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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. [ABSTRACT FROM AUTHOR]

Background Apparent diffusion coefficient (ADC) maps of inhaled hyperpolarized gases have shown promise in the characterization of emphysema in patients with chronic obstructive pulmonary disease (COPD), yet an easily interpreted quantitative metric beyond mean and standard deviation has not been established. Purpose To introduce a quantitative framework with which to characterize emphysema burden based on hyperpolarized helium 3 ( 3 He) and xenon 129 ( 129 Xe) ADC maps and compare its diagnostic performance with CT-based emphysema metrics and pulmonary function tests (PFTs). Materials and Methods Twenty-seven patients with mild, moderate, or severe COPD and 13 age-matched healthy control subjects participated in this retrospective study. Participants underwent CT and multiple b value diffusion-weighted 3 He and 129 Xe MRI examinations and standard PFTs between August 2014 and November 2017. ADC-based emphysema index was computed separately for each gas and b value as the fraction of lung voxels with ADC values greater than in the healthy group 99th percentile. The resulting values were compared with quantitative CT results (relative lung area <-950 HU) as the reference standard. Diagnostic performance metrics included area under the receiver operating characteristic curve (AUC). Spearman rank correlations and Wilcoxon rank sum tests were performed between ADC-, CT-, and PFT-based metrics, and intraclass correlation was performed between repeated measurements. Results Thirty-six participants were evaluated (mean age, 60 years ± 6 [standard deviation]; 20 women). ADC-based emphysema index was highly repeatable (intraclass correlation coefficient > 0.99) and strongly correlated with quantitative CT ( r = 0.86, P < .001 for 3 He; r = 0.85, P < .001 for 129 Xe) with high AUC (≥0.93; 95% confidence interval [CI]: 0.85, 1.00). ADC emphysema indices were also correlated with percentage of predicted diffusing capacity of lung for carbon monoxide ( r = -0.81, P < .001 for 3 He; r = -0.80, P < .001 for 129 Xe) and percentage of predicted residual lung volume divided by total lung capacity ( r = 0.65, P < .001 for 3 He; r = 0.61, P < .001 for 129 Xe). Conclusion Emphysema index based on hyperpolarized helium 3 or xenon 129 diffusion MRI provides a repeatable measure of emphysema burden, independent of gas or b value, with similar diagnostic performance as quantitative CT or pulmonary function metrics. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Schiebler and Fain in this issue.

Background: Deformable image registration (DIR)-based lung ventilation mapping is attractive due to its simplicity, and also challenging due to its susceptibility to errors and uncertainties. In this study, we explored the use of 3D Hyperpolarized (HP) gas tagging MRI to evaluate DIR-based lung ventilation., Method and Material: Three healthy volunteers included in this study underwent both 3D HP gas tagging MRI (t-MRI) and 3D proton MRI (p-MRI) using balanced steady-state free precession pulse sequence at end of inhalation and end of exhalation. We first obtained the reference displacement vector fields (DVFs) from the t-MRIs by tracking the motion of each tagging grid between the exhalation and the inhalation phases. Then, we determined DIR-based DVFs from the p-MRIs by registering the images at the two phases with two commercial DIR algorithms. Lung ventilations were calculated from both the reference DVFs and the DIR-based DVFs using the Jacobian method and then compared using cross correlation and mutual information., Results: The DIR-based lung ventilations calculated using p-MRI varied considerably from the reference lung ventilations based on t-MRI among all three subjects. The lung ventilations generated using Velocity AI were preferable for the better spatial homogeneity and accuracy compared to the ones using MIM, with higher average cross correlation (0.328 vs 0.262) and larger average mutual information (0.528 vs 0.323)., Conclusion: We demonstrated that different DIR algorithms resulted in different lung ventilation maps due to underlining differences in the DVFs. HP gas tagging MRI provides a unique platform for evaluating DIR-based lung ventilation., (© 2018 American Association of Physicists in Medicine.)

