Compressed sensing in hyperpolarized 3He Lung MRI

In this work, the application of compressed sensing techniques to the acquisition and reconstruction of hyperpolarized ³He lung MR images was investigated. The sparsity of ³He lung images in the wavelet domain was investigated through simulations based on fully sampled Cartesian two‐dimensional and three‐dimensional ³He lung ventilation images, and the k‐spaces of 2D and 3D images were undersampled randomly and reconstructed by minimizing the L1 norm. The simulation results show that temporal resolution can be readily improved by a factor of 2 for two‐dimensional and 4 to 5 for three‐dimensional ventilation imaging with ³He with the levels of signal to noise ratio (SNR) (～19) typically obtained. The feasibility of producing accurate functional apparent diffusion coefficient (ADC) maps from undersampled data acquired with fewer radiofrequency pulses was also demonstrated, with the preservation of quantitative information (mean ADC_cs ～ mean ADC_full ～ 0.16 cm² sec^?1). Prospective acquisition of 2‐fold undersampled two‐dimensional ³He images with a compressed sensing k‐space pattern was then demonstrated in a healthy volunteer, and the results were compared to the equivalent fully sampled images (SNR_cs = 34, SNR_full = 19). Magn Reson Med 63:1059–1069, 2010. © 2010 Wiley‐Liss, Inc.     

Functional MRI of the lung using hyperpolarized 3-helium gas

Lung imaging has traditionally relied on x-ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment.     

Rapid hyperpolarized 3He diffusion MRI of healthy and emphysematous human lungs using an optimized interleaved-spiral pulse sequence

PURPOSE: To develop and validate an interleaved-spiral diffusion pulse sequence capable of hyperpolarized (3)He MR imaging of the whole lung in less than 10 seconds. MATERIALS AND METHODS: Hyperpolarized (3)He diffusion measurements were performed in seven healthy volunteers and five patients with emphysema using an interleaved-spiral pulse sequence that provided 11 contiguous 15-mm thick coronal ADC maps, with an in-plane resolution of 3.9 mm, covering the whole lung in 5.5 seconds. The resulting means and SDs of ADC values were compared statistically to those from a gradient-echo pulse sequence with identical resolution and diffusion-weighting gradients that acquired five ADC maps in 10.5 seconds. RESULTS: High-quality diffusion-weighted interleaved-spiral images covering the whole lung were obtained, and showed no significant susceptibility-induced image degradation compared to corresponding gradient-echo images. On a subject-by-subject basis, the means and SDs of ADC values for the interleaved-spiral technique were not statistically different from those for the gradient-echo technique. The mean ADC values from the two techniques were highly correlated on a section-by-section basis (R = 0.99). CONCLUSION: The interleaved-spiral diffusion pulse sequence permits rapid acquisition of contiguous ADC maps covering the whole lung during a short breath-hold period, and provides ADC values that are statistically equivalent to those from standard gradient-echo techniques.     

Using hyperpolarized 3He MRI to evaluate treatment efficacy in cystic fibrosis patients

Purpose:

To use hyperpolarized (HP) ³He MR imaging to assess functional lung ventilation in subjects with cystic fibrosis (CF) before and after treatment.

Materials and Methods:

We performed HP ³He static ventilation MRI scans on three subjects, using a Philips 3.0 Tesla (T) Achieva MRI scanner, before and after 11 days of in‐patient treatment with combined intravenous and inhaled therapies for pulmonary exacerbations of CF. We also collected spirometry data. We quantified pulmonary ventilation volume measured with HP ³He MRI using an advanced semi‐automated analysis technique.

Results:

Following 11 days of treatment with intravenous antibiotics, hypertonic saline, and rhDNase, HP ³He MR images in one subject displayed a 25% increase in total ventilation volume. Total ventilation volume in the other two subjects slightly decreased. All three subjects showed increases in FEV₁ and FVC following treatment.

Conclusion:

In all subjects, the HP ³He MR images provided detailed information on precisely where in the lungs gas was reaching. These data provide additional support for the conclusion that HP noble gas MRI can be a powerful tool for evaluating lung ventilation in patients with cystic fibrosis, but also raise important questions about the correlation between spirometry and HP gas MRI measurements. J. Magn. Reson. Imaging 2011. © 2011 Wiley Periodicals, Inc.     

