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Hyperpolarized (HP) 129 Xe MRI uniquely images pulmonary ventilation, gas exchange, and terminal airway morphology rapidly and safely, providing novel information not possible using conventional imaging modalities or pulmonary function tests. As such, there is mounting interest in expanding the use of biomarkers derived from HP 129 Xe MRI as outcome measures in multi-site clinical trials across a range of pulmonary disorders. Until recently, HP 129 Xe MRI techniques have been developed largely independently at a limited number of academic centers, without harmonizing acquisition strategies. To promote uniformity and adoption of HP 129 Xe MRI more widely in translational research, multi-site trials, and ultimately clinical practice, this position paper from the 129 Xe MRI Clinical Trials Consortium (https://cpir.cchmc.org/XeMRICTC) recommends standard protocols to harmonize methods for image acquisition in HP 129 Xe MRI. Recommendations are described for the most common HP gas MRI techniques-calibration, ventilation, alveolar-airspace size, and gas exchange-across MRI scanner manufacturers most used for this application. Moreover, recommendations are described for 129 Xe dose volumes and breath-hold standardization to further foster consistency of imaging studies. The intention is that sites with HP 129 Xe MRI capabilities can readily implement these methods to obtain consistent high-quality images that provide regional insight into lung structure and function. While this document represents consensus at a snapshot in time, a roadmap for technical developments is provided that will further increase image quality and efficiency. These standardized dosing and imaging protocols will facilitate the wider adoption of HP 129 Xe MRI for multi-site pulmonary research.

Premature infants often require mechanical ventilation and oxygen therapy, which can result in bronchopulmonary dysplasia (BPD), characterized by developmental arrest and impaired lung function. Conventional clinical methods for assessing the prenatal lung are not adequate for the detection and assessment of long-term health risks in infants with BPD, highlighting the need for a noninvasive tool for the characterization of lung microstructure and function. Theoretical diffusion models, like the model of xenon exchange (MOXE), interrogate alveolar gas exchange by predicting the uptake of inert hyperpolarized (HP) 129Xe gas measured with HP 129Xe magnetic resonance spectroscopy (MRS). To investigate HP 129Xe MRS as a tool for noninvasive characterization of pulmonary microstructural and functional changes in vivo, HP 129Xe gas exchange data were acquired in an oxygen exposure rat model of BPD that recapitulates the fewer and larger distal airways and pulmonary vascular stunting characteristics of BPD. Gas exchange parameters from MOXE, including airspace mean chord length ( Lm), apparent hematocrit in the pulmonary capillaries (HCT), and pulmonary capillary transit time ( tx), were compared with airspace mean axis length and area density (MAL and ρA) and percentage area of tissue and air (PTA and PAA) from histology. Lm was significantly larger in the exposed rats ( P = 0.003) and correlated with MAL, ρA, PTA, and PAA (0.59x are also discussed. These findings support the use of HP 129Xe MRS for detecting fewer, enlarged distal airways in this rat model of BPD, and potentially in humans.

Rationale and Objectives Phase resolved functional lung (PREFUL) magnetic resonance imaging (MRI) is a free-breathing 1H-based technique that produces maps of fractional ventilation (FV). This study compared ventilation defect percent (VDP) calculated using PREFUL to hyperpolarized (HP) 129Xe MRI and pulmonary function tests in pediatric cystic fibrosis (CF). Materials and Methods 27 pediatric participants were recruited (mean age 13.0 ± 2.7), including 6 with clinically stable CF, 11 CF patients undergoing a pulmonary exacerbation (PEx), and 10 healthy controls. Spirometry was performed to measure forced expiratory volume in 1 second (FEV1), along with nitrogen multiple breath washout to measure lung clearance index (LCI). VDP was calculated from single central coronal slice PREFUL FV maps and the corresponding HP 129Xe slice. Results The stable CF group had a normal FEV1 (p = 0.41) and elevated LCI (p = 0.007). The CF PEx group had a decreased FEV1 (p Conclusion PREFUL MRI is feasible in pediatric CF, distinguishes patients undergoing pulmonary exacerbations compared to healthy subjects, and correlates with HP 129Xe MRI as well as functional measures of disease severity. PREFUL MRI does not require breath-holds and is straight forward to implement on any MRI scanner.

