to the airway. We developed an analytic relationship to allow us to vary the stimulus level driving any one of six muscle pairs, each with a different anatomic orientation, to evaluate the relationship between those parameters and upper airway volume. With data generated from bilateral electrical stimulation of upper airway muscles, we described a shape factor which allowed us to predict the maximum force produced at optimal length. These findings were applied to a length/tension curve common to striated muscle to allow us to examine the muscle behavior at lengths other than optimal. The position of each muscle was described in spherical coordinates relative to an elastic cylinder, which represented the isolated, sealed upper airway. These coordinates defined the direction in which the force generated by each muscle pair would be applied. Three compliance constants determined the change in airway dimensions produced by the muscle force. This system and its variables were used to calculate the change in volume of the sealed upper airway chamber resulting from muscle contraction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigations of the supramolecular structure of individual diphenylalanine nano- and microtubes by polarized Raman microspectroscopy

Polarized Raman microspectroscopy and atomic force microscopy were used to obtain quantitative information regarding the molecular structure of individual diphenylalanine (FF) nano- and microtubes. The frequencies of the Raman spectral bands corresponding to the amide I (1690 cm(-1)) and amide III (1249 cm(-1)) indicated that the FF-molecules interact by hydrogen bonding at the N-H and not at the C═O sites. The calculated mean orientation angles of the principal axes of the Raman tensors (PARTs) obtained from the polarized Raman spectral measurements were 41 ± 4° for the amide I and 59 ± 5° for amide III. On the basis of the orientation of the PART for the amide I mode, it was found that the C═O bond is oriented at an angle of 8 ± 4° to the tube axis. These values did not vary significantly with the diameter of the tubes (range 400-1700 nm) and were in agreement with the molecular structure proposed previously for larger crystalline specimens.     

Departures from the physical optimality in the bronchial tree of rats (Rattus norvegicus)

We studied the departure from the physical optimality of the bronchial tree of rats using both i) the minimum volume and power and ii) the minimum surface and drag criteria, considering the bronchial junction as the unit study based on Zamir's model for vascular trees. Our results show deviations of the junctions of the bronchial tree from the expected optimums in the proximal airway that can be explained by both, the turbulent or transitional flow regime, and the airway's necessity to distribute its terminal branches in the alveolar surface filling the thoracic volume. The departures of the observed values at the optimum for the minimum volume and power were significantly different than the obtained departure values for the minimum surface and drag criteria. The departure from the optimum was directly related to the diameter of the smallest branch. The slopes of the regressions for the two criteria were different. The regression lines intercept at a bronchial diameter d2 = 0.129 mm. This result agreed with the idea that the tube diameter is limited at small values by the increasing flow resistance with decreasing tube diameter while at large values is limited by the increasing tube volume and dead space with increasing tube diameter.     

基于Linux平台的林木EST序列分析系统的构建及应用

利用Phred/Phrap/Consed、cross.match、RepeatMasker、Blast等软件和自主开发程序,基于Linux操作系统,构建了林木EST序列分析系统,完成了从测序峰图向核酸序列的转化、载体序列的去除、重复序列鉴定、EST序列分类和组装、EST序列功能注释与功能分类以及SSR、SNP的发掘。并通过使用Perl语言结合bioperl模块写的脚本程序使分析过程自动化,从而可以快速地对大批林木EST数据进行分析,为林木的功能基因组学研究提供有用的信息。     

Evidence for Functional Groupings of Vibrissae across the Rodent Mystacial Pad

During natural exploration, rats exhibit two particularly conspicuous vibrissal-mediated behaviors: they follow along walls, and “dab” their snouts on the ground at frequencies related to the whisking cycle. In general, the walls and ground may be located at any distance from, and at any orientation relative to, the rat’s head, which raises the question of how the rat might determine the position and orientation of these surfaces. Previous studies have compellingly demonstrated that rats can accurately determine the horizontal angle at which a vibrissa first touches an object, and we therefore asked whether this parameter could provide the rat with information about the pitch, distance, and yaw of a surface relative to its head. We used a three-dimensional model of the whisker array to construct mappings between the horizontal angle of contact of each vibrissa and every possible (pitch, distance, and yaw) configuration of the head relative to a flat surface. The mappings revealed striking differences in the patterns of contact for vibrissae in different regions of the array. The exterior (A, D, E) rows provide information about the relative pitch of the surface regardless of distance. The interior (B, C) rows provide distance cues regardless of head pitch. Yaw is linearly correlated with the difference between the number of right and left whiskers touching the surface. Compared to the long reaches that whiskers can make to the side and below the rat, the reachable distance in front of the rat’s nose is relatively small. We confirmed key predictions of these functional groupings in a behavioral experiment that monitored the contact patterns that the vibrissae made with a flat vertical surface. These results suggest that vibrissae in different regions of the array are not interchangeable sensors, but rather functionally grouped to acquire particular types of information about the environment.