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Purpose: To evaluate regional anisotropy of lung-airspace orientation by assessing the dependence of helium-3 ((3) He) apparent diffusion coefficient (ADC) values on the direction of diffusion sensitization at two field strengths., Materials and Methods: Hyperpolarized (3) He diffusion-weighted magnetic resonance imaging (MRI) of the lung was performed at 0.43T and 1.5T in 12 healthy volunteers. A gradient-echo pulse sequence was used with a bipolar diffusion-sensitization gradient applied separately along three orthogonal directions. ADC maps, median ADC values, and signal-to-noise ratios were calculated from the diffusion-weighted images. Two readers scored the ADC maps for increased values at lung margins, major fissures, or within focal central regions., Results: ADC values were found to depend on the direction of diffusion sensitization (P < 0.01, except for craniocaudal vs. anteroposterior directions at 1.5T) and were increased at the lateral and medial surfaces for left-right diffusion sensitization (12 of 12 subjects); at the apex and base (9 of 12), and along the major fissure (8 of 12), for craniocaudal diffusion sensitization; and at the most anterior and posterior lung (10 of 12) for anteroposterior diffusion sensitization. Median ADC values at 0.43T (0.201 ± 0.017, left-right; 0.193 ± 0.019, craniocaudal; and 0.187 ± 0.017 cm(2) /s, anteroposterior) were slightly lower than those at 1.5T (0.205 ± 0.017, 0.197 ± 0.017 and 0.194 ± 0.016 cm(2) /s, respectively; P < 0.05)., Conclusion: These findings indicate that diffusion-weighted hyperpolarized (3) He MRI can detect regional anisotropy of lung-airspace orientation, including that associated with preferential orientation of terminal airways near pleural surfaces., (© 2015 Wiley Periodicals, Inc.)

Purpose: To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon-129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects., Materials and Methods: A three-dimensional, multi-echo, radial-trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue-to-gas, RBC-to-gas, and RBC-to-tissue) were calculated from the images for quantitative comparison., Results: Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior-to-posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole-lung values of total dissolved Xe129 to gas, tissue-to-gas, and RBC-to-gas ratios in healthy subjects were significantly larger than those in diseased subjects., Conclusion: Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics., (Copyright © 2013 Wiley Periodicals, Inc.)

Purpose: To develop and test a method to noninvasively assess the functional lung microstructure., Materials and Methods: The Multiple exchange time Xenon polarization Transfer Contrast technique (MXTC) encodes xenon gas-exchange contrast at multiple delay times permitting two lung-function parameters to be derived: (i) MXTC-F, the long exchange-time depolarization value, which is proportional to the tissue to alveolar-volume ratio and (ii) MXTC-S, the square root of the xenon exchange-time constant, which characterizes thickness and composition of alveolar septa. Three healthy volunteers, one asthmatic, and two chronic obstructive pulmonary disease (COPD) (GOLD stage I and II) subjects were imaged with MXTC MRI. In a subset of subjects, hyperpolarized xenon-129 ADC MRI and CT imaging were also performed., Results: The MXTC-S parameter was found to be elevated in subjects with lung disease (P-value = 0.018). In the MXTC-F parameter map it was feasible to identify regional loss of functional tissue in a COPD patient. MXTC-F maps showed excellent regional correlation with CT and ADC (P ≥ 0.90) in one COPD subject., Conclusion: The functional tissue-density parameter MXTC-F showed regional agreement with other imaging techniques. The newly developed parameter MXTC-S, which characterizes the functional thickness of alveolar septa, has potential as a novel biomarker for regional parenchymal inflammation or thickening., (Copyright © 2011 Wiley-Liss, Inc.)