Diffusion-weighted, hyperpolarized 129Xe MRI is useful for the characterization of microstructural changes in the lung. A stretched exponential model was proposed for morphometric extraction of the mean chord length (Lm) from diffusion-weighted data. The stretched exponential model enables accelerated mapping of Lm in a single-breathhold using compressed sensing. Our purpose was to compare Lm maps obtained from stretched-exponential model analysis of accelerated versus unaccelerated diffusion-weighted 129Xe MRI data obtained from healthy/injured rat lungs. Lm maps were generated using a stretched-exponential model analysis of previously acquired fully sampled diffusion-weighted 129Xe rat data (b values = 0 … 110 s/cm2) and compared to Lm maps generated from retrospectively undersampled data simulating acceleration factors of 7/10. The data included four control rats and five rats receiving whole-lung irradiation to mimic radiation-induced lung injury. Mean Lm obtained from the accelerated/unaccelerated maps were compared to histological mean linear intercept. Accelerated Lm estimates were similar to unaccelerated Lm estimates in all rats, and similar to those previously reported (

PURPOSE To assess the feasibility of hyperpolarized 129 Xe multiple-breath washout MRI in pediatric cystic fibrosis (CF) participants with preserved lung function. Fractional ventilation (r), defined as the fractional gas replacement per breath, was mapped using 2 signal models: (1) constant T1 and (2) variable T1 as a function of the hyperpolarized gas washout. METHODS A total of 17 pediatric participants were recruited (mean age 11.7 ± 2.8 years), including 7 children with clinically stable CF and 10 aged-matched healthy controls. Pulmonary function tests were performed, including spirometry, to measure the forced expiratory volume in 1 second and nitrogen multiple-breath washout to measure the lung clearance index. Hyperpolarized 129 Xe MRI was performed during consecutive breaths of air following a single 129 Xe inhalation, and fractional ventilation maps were calculated. RESULTS The forced expiratory volume in 1 second was similar in both groups (P = .32), but there was a statistically significant difference in lung clearance index between healthy and CF participants (P = .001). With variable T1 modeling, CF participants had a mean r of 0.44 ± 0.08 and healthy participants had a mean r of 0.37 ± 0.12 (P = .20). With constant T1 modeling, CF participants had a mean r' of 0.48 ± 0.08, and healthy participants had a mean r' of 0.43 ± 0.12 (P = .32). Therefore, assuming a constant T1 leads to a relative bias in r of 15.1% ± 6.4% and 20.8% ± 7.4% for CF and healthy participants, respectively (P = .12). CONCLUSION This study demonstrates that hyperpolarized 129 Xe multiple-breath washout imaging is feasible in pediatric participants with CF, and inclusion of variable T1 modeling reduces bias in the fractional ventilation measurements.

Background The ventilation defect percent (VDP), measured from hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI), is sensitive to functional changes in cystic fibrosis (CF) lung disease. The purpose of this study was to measure and compare VDP from HP 129Xe MRI acquired at two institutions in stable pediatric CF subjects with preserved lung function. Methods This retrospective analysis included 26 participants from two institutions (18 CF, 8 healthy, age range 10–17). Pulmonary function tests, N2 multiple breath washout (to measure lung clearance index, LCI), and HP 129Xe MRI were performed. VDP measurements were compared between two trained analysts using mean-anchored linear binning. Correlations were investigated for VDP compared to the forced expiratory volume in one second (FEV1) and LCI. Results VDP measurements agreed for the two analysts with an intraclass correlation coefficient of 0.99. In the combined dataset, VDP measured by Analyst 1 was 5.96 ± 1.82% and 15.96 ± 6.76% for the healthy and CF groups, respectively (p = .0004). Analyst 2 showed similar differences between healthy and CF (p = .0003). VDP measured by either analyst was shown to correlate with FEV1 (R2 = 0.33, p = .003; and R2 = 0.26, p = .009 for Analysts 1 and 2, respectively) and LCI (R2 = 0.76, p Conclusion HP 129Xe MRI provides a robust measurement of ventilation heterogeneity in stable pediatric CF subjects at two sites. Since measurements performed at two sites yielded similar VDP values with near-identical values between different analysts, implementation of the technique in multi-center trials in CF appears feasible.

