Hyperpolarized 3He Research Articles

Rapid 3-D mapping of hyperpolarized 3He spin-lattice relaxation times using variable flip angle gradient echo imaging with application to alveolar oxygen partial pressure measurement in rat lungs

The purpose of this work was to develop a rapid 3-D, variable flip angle (VFA) method for measurement of hyperpolarized (3)He T(1) which accounts for the effects of radiofrequency (RF) pulses without the need for additional flip angle information. The 3-D, VFA method was validated in vitro over a range of oxygen partial pressures ranging from 0.04 to 0.52 atm. The approach was also tested in vivo in five healthy rats as a function of increasing number of wash-out breaths. The T(1) accuracy of the VFA method in the presence of flip angle mis-setting and RF field non-uniformity was compared with the CFA method using simulations and experiments. T(1) measurements were found to provide p(A)O(2) estimates, both in vitro and in vivo consistent with those predicted based on gas dilution and/or ventilation para- meters. For the RF pulse mis-setting (4%) and RF field non-uniformity (3%) used here, the VFA method provided a T(1) accuracy of better than 5% compared to 12% for the CFA method. With sufficient RF field homogeneity (3%) and proper calibration (4%), the VFA approach can provide rapid and reliable 3-D T(1) mapping of hyperpolarized (3)He without the need for additional flip angle information.

Assessment of in vitro vs. in vivo lung structure using hyperpolarized helium-3 diffusion magnetic resonance imaging

The purpose of this study was to assess the properties of a model system for hyperpolarized He-3 (HHe) diffusion MR imaging created from the lungs of New Zealand white rabbits by drying the lungs while inflated at constant pressure. The dried lungs were prepared by sacrificing the animal, harvesting the lungs en bloc and dehydrating the lungs for several days using dry compressed air. In four rabbits, the apparent diffusion coefficient (ADC) of HHe gas was measured in vivo and, within 1 week, in vitro in the dried lungs. To assess long-term repeatability, in vitro ADC values were measured again 3 months later. Dried lungs from four additional rabbits were imaged twice on the same day to assess the short-term repeatability of ADC measurements, and tissue samples from these lungs were then removed for histology. In vivo and in vitro ADC maps showed similar features and similar distributions of ADC values; mean in vivo and in vitro ADC values differed by less than 12%. The in vitro mean ADC values were highly reproducible, with no more than 5% difference between measurements for the short-term repeatability and less than 17% difference between measurements for the long-term repeatability. Histological samples from the dried lungs demonstrated that the lung structure remained intact. These results suggest that the dried lungs are a useful and inexpensive alternative to human or in vivo animal studies for HHe diffusion MR sequence development, testing and optimization.

Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling

Image functional modeling (IFM) has been introduced as a method to simultaneously synthesize imaging and mechanical data with computational models to determine the degree and location of airway constriction in asthma. Using lung imaging provided by hyperpolarized (3)He MRI, we advanced our IFM method to require matching not only to ventilation defect location but to specific ventilation throughout the lung. Imaging and mechanical data were acquired for four healthy and four asthmatic subjects pre- and postbronchial challenge. After provocation, we first identified maximum-size airways leading exclusively to ventilation defects and highly constricted them. Constriction patterns were then found for the remaining airways to match mechanical data. Ventilation images were predicted for each pattern, and visual and statistical comparisons were done with measured data. Results showed that matching of ventilation defects requires severe constriction of small airways. The mean constriction of such airways leading to the ventilation defects needed to be 70-80% rather than fully closed. Also, central airway constriction alone could not account for dysfunction seen in asthma, so small airways must be involved.

A robust protocol for regional evaluation of methacholine challenge in mouse models of allergic asthma using hyperpolarized 3He MRI.