Purpose: To evaluate T 2 , T2*, and signal-to-noise ratio (SNR) for hyperpolarized helium-3 ( 3 He) MRI of the human lung at three magnetic field strengths ranging from 0.43T to 1.5T., Methods: Sixteen healthy volunteers were imaged using a commercial whole body scanner at 0.43T, 0.79T, and 1.5T. Whole-lung T 2 values were calculated from a Carr-Purcell-Meiboom-Gill spin-echo-train acquisition. T2* maps and SNR were determined from dual-echo and single-echo gradient-echo images, respectively. Mean whole-lung SNR values were normalized by ventilated lung volume and administered 3 He dose., Results: As expected, T 2 and T2* values demonstrated a significant inverse relationship to field strength. Hyperpolarized 3 He images acquired at all three field strengths had comparable SNR values and thus appeared visually very similar. Nonetheless, the relatively small SNR differences among field strengths were statistically significant., Conclusions: Hyperpolarized 3 He images of the human lung with similar image quality were obtained at three field strengths ranging from 0.43T and 1.5T. The decrease in susceptibility effects at lower fields that are reflected in longer T 2 and T2* values may be advantageous for optimizing pulse sequences inherently sensitive to such effects. The three-fold increase in T2* at lower field strength would allow lower receiver bandwidths, providing a concomitant decrease in noise and relative increase in SNR. Magn Reson Med 78:1458-1463, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 International Society for Magnetic Resonance in Medicine.)

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 and validate a method for acquiring helium-3 ((3) He) and proton ((1) H) three-dimensional (3D) image sets of the human lung with isotropic spatial resolution within a 10-s breath-hold by using compressed sensing (CS) acceleration, and to assess the fidelity of undersampled images compared with fully sampled images., Methods: The undersampling scheme for CS acceleration was optimized and tested using (3) He ventilation data. Rapid 3D acquisition of both (3) He and (1) H data during one breath-hold was then implemented, based on a balanced steady-state free-precession pulse sequence, by random undersampling of k-space with reconstruction by means of minimizing the L1 norm and total variance. CS-reconstruction fidelity was evaluated quantitatively by comparing fully sampled and retrospectively undersampled image sets., Results: Helium-3 and (1) H 3D image sets of the lung with isotropic 3.9-mm resolution were acquired during a single breath-hold in 12 s and 8 s using acceleration factors of 2 and 3, respectively. Comparison of fully sampled and retrospectively undersampled (3) He and (1) H images yielded mean absolute errors <10% and structural similarity indices >0.9., Conclusion: By randomly undersampling k-space and using CS reconstruction, high-quality (3) He and (1) H 3D image sets with isotropic 3.9-mm resolution can be acquired within an 8-s breath-hold., (© 2014 Wiley Periodicals, Inc.)

Purpose: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion., Methods and Materials: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks., Results: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung., Conclusion: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

Rationale and Objectives: Diffusion magnetic resonance imaging (MRI) with hyperpolarized (3)He gas is a powerful technique for probing the characteristics of the lung microstructure. A key parameter for this technique is the diffusion time, which is the period during which the atoms are allowed to diffuse within the lung for measurement of the signal attenuation. The relationship between diffusion time and the length scales that can be explored is discussed, and representative, preliminary results are presented from ongoing studies of the human lung for diffusion times ranging from milliseconds to several seconds., Materials and Methods: (3)He diffusion MRI of the human lung was performed on a 1.5T Siemens Sonata scanner. Using gradient echo-based and stimulated echo-based techniques for short and medium-to-long diffusion times, respectively, measurements were performed for times ranging from 2 milliseconds to 6.5 seconds in two healthy subjects, a subject with subclinical chronic obstructive pulmonary disease and a subject with bronchopulmonary dysplasia., Results: In healthy subjects, the apparent diffusion coefficient decreased by about 10-fold, from approximately 0.2 to 0.02 cm(2)/second, as the diffusion time increased from approximately 1 millisecond to 1 second. Results in subjects with disease suggest that measurements made at diffusion times substantially longer than 1 millisecond may provide improved sensitivity for detecting certain pathologic changes in the lung microstructure., Conclusions: With appropriately designed pulse sequences it is possible to explore the diffusion of hyperpolarized (3)He in the human lung over more than a 1,000-fold variation of the diffusion time. Such measurements provide a new opportunity for exploring and characterizing the microstructure of the healthy and diseased lung.

A stimulated-echo-based technique was developed to measure the regional apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breathhold for diffusion times of 25 ms or greater. Compared to previous methods, a substantially shorter minimum diffusion time was achieved by decoupling diffusion sensitization from image acquisition. A hyperpolarized-gas phantom was used to validate the method, which was then tested in four healthy subjects in whom regional ADC maps were acquired with diffusion times of 50, 200, and 1500 ms and a tag wavelength of 5 or 10 mm. ADC values from healthy subjects were in good agreement with reported literature values and decreased with increasing diffusion time. Mean ADC values were approximately 0.07, 0.03, and 0.015 cm2/s for diffusion times of 50, 200, and 1500 ms, respectively. ADC maps were generally homogeneous, with similar mean values when measured with the same parameters in different subjects., ((c) 2008 Wiley-Liss, Inc.)