Introduction Newer proton MRI methods may be complementary to conventional respiratory diagnostics like computed tomography (CT) and spirometry. Non-contrast Ultrashort Echo Time (UTE) MRI acquires high resolution structural images, comparable to CT, and gradient-echo combined with phase-resolved functional lung (PREFUL) processing methods can produce spatial assessments of lung function. The need for such MRI methods is exemplified by cystic fibrosis (CF), where rapid development of novel therapeutics demands an equivalent change in our ability to monitor lung disease. Aim To evaluate lung structure and function using UTE and PREFUL MRI methods in people with CF with at least one F508-del mutation pre-Trikafta therapy. Methods 5 people with CF (12–21 years; n=4 homozygous F508-del; n=3 on Symkevi) underwent a single MRI scanning session performed on a 3T Philips Ingenia scanner. UTE-MRI was collected during a 10-second breath-hold (n=2) or free breathing with a respiratory-gated acquisition (n=3). PREFUL-MRI was performed using a continuous single coronal slice Fast Field Echo acquisition during 2 minutes of free breathing (n=5). PREFUL analysis was performed using a semiautomated k-means segmentation algorithm in MATLAB. 1 A region of interest (ROI) at the diaphragm was defined, images with extremes of signal intensity were removed and those remaining sorted into a sinusoidal pattern of signal intensity within the ROI. Thoracic masking and a pulmonary vessel filter were applied followed by k-means clustering analysis to demonstrate normal ventilation and ventilation defect. Ventilation defect percentage (VDP) was calculated by dividing the ventilation defect volume by the lung mask volume. Results MRI scanning was well-tolerated and both UTE and PREFUL acquisitions were completed in all participants. VDP values ranged from 8.09–36.65%, with the individual with the lowest FEV1 having the highest VDP (figure 1). Discussion Our findings demonstrate the feasibility of combined structural and functional lung MRI assessment in people with CF. These non-contrast approaches do not require additional specialised equipment, such as hyperpolarised gas, and could be obtained using standard clinical MRI scanners. In the future, functional lung MRI may facilitate longitudinal assessment of response to disease modifying therapies, such as CFTR modulators. Reference Couch, et al. Academic Radiology 2020. doi:10.1016/j.acra.2020.05.008.

Treatment response in Cystic Fibrosis (CF) is traditionally monitored using pulmonary function tests (PFTs), such as spirometry. However, PFTs can be insensitive to treatment, particularly in early CF lung disease [1]. Hyperpolarized (HP) 129Xe MRI (Xe-MRI) has been shown to be feasible in children [2], more sensitive to early CF lung disease compared to PFTs [3 and captures improvements in ventilation inhomogeneity in pediatric CF patients receiving intravenous antibiotic treatment for a PEx [4]. However, access to hyperpolarized 129Xe gas is not widely available and Xe-MRI requires subjects to perform an extended breath-hold (10–15 s), which is challenging for very sick children. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Munidasa reports grants from Cystic Fibrosis Centre, grants from Natural Sciences and Engineering Research Council of Canada, grants from Canadian Institutes of Health Research, during the conduct of the study. Conflict of interest: Dr. Couch reports that he was supported by a MITACS Elevate Postdoctoral Fellowship, which was funded in part by Siemens Healthcare Limited. Dr. Couch is currently an employee of Siemens Healthcare Limited. This employment began after the conclusion of the study. Conflict of interest: Dr. Rayment reports other from Polarean Inc, outside the submitted work. Conflict of interest: Dr. Voskrebenzev reports In addition, Dr. Voskrebenzev has a patent Method of quantitative magnetic resonance lung imaging Conflict of interest: Dr. Seethamraju reports personal fees from Siemens Medical Solutions, USA Inc., outside the submitted work. Conflict of interest: Dr. Vogel-Claussen reports grants from Siemens Healthineers, during the conduct of the study; grants and personal fees from Boehringer Ingelheim, grants from GSK, grants and personal fees from Astra Zeneca, outside the submitted work; In addition, Dr. Vogel-Claussen has a patent Voskrebenzev, Gutberlet, Vogel-Claussen „Method of quantitative magnetic resonance lung imaging“Nr. EP3107066, US-2016-0367200-A1 22.12.2016 licensed to Siemens Healthineers. Conflict of interest: Dr. Ratjen has nothing to disclose. Conflict of interest: Dr. Santyr reports grants and non-financial support from Siemens Healthineers, grants from Canadian Institutes of Health Research, during the conduct of the study; grants and non-financial support from Siemens Healthineers, outside the submitted work.