Hyperpolarized (HP) (3)He magnetic resonance imaging has been recently used to produce high-resolution images of pulmonary ventilation after methacholine (MCh) challenge in mouse models of allergic inflammation. This capability presents an opportunity to gain new insights about these models and to more sensitively evaluate new drug treatments in the pre-clinical setting. In the current study, we present our initial experience using two-dimensional (2D), time-resolved (3)He MRI of MCh challenge-induced airways hyperreactivity (AHR) to compare ovalbumin-sensitized and challenged (N = 8) mice to controls (N = 8). Imaging demonstrated that ovalbumin-sensitized and challenged animals exhibited many large ventilation defects even prior to MCh challenge (four out of eight) compared to no defects in the control animals. Additionally, the ovalbumin-sensitized and challenged animals experienced a greater number of ventilation defects (4.5 +/- 0.4) following MCh infusion than did controls (3.3 +/- 0.6). However, due to variability in MCh delivery that was specific to the small animal MRI environment, the difference in mean defect number was not statistically significant. These findings are reviewed in detail and a comprehensive solution to the variability problem is presented that has greatly enhanced the magnitude and reproducibility of the MCh response. This has permitted us to develop a new imaging protocol consisting of a baseline 3D image, a time-resolved 2D series during MCh challenge, and a post-MCh 3D image that reveals persistent ventilation defects.

Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He) Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

Progression of Emphysema Evaluated by MRI Using Hyperpolarized 3He (HP 3He) Measurements in Patients with Alpha-1-Antitrypsin (A1AT) Deficiency Compared with CT and Lung Function Tests

Calibration of RF transmitter voltages for hyperpolarized gas MRI

MRI with hyperpolarized gases, (3)He, (129)Xe, (13)C, and others, has the potential to become an important diagnostic technique for clinical imaging. Due to the nonreversible loss of magnetization in hyperpolarized gas imaging, the choice of the flip angle is a major factor that influences the signal intensity, and hence, the signal-to-noise ratio. Conventional automated radiofrequency (RF) calibration procedures for (1)H imaging are not suitable for hyperpolarized gas imaging. Herein, we have demonstrated a simple procedure for RF calibration for magnetic resonance imaging (MRI) with hyperpolarized gases that is easily adaptable to clinical settings. We have demonstrated that there exists a linear relationship between the RF transmitter voltages required to obtain the same nutation angle for protons (V(1H)) and hyperpolarized gas nuclei (V(3He)). For our (1)H and (3)He coils we found that V(3He) = 1.937 . V(1H) with correlation coefficient r(2) = 0.97. This calibration can be done as a one-time procedure during the routine quality assurance (QA) protocol. The proposed procedure was found to be extremely robust in routine scanning and provided an efficient method to achieve a desired flip angle, thus allowing optimum image quality.

Commentaries on Viewpoint: Use of mean airspace chord length to assess emphysema

to the editor: Although mean airspace chord length ( L m) lacks the elegance of some stereology methods and requires careful attention to technique ([4][1]), Mitzner ([3][2]) argues that L m has utility in studying experimental emphysema. Clearly, L m reflects the dimensions of alveoli but is not a

Last Word on Viewpoint: Use of mean airspace chord length to assess emphysema

Last Word on Viewpoint: Use of mean airspace chord length to assess emphysema

The difference in ventilation heterogeneity between asthmatic and healthy subjects quantified using hyperpolarized 3He MRI

In this pilot study, algorithms for quantitatively evaluating the distribution and heterogeneity of human ventilation imaged with hyperpolarized (HP) (3)He MRI were developed for the goal of examining structure-function relationships within the asthmatic lung. Ten asthmatic and six healthy human subjects were imaged with HP (3)He MRI before bronchial challenge (pre-MCh), after bronchial challenge (post-MCh), and after a series of deep inspirations (post-DI) following challenge. The acquired images were rigidly coregistered. Local voxel fractional ventilation was computed by setting the sum of the pixel intensity within the lung region in each image to 1 liter of inhaled (3)He mixture. Local ventilation heterogeneity was quantified by computing regional signal coefficient of variation. Voxel fractional ventilation histograms and overall heterogeneity scores were then calculated. Asthmatic subjects had a higher ventilation heterogeneity to begin with (P = 0.025). A methacholine challenge elevated ventilation heterogeneity for all subjects (difference: P = 0.08). After a DI postchallenge, this heterogeneity reversed substantially toward the baseline state for healthy subjects but only minimally in asthmatic subjects. This difference was significant in absolute quantity (difference: P = 0.007) as well as relative to the initial increase (difference: P = 0.03). These findings suggest that constriction heterogeneity is not a characteristic unique to asthmatic airway trees but rather a behavior intrinsic to all airway trees when provoked. Once ventilation heterogeneity is established, it is the lack of reversal following DIs that distinguishes asthmatics from non-asthmatics.

