Functional imaging of airway narrowing
Introduction
In this chapter we will focus on the use of high resolution computed tomography (HRCT) to visualize airway size in vivo. Although other imaging modalities have potential to see into the lung in vivo, none presently have the convenience, the accessibility nor the resolution required to visualize airways. Although magnetic resonance imaging (MRI) avoids the potential concern about ionizing radiation, there is insufficient signal from airway walls to visualize anything but the largest airways. Inhaling hyperpolarized noble gases can provide a much stronger signal in MRI, but such experiments are technically cumbersome, costly and not generally available.
This report will review studies that illustrate the insights that can be obtained with HRCT as used in animals and humans. While several investigators have used HRCT to examine contraction of airways to various bronchoconstrictors (Okazawa et al., 1996, Kee et al., 1996, McNitt-Gray et al., 1997, Goldin et al., 1998, Han et al., 2000, Amirav et al., 2001), in this report we will focus on work from our laboratory that demonstrates the unique ability of HRCT to dissect mechanisms of airway contraction in vivo. Specifically, we will describe the use of HRCT to study the ability of individual airways to contract to closure. A second group of experiments deals with the effect of deep inspiration on individual airways. There are no other methods that allow this kind of insight or investigation of airway behavior in vivo.
Section snippets
Maximal contraction
When airways constrict in vitro, they generally do not exhibit a plateau effect to an agonist challenge, but continue to constrict to increasing concentrations of agonist until complete airway closure occurs (Armour et al., 1984, DeJongste et al., 1988). Thus, any apparent limitation in airway narrowing in vivo must be due to mechanisms not directly related to limitations associated with airway smooth muscle contraction. The appearance of a plateau in vivo (Woolcock et al., 1984, Sterk et al.,
Effects of deep inspiration (DI) on airway constriction
It has been known for many years that the response of asthmatic subjects to a deep inspiration differs from that observed in normal healthy subjects (Gayrard et al., 1975, Fish et al., 1977, Fish et al., 1981, Orehek et al., 1980, Beaupre and Orehek, 1982, Wheatley et al., 1989, Bousquet et al., 1996). A deep inspiration causes a fall in airway resistance in normal subjects, whereas asthmatic subjects demonstrate either no change or a slight increase in airway resistance. Skloot et al. (1995)
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Canine models of asthma and COPD
2008, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :Many of the mediators of anaphylaxis, including histamine produce regional heterogeneity of ventilation in the lung [43,44]. Furthermore, studies using high-resolution computed tomography demonstrate that complete closure of both central and peripheral airways occurs in dogs after broncoprovacation with spasmogens such as histamine or methacholine [47]. Therefore, constriction of both central and distal airways occurs in dogs with bronchoconstrictor challenge, which is similar to the changes in airway mechanics seen in human asthma.
Effects of graded exercise on bronchial blood flow and airway dimensions in sheep
2007, Pulmonary Pharmacology and TherapeuticsCitation Excerpt :The final outcome in terms of a net integrated effect on the bronchial wall and its circulation in freely exercising man and other mammals remains unclear [1]. There is, therefore, recent interest in new techniques which can accurately target specific airways and their blood flow, and examine mechanisms [1,15]. High-resolution computed tomography has shown clearly in man and animals that lower airways of different size, and with different degrees of methacholine-induced tone, vary in their response to controlled lung inflation [10,15].
Transport and deposition of respiratory aerosols in models of childhood asthma
2006, Journal of Aerosol ScienceCitation Excerpt :To represent asthma associated airway constriction, a 30% diameter reduction was implemented. This reduction in diameter is consistent with the observations of Brown and Mitzner (2003), who report a minimum of 30% diameter reduction (50% area reduction) for a canine model with exposure to methacholine aerosol. A number of other asthma related imaging studies report significant variations in cross-sectional area reductions ranging from 30% to complete closure (Goldin et al., 1998; Okazawa et al., 1996).
Imaging physiological parameters with hyperpolarized gas MRI
2005, Progress in Nuclear Magnetic Resonance Spectroscopy