Conventional pulmonary function tests appear normal in early cystic fibrosis (CF) lung disease. Therefore, new diagnostic approaches are required that can detect CF lung disease in children and monitor treatment response. Hyperpolarized (HP) gas (129Xe and 3He) magnetic resonance imaging (MRI) is a powerful, emergent tool for mapping regional lung function and may be well suited for studying pediatric CF. HP gas MRI is well tolerated, reproducible, and it can be performed longitudinally without the need for ionizing radiation. In particular, quantification of the distribution of ventilation, or ventilation defect percent (VDP), has been shown to be a sensitive indicator of CF lung disease and correlates well with pulmonary function tests. This article presents the current state of CF diagnosis and treatment and describes the potential role of HP gas MRI for detection of early CF lung disease and following the effects of interventions. The typical HP gas imaging workflow is described, along with a discussion of image analysis to calculate VDP, dosing considerations, and the reproducibility of VDP. The potential use of VDP as an outcome measure in CF is discussed, by considering the correlation with pulmonary function measures, preliminary interventional studies, and case studies involving longitudinal imaging and pulmonary exacerbations. Finally, emerging HP gas imaging techniques such as multiple breath washout imaging are introduced, followed by a discussion of future directions. Overall, HP gas MRI biomarkers are expected to provide sensitive outcome measures that can be used in disease surveillance as well as interventional studies involving novel CF therapies.

Purpose The purpose of this work was to use magnetic resonance imaging (MRI) of hyperpolarized (HP) 129 Xe dissolved in pulmonary tissue (PT) and red blood cells (RBCs) to detect regional changes to PT structure and perfusion in a partial-lung rat model of radiation-induced lung injury and compare with histology. Methods and materials The right medial region of the lungs of 6 Sprague-Dawley rats was irradiated (20 Gy, single-fraction). A second nonirradiated cohort served as the control group. Imaging was performed 4 weeks after irradiation to quantify intensity and heterogeneity of PT and RBC 129 Xe signals. Imaging findings were correlated with measures of PT and RBC distribution. Results Asymmetric (right vs left) changes in 129 Xe signal intensity and heterogeneity were observed in the irradiated cohort but were not seen in the control group. PT signal was observed to increase in intensity and heterogeneity and RBC signal was observed to increase in heterogeneity in the irradiated right lungs, consistent with histology. Conclusion Regional changes to PT and RBC 129 Xe signals are detectable 4 weeks following partial-lung irradiation in rats.

