Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling.

Image functional modeling (IFM) has been introduced as a method to simultaneously synthesize imaging and mechanical data with computational models to determine the degree and location of airway constriction in asthma. Using lung imaging provided by hyperpolarized (3)He MRI, we advanced our IFM method to require matching not only to ventilation defect location but to specific ventilation throughout the lung. Imaging and mechanical data were acquired for four healthy and four asthmatic subjects pre- and postbronchial challenge. After provocation, we first identified maximum-size airways leading exclusively to ventilation defects and highly constricted them. Constriction patterns were then found for the remaining airways to match mechanical data. Ventilation images were predicted for each pattern, and visual and statistical comparisons were done with measured data. Results showed that matching of ventilation defects requires severe constriction of small airways. The mean constriction of such airways leading to the ventilation defects needed to be 70-80% rather than fully closed. Also, central airway constriction alone could not account for dysfunction seen in asthma, so small airways must be involved.

The difference in ventilation heterogeneity between asthmatic and healthy subjects quantified using hyperpolarized 3He MRI.

In this pilot study, algorithms for quantitatively evaluating the distribution and heterogeneity of human ventilation imaged with hyperpolarized (HP) (3)He MRI were developed for the goal of examining structure-function relationships within the asthmatic lung. Ten asthmatic and six healthy human subjects were imaged with HP (3)He MRI before bronchial challenge (pre-MCh), after bronchial challenge (post-MCh), and after a series of deep inspirations (post-DI) following challenge. The acquired images were rigidly coregistered. Local voxel fractional ventilation was computed by setting the sum of the pixel intensity within the lung region in each image to 1 liter of inhaled (3)He mixture. Local ventilation heterogeneity was quantified by computing regional signal coefficient of variation. Voxel fractional ventilation histograms and overall heterogeneity scores were then calculated. Asthmatic subjects had a higher ventilation heterogeneity to begin with (P = 0.025). A methacholine challenge elevated ventilation heterogeneity for all subjects (difference: P = 0.08). After a DI postchallenge, this heterogeneity reversed substantially toward the baseline state for healthy subjects but only minimally in asthmatic subjects. This difference was significant in absolute quantity (difference: P = 0.007) as well as relative to the initial increase (difference: P = 0.03). These findings suggest that constriction heterogeneity is not a characteristic unique to asthmatic airway trees but rather a behavior intrinsic to all airway trees when provoked. Once ventilation heterogeneity is established, it is the lack of reversal following DIs that distinguishes asthmatics from non-asthmatics.

Investigation of hyperpolarized 3He magnetic resonance imaging utility in examining human airway diameter behavior in asthma through comparison with high-resolution computed tomography.

RATIONALE AND OBJECTIVES: Application of a previously developed model-based algorithm on hyperpolarized (HP) (3)He magnetic resonance (MR) dynamic projection images of phantoms was extended to investigate the utility of HP (3)He MR imaging (MRI) in quantifying airway caliber changes associated with asthma. MATERIALS AND METHODS: Airways of seven volunteers were imaged and measured using HP (3)He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data were obtained at functional residual capacity and 1 L above functional residual capacity. RESULTS: Comparison of the resultant data showed that HP (3)He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37% to 43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did yield the observation that 49% to 69% of these airways displayed bronchodilation following MCh challenge. CONCLUSION: The current implementation of HP (3)He MRI did not match the MCh-induced postchallenge-to-prechallenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation.

Comparison of airway diameter measurements from an anthropomorphic airway tree phantom using hyperpolarized 3He MRI and high-resolution computed tomography.

An anthropomorphic airway tree phantom was imaged with both hyperpolarized (HP) 3He MRI using a dynamic projection scan and computed tomography (CT). Airway diameter measurements from the HP 3He MR images obtained using a newly developed model-based algorithm were compared against their corresponding CT values quantified with a well-established method. Of the 45 airway segments that could be evaluated with CT, only 14 airway segments (31%) could be evaluated using HP 3He MRI. No airway segments smaller than approximately 4 mm in diameter and distal to the fourth generation were adequate for analysis in MRI. For the 14 airway segments measured, only two airway segments yielded a non-equivalent comparison between the two imaging modalities, while eight more had inconclusive comparison results, leaving only four airway segments (29%) that satisfied the designed equivalence criteria. Some of the potential problems in airway diameter quantification described in the formulation of the model-based algorithm were observed in this study. These results suggest that dynamic projection HP 3He MRI may have limited utility for measuring airway segment diameters, particularly those of the central airways.

Measurement of the internal diameter of plastic tubes from projection MR images using a model-based least-squares fit approach.

Hyperpolarized (HP) 3He MRI is an emerging tool in the diagnosis and evaluation of pulmonary diseases involving bronchoconstriction, such as asthma. Previously, airway diameters from dynamic HP 3He MR images of the lung were assessed manually and subjectively, and were thus prone to uncertainties associated with human error and partial volume effects. A model-based algorithm capable of fully utilizing pixel intensity profile information and attaining subpixel resolution has been developed to measure surrogate airway diameters from HP 3He MR static projection images of plastic tubes. This goal was achieved by fitting ideal pixel intensity profiles for various diameter (6.4 to 19.1 mm) circular tubes to actual pixel intensity data. A phantom was constructed from plastic tubes of various diameters connected in series and filled with water mixed with contrast agent. Projection MR images were then taken of the phantom. The favorable performance of the model-based algorithm compared to manual assessment demonstrates the viability of our approach. The manual and algorithm approaches yielded diameter measurements that generally stayed within 1 x the pixel dimension. However, inconsistency of the manual approach can be observed from the larger standard deviations of its measured values. The method was then extended to HP 3He MRI, producing encouraging results at tube diameters characteristic of airways beyond the second generation, thereby justifying their application to lung airway imaging and measurement. Potential obstacles when measuring airway diameters using this method are discussed.

Quantification of airway diameters and 3D airway tree rendering from dynamic hyperpolarized 3He magnetic resonance imaging.

As another step toward extracting quantitative information from hyperpolarized 3He MRI, airway diameters in humans were measured from projection images and multislice images of the lungs. Values obtained were in good agreement with the Weibel lung morphometry model. The measurement of airway caliber can now be achieved without the use of ionizing radiation. Furthermore, it was demonstrated that 3D airway tree renderings could be constructed from the multislice data. Both the measurement of airway diameters and the rendering of 3D airway information hold promise for the clinical assessment of bronchoconstrictive diseases such as asthma and the associated evaluation of treatment effectiveness. Work is being done to address the uncertainties of the manually intensive methods we have developed.