Detection of simulated pulmonary embolism in a porcine model using hyperpolarized 3He MRI.

Several radiological imaging modalities are available to assist with the clinical diagnosis of pulmonary embolism (PE). The most frequently used techniques-nuclear medicine ventilation-perfusion (VP) scan, computed tomography (CT), magnetic resonance angiography (MRA), and pulmonary angiography (PA)-all have literature-supported, substantial limitations with respect to timeliness and patient safety. Hyperpolarized 3He magnetic resonance gas distribution imaging (HP 3He MRI) recently has shown potential as a safer and faster alternative. In this study, we performed HP 3He MRI on a porcine model (N = 6) of simulated PE using selective occlusion balloon catheterization (N = 4) and nonselective aged autologous clot injection (N = 1). The technique was also performed on a normal pig and again after the animal was killed. Temporal depletion of regional HP 3He MRI signal intensity provided for a qualitative assessment of simulated PE (N = 4), and regional PAO2 (alveolar partial pressure of oxygen) was calculated in affected airspaces for a quantitative assessment of simulated PE (N = 1). The preliminary results suggest that HP (3)He MRI shows promise as a means of assessing regional pulmonary perfusion abnormalities in the porcine models of simulated PE that were used in this study.     

Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.

In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.     

Assessment of the lung microstructure in patients with asthma using hyperpolarized 3He diffusion MRI at two time scales: comparison with healthy subjects and patients with COPD

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.     

Improved technique for measurement of regional fractional ventilation by hyperpolarized 3He MRI

Quantitative measurement of regional lung ventilation is of great significance in assessment of lung function in many obstructive and restrictive pulmonary diseases. A new technique for regional measurement of fractional ventilation using hyperpolarized ³He MRI is proposed, addressing the shortcomings of an earlier approach that limited its use to small animals. The new approach allows for the acquisition of similar quantitative maps over a shortened period and requires substantially less ³He gas. This technique is therefore a better platform for implementation in large species, including humans. The measurements using the two approaches were comparable to a great degree, as verified in a healthy rat lung, and are very reproducible. Preliminary validation is performed in a lung phantom system. Volume dependency of measurements was assessed both in vivo and in vitro. A scheme for selecting an optimum flip angle is proposed. In addition, a dead space modeling approach is proposed to yield more accurate measurements of regional fractional ventilation using either method. Finally, sensitivity of the new technique to model parameters, noise, and number of included images were assessed numerically. As a prelude to application in humans, the technique was implemented in a large animal study successfully. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Dynamic radial projection MRI of inhaled hyperpolarized 3He gas.

A radial projection sliding-window sequence has been developed for imaging the rapid flow of (3)He gas in human lungs. The short echo time (TE) of the radial sequence lends itself to fast repetition times, and thus allows a rapid update in the image when it is reconstructed with a sliding window. Oversampling in the radial direction combined with angular undersampling can further reduce the time needed to acquire a complete image data set, without significantly compromising spatial resolution. Controlled flow phantom experiments using hyperpolarized (3)He gas exemplify the temporal resolution of the method. In vivo studies on three healthy volunteers, one patient with chronic obstructive pulmonary disease (COPD), and one patient with hemiparalysis of the right diaphragm demonstrate that it is possible to accurately resolve the passage of gas down the trachea and bronchi and into the peripheral lung.     

Optimization of scan parameters in pulmonary partial pressure oxygen measurement by hyperpolarized 3He MRI.

The dependence of hyperpolarized (HP) (3)He T(1) on local oxygen concentration provides the basis for measuring the partial pressure of oxygen (pO(2)) and oxygen depletion rate (R) in the lungs. Precise measurements of this type are difficult because the oxygen effect manifests itself through a decay of signal, leading to noisy images at the end of the series. The depolarization caused by RF excitation pulses further complicates the problem. It is therefore important to optimize scan parameters, such as measurement timing and flip angle, to obtain accurate and reproducible measurements. This work presents a new single-acquisition technique in conjunction with the multiple regression fitting method for data evaluation. Analytical expressions for the measurement uncertainties are derived. A total of four types of single-acquisition timing schemes are investigated; simulation shows a large uncertainty variation between these schemes (pO(2): 7.5-30.2%; R: 47.4-173.7%). A basic procedure for optimizing scan parameters is then described. A phantom experiment was conducted to verify the simulation results. Repeated in vivo measurements with the optimal scheme in a rabbit experiment showed that average variation of global mean is 6.2% for pO(2) and 12.0% for R, and that the average variation of percentiles (10th, 25th, 50th, 75th, and 90th) is 8.7% for pO(2) and 19.0% for R.     

