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Diffusion‐weighted magnetic resonance imaging (MRI) provides a way to generate in vivo lung images with contrast sensitive to the molecular displacement of inhaled gas at subcellular length scales. Here, we aimed to evaluate hyperpolarized 3 He MRI estimates of the alveolar dimensions in 38 healthy elderly never‐smokers (73 ± 6 years, 15 males) and 21 elderly ex‐smokers (70 ± 10 years, 14 males) with ( n = 8, 77 ± 6 years) and without emphysema ( n = 13, 65 ± 10 years). The ex‐smoker and never‐smoker subgroups were significantly different for FEV 1 /FVC ( P = 0.0001) and DL CO ( P = 0.009); while ex‐smokers with emphysema reported significantly diminished FEV 1 /FVC ( P = 0.02) and a trend toward lower DL CO ( P = 0.05) than ex‐smokers without emphysema. MRI apparent diffusion coefficients (ADC) and CT measurements of emphysema (relative area–CT density histogram, RA 950 ) were significantly different ( P = 0.001 and P = 0.007) for never‐smoker and ex‐smoker subgroups. In never‐smokers, the MRI estimate of mean linear intercept (260 ± 27 μ m) was significantly elevated as compared to the results previously reported in younger never‐smokers (210 ± 30 μ m), and trended smaller than in the age‐matched ex‐smokers (320 ± 72 μ m, P = 0.06) evaluated here. Never‐smokers also reported significantly smaller internal (220 ± 24 μ m, P = 0.01) acinar radius but greater alveolar sheath thickness (120 ± 4 μ m, P 0.0001) than ex‐smokers. Never‐smokers were also significantly different than ex‐smokers without emphysema for alveolar sheath thickness but not ADC, while ex‐smokers with emphysema reported significantly different ADC but not alveolar sheath thickness compared to ex‐smokers without CT evidence of emphysema. Differences in alveolar measurements in never‐ and ex‐smokers demonstrate the sensitivity of MRI measurements to the different effects of smoking and aging on acinar morphometry.

Gas transport across polymeric membranes is fundamental to many filtering and separation technologies. To elucidate transport mechanisms, and understand the behaviors of membrane materials, accurate measurement of transport properties is required. We report a new magnetic resonance imaging (MRI) methodology to measure membrane gas phase diffusion coefficients. The MRI challenges of low spin density and short gas phase relaxation times, especially for hydrogen gas, have been successfully overcome with a modified one-dimensional, single-point ramped imaging with T(1) enhancement, measurement. We have measured the diffusion coefficients of both hydrogen gas and sulfur-hexafluoride in a model polymeric membrane of potential interest as a gas separator in metal hydride batteries. The experimental apparatus is a modified one-dimensional diaphragm cell which permits measurement of the diffusion coefficient in experimental times of less than 1 min. The H(2) gas diffusion coefficient in the membrane was 0.54 +/- 0.01 mm(2)/s, while that of sulfur-hexafluoride was 0.14 +/- 0.01 mm(2)/s, at ambient conditions.

A multiple echo, single point imaging technique, employing a local surface coil probe, is presented for examination of thin film samples. Depth images with a nominal resolution of 5 microm were acquired with acquisition times on the order of 10 min. The method may be used to observe dynamic phenomenon such as polymerization, wetting, and drying in thin film samples. It is readily adapted to spatially resolved diffusion coefficient and T2 relaxation time mapping.

