[Show abstract][Hide abstract] ABSTRACT: The Zone model of pulmonary perfusion predicts that exercise reduces perfusion heterogeneity because increased vascular pressure redistributes flow to gravitationally nondependent lung, and causes dilation and recruitment of blood vessels. However, during exercise in animals, perfusion heterogeneity as measured by the relative dispersion (RD, SD/mean) is not significantly decreased. We evaluated the effect of exercise on pulmonary perfusion in 6 healthy supine humans using magnetic resonance imaging (MRI).
Data were acquired at rest, while exercising (~27% of maximal oxygen consumption) using a MRI compatible ergometer, and in recovery. Images were acquired in most of the right lung in the sagittal plane at functional residual capacity, using a 1.5T MR scanner equipped with a torso coil. Perfusion was measured using arterial spin labeling (ASL-FAIRER) and regional proton density using a fast multi-echo gradient-echo sequence. Perfusion images were corrected for coil-based signal heterogeneity, large conduit vessels removed and quantified in ml/min/ml (perfusion) and also normalized for density and quantified in ml/min/g (density normalized perfusion, DNP) accounting for tissue redistribution.
DNP increased during exercise (11.1±3.5 rest, 18.8±2.3 exercise, 13.2±2.2 recovery, ml/min/g, p<0.0001) and the increase was largest in nondependent lung (110±61% increase in nondependent, 63±35% in mid, 70±33% in dependent, p<0.005). The RD of perfusion decreased with exercise (0.93±0.21 rest, 0.73±0.13 exercise, 0.94 ±0.18 recovery p<0.005). The RD of DNP showed a similar trend (0.82±0.14 rest, 0.75±0.09 exercise, 0.81±0.10 recovery, p=0.13).
In contrast to animal studies, in supine humans, mild exercise decreased perfusion heterogeneity, consistent with Zone model predictions.
[Show abstract][Hide abstract] ABSTRACT: Introduction: Heavy exercise increases ventilation-perfusion mismatch and decreases pulmonary gas exchange efficiency. Previous work using magnetic resonance imaging (MRI) arterial spin labeling (ASL) in athletes has shown that after 45 min of heavy exercise the spatial heterogeneity of pulmonary blood flow was increased in recovery. We hypothesized that the heterogeneity of regional specific ventilation (SV, the local tidal volume over functional residual capacity ratio) would also be increased following sustained exercise consistent with the previously documented changes in blood flow heterogeneity. Methods: Trained subjects (n=6, VO2max=61±7mL•kg(-1)•min(-1)) cycled 45min at their individually determined ventilatory threshold. Oxygen-enhanced MRI was used to quantify SV in a sagittal slice of the right lung in supine posture before (pre-exercise) and 15-min and 60-min post-exercise. ASL was used to measure pulmonary blood flow in the same slice bracketing the SV measures. Heterogeneity of SV and blood flow were quantified by relative dispersion (RD=SD/mean). Results: The alveolar-arterial oxygen difference was increased during exercise: 23.3±5.3 torr compared to rest: 6.3±3.7 torr, indicating a gas exchange impairment during exercise. No significant change in RD of SV was seen after exercise: pre-exercise 0.78±0.15, 15-min post 0.81±0.13, 60-min post 0.78±0.08 (P=0.5). The RD of blood flow increased significantly post-exercise: pre-exercise 1.00±0.12, 15-min post 1.15±0.10, 45-min post 1.10±0.10, 60-min post 1.19±0.11, 90 min 1.11±0.12 (P<0.005). Conclusion: The lack of a significant change in RD of SV post-exercise despite an increase in the RD of blood-flow, suggests that airways may be less susceptible to the effects of exercise than blood vessels.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the nature of small scale lung deformation between multiple pulmonary magnetic resonance images, two different kinematic intensity based image registration techniques: affine and bicubic Hermite interpolation were tested. The affine method estimates uniformly distributed deformation metrics throughout the lung. The bicubic Hermite method allows the expression of heterogeneously distributed deformation metrics such as Lagrangian strain. A cardiac triggered inversion recovery technique was used to obtain 10 sequential images of pulmonary vessel structure in a sagittal plane in the right lung at FRC in 4 healthy subjects (Age: 28.5(6.2)). One image was used as the reference image, and the remaining images (target images) were warped onto the reference image using both image registration techniques. The normalized correlation between the reference and the transformed target images within the lung domain was used as a cost function for optimization, and the root mean square (RMS) of image intensity difference was used to evaluate the quality of the registration. Both image registration techniques significantly improved the RMS compared with non-registered target images (p= 0.04). The spatial mean (µE) and standard deviation (σ(E)) of Lagrangian strain were computed based on the spatial distribution of lung deformation approximated by the bicubic Hermite method, and were measured on the order of 10(-3) or less, which is virtually negligible. As a result, small scale lung deformation between FRC lung volumes is spatially uniform, and can be simply characterized by affine deformation even though the bicubic Hermite method is capable of expressing complicated spatial patterns of lung deformation.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 08/2012; 2012:5298-301. DOI:10.1109/EMBC.2012.6347190
[Show abstract][Hide abstract] ABSTRACT: To validate a fast gradient echo sequence for rapid (9 s) quantitative imaging of lung water.