Purpose Hyperpolarized (HP) gas MRI of the rodent lung is of great interest because of the increasing need for novel biomarkers with which to develop new therapies for respiratory diseases. The use of fast gradient-recalled echo (FGRE) for high-resolution HP gas rodent lung MRI is challenging as a result of signal loss caused by significant diffusion weighting, particularly in the larger airways. In this work, a modified FGRE approach is described for HP 3He rodent lung MRI using a centric-out readout scheme (ie, x-centric), allowing high-resolution, density-weighted imaging. Methods HP 3He x-centric imaging was performed in a phantom and compared with a conventional partial-echo FGRE acquisition for in-plane spatial resolutions varying between 39 and 312 µm. Partial-echo and x-centric acquisitions were also compared for high spatial-resolution breath-hold (1 s) imaging of rodent lungs. Results X-centric provided improved signal-to-noise ratio efficiency by a factor of up to 13/1.7 and 6.7/1.8, compared with the partial-echo FGRE for the airways/parenchyma of mouse and rat, respectively, at high spatial resolutions in vivo (

Purpose: To assess the feasibility of hyperpolarized (HP) 129Xe MRI for detection of early stage radiation-induced lung injury (RILI) in a rat model involving unilateral irradiation by assessing differences in gas exchange dynamics between irradiated and unirradiated lungs. Methods: The dynamics of gas exchange between alveolar air space and pulmonary tissue (PT), PT and red blood cells (RBCs) was measured using single-shot spiral iterative decomposition of water and fat with echo asymmetry and least-squares estimation images of the right and left lungs of two age-matched cohorts of Sprague Dawley rats. The first cohort (n = 5) received 18 Gy irradiation to the right lung using a 60Co source and the second cohort (n = 5) was not irradiated and served as the healthy control. Both groups were imaged two weeks following irradiation when radiation pneumonitis (RP) was expected to be present. The gas exchange data were fit to a theoretical gas exchange model to extract measurements of pulmonary tissue thickness (LPT) and relative blood volume (VRBC) from each of the right and left lungs of both cohorts. Following imaging,lung specimens were retrieved and percent tissue area (PTA) was assessed histologically to confirm RP and correlate with MRI measurements. Results: Statistically significant differences in LPT and VRBC were observed between the irradiated and non-irradiated cohorts. In particular, LPT of the right and left lungs was increased approximately 8.2% and 5.0% respectively in the irradiated cohort. Additionally, VRBC of the right and left lungs was decreased approximately 36.1% and 11.7% respectively for the irradiated cohort compared to the non-irradiated cohort. PTA measurements in both right and left lungs were increased in the irradiated group compared to the non-irradiated cohort for both the left (P < 0.05) and right lungs (P < 0.01) confirming the presence of RP. PTA measurements also correlated with the MRI measurements for both the non-irradiated (r = 0.79, P < 0.01) and irradiated groups (r = 0.91, P < 0.01). Conclusions: Regional RILI can be detected two weeks post-irradiation using HP 129Xe MRI and analysis of gas exchange curves. This approach correlates well with histology and can potentially be used clinically to assess radiation pneumonitis associated with early RILI to improve radiation therapy outcomes.

Purpose Radiation-induced lung injury (RILI) is still the major dose-limiting toxicity related to lung cancer radiation therapy, and it is difficult to predict and detect patients who are at early risk of severe pneumonitis and fibrosis. The goal of this proof-of-concept preclinical demonstration was to investigate the potential of hyperpolarized 129Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. Methods Hyperpolarized 129Xe MRI was performed using eight different diffusion sensitizations (0.0–115 s/cm2) in a small group of control rats (n = 4) and rats 2 wk after radiation exposure (n = 5). The diffusion-weighted images were used to obtain morphological estimates of the pulmonary parenchyma including external radius (R), internal radius (r), alveolar sleeve depth (h), and mean airspace chord length (Lm). The histological mean linear intercept (MLI) were obtained for five control and five irradiated animals. Results Mean R, r, and Lm were both significantly different (P

phometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro-structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pAO2) maps by extracting the unrestricted diffusion coefficient (D0) of xenon as a morphometric parameter. Methods: In this proof-of-concept demonstration, morphometry was performed using multi b-value (0, 12, 20, 30 s/cm 2 ) DW hyperpolarized 129 Xe images obtained in four neversmokers and four COPD ex-smokers. Morphometric parameters and D0 maps were computed and the latter used to generate [Xe] and pAO2 maps. Xenon concentration phantoms estimating a range of values mimicking those observed in vivo were also investigated. Results: Xenon D0 was significantly increased (P ¼0.035) in COPD (0.14 60.03 cm 2 /s) compared with never-smokers (0.12 60.02 cm 2 /s). COPD ex-smokers also had significantly decreased [Xe] (COPD ¼8 67% versus never-smokers ¼ 13 68%, P ¼0.012) and increased pAO2 (COPD ¼18 63% versus never-smokers ¼15 63%, P ¼0.009) compared with never-smokers. Phantom measurements showed the expected dependence of D0 on [Xe] over the range of concentrations anticipated in vivo. Conclusion: DW hyperpolarized 129 Xe MRI morphometry can be used to simultaneously map [Xe] and pAO2 in addition to providing micro-structural biomarkers of emphysematous destruction in COPD. Phantom measurements of D0([Xe]) supported the hypotheses that differences in subjects may reflect differences in functional residual capacity. Magn Reson Med 000:000–000, 2014. V C 2014 Wiley Periodicals, Inc.

MRI of hyperpolarized 129Xe gas and 13C-enriched substrates (e.g. pyruvate) presents an unprecedented opportunity to map anatomical, functional and metabolic changes associated with lung injury. In particular, inhaled hyperpolarized 129Xe gas is exquisitely sensitive to changes in alveolar microanatomy and function accompanying lung inflammation through decreases in the apparent diffusion coefficient (ADC) of alveolar gas and increases in the transfer time (Ttr) of xenon exchange from the gas and into the dissolved phase in the lung. Furthermore, metabolic changes associated with hypoxia arising from lung injury may be reflected by increases in lactate-to-pyruvate signal ratio obtained by magnetic resonance spectroscopic imaging following injection of hyperpolarized [1-13C]pyruvate. In this work, the application of hyperpolarized 129Xe and 13C MRI to radiation-induced lung injury (RILI) is reviewed and results of ADC, Ttr and lactate-to-pyruvate signal ratio changes in a rat model of RILI are summarized. These results are consistent with conventional functional (i.e. blood gases) and histological (i.e. tissue density) changes, and correlate significantly with inflammatory cell counts (i.e. macrophages). Hyperpolarized MRI may provide an earlier indication of lung injury associated with radiotherapy of thoracic tumors, potentially allowing adjustment of treatment before the onset of severe complications and irreversible fibrosis. Copyright © 2014 John Wiley & Sons, Ltd.

Purpose Radiation Pneumonitis (RP) limits radiotherapy. Detection of early metabolic changes in the lungs associated with RP may provide an opportunity to adjust treatment before substantial toxicities occur. In this work, regional lactate-to-pyruvate signal ratio (lac/pyr) was quantified in rat lungs and heart following administration of hyperpolarized 13 C-pyruvate magnetic resonance imaging (MRI) at day 5, 10, 15 and 25-post conformal radiotherapy. These results were also compared to histology and blood analyses. Methods The lower right lungs of 12 Sprague Dawley rats were irradiated in 2 fractions with a total dose of 18.5Gy using a modified micro-CT system. Regional lactate and pyruvate data were acquired from three irradiated and three age-matched healthy rats at each time point on days 5, 10, 15 and 25-post radiotherapy. Arterial blood was collected from each animal prior to the 13 C-pyruvate injection and was analyzed for blood lactate concentration and arterial oxygen concentration (p a O 2 ). Macrophage count was computed from the histology of all rat lungs. Results A significant increase in lac/pyr was observed in both right and left lungs of the irradiated cohort compared to the healthy cohort for all time points. No increase in lac/pyr was observed in the hearts of the irradiated cohort compared to the hearts of the healthy cohorts. Blood lactate concentration and p a O 2 did not show a significant change between the irradiated and the healthy cohorts. Macrophage count in both right and left lungs was elevated for the irradiated cohort compared to the healthy cohort. Conclusions Metabolic changes associated with RP may be mapped as early as five days post conformal radiotherapy. Over the small sample size in each cohort, elevated macrophage count, consistent with early phase of inflammation was highly correlated to increases in lac/pyr in both the irradiated and unirradiated lungs. Further experiments with larger sample size may improve the confidence of this finding.