Purpose: Radiation induced lung injury (RILI) is a common side effect for patients undergoing thoracic radiation therapy (RT). RILI can lead to temporary or permanent loss of lung function and in extreme cases, death. Combining functional lung imaging information with conventional radiation treatment plans may lead to more desirable treatment plans that reduce lung toxicity and improve the quality of life for lung cancer survivors. Magnetic Resonance Imaging of the lung following inhalation of hyperpolarized{sup 129}Xe may provide a useful nonionizing approach for probing changes in lung function and structure associated with RILI before, during, or after RT (early and late time-points). Methods: In this study, dynamic{sup 129}Xe MR spectroscopy was used to measure whole-lung gas transfer time constants for lung tissue and red blood cells (RBC), respectively (T{sub Tr-tissue} and T{sub Tr-RBC}) in groups of rats at two weeks and six weeks following 14 Gy whole-lung exposure to radiation from a {sup 60}Co source. A separate group of six healthy age-matched rats served as a control group. Results: T{sub Tr-tissue} values at two weeks post-irradiation (51.6 ± 6.8 ms) were found to be significantly elevated (p < 0.05) with respect to the healthy control group (37.2 ± 4.8 ms).more » T{sub Tr-RBC} did not show any significant changes between groups. T{sub Tr-tissue} was strongly correlated with T{sub Tr-RBC} in the control group (r = 0.9601 p < 0.05) and uncorrelated in the irradiated groups. Measurements of arterial partial pressure of oxygen obtained by arterial blood sampling were found to be significantly decreased (p < 0.05) in the two-week group (54.2 ± 12.3 mm Hg) compared to those from a representative control group (85.0 ± 10.0 mm Hg). Histology of a separate group of similarly irradiated animals confirmed the presence of inflammation due to radiation exposure with alveolar wall thicknesses that were significantly different (p < 0.05). At six weeks post-irradiation, T{sub Tr-tissue} returned to values (35.6 ± 9.6 ms) that were not significantly different from baseline. Conclusions: Whole-lung tissue transfer time constants for{sup 129}Xe (T{sub Tr-tissue}) can be used to detect the early phase of RILI in a rat model involving 14 Gy thoracic {sup 60}Co exposure as early as two weeks post-irradiation. This knowledge combined with more sophisticated models of gas exchange and imaging techniques, may allow functional lung avoidance radiation therapy planning to be achievable, providing more beneficial treatment plans and improved quality of life for recovering lung cancer patients.« less

Purpose: To use hyperpolarized ,13C Magnetic Resonance Spectroscopy for early detection of Radiation Induced Lung Injury (RILI) by quantifying the ratio between metabolites of , 13C‐lactate and ,13C‐pyruvateMethods: Rats were irradiated with dose of 14 Gy to the thorax region to induced RILI using a ,13Co source. The contrast agent, ,13C‐pyruvate was hyperpolarized using Dynamic Nuclear Polarization (DNP) that increases signal intensity by four orders of magnitude. It was injected into the animals two weeks post irradiation and dynamic, 13C‐spectroscopy was performed. Proton Images were acquires prior to the spectroscopy for proper localization of the thorax region. Results: A factor of more than two increase in the,13C‐lactate to,13C‐ pyruvate ratio was observed for the irradiated rats compared to the normal animals. This result supports the hypothesis that an increase in production of lactate is evident with onset of hypoxia, which is a consequence of RILI. Conclusions: Significantly higher ratio of ,13C‐lactate to ,13C‐pyruvate is seen the irradiated animals compared to the normal animals demonstrating the feasibility of using ,13C pyruvate to probe in in vivo metabolism and its use as an early market for onset of RILI.

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.

Magnetic Resonance (MR) imaging using hyperpolarized noble gases (HNG's), 3He and 129Xe, provide non-invasive approaches for probing lung function and structure. In particular, measurement of HNG ventilated lung volumes (e.g., ventilation defects) and apparent diffusion coefficients (ADC) are useful for characterizing chronic obstructive pulmonary disease (COPD) and emphysema. Of particular interest, hyperpolarized 129Xe also dissolves in the lung parenchyma and blood compartments, offering an interesting palette of potential biomarkers of pulmonary disease, including quantifying xenon diffusing capacity in inflammatory disease and may be useful for assessing pulmonary perfusion. 129Xe dissolved in tissue and blood experience large chemical shifts and can be selectively saturated and allowed to recover as a function of delay time as in the chemically selective saturation recovery (CSSR) technique. CSSR has previously been used to study surface-to-volume ratio (S/V) and diffusing capacity of xenon (DXe) in the lung which is analogous to diffusing capacity of carbon monoxide. In this work, the 129Xe CSSR technique is used to measure S/V ratios and Dxelp in whole healthy rat lungs as a function of ventilated lung volume assessed with 3He MR imaging. The data follow theoretically predicted trends for Ttr, S/V and DXeLP. In parallel to this study, 3D 129Xe imaging was also investigated and compared to 3He for lung volume assessment in an effort to remove the reliance on 3He which is costly and scarce. Absolute ventilated volumes (|VLV|) derived from preliminary results for 3He and 129Xe were 9.74 mL and 9.14 mL respectively for a pressure of 9.1cmH2O.