MR imaging of apparent 3He gas transport in narrow pipes and rodent airways

High sensitivity makes hyperpolarized 3He an attractive signal source for visualizing gas flow with magnetic resonance (MR) imaging. Its rapid Brownian motion, however, can blur observed flow lamina and alter measured diffusion rates when excited nuclei traverse shear-induced velocity gradients during data acquisition. Here, both effects are described analytically, and predicted values for measured transport during laminar flow through a straight, 3.2-mm diameter pipe are validated using two-dimensional (2D) constant-time images of different binary gas mixtures. Results show explicitly how measured transport in narrow conduits is characterized by apparent values that depend on underlying gas dynamics and imaging time. In ventilated rats, this is found to obscure acquired airflow images. Nevertheless, flow splitting at airway branches is still evident and use of 3D vector flow mapping is shown to reveal surprising detail that highlights the correlation between gas dynamics and lung structure.

Mapping and quantifying hyperpolarized 3He magnetic resonance imaging apparent diffusion coefficient gradients

We measured hyperpolarized 3He magnetic resonance imaging (MRI) apparent diffusion coefficients (ADC) and quantified ADC gradients in each three-by-three voxel region of interest (ROI). Such local ADC gradients can be represented in vector maps showing the magnitude (|G3x3|) and direction of ADC gradients, providing a qualitative visualization tool and quantitative measurement of airway and air space heterogeneity. Twenty-four subjects (15 male, mean age=67+/-7 yr) with global initiative for chronic obstructive lung disease (GOLD) stage II (n=9, mean age 68+/-6 yr), GOLD stage III chronic obstructive pulmonary disease (COPD; n=7, mean age 67+/-8 yr), and age-matched healthy volunteers (n=8, mean age 67+/-6 yr) were enrolled based on their age and spirometry results. Hyperpolarized 3He MRI was performed on a whole body 3.0 Tesla system. Mean 3He ADC and ADC standard deviation were calculated for the center coronal slice, and the mean magnitude and direction of the ADC gradient vectors were calculated for each three-by-three voxel matrix (|G3x3|). While the 3He ADC standard deviation was not significantly different, mean |G3x3| was significantly different between subjects with stage II (0.14+/-0.03 cm/s) and stage III COPD (0.19+/-0.03 cm/s; P<0.005) and between healthy subjects (0.12+/-0.03 cm/s) and those with stage II COPD (P<0.02). The second order statistic |G3x3| may provide a sensitive measure of ADC heterogeneity for ROI representing 9.4x9.4x30 mm or 2.6 cm3 of lung tissue.

An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging

We describe the design and operation of an open-access, very-low-field, magnetic resonance imaging (MRI) system for in vivo hyperpolarized 3He imaging of the human lungs. This system permits the study of lung function in both horizontal and upright postures, a capability with important implications in pulmonary physiology and clinical medicine, including asthma and obesity. The imager uses a bi-planar B 0 coil design that produces an optimized 65 G (6.5 mT) magnetic field for 3He MRI at 210 kHz. Three sets of bi-planar coils produce the x, y, and z magnetic field gradients while providing a 79-cm inter-coil gap for the imaging subject. We use solenoidal Q-spoiled RF coils for operation at low frequencies, and are able to exploit insignificant sample loading to allow for pre-tuning/matching schemes and for accurate pre-calibration of flip angles. We obtain sufficient SNR to acquire 2D 3He images with up to 2.8 mm resolution, and present initial 2D and 3D 3He images of human lungs in both supine and upright orientations. 1H MRI can also be performed for diagnostic and calibration reasons.