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized (3)He: preliminary studies in healthy and diseased lungs.

An optimized interleaved-spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized (3)He, and tested in healthy volunteers and patients with lung disease. Off-resonance artifacts were minimized by using a short data-sampling period per interleaf, and gradient-fidelity errors were compensated for by using measured k-space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding-window reconstruction, cine-movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility- and motion-induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas-flow dynamics.     

MRI of hyperpolarized 3He gas in human paranasal sinuses

In this study, MRI of hyperpolarized ³He gas in human para-nasal sinuses is presented. Helium images were obtained at 1.5 T, using a surface coil and a 2D, fast gradient-echo sequence with a nominal constant flip angle of 12°. Coronal images of 20-mm thick slices were generated and compared with proton images of the corresponding sections. The images enable visualization of the paranasal sinuses and the nasal cavity, suggesting a potential use of this method not only in identifying the anatomical configuration of these pneumatic spaces, but also in assessing sinus ventilation.     

Effects of ozone exposure in rat lungs investigated with hyperpolarized 3 He MRI

PURPOSE: To investigate the effects of subchronic ozone exposure on rat lung ventilation using hyperpolarized (HP) (3)He MRI. MATERIALS AND METHODS: A total of 24 Sprague-Dawley rats, distributed in one control group and four groups exposed to 0.5 ppm ozone concentration for two days or six days, either continuously (22 hours/day) or alternatingly (12 hours/day). A three-step MRI protocol was designed and applied to each animal, including: 1) (3)He gas distribution images acquired at inspiratory capacity, 2) measurements of intrapulmonary (3)He diffusion coefficients, and 3) dynamic ventilation acquisitions performed during lung filling with (3)He. RESULTS: No differentiation between animals exposed to ozone and control animals was observed from the ventilation images obtained at inspiratory capacity. The (3)He diffusion coefficients were not statistically different from one group to another. Ventilation defects, appearing as delayed lung filling regions and heterogeneous lung filling, were observed in the dynamic lung ventilation image series. The percentage of animals with ventilation defects in the control, two-day, and six-day exposed groups were equal to 20%, 43% and 75%, respectively. In the subgroup of the animals exposed six days for 12 hours per day, the percentage of animals exhibiting ventilation defects was equal to 85%. CONCLUSION: Heterogeneous obstructive patterns in an experimental animal model of subchronic ozone exposure were observed using HP (3)He MRI.     

Long‐range diffusion of hyperpolarized 3He in rats

Based on a stimulated‐echo technique, a method to construct an apparent diffusion coefficient (ADC) map of hyperpolarized ³He in a long‐range diffusion scale is presented with a phase‐cycle alternative to remove all unwanted echoes. The approach was successfully applied to determine in vivo diffusion constants in rat lungs. The ADC values in healthy rats show a good agreement with reported values for diffusion times of ≈. These long diffusivity measurements may be sensitive to detect emphysema progression or tissue remodeling and thus have enormous potential for the diagnosis and tracking of disease progression and for drug evaluation. Magn Reson Med 61:54–58, 2009. © 2008 Wiley‐Liss, Inc.     

Advantages of parallel imaging in conjunction with hyperpolarized helium--a new approach to MRI of the lung.

Hyperpolarized helium (3He) gas MRI has the potential to assess pulmonary function. The non-equilibrium state of hyperpolarized 3He results in the continual depletion of the signal level over the course of excitations. Under non-equilibrium conditions the relationship between the signal-to-noise ratio (SNR) and the number of excitations significantly deviates from that established in the equilibrium state. In many circumstances the SNR increases or remains the same when the number of data acquisitions decreases. This provides a unique opportunity for performing parallel MRI in such a way that both the temporal and spatial resolution will increase without the conventional decrease in the SNR. In this study an analytical relationship between the SNR and the number of excitations for any flip angle was developed. Second, the point-spread function (PSF) was utilized to quantitatively demonstrate the unconventional SNR behavior for parallel imaging in hyperpolarized gas MRI. Third, a 24-channel (24ch) receive and two-channel (2ch) transmit phased-array system was developed to experimentally prove the theoretical predictions with 3He MRI. The in vivo experimental results prove that significant temporal resolution can be gained without the usual SNR loss in an equilibrium system, and that the entire lung can be scanned within one breath-hold (approximately 13 s) by applying parallel imaging to 3D data acquisition.     