Purpose: To propose and test the feasibility of a novel method for quantifying 3D regional pulmonary kinematics from hyperpolarized helium-3 tagged MRI in human subjects using a tailored image processing pipeline and a recently developed nonrigid registration framework., Materials and Methods: Following image acquisition, inspiratory and expiratory tagged (3)He magnetic resonance (MR) images were preprocessed using various image filtering techniques to enhance the tag surfaces. Segmentation of the three orthogonal sets of tag planes in each lung produced distinct point-set representations of the tag surfaces. Using these labeled point-sets, deformation fields and corresponding strain maps were obtained via nonrigid point-set registration. Kinematic analysis was performed on three volunteers., Results: Tag lines in inspiratory and expiratory images were coregistered producing a continuous 3D correspondence mapping. Average displacement and directional strains were calculated in three subjects in the inferior, mid, and superior portions of the right and left lungs. As expected, the predominant direction of displacements with expiration is from inferior to superior., Conclusion: Kinematic quantitation of pulmonary motion using tagged (3)He MRI is feasible using the applied image preprocessing filtering techniques and nonrigid point-set registration. Potential benefits from regional pulmonary kinematic quantitation include the facilitation of diagnosis and local assessment of disease progression., (Copyright 2010 Wiley-Liss, Inc.)

Purpose: To investigate short- and long-time-scale (3)He diffusion in asthma., Materials and Methods: A hybrid MRI sequence was developed to obtain co-registered short- and long-time-scale apparent diffusion coefficient (ADC) maps during a single breath-hold. The study groups were: asthma (n = 14); healthy (n = 14); chronic obstructive pulmonary disease (COPD) (n = 9). Correlations were made between mean-ADC and %ADC-abn (abnormal) (%pixels with ADC > mean +2 SD of healthy) at both time scales and spirometry. Sensitivities were determined using receiver operating characteristic (ROC) analysis., Results: For asthmatics, the short- and long-time-scale group-mean ADCs were 0.254 +/- 0.032 cm(2)/s and 0.0237 +/- 0.0055 cm(2)/s, respectively, representing a 9% and 27% (P = 0.038 and P = 0.005) increase compared to the healthy group. The group-mean %ADC-abn were 6.4% +/- 3.7% and 17.5% +/- 14.2%, representing a 107% and 272% (P = 0.004 and P = 0.006) increase. For COPD much greater elevations were observed. %ADC-abn provided better discrimination than mean-ADC between asthmatic and healthy subjects. In asthmatics ADC did not correlate with spirometry., Conclusion: With long-time scale (3)He diffusion magnetic resonance imaging (MRI) changes in lung microstructure were detected in asthma that more conspicuous regionally than at the short time scale. The hybrid diffusion method is a novel means of identifying small airway disease., ((c) 2008 Wiley-Liss, Inc.)

Purpose: To examine the utility of a (3)He spectroscopic q-space technique for detecting changes in lung morphometry in vivo., Materials and Methods: A diffusion-weighted spectroscopy sequence was used to collect global diffusion data from healthy adults (N = 11), healthy children (N = 5), and chronic obstructive pulmonary disease (COPD) patients (N = 2) using 40 cc of hyperpolarized (3)He gas within a two second breathhold. Displacement probability profiles (DPP) were obtained by Fourier transformation of diffusion data with respect to q. A bi-Gaussian model was used to decompose the DPPs into narrow and broad components, characterized by root-mean-square displacements X(rms1) and X(rms2), respectively., Results: In healthy adults, the narrow component (X(rms,1)) of the DPP had a mean displacement of 188 +/- 10 microm, slightly less than the reported average size of the alveoli. The broad component (X(rms,2)) had a mean value of 474 +/- 44 microm, comparable to the diameter of the respiratory bronchioles in the acinus. In children, both X(rms1) (167 +/- 4 microm) and X(rms2) (382 +/- 22 microm) compared to healthy adults (P < 0.01). In COPD patients, the mean displacements were elevated (X(rms1): 265 +/- 71 microm; X(rms2): 530 +/- 109 microm) compared to healthy adults. Excellent correlation was found between rms displacements and age (age vs. X(rms,1): r = 0.78, P < 0.001; age vs. X(rms,2): r = 0.90, P < 0.001)., Conclusion: The q-space parameters agreed remarkably well with published alveolar morphometry data. The results suggest that the technique may be sensitive to disease, as evident from the elevated mean displacements in COPD patients compared to healthy volunteers. Detailed lung microstructural information can be obtained using a very low volume of inhaled (3)He., ((c) 2006 Wiley-Liss, Inc.)