Eleven excised pig lungs were imaged with a fast GRE sequence in triplicate, in the sagittal plane at 2 levels of inflation pressure (5 and 15 cm H(2) O), an intervention that alters T(2) *, but not total lung water. Images were acquired alternating between two closely-spaced echoes and data were fit (voxel-by-voxel) to a single exponential to determine T(2) * and water content, and compared with gravimetric measurements of total water.
T(2) * averaged 1.08 ± 0.02 ms at 5 cm H(2) O and 1.02 ± 0.02 ms at 15 cm H(2) O (P < 0.05). The measure was reliable (R(2) = 0.99), with an average mean error of 1.8%. There was a significant linear relationship between the two measures of water content: The regression equations for the relationship were y = 0.92x + 19 (R(2) = 0.94), and y = 1.04x + 4 (R(2) = 0.96), for 5 and 15 cm H(2) O inflation pressure respectively. Y-intercepts were not statistically different from zero (P = 0.86).
The multi-echo GRE sequence is a reliable and valid technique to assess water content in the lung. This technique enables rapid assessment of lung water, which is advantageous for in vivo studies.
Journal of Magnetic Resonance Imaging 07/2011; 34(1):220-4. DOI:10.1002/jmri.22600 · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This demonstrates a MR imaging method to measure the spatial distribution of pulmonary blood flow in healthy subjects during normoxia (inspired O(2), fraction (F(I)O(2)) = 0.21) hypoxia (F(I)O(2) = 0.125), and hyperoxia (F(I)O(2) = 1.00). In addition, the physiological responses of the subject are monitored in the MR scan environment. MR images were obtained on a 1.5 T GE MRI scanner during a breath hold from a sagittal slice in the right lung at functional residual capacity. An arterial spin labeling sequence (ASL-FAIRER) was used to measure the spatial distribution of pulmonary blood flow and a multi-echo fast gradient echo (mGRE) sequence was used to quantify the regional proton (i.e. H(2)O) density, allowing the quantification of density-normalized perfusion for each voxel (milliliters blood per minute per gram lung tissue). With a pneumatic switching valve and facemask equipped with a 2-way non-rebreathing valve, different oxygen concentrations were introduced to the subject in the MR scanner through the inspired gas tubing. A metabolic cart collected expiratory gas via expiratory tubing. Mixed expiratory O(2) and CO(2) concentrations, oxygen consumption, carbon dioxide production, respiratory exchange ratio, respiratory frequency and tidal volume were measured. Heart rate and oxygen saturation were monitored using pulse-oximetry. Data obtained from a normal subject showed that, as expected, heart rate was higher in hypoxia (60 bpm) than during normoxia (51) or hyperoxia (50) and the arterial oxygen saturation (SpO(2)) was reduced during hypoxia to 86%. Mean ventilation was 8.31 L/min BTPS during hypoxia, 7.04 L/min during normoxia, and 6.64 L/min during hyperoxia. Tidal volume was 0.76 L during hypoxia, 0.69 L during normoxia, and 0.67 L during hyperoxia. Representative quantified ASL data showed that the mean density normalized perfusion was 8.86 ml/min/g during hypoxia, 8.26 ml/min/g during normoxia and 8.46 ml/min/g during hyperoxia, respectively. In this subject, the relative dispersion, an index of global heterogeneity, was increased in hypoxia (1.07 during hypoxia, 0.85 during normoxia, and 0.87 during hyperoxia) while the fractal dimension (Ds), another index of heterogeneity reflecting vascular branching structure, was unchanged (1.24 during hypoxia, 1.26 during normoxia, and 1.26 during hyperoxia). Overview. This protocol will demonstrate the acquisition of data to measure the distribution of pulmonary perfusion noninvasively under conditions of normoxia, hypoxia, and hyperoxia using a magnetic resonance imaging technique known as arterial spin labeling (ASL). Rationale: Measurement of pulmonary blood flow and lung proton density using MR technique offers high spatial resolution images which can be quantified and the ability to perform repeated measurements under several different physiological conditions. In human studies, PET, SPECT, and CT are commonly used as the alternative techniques. However, these techniques involve exposure to ionizing radiation, and thus are not suitable for repeated measurements in human subjects.