Carbon‐13 (13C) can be hyperpolarized by Dynamic Nuclear Polarization (DNP) to increase the signal by 10,000 times. By hyperpolarizing 13C in the pyruvate molecule, radiation—induced lung injury (RILI) may be studied with Magnetic Resonance Imaging. In‐vivo, pyruvate breaks down into lactate, alanine, bicarbonate and other metabolites in a time‐dependent manner. The early stages of RILI lead to higher concentration of lactate in tissues. Therefore the ratio of pyruvate to lactate measured in rat lungs, following irradiation may provide an early indication of RILI. In the present study, dynamic MRspectroscopic techniques are developed to ensure proper quantification of these metabolites. [1‐13C] labelled pyruvate (CIL, Cambridge, MA) was hyperpolarized by a commercially‐available DNP system (Hypersense, Oxford Instruments). The DNP system utilizes low temperature (1.4 °K), high magnetic field strength (3.35 T) and irradiation with a microwave source (94.15 GHz) to polarize the pyruvate. Data were obtained following bolus injection of 3 ml of 0.8 mM [1‐13C] pyruvic acid in the tail vein of healthy Sprague Dawley rats (400–450 g) following an animal care protocol approved by the Animal Use Subcommittee of the University Council on Animal Care at the University of Western Ontario. Pyruvate and lactate signals were identified based on their chemical shift from the obtained in‐vivo dynamic spectra. The relative signal strength from these metabolites was quantified. This study demonstrated the capability of quantification of hyperpolarized [1‐13C] labeled pyruvate and lactate from in‐vivo dynamic spectra in rats which represents an important step toward studies of RILI.

Hyperpolarized Helium‐3 (3He) Magnetic Resonance(MR)imaging is a novel technique used for investigating structural and functional properties of the lungin vivo. In particular, 3He diffusionmeasurements have shown remarkable sensitivity for diagnosing Chronic Obstructive Pulmonary Disease (COPD), particularly emphysema. Restricted diffusion reduces the free diffusion coefficient, thus resulting in a measured apparent diffusion coefficient (ADC) related to the size of the acinus and alveoli. ADC has been predicted to behave anisotropically, and can be described by two components: (i) a longitudinal component along the acinus and (ii) a transverse component perpendicular to the acinus which depend on the diffusion time (δ). We measured3He ADC at both ultra short (< 1 ms) and long (δ=50 ms ‐ 1 s) diffusion times in both healthy rat lungs and rat lungs instilled with elastase to simulate emphysema. Ultra‐short domain ADC maps were measured using a 3.0 T MRimaging system, where the transverse ADC component was found to be most sensitive to elastase damage for diffusion times near 360 μs, consistent with theoretical models. Whole‐lung long‐range ADC measurements were acquired using a 74 mT MRimaging system, since the low magnetic field has the advantage of longer T2* from reduced susceptibility differences at the air‐tissue interfaces. Measured ADC correlated well with histology (i.e. mean linear intercept). Possible extension of this work to hyperpolarized Xenon‐129 (129Xe) anisotropic ADC measurements at low field is discussed, as an optimal diffusion time of 20.8 ms has been predicted, more favorable for clinical studies