Effects of diffusion time on short‐range hyperpolarized ³He diffusivity measurements in emphysema

Abstract

Purpose:To characterize the effect of diffusion time on short-range hyperpolarized 3 He magnetic resonance imaging (MRI) diffusion measurements across a wide range of emphysema severity. Materials and Methods:3 He diffusion MRI was performed on 19 lungs or lobes resected from 18 subjects with varying degrees of emphysema using three diffusion times (1.6 msec, 5 msec, and 10 msec) at constant b value. Emphysema severity was quantified as the mean apparent diffusion coefficient (ADC) and as the percentage of pixels with ADC higher than multiple thresholds from 0.30 -0.55 cm 2 /sec (ADC index). Quantitative histology (mean linear intercept) was obtained in 10 of the lung specimens from 10 of the subjects. HYPERPOLARIZED3 He magnetic resonance imaging (MRI) depicts inhaled gas within the lungs. By applying diffusion-sensitizing gradients and measuring resultant changes in 3 He signal intensity, the restricted diffusion of 3 He within the airspaces of the lung can be quantified within each pixel as an apparent diffusion coefficient (ADC). Measuring the ADC over short diffusion times (milliseconds) has been used as a means of quantifying the increase in the size of lung airspaces, which defines emphysema. The 3 He ADC distinguishes individuals with and without emphysema (1,2), and is increased in many smokers with normal pulmonary function, suggesting that it is sensitive to the early stages of emphysema (3). Studies demonstrating that the ADC correlates with computed tomography (CT) measurements of lung attenuation (4,5) and with quantitative histologic measurements of airspace size (6 -8) further support its validity for quantifying emphysema. 3 He ADC measurements also appear to have good reproducibility (9 -11). Consequently, the 3 He ADC has

Regional function-structure relationships in lungs of an elastase murine model of emphysema

“…It also suggests that R may not be as sensitive to early changes in lung morphology but may become very sensitive once the disease exceeds a critical point. A DC BC and l og(L x ), as previously described (18,28), are strongly correlated (product moment correlation coefficient: 0.85, P ϭ 0.002), and A DC BC monotonically increases as l og(L x ) increases, so we anticipate that the ADC, like l og(L x ), will be sensitive to early changes in airway structure and, thus, suitable for early disease detection.…”

“…We based this hypothesis on three suppositions. The first is that ADC will be a sensitive measure of alveolar destruction and that it can be used to grade tissue destruction radiographically, comparable to the use of chord length (L x ) to grade emphysema using histological samples (18,33,52). The second supposition is that HP MRI fractional ventilation is a sensitive measure of the airflow obstruction induced by emphysema with the potential to determine contrasts significant enough to differentiate diseased from normal lung segments (13,45).…”

The influence of lung airways branching structure and diffusion time on measurements and models of short-range 3He gas MR diffusion

“…This is particularly the case when attempting to quantify morphological changes in important clinical questions such as early onset of emphysema [27] or the alveolarization of developing lungs [29], where, far-reaching clinical conclusions have been drawn about the nature of the micro-structural modifications caused by disease and growth. The results and models presented in this work may help in the development of a more realistic theoretical framework for in vivo lung morphometry using 3 He diffusion MR.…”

“…The reason for the absence of this dependence is not apparent, but may be due in part to extrapolating results obtained for a single diffusion time D = 1.8 ms [10] to a wider range of diffusion times in which the model has not been tested. The omission of this dependence is particularly significant since the cylinder model has been used to draw important clinical conclusions from the interpretation of diffusion data obtained at diffusion times up to 10 ms [27] and conclusions about the nature of structural changes in emphysema were extracted based on the assumption of a diffusion time independence of D L0 . Furthermore, the values of D L0 predicted by the cylinder model are also significantly smaller than those obtained with both the branching duct model and the long duct models for D < 4 ms.…”

Direct comparison of 129Xe diffusion measurements with quantitative histology in human lungs

“…During the 5-ms diffusion time in our experiments, a gas atom would most likely encounter one or more tissue walls that restrict motion without drifting outside of one alveolar duct. Although discussion on the importance of diffusion time and modeling has been debated extensively in the literature (48,49), experiments with 3 He have demonstrated that the diffusion time has a relatively small effect on the measured ADC compared with differences seen as a result of airspace enlargement (50). In the future we will explore multiple b-value diffusion experiments with xenon.…”