Quantitative measurements of regional lung ventilation using helium‐3 MRI in a methacholine‐induced bronchoconstriction model

Abstract

Purpose: To demonstrate ventilation changes in an animal model of methacholine-induced bronchoconstriction using hyperpolarized (HP) helium-3 (He-3) MRI. Materials and Methods:Bronchoconstriction was induced in 11 healthy rats using an intravenous injection of methacholine. The He-3 was laser-polarized using a custom-built system. MRI studies were performed on a 2-Tesla bore magnet. Coronal dynamic ventilation images were obtained using a single inhalation of the laser-polarized He-3 gas before and after methacholine injection. Ventilation image series were processed on a pixelby-pixel basis to generate three regional ventilation parameters: gas flow rate, filling time, and maximum gas volume. Student's paired t-test was used for analysis.Results: Ventilation image series with a temporal resolution of 5 msec were obtained before and after methacholine challenge. Quantitative regional gas dynamic information demonstrated statistically significant differences between the baseline and constricted states. Following methacholine injection, the mean flow values were significantly lower for the right lung (RL) (P ϭ 0.006) and left lung (LL) (P ϭ 0.024), while the mean filling time was found to be greater (RL: P ϭ 0.08, LL: P ϭ 0.021). Gas volume values at maximum inspiration were found to be significantly lower after methacholine (RL: P ϭ 0.002; LL: P ϭ 0.036). Conclusion:He-3 MRI demonstrated and quantified regional ventilation changes in bronchoconstriction conditions in rats. EARLY HYPERPOLARIZED (HP) helium-3 (He-3) MRI studies in humans focused on static imaging of airways and airspaces in an inspiratory breath-hold. However, additional imaging strategies are required to improve the method, especially when obtaining lung function information. Typically, a temporal resolution of a few hundred milliseconds is required in order to monitor the ventilation process. Several approaches that rely on the use of fast imaging sequences during a single gas inspiration have been developed. The feasibility of such techniques, using fast low-angle shot (FLASH), rapid acquisition with relaxation enhancement (RARE), echoplanar imaging (EPI), or spiral acquisition, has already been described (1-6). In a previous work, a radial acquisition strategy combined with the sliding window method (7) was developed. This methodological approach, which is referred to as Sliding Pulmonary Imaging for Respiratory Overview (SPIRO) (8), enables the acquisition of quantitative local gas dynamic information using a single breath of polarized gas. Quantitative ventilation parameters, such as gas arrival time, average inflation rate (AIR), maximum gas volume, and filling time, could be obtained in small animals at the pixel level. In this work we demonstrate ventilation changes in an animal model of methacholine-induced bronchoconstriction using the SPIRO technique. MATERIALS AND METHODS Laser-Polarized He-3 Preparation and AdministrationHP He-3 was prepared using a custom-built polarizer based on a spin-exchange technique (9 -12). He-3 polarization l...

Rapid and efficient mapping of regional ventilation in the rat lung using hyperpolarized 3He with Flip angle variation for offset of RF and relaxation (FAVOR)

“…This is important for capturing rapid airway bronchoconstriction/dilation responses (Ͻ1 min) associated with the MCh challenge in rodents and humans (6,7,18,19). Alternate means for capturing fast bronchoconstriction include the sliding pulmonary imaging for respiratory overview (SPIRO) technique (4,20). This technique is capable of making images with 5 ms temporal spacing over 5 sec and regional measurements of average inflation rate, filling time, and maximum volume.…”

“…Perhaps most important, the conventional technique involving multiple 3 He and air breathing cycles requires several minutes (Ϸ10 min) for a single ventilation map, which is likely too slow to capture rapid changes in ventilation associated with short-duration bronchoconstriction such as a methacholine (MCh) challenge (Ͻ1 min), similar to asthma (4,5). Previous work has been limited to measurement of pre-and postsensitization effects or postlong-term challenge in part due to the time required to measure ventilation using the conventional method.…”

Functional MRI of the Lung

“…The velocity of HP gas in the lungs can be measured from velocity-encoded MR imaging sequences and HP gases lung inflow or outflow can be derived from dynamic ventilation image series [44]. Among other applications, these dynamic gas MRI techniques have been used in animal models for the evaluation of bronchoconstrictive drug effects [45] and in clinical studies following lung transplant in patients [46]. Chemical shift imaging has been demonstrated using HP 129Xe.…”

“…More recently, pO 2 imaging and oxygen depletion rate imaging was extended to small animal studies in rats and mice [52,53]. The potential of 3He MRI for assessing airways constriction has been demonstrated in methacholineinduced bronchoconstriction in rat models [45]. Using a Cine-MRI approach in which image acquisition was synchronized with the inhalation of the gas mixture (3He with oxygen and nitrogen), heterogeneously distributed airways constriction was observed, resulting in a partition of the lung between ventilated and non-ventilated regions.…”

Spatially resolved assessment of serotonin‐induced bronchoconstrictive responses in the rat lung using 3He ventilation MRI under spontaneous breathing conditions

“…Chen and Johnson (1) have observed heterogeneously distributed ventilation defects following methacholine challenge in rats. Mosbah et al (2) reported delayed distal lung filling following intravenous injection of methacholine in rats. Similarly, airway closures and ventilation losses were observed in mouse models of asthma, with the animals being sensitized to ovalbumin and challenged with methacholine (3,4).…”