Investigation of Hyperpolarized 3He Magnetic Resonance Imaging Utility in Examining Human Airway Diameter Behavior in Asthma Through Comparison with High-Resolution Computed Tomography

Application of a previously developed model-based algorithm on hyperpolarized (HP) (3)He magnetic resonance (MR) dynamic projection images of phantoms was extended to investigate the utility of HP (3)He MR imaging (MRI) in quantifying airway caliber changes associated with asthma. Airways of seven volunteers were imaged and measured using HP (3)He MRI and multidetector-row computed tomography (MDCT) before and after a methacholine (MCh) challenge. MDCT data were obtained at functional residual capacity and 1 L above functional residual capacity. Comparison of the resultant data showed that HP (3)He MRI did not match MDCT in measuring the ratios of airway calibers before and after the MCh challenge in 37% to 43% of the airways from the first six generations at the two lung volumes tested. However, MDCT did yield the observation that 49% to 69% of these airways displayed bronchodilation following MCh challenge. The current implementation of HP (3)He MRI did not match the MCh-induced postchallenge-to-prechallenge airway caliber ratios as measured with MDCT. Elevated parenchymal tethering due to bronchoconstriction-induced hyperinflation was proposed as a possible explanation for this airway dilation.

The Role of Collateral Paths in Long-range Diffusion of 3He in Lungs

The hyperpolarized (3)He long-range diffusion coefficient (LRDC) in lungs is sensitive to changes in lung structure due to emphysema, reflecting the increase in collateral paths resulting from tissue destruction. However, no clear understanding of LRDC in healthy lungs has emerged. Here we compare LRDC measured in healthy lungs with computer simulations of diffusion along the airway tree with no collateral connections. Computer simulations of diffusion of spatially modulated spin magnetization were performed in computer-generated, symmetric-branching models of lungs and compared with existing LRDC measurements in canine and human lungs. The simulations predict LRDC values of order 0.001 cm(2)/sec, approximately 20 times smaller than the measured LRDC. We consider and rule out possible mechanisms for LRDC not included in the simulations: incomplete breath hold, cardiac motion, and passage of dissolved (3)He through airway walls. However, a very low density of small (micron) holes in the airways is shown to account for the observed LRDC. It is proposed that LRDC in healthy lungs is determined by small collateral pathways.

3D hyperpolarized He-3 MRI of ventilation using a multi-echo projection acquisition.

A method is presented for high-resolution 3D imaging of the whole lung using inhaled hyperpolarized (HP) He-3 MR with multiple half-echo radial trajectories that can accelerate imaging through undersampling. A multiple half-echo radial trajectory can be used to reduce the level of artifact for undersampled 3D projection reconstruction (PR) imaging by increasing the amount of data acquired per unit time for HP He-3 lung imaging. The point spread functions (PSFs) for breath-held He-3 MRI using multiple half-echo trajectories were evaluated using simulations to predict the effects of T(2)* and gas diffusion on image quality. Results from PSF simulations were consistent with imaging results in volunteer studies showing improved image quality with increasing number of echoes using up to 8 half-echoes. The 8-half-echo acquisition is shown to accommodate lost breath-holds as short as 6 sec using a retrospective reconstruction at reduced resolution and also to allow reduced breath-hold time compared with an equivalent Cartesian trajectory. Furthermore, preliminary results from a 3D dynamic inhalation-exhalation maneuver are demonstrated using the 8-half-echo trajectory. Results demonstrate the first high-resolution 3D PR imaging of ventilation and respiratory dynamics in humans using HP He-3 MR.

