Wilfred W. Lam

Hyperpolarized 3He ventilation defects and apparent diffusion coefficients in chronic obstructive pulmonary disease: preliminary results at 3.0 Tesla.

Objective:Hyperpolarized 3He magnetic resonance imaging (3He MRI) at 3.0 Tesla of healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was performed for quantitative evaluation of ventilation defects and apparent diffusion coefficients (ADC) and for comparison to published results acquired at 1.5 Tesla. The reproducibility of 3He ADC and ventilation defects was also assessed in subjects scanned 3 times, twice within 10 minutes, and again within 7 ± 2 days of the first MRI visit. Materials and Methods:Hyperpolarized 3He MRI was performed in 6 subjects. Two interleaved images with and without additional diffusion sensitization were acquired with the first image serving as a ventilation image from which defect score and volume were measured and the combination of the 2 images used to compute ADC maps and ADC histograms. Results:3He MRI at 3.0 Tesla showed increased mean ADC and ADC standard deviation for subjects with COPD compared with healthy volunteers (ADC healthy volunteer (0.24 ± 0.12 cm2/s), mild-moderate COPD (0.34 ± 0.14 cm2/s), and severe COPD (0.47 ± 0.21 cm2/s), and these values were similar to previously reported results acquired at 1.5 Tesla. Reproducibility of mean ADC was high (coefficient of variation 2% in severe COPD, 3% in mild-moderate COPD, 4% in healthy volunteers) across all 3 scans. Higher same-day scan reproducibility was observed for ventilation defect volume compared with 1-week scan reproducibility in this small group of subjects. Conclusions:ADC values for emphysematous lungs were significantly increased compared with healthy lungs in age-matched subjects, and all values were comparable to those reported previously at 1.5 Tesla. Ventilation defect score and ventilation defect volume results were also comparable to results previously reported in COPD subjects Reproducibility of ADC for same-day scan-rescan and 7-day rescan was high and similar to previously reported results.

Rapid multislice imaging of hyperpolarized 13C pyruvate and bicarbonate in the heart.

Hyperpolarization of spins via dynamic nuclear polarization (DNP) has been explored as a method to non‐invasively study real‐time metabolic rocesses occurring in vivo using 13C‐labeled substrates. Recently, hyperpolarized 13C pyruvate has been used to characterize in vivo cardiac metabolism in the rat and pig. Conventional 3D spectroscopic imaging methods require in excess of 100 excitations, making it challenging to acquire a full cardiac‐gated, breath‐held, whole‐heart volume. In this article, the development of a rapid multislice cardiac‐gated spiral 13C imaging pulse sequence consisting of a large flip‐angle spectral‐spatial excitation RF pulse combined with a single‐shot spiral k‐space trajectory for rapid imaging of cardiac metabolism is described. This sequence permits whole‐heart coverage (6 slices, 8.8‐mm in‐plane resolution) in any plane, allowing imaging of the metabolites of interest, [1‐ 13C] pyruvate, [1‐ 13C] lactate, and 13C bicarbonate, within a single breathhold. Pyruvate and bicarbonate cardiac volumes were acquired, while lactate images were not acquired due to low lactate levels in the animal model studied. The sequence was demonstrated with phantom experiments and in vivo testing in a pig model. Magn Reson Med, 2010.

Simultaneous investigation of cardiac pyruvate dehydrogenase flux, Krebs cycle metabolism and pH, using hyperpolarized [1,2-(13)C2]pyruvate in vivo.

13C MR spectroscopy studies performed on hearts ex vivo and in vivo following perfusion of prepolarized [1‐13C]pyruvate have shown that changes in pyruvate dehydrogenase (PDH) flux may be monitored non‐invasively. However, to allow investigation of Krebs cycle metabolism, the 13C label must be placed on the C2 position of pyruvate. Thus, the utilization of either C1 or C2 labeled prepolarized pyruvate as a tracer can only afford a partial view of cardiac pyruvate metabolism in health and disease. If the prepolarized pyruvate molecules were labeled at both C1 and C2 positions, then it would be possible to observe the downstream metabolites that were the results of both PDH flux (13CO2 and H13CO3‐) and Krebs cycle flux ([5‐13C]glutamate) with a single dose of the agent. Cardiac pH could also be monitored in the same experiment, but adequate SNR of the 13CO2 resonance may be difficult to obtain in vivo. Using an interleaved selective RF pulse acquisition scheme to improve 13CO2 detection, the feasibility of using dual‐labeled hyperpolarized [1,2‐13C2]pyruvate as a substrate for dynamic cardiac metabolic MRS studies to allow simultaneous investigation of PDH flux, Krebs cycle flux and pH, was demonstrated in vivo. Copyright

Design of spectral-spatial outer volume suppression RF pulses for tissue specific metabolic characterization with hyperpolarized 13C pyruvate.

[1-(13)C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream (13)C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-(13)C] lactate and [1-(13)C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.

Hyperpolarized noble gas magnetic resonance imaging of the animal lung: Approaches and applications

Hyperpolarized noble gas (HNG) magnetic resonance (MR) imaging is a very promising noninvasive tool for the investigation of animal models of lung disease, particularly to follow longitudinal changes in lung function and anatomy without the accumulated radiation dose associated with x rays. The two most common noble gases for this purpose are H3e (helium 3) and X129e (xenon 129), the latter providing a cost-effective approach for clinical applications. Hyperpolarization is typically achieved using spin-exchange optical pumping techniques resulting in ∼10 000-fold improvement in available magnetization compared to conventional Boltzmann polarizations. This substantial increase in polarization allows high spatial resolution (<1 mm) single-slice images of the lung to be obtained with excellent temporal resolution (<1 s). Complete three-dimensional images of the lungs with 1 mm slice thickness can be obtained within reasonable breath-hold intervals (<20 s). This article provides an overview of the current met...

