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

Changes in lung function and structure were studied using hyperpolarized (3)He MRI in an elastase-induced murine model of emphysema. The combined analysis of the apparent diffusion coefficient (ADC) and fractional ventilation (R) were used to distinguish emphysematous changes and also to develop a model for classifying sections of the lung into diseased and normal. Twelve healthy male BALB/c mice (26 ± 2 g) were randomized into healthy and elastase-induced mice and studied ∼8-11 wk after model induction. ADC and R were measured at a submillimeter planar resolution. Chord length (L(x)) data were analyzed from histology samples from the corresponding imaged slices. Logistic regression was applied to estimate the probability that an imaged pixel came from a diseased animal, and bootstrap methods (1,000 samples) were used to compare the regression results for the morphological and imaging results. Multivariate ANOVA (MANOVA) was used to analyze transformed ADC (ADC(BC)), and R (R(BC)) data and also to control for the experiment-wide error rate. MANOVA and ANOVA showed that elastase induced a statistically measureable change in the average transformed L(x) and ADC(BC) but not in the average R(BC). Marginal mean analysis demonstrated that ADC(BC) was on average 0.19 [95% confidence interval (CI): 0.16, 0.22] higher in the emphysema group, whereas R(BC) was on average 0.05 (95% CI: 0.04, 0.06) lower. Logistic regression supported the hypothesis that ADC(BC) and R(BC), together, were better at differentiating normal from diseased tissue than either measurement alone. The odds ratios for ADC(BC) and R(BC) were 7.73 (95% CI: 5.23, 11.42) and 9.14 × 10(-5) (95% CI: 3.33 × 10(-5), 25.06 × 10(-5)), respectively. Using a 50% probability cutoff, this model classified 70.6% of pixels correctly. The sensitivity and specificity of this model at the 50% cutoff were 74.9% and 65.2%, respectively. The area under the receiver operating characteristic curve was 0.76 (95% CI: 0.74, 0.78). The regression model presented can be used to map MRI data to disease probability maps. These probability maps present a future possibility of using both measurements in a more clinically feasible method of diagnosing this disease.

A multislice single breath-hold scheme for imaging alveolar oxygen tension in humans.

Reliable, noninvasive, and high-resolution imaging of alveolar partial pressure of oxygen (p(A)O(2)) is a potentially valuable tool in the early diagnosis of pulmonary diseases. Several techniques have been proposed for regional measurement of p(A)O(2) based on the increased depolarization rate of hyperpolarized (3) He. In this study, we explore one such technique by applying a multislice p(A)O(2) -imaging scheme that uses interleaved-slice ordering to utilize interslice time-delays more efficiently. This approach addresses the low spatial resolution and long breath-hold requirements of earlier techniques, allowing p(A)O(2) measurements to be made over the entire human lung in 10-15 s with a typical resolution of 8.3 × 8.3 × 15.6 mm(3). PO(2) measurements in a glass syringe phantom were in agreement with independent gas analysis within 4.7 ± 4.1% (R = 0.9993). The technique is demonstrated in four human subjects (healthy nonsmoker, healthy former smoker, healthy smoker, and patient with COPD), each imaged six times on 3 different days during a 2-week span. Two independent measurements were performed in each session, consisting of 12 coronal slices. The overall p(A)O(2) mean across all subjects was 95.9 ± 12.2 Torr and correlated well with end-tidal O(2) (R = 0.805, P < 0.0001). The alveolar O(2) uptake rate was consistent with the expected range of 1-2 Torr/s. Repeatable visual features were observed in p(A)O(2) maps over different days, as were characteristic differences among the subjects and gravity-dependent effects.

Quantitative imaging of alveolar recruitment with hyperpolarized gas MRI during mechanical ventilation.

The aim of this study was to assess the utility of (3)He MRI to noninvasively probe the effects of positive end-expiratory pressure (PEEP) maneuvers on alveolar recruitment and atelectasis buildup in mechanically ventilated animals. Sprague-Dawley rats (n = 13) were anesthetized, intubated, and ventilated in the supine position ((4)He-to-O(2) ratio: 4:1; tidal volume: 10 ml/kg, 60 breaths/min, and inspiration-to-expiration ratio: 1:2). Recruitment maneuvers consisted of either a stepwise increase of PEEP to 9 cmH(2)O and back to zero end-expiratory pressure or alternating between these two PEEP levels. Diffusion MRI was performed to image (3)He apparent diffusion coefficient (ADC) maps in the middle coronal slices of lungs (n = 10). ADC was measured immediately before and after two recruitment maneuvers, which were separated from each other with a wait period (8-44 min). We detected a statistically significant decrease in mean ADC after each recruitment maneuver. The relative ADC change was -21.2 ± 4.1 % after the first maneuver and -9.7 ± 5.8 % after the second maneuver. A significant relative increase in mean ADC was observed over the wait period between the two recruitment maneuvers. The extent of this ADC buildup was time dependent, as it was significantly related to the duration of the wait period. The two postrecruitment ADC measurements were similar, suggesting that the lungs returned to the same state after the recruitment maneuvers were applied. No significant intrasubject differences in ADC were observed between the corresponding PEEP levels in two rats that underwent three repeat maneuvers. Airway pressure tracings were recorded in separate rats undergoing one PEEP maneuver (n = 3) and showed a significant relative difference in peak inspiratory pressure between pre- and poststates. These observations support the hypothesis of redistribution of alveolar gas due to recruitment of collapsed alveoli in presence of atelectasis, which was also supported by the decrease in peak inspiratory pressure after recruitment maneuvers.