Measurements of regional alveolar oxygen pressure using hyperpolarized 3He MRI

RATIONALE AND OBJECTIVES: The aim of this work is to review hyperpolarized (HP) helium-3 (3He) magnetic resonance imaging (MRI) methods to measure regional alveolar oxygen partial pressure (P(A)O2) and oxygen depletion rate (R) in the lung. We point out limitations of the methods and suggest improvements to increase their accuracy. MATERIALS AND METHODS: P(A)O2 and R can be extracted from series of HP gas images acquired during breath hold by making use of the depolarizing effect of oxygen on HP gas. To separate oxygen-induced depolarization from other depolarizing effects, several techniques can be used. We review currently used techniques and point out their advantages and limitations. RESULTS: We show that the precision of oxygen measurements depends on a variety of parameters and can vary within the measurement volume. Accuracy of the measurement also can be influenced by diffusion of oxygen and polarized 3He and generally is different for single-slice and multislice measurements. We present numerical simulations, phantom data, and in vivo data for illustration. CONCLUSION: HP 3He MRI is a noninvasive, nonionizing, and repeatable imaging method that allows for quantitative analysis of lung function. The current techniques for measuring P(A)O2 have the potential to deliver clinically relevant functional images.     

Quantitative measurement of regional lung ventilation using 3He MRI.

A new strategy for a quantitative measurement of regional pulmonary ventilation using hyperpolarized helium-3 (3He) MRI has been developed. The method employs the build-up of the signal intensity after a variable number of (3)He breaths. A mathematical model of the signal dynamics is presented, from which the local ventilation, defined as the fraction of gas exchanged per breath within a given volume, is calculated. The model was used to create ventilation maps of coronal slices of guinea pig lungs. Ventilation values very close to 1 were found in the trachea and the major airways. In the lung parenchyma, regions adjacent to the hilum showed values of 0.6-0.8, whereas 0.2-0.4 was measured in peripheral regions. Monte Carlo simulations were used to investigate the accuracy of the method and its limitations. The simulations revealed that, at presently attainable signal-to-noise ratios, the ventilation parameter can be determined with a relative uncertainty of <5% over a wide range of values.     

Asymmetric quadrature split birdcage coil for hyperpolarized 3He lung MRI at 1.5T

An asymmetric quadrature birdcage body coil for hyperpolarized (HP) ³He lung imaging at 1.5T is presented. The coil is designed to rest on top of the patient support and be used as a temporary insert in a clinical system. A two‐part construction facilitates patient access and the asymmetric design makes maximal use of available bore space to ensure comfort. Highly homogeneous, circularly polarized RF magnetic fields are produced at 48.5 MHz using a conformal mapping method for the geometrical design, combined with an algebraic method to calculate the individual capacitance values on the birdcage coil's ladder network. Efficiency and isolation from the system's proton body coil are ensured by an integrated RF screen. The design methodology is readily applicable to other field strengths or nuclei. Improvements over existing ³He coils were found in terms of sensitivity and transmit field homogeneity, an important feature in HP MRI. Magn Reson Med 60:431–438, 2008. © 2008 Wiley‐Liss, Inc.     

Feature analysis of hyperpolarized helium‐3 pulmonary MRI: A study of asthmatics versus nonasthmatics

A computational framework is described that was developed for quantitative analysis of hyperpolarized helium‐3 MR lung ventilation image data. This computational framework was applied to a study consisting of 55 subjects (47 asthmatic and eight normal). Each subject was imaged before and after respiratory challenge and also underwent spirometry. Approximately 1600 image features were calculated from the lungs in each image. Both the image and 27 spirometric features were ranked based on their ability to characterize clinical diagnosis using a mutual information‐based feature subset selection algorithm. It was found that the top image features perform much better compared with the current clinical gold‐standard spirometric values when considered individually. Interestingly, it was also found that spirometric values are relatively orthogonal to these image feature values in terms of informational content. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.