Improved technique for measurement of regional fractional ventilation by hyperpolarized 3He MRI

Obstructive and restrictive lung diseases such as emphysema, asthma, and cystic fibrosis adversely affect gas flow in the lungs and therefore compromise regional lung ventilation. Noninvasive assessment of regional lung function is therefore of critical importance in quantifying the severity of the disease, evaluating response to therapy, and predicting the clinical outcome. Pulmonary function tests (such as spirometry and diffusing capacity) provide an inexpensive yet insensitive measure of lung function (1,2). These techniques only provide a global measure of lung function and, contrary to noninvasive imaging techniques, can be insensitive to regional alterations in lung function (3,4). The common clinical lung imaging technique is radio-nuclide ventilation-perfusion scintigraphy, e.g., with 133Xe (5). Qualitative information about regional ventilation can also be obtained using radioactive aerosols (6). Although noninvasive and widely available, these techniques suffer from poor spatial resolution and exposure to radioactive materials. Regional pulmonary ventilation has also been measured from CT images using certain contrast agents, most commonly the radiodense tracer gas xenon (7). CT techniques provide high spatial resolution and a high degree of anatomic localization of the change of regional lung attenuation during the wash-in and subsequent washout of xenon (8). This technique, however, requires repeated measurements and therefore repeated exposure to ionizing radiation (9). Additionally, xenon has anesthetic and sedative properties that limit the concentration, the achievable contrast enhancement, and consequently the signal-to-noise ratio (SNR) (10). Hyperpolarized 3He MRI (HP 3He MRI) has become an attractive imaging modality for regional assessment of lung function (11,12), with promising temporal and spatial resolution and a very attractive safety profile. HP 3He MRI has opened the possibility for noninvasive visualization of ventilated lung airspaces and has recently been used in assessment of asthma, emphysema, and cystic fibrosis (13–15), as well as bronchiolitis obliterans post–lung transplantation (16). Static spin density 3He images can be obtained during a breath hold to detect ventilation defects (17). Defect maps and deviations in dynamic ventilation patterns have been shown on HP 3He MR images reflecting gas trapping in these conditions (13,18). Nevertheless, a more effective assessment of pulmonary diseases requires an imaging technique capable of providing quantitative gas replacement and distribution parameters. For instance, emphysema and asthma are characterized by diminished regional gas flow and exhibit an inhomogeneous gas distribution. Quantitative measurement of these pulmonary parameters is therefore the subject of ongoing research. Deninger et al. (19) developed a technique for quantitative measurement of regional pulmonary ventilation based on signal buildup in the lung following a sequence of HP 3He breaths. This technique, however, in its proposed form is limited to use in small animals as it requires many HP 3He breaths and a relatively long acquisition time. These properties made the implementation of this technique impractical in large animals and in humans. In this manuscript, an improved technique for imaging quantitative regional lung ventilation is developed and described, which allows for acquisition of similar regional ventilation information over a much shorter time scale and with substantially fewer HP 3He breaths. Furthermore, this work discusses some important issues related to dead-space modeling as relevant to regional measurements of lung ventilation.