Comparison of hyperpolarized 3He MRI with Xe‐enhanced computed tomography imaging for ventilation mapping of rat lung

Lung ventilation was mapped in five healthy Brown Norway rats (210–377 g) using both hyperpolarized 3He MRI and Xe‐enhanced computed tomography (Xe‐CT) under similar ventilator conditions. Whole‐lung measurements of ventilation r obtained with 3He MRI were not significantly different from those obtained from Xe‐CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two‐tailed paired t‐test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the 3He MRI method was found to be 0.17 ± 0.04 cm−1, whereas the average S/I gradient obtained using the Xe‐CT method was found to be 0.016 ± 0.005 cm−1. In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two‐tailed paired t‐test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality. Copyright

Comparison of hyperpolarized 3He MRI rat lung volume measurement with micro‐computed tomography

In this study, the upper‐limit volume (gas plus partial tissue volume) as well as absolute volume (gas only) of lungs measured with hyperpolarized 3He‐MR imaging is compared with that determined by micro‐computed tomography (CT) under similar ventilation conditions in normal rats. Five Brown Norway rats (210–259 g) were ventilated with O2, alternately with 3He, using a computer‐controlled ventilator, and 3D density‐weighted images of the lungs were acquired during a breath hold after six wash‐in breaths of 3He. The rats were then transferred to a micro‐CT scanner, and a similar experimental setup was used to obtain images of the lungs during a breath hold of air with an airway pressure equal to that of the MR imaging breath hold. The upper‐limit and absolute volumes obtained from 3He‐MR and micro‐CT methods were not significantly different (p > 0.05). The good agreement between the lung volumes measured with the two imaging methods suggests that 3He‐MR imaging can be used for quantitative analysis of lung volume changes in longitudinal studies without the exposure to the ionizing radiation which accompanies micro‐CT imaging. Copyright

Measurement of alveolar oxygen partial pressure in the rat lung using Carr-Purcell-Meiboom-Gill spin–spin relaxation times of hyperpolarized 3He and 129Xe at 74 mT

Regional measurement of alveolar oxygen partial pressure can be obtained from the relaxation rates of hyperpolarized noble gases, 3He and 129Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin–spin relaxation rate (R2) of 3He at low magnetic field strengths (<0.1 T) in vivo. R2 measurements can be achieved efficiently using the Carr‐Purcell‐Meiboom‐Gill pulse sequence. In this work, alveolar oxygen partial pressure measurements based on Carr‐Purcell‐Meiboom‐Gill R2 values of hyperpolarized 3He and 129Xe in vitro and in vivo in the rat lung at low magnetic field strength (74 mT) are presented. In vitro spin–spin relaxivity constants for 3He and 129Xe were determined to be (5.2 ± 0.6) ×10−6 Pa−1 sec−1 and (7.3 ± 0.4) ×10−6 Pa−1 s−1 compared with spin‐lattice relaxivity constants of (4.0 ± 0.4) ×10−6 Pa−1 s−1 and (4.3 ± 1.3) × 10−6 Pa−1 s−1, respectively. In vivo experimental measurements of alveolar oxygen partial pressure using 3He in whole rat lung show good agreement (r2 = 0.973) with predictions based on lung volumes and ventilation parameters. For 129Xe, multicomponent relaxation was observed with one component exhibiting an increase in R2 with decreasing alveolar oxygen partial pressure. Magn Reson Med, 2010.

Sci—Fri AM: Imaging — 02: Regional Ventilation Mapping of the Rat Lung Using Hyperpolarized 3He Magnetic Resonance Imaging

With the addition of inhaled contrast agents, namely hyperpolarized 3He and 129Xe, Magnetic Resonance(MR)imaging has the ability to measure anatomical and functional changes associated with disease progression in the rodent lung. Hyperpolarized 3He MRimaging has been used to measure regional ventilation in the normal rat lung using the dynamic gas signal from inside the lungs. This method employs a variable flip angle approach (FAVOR) to mitigate the effects of RF pulses and relaxation both in the ventilator system and in the rat lung. Theoretical models are used to fit signal enhancement curves to generate two‐dimensional maps of the ventilation parameter, r, which is defined as the percent refreshment of gas per unit volume per breath. Healthy Sprague‐Dawley rats (∼525 g) were anesthetized and ventilated with hyperpolarized 3He using a custom ventilator system. Imaging experiments were performed at 3.0 T and 2D projection images were acquired. The average r value obtained for the whole lung (r = 0.30 ± 0.02) agreed with expected values based on geometrical calculations. The ventilation gradient calculated in the anterior/posterior direction agreed with previously published xenon‐enhanced CT results; however, there is no significant precedent for known ventilation gradients in the superior/inferior direction. In the future, these imaging techniques will be extended to measure ventilation gradients in all three dimensions using hyperpolarized 129Xe. The development of imaging tools to regionally quantify ventilation is expected to improve our understanding of breathing physiology in both normal rat lungs as well as rat models of asthma.