Journal of Visualized Experiments 01/2011; DOI:10.3791/2712 · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is a gravitational influence on pulmonary perfusion, including in the most dependent lung, where perfusion is reduced, termed Zone 4. Studies using xenon-133 show Zone 4 behaviour, present in the dependent 4 cm at total lung capacity (TLC), affects the dependent 11 cm at functional residual capacity (FRC) and almost all the lung at residual volume (RV). These differences were ascribed to increased resistance in extra-alveolar vessels at low lung volumes although other mechanisms have been proposed. To further evaluate the behaviour of perfusion in dependent lung using a technique that directly measures pulmonary perfusion and corrects for tissue distribution by measuring regional proton density, seven healthy subjects (age = 38 ± 6 years, FEV₁ = 104 ± 7% predicted) underwent magnetic resonance imaging in supine posture. Data were acquired in the right lung during breath-holds at RV, FRC and TLC. Arterial spin labelling quantified regional pulmonary perfusion, which was normalized for regional proton density measured using a fast low-angle shot technique. The height of the onset of Zone 4 behaviour was not different between lung volumes (P = 0.23). There were no significant differences in perfusion (expressed as ml min⁻¹ g⁻¹) between lung volumes in the gravitationally intermediate (RV = 8.9 ± 3.1, FRC = 8.1 ± 2.9, TLC = 7.4 ± 3.6; P = 0.26) and dependent lung (RV = 6.6 ± 2.4, FRC = 6.1 ± 2.1, TLC = 6.4 ± 2.6; P = 0.51). However, at TLC perfusion was significantly lower in non-dependent lung than at FRC or RV (3.6 ± 3.3, 7.7 ± 1.5, 7.9 ± 2.0, respectively; P < 0.001). These data suggest that the mechanism of the reduction in perfusion in dependent lung is unlikely to be a result of lung volume related increases in resistance in extra-alveolar vessels. In supine posture, the gravitational influence on perfusion is remarkably similar over most of the lung, irrespective of lung volume.
The Journal of Physiology 10/2010; 588(Pt 23):4759-68. DOI:10.1113/jphysiol.2010.196063 · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Specific ventilation (SV) is the ratio of fresh gas entering a lung region divided by its end-expiratory volume. To quantify the vertical (gravitationally dependent) gradient of SV in eight healthy supine subjects, we implemented a novel proton magnetic resonance imaging (MRI) method. Oxygen is used as a contrast agent, which in solution changes the longitudinal relaxation time (T1) in lung tissue. Thus alterations in the MR signal resulting from the regional rise in O(2) concentration following a sudden change in inspired O(2) reflect SV-lung units with higher SV reach a new equilibrium faster than those with lower SV. We acquired T1-weighted inversion recovery images of a sagittal slice of the supine right lung with a 1.5-T MRI system. Images were voluntarily respiratory gated at functional residual capacity; 20 images were acquired with the subject breathing air and 20 breathing 100% O(2), and this cycle was repeated five times. Expired tidal volume was measured simultaneously. The SV maps presented an average spatial fractal dimension of 1.13 ± 0.03. There was a vertical gradient in SV of 0.029 ± 0.012 cm(-1), with SV being highest in the dependent lung. Dividing the lung vertically into thirds showed a statistically significant difference in SV, with SV of 0.42 ± 0.14 (mean ± SD), 0.29 ± 0.10, and 0.24 ± 0.08 in the dependent, intermediate, and nondependent regions, respectively (all differences, P < 0.05). This vertical gradient in SV is consistent with the known gravitationally induced deformation of the lung resulting in greater lung expansion in the dependent lung with inspiration. This SV imaging technique can be used to quantify regional SV in the lung with proton MRI.