We present a new pulse sequence for measuring very-short-time-scale restricted diffusion of hyperpolarized noble gases. The pulse sequence is based on concatenating a large number of bipolar diffusion-sensitizing gradients to increase the diffusion attenuation of the MR signal while maintaining a fundamentally short diffusion time. However, it differs in several respects from existing methods that use oscillating diffusion gradients for this purpose. First, a wait time is inserted between neighboring pairs of gradient pulses; second, consecutive pulse pairs may be applied along orthogonal axes; and finally, the diffusion-attenuated signal is not simply read out at the end of the gradient train but is periodically sampled during the wait times between neighboring pulse pairs. The first two features minimize systematic differences between the measured (apparent) diffusion coefficient and the actual time-dependent diffusivity, while the third feature optimizes the use of the available MR signal to improve the precision of the diffusivity measurement in the face of noise. The benefits of this technique are demonstrated using theoretical calculations, Monte-Carlo simulations of gas diffusion in simple geometries, and experimental phantom measurements in a glass sphere containing hyperpolarized (3)He gas. The advantages over the conventional single-bipolar approach were found to increase with decreasing diffusion time, and thus represent a significant step toward making accurate surface-to-volume measurements in the lung airspaces.

We demonstrate a method for simulating restricted diffusion of hyperpolarized gases in lung airspaces that does not rely on an idealized analytic model of alveolar structure. Instead, the restricting geometry was generated from digital representations of histological sections of actual lung tissue obtained from a rabbit model of emphysema. Monte-Carlo simulations of restricted diffusion were performed in the short-time-scale regime, for which the time-dependent diffusivity is quantitatively related to the surface-to-volume ratio (S/V) of the pore space. In each of the eight samples studied, the S/V extracted from the simulated time-dependent diffusivity curves differed by less than 3% from direct assessment of S/V using image-processing methods. Simulated MRI measurements of apparent diffusion coefficients (ADCs) were performed in three representative lung sections to determine the effect of realistic gradient pulse shapes on the extracted S/V values. It was confirmed that ADCs measured at short diffusion times using either narrow or square gradient pulses yield accurate S/V values based on previously derived theoretical relationships. Simulations of triangular and sinusoidal diffusion-sensitizing gradients were then used to quantify the modifications required to extract accurate S/V values from ADC measurements obtained using more realistic gradient waveforms.

A new technique is demonstrated in six healthy human subjects that combines grid-tagging and hyperpolarized helium-3 MRI to assess regional lung biomechanical function and quantitative ventilation. 2D grid-tagging, achieved by applying sinc-modulated RF-pulse trains along the frequency- and phase-encoding directions, was followed by a multislice fast low-angle shot (FLASH)-based acquisition at inspiration and expiration. The displacement vectors, first and second principal strains, and quantitative ventilation were computed, and mean values were calculated for the upper, middle, and lower lung regions. Displacements in the lower region were significantly greater than those in either the middle or upper region (P < 0.005), while there were no significant differences between the three regions for the two principal strains and quantitative ventilation (P = 0.11-0.92). Variations in principal strains and ventilation were greater between subjects than between lung zones within individual subjects. This technique has the potential to provide insight into regional biomechanical alterations of lung function in a variety of lung diseases.

A stimulated-echo-based technique was developed to measure the long-time-scale apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath-hold acquisition. Computer simulations were used to evaluate the performance of the technique and guide the selection of appropriate parameter values for obtaining accurate ADC values. The technique was used in 10 healthy subjects and two subjects with chronic obstructive pulmonary disease (COPD) to measure the global ADC for diffusion times between a few tenths of a second and several seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s. The reproducibility of the technique and its sensitivity to the direction of diffusion sensitization were also investigated. In healthy subjects, global ADC values decreased by severalfold over the range of diffusion times measured (mean values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s, respectively). ADC maps were generally uniform, with mean values similar to the corresponding global values. For the two COPD subjects, global ADC values were substantially greater than those of every healthy subject at all diffusion times measured. In addition, regional elevations of ADC values were far more conspicuous on long-time-scale ADC maps than on short-time-scale ADC maps., (Copyright 2006 Wiley-Liss, Inc.)