Purpose MRI using hyperpolarized noble gases, 3He and 129Xe, provides noninvasive assessments of lung structure and function. Previous work demonstrated that absolute ventilated lung volumes (aVLV) measured in rats using hyperpolarized 3He agree well with micro-CT. Methods In this work, aVLV measurements were performed in rats using hyperpolarized 129Xe MRI and compared with hyperpolarized 3He measurements of aVLV under matched ventilation conditions. Whole-lung compliance was also determined. Partial volume, apparent diffusion coefficient, and effective transverse relaxation time corrections were applied during postprocessing to reduce bias between methods. Results Mean apparent diffusion coefficient of the trachea was 0.83 ± 0.09 cm2/s and 0.067 ± 0.011 cm2/s for 3He and 129Xe, respectively. Mean apparent diffusion coefficient of parenchyma was 0.21 ± 0.07 cm2/s and 0.027 ± 0.008 cm2/s for 3He and 129Xe, respectively. Mean transverse relaxation time values were 1.57 ± 0.25 ms and 2.80 ± 0.25 ms for 3He and 129Xe, respectively, in a model trachea and 3.18 ± 1.00 ms and 4.88 ± 0.60 ms for 3He and 129Xe, respectively, for lung parenchyma. Mean aVLV values were 7.07 ± 0.67 mL and 6.99 ± 1.00 mL at 14 cmH2O and 4.88 ± 0.71 mL and 5.36 ± 0.76 mL at 10 cmH2O obtained with 3He and 129Xe, respectively, demonstrating good agreement between 129Xe and 3He. Conclusions 129Xe offers an important alternative to 3He for hyperpolarized gas MRI of aVLV in rats. Magn Reson Med 71:1130–1136, 2014. © 2013 Wiley Periodicals, Inc.

Purpose The goal of this work was to investigate lung morphological changes associated with chronic obstructive pulmonary disease (COPD) using hyperpolarized 129Xe diffusion-weighted MRI. Methods Hyperpolarized 129Xe MRI was performed at three different nonzero diffusion sensitizations (b-value = 12, 20, and 30 s/cm2) in the lungs of four subjects with COPD and four healthy volunteers. The image signal intensities were fit as a function of b-value to obtain anisotropic diffusion coefficient maps for all subjects. The image signal intensities were also fit to a morphological model allowing extraction of length scales associated with the terminal airways: external radius (R), internal radius (r), mean airspace chord length (Lm), and depth of alveolar sleeve (h). Results Longitudinal (DL) and transverse (DT) anisotropic diffusion coefficients were both significantly increased (both P= 0.004) in the COPD subjects (0.102 ± 0.02 cm2/s and 0.072 ± 0.02 cm2/s, respectively) compared with the healthy subjects (0.083 ± 0.011 cm2/s and 0.046 ± 0.017 cm2/s, respectively). Significant morphological differences were observed between the COPD subjects and healthy volunteers, specifically decreases in h (68 ± 36 µm vs. 95 ± 710 µm, respectively, P = 0.019) and increases in Lm (352 ± 57 µm vs. 253 ± 37 µm, respectively, P = 0.002) consistent with values obtained previously using hyperpolarized 3He MRI in similar subjects. Conclusions Diffusion-weighted hyperpolarized 129Xe MRI is a promising technique for mapping changes in human lung morphology and may be useful for early detection of emphysema associated with COPD. Magn Reson Med 70:1699–1706, 2013. © 2013 Wiley Periodicals, Inc.