[Show abstract][Hide abstract] ABSTRACT: Rapid infusion of intravenous saline, a model of pulmonary interstitial edema, alters the distribution of pulmonary perfusion, raises pulmonary capillary blood volume, and increases bronchial wall thickness in humans. We hypothesized that infusion would disrupt pulmonary gas exchange by increasing ventilation/perfusion (V̇ A/Q̇ ) inequality as opposed to a diffusive impairment in O2 exchange. Seven males (26 ± 3 yr; FEV1: 110 ± 16% predicted.) performed spirometry and had V̇ A/Q̇ mismatch measured using the multiple inert gas elimination technique, before and after 20 ml/kg iv of normal saline delivered in ∼30 min. Infusion increased thoracic fluid content from transthoracic impedance by 12% (P < 0.0001) and left FVC unchanged but reduced expiratory flows (FEF25-75 falling from 5.1 ± 0.4 to 4.2 ± 0.4 l/s, P < 0.05). However, V̇ A/Q̇ mismatch as measured by the log standard deviation of the ventilation (LogSDV̇ ) and perfusion (LogSDQ̇ ) distributions remained unchanged; LogSDV̇ : 0.40 ± 0.03 pre, 0.38 ± 0.04 post, NS; LogSDQ̇ : 0.38 ± 0.03 pre, 0.37 ± 0.03 post, NS. There was no significant change in arterial PO2 (99 ± 2 pre, 99 ± 3 mmHg post, NS) but arterial PCO2 was decreased (38.7 ± 0.6 pre, 36.8 ± 1.2 mmHg post, P < 0.05). Thus, infusion compressed small airways and caused a mild degree of hyperventilation. There was no evidence for a diffusive limitation to O2 exchange, with the measured-predicted alveolar-arterial oxygen partial pressure difference being unaltered by infusion at FIO2 = 0.125 (4.3 ± 1.0 pre, 5.2 ± 1.0 post, NS). After infusion, the fraction of perfusion going to areas with V̇A/Q̇ < 1 was increased when a subject breathed a hyperoxic gas mixture [0.72 ± 0.06 (FIO2 = 0.21), 0.80 ± 0.06 (FIO2 = 0.30), P < 0.05] with similar effects on ventilation in the face of unchanged V̇A and Q̇ . These results suggest active control of blood flow to regions of decreased ventilation during air breathing, thus minimizing the gas exchange consequences.
[Show abstract][Hide abstract] ABSTRACT: To evaluate lung water density at three different levels of lung inflation in normal lungs using a fast gradient echo sequence developed for rapid imaging.
Ten healthy volunteers were imaged with a fast gradient echo sequence that collects 12 images alternating between two closely spaced echoes in a single 9-s breathhold. Data were fit to a single exponential to determine lung water density and T(2) (*). Data were evaluated in a single imaging slice at total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV). Analysis of variance for repeated measures was used to statistically evaluate changes in T(2) (*) and lung water density across lung volumes, imaging plane, and spatial locations in the lung.
In normal subjects (n = 10), T(2) (*) (and [lung density/water density]) was 1.2 +/- 0.1 msec (0.10 +/- 0.02), 1.8 +/- 0.2 ms (0.25 +/- 0.04), and 2.0 +/- 0.2 msec (0.27 +/- 0.03) at TLC, FRC, and RV, respectively. Results also show that there is a considerable intersubject variability in the values of T(2) (*).
Data show that T(2) (*) in the lung is very short, and varies considerably with lung volume. Thus, if quantitative assessment of lung density within a breathhold is to be measured accurately, then it is necessary to also determine T(2) (*).
Journal of Magnetic Resonance Imaging 09/2009; 30(3):527-34. DOI:10.1002/jmri.21866 · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Prone posture increases cardiac output and improves pulmonary gas exchange. We hypothesized that, in the supine posture, greater compression of dependent lung limits regional blood flow. To test this, MRI-based measures of regional lung density, MRI arterial spin labeling quantification of pulmonary perfusion, and density-normalized perfusion were made in six healthy subjects. Measurements were made in both the prone and supine posture at functional residual capacity. Data were acquired in three nonoverlapping 15-mm sagittal slices covering most of the right lung: central, middle, and lateral, which were further divided into vertical zones: anterior, intermediate, and posterior. The density of the entire lung was not different between prone and supine, but the increase in lung density in the anterior lung with prone posture was less than the decrease in the posterior lung (change: +0.07 g/cm(3) anterior, -0.11 posterior; P < 0.0001), indicating greater compression of dependent lung in supine posture, principally in the central lung slice (P < 0.0001). Overall, density-normalized perfusion was significantly greater in prone posture (7.9 +/- 3.6 ml.min(-1).g(-1) prone, 5.1 +/- 1.8 supine, a 55% increase; P < 0.05) and showed the largest increase in the posterior lung as it became nondependent (change: +71% posterior, +58% intermediate, +31% anterior; P = 0.08), most marked in the central lung slice (P < 0.05). These data indicate that central posterior portions of the lung are more compressed in the supine posture, likely by the heart and adjacent structures, than are central anterior portions in the prone and that this limits regional perfusion in the supine posture.