Optogalvanic spectroscopy using 389 nm coherent light source accurately tuned to resonance frequency of 23S->33P of 3He

An efficient 389nm coherent light source, made possible through the single-pass second-harmonic generation of a picosecond Ti:sapphire laser with a periodically poled lithium niobate waveguide, was developed for the metastability exchange optical pumping of hyperpolarized 3He gas, which is applicable to imaging with nuclear magnetic resonance. The second-harmonic light provided such a broad spectrum that some split sub-levels of its metastable state under an applied magnetic field could be pumped efficiently and simultaneously. Optogalvanic spectroscopy using the light source indicated that the spectral width of 3He was much less than 70GHz, which was similar to the spectral width of the light source.

Can hyperpolarized 3He MRI detect radiation induced lung damage?

Can hyperpolarized 3He MRI detect radiation induced lung damage?

Imaging the Lung in Radiotherapy: Where 4D Meets Multimodality

SummaryThe increasing research and clinical interest in the intrafractional motion management of lung tumour radiation treatment is in part fuelled by the availability of multiple 4D modalities that resolve temporal information of the tumour motion. These improved imaging modalities allow the escalation of dose to the tumour besides enhancing the conformality of the dose to a moving tumour, which could improve the local control rate. Magnetic resonance imaging (MRI; including dynamic MRI and hyperpolarized 3He tagging), 4DCT, fluoroscopy and EM transponders are reviewed in this article. The working mechanisms, advantages/disadvantages and unique information of these techniques and their contribution to the management of lung cancer are discussed.

Extending the range of diffusion times for regional measurement of the 3He ADC in human lungs

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.

Schnelles In-vivo-19F-MRT-T1-Mapping zur Messung der Konzentration von fluorinierten Gasen in der Lunge

Ziele: Despite the great success of applying hyperpolarized 3He and 129Xe in the field of morphological and functional MR-imaging of lungs both contrast gases still remain mostly research tools. Therefore, the interest in using thermally polarized fluorinated gases, such as SF6, C2F6 and C4F8 in the MRI-investigations of lungs has grown. The short T1 relaxation time of these gases (1–50ms at 1bar) allows for a short measurement time (<10 s) if imaging is performed in a large animal. As the fraction of fluorinated gases is not linearly correlated to the spin density due to T1 weighting other functional MR parameters are necessary for gas concentration quantification. One of such parameters is the T1 relaxation time itself. The aim of this study was to prove the feasibility of the 19F T1 mapping for the estimation of local partial pressure of fluorinated gases in vivo. Methode: For all experiments, the variable flip angle (VFA) technique was used. First, a variety of investigations on phantoms containing mixtures of C4F8 and O2 in different proportions aiming to proof the VFA method for fluorinated gases were done. Next, ex-vivo measurements in rat lungs were performed to test the method efficiency. The rat was ventilated in-vivo with a mixture of 80% C4F8 with 20% of O2 and then, immediately after death, 5ml of C4F8 were injected additionally. Finally, in-vivo experiments in domestic pig (20–25kg) lungs were done using the same mixture. The scan time in all measurements during inspiratory hold was 60–70 s. All experiments were run on a Siemens Magnetom Vision Experimental 1.5T whole body MRI system using a 25cm birdcage coil. Ergebnis: In the ex-vivo T1-maps regions with various T1 can be identified corresponding to variations of C4F8 concentration. The in-vivo measurements results show essentially broad T1- time distribution (and therefore related C4F8 concentration) that obviously reflects a metabolic processes of gas exchange. In this case metabolic changes of the proportions of gas mixtures (C4F8:O2:CO2) in different lung regions could lead to corresponding variations of T1. Schlussfolgerung: In conclusion, the applicability of the VFA method of T1 measurement for the in-vivo MRI-measurement of lungs with heavy fluorinated gases was demonstrated. The sensitivity of the method is sufficient enough to detect 5–10% variations of gas mixture content in-vivo. Combined with diffusion weighted 19F imaging techniques this may open up a number of new options for the study of lung functions and pathology.