Radiation-induced lung injury limits radiotherapy of thoracic cancers. Detection of radiation pneumonitis associated with early radiation-induced lung injury (2-4 weeks postirradiation) may provide an opportunity to adjust treatment, before the onset of acute pneumonitis and/or irreversible fibrosis. In this study, localized magnetic resonance (MR) spectroscopy and imaging of hyperpolarized (13)C-pyruvate (pyruvate) and (13)C-lactate (lactate) were performed in the thorax and kidney regions of rats 2 weeks following whole-thorax irradiation (14 Gy). Lactate-to-pyruvate signal ratio was observed to increase by 110% (P < 0.01), 57% (P < 0.02), and 107% (P < 0.01), respectively, in the thorax, lung, and heart tissues of the radiated rats compared with healthy age-matched rats. This was consistent with lung inflammation confirmed using cell micrographs of bronchioalveolar lavage specimens and decreases in arterial oxygen partial pressure (paO2), indicative of hypoxia. No statistically significant difference was observed in either lactate-to-pyruvate signal ratios in the kidney region (P = 0.50) between the healthy (0.215 ± 0.100) and radiated cohorts (0.215 ± 0.054) or in blood lactate levels (P = 0.69) in the healthy (1.255 ± 0.247 mmol/L) and the radiated cohorts (1.325 ± 0.214 mmol/L), confirming that the injury is localized to the thorax. This work demonstrates the feasibility of hyperpolarized (13)C metabolic MR spectroscopy and imaging for detection of early radiation-induced lung injury.

Rationale and Objectives The objective of this study was to evaluate the tolerability of hyperpolarized 129 Xe gas inhaled from functional residual capacity and magnetic resonance imaging in healthy subjects and those with pulmonary disease. Materials and Methods Twelve healthy volunteers (mean age, 59 ± 17 years), seven subjects with asthma (mean age, 47 ± 7 years), 10 subjects with chronic obstructive pulmonary disease (mean age, 74 ± 4 years), three subjects with cystic fibrosis (mean age, 27 ± 10 years), and a single subject with radiation-induced lung injury (age, 66 years) were enrolled and evaluated over 43 visits with 136 anoxic inhalations of 500 mL 129 Xe gas mixed with 500 mL 4 He gas. Oxygen saturation and heart rate were monitored during the breath-hold and imaging; subjects were queried for adverse events (AEs) before and immediately following gas inhalation and for 24 hours after the last dose. Results No subjects withdrew from the study or reported serious, hypoxic, or severe AEs. Over the course of 136 dose administrations, two mild AEs (1%) were reported in two different subjects (two of 33 [6%]). One of these AEs (light-headedness) was temporally related and judged as possibly related to 129 Xe administration and resolved without treatment within 2 minutes. Statistically significant but clinically insignificant changes in oxygen saturation and heart rate were observed after inhalation ( P Conclusions Inhalation of hyperpolarized 129 Xe gas and subsequent magnetic resonance imaging were well tolerated in healthy subjects and ambulatory subjects with obstructive and restrictive pulmonary disease.

Lung ventilation was mapped in seven healthy male Sprague-Dawley rats (433 ± 24 g) using hyperpolarized 129Xe magnetic resonance imaging (MRI) at 3.0 T, and validated with hyperpolarized 3He MRI under similar ventilator conditions. Ventilation maps were obtained using flip angle variation for offset of RF and relaxation (FAVOR) which is a multiple breath imaging technique that extracts the fractional ventilation parameter, r, on a pixel-by-pixel basis from the dynamic signal enhancement. r is defined as the fractional refreshment of gas per breath. Under the ventilator conditions used in this work, whole-lung measurements of fractional ventilation obtained using hyperpolarized 129Xe were not significantly different from those obtained using hyperpolarized 3He (p = 0.8125 by a Wilcoxon matched pairs test). Fractional ventilation gradients calculated in the superior/inferior (S/I) and anterior/posterior (A/P) directions obtained using hyperpolarized 129Xe were not significantly different from those obtained using hyperpolarized 3He (p = 0.9375 and p = 0.1563, for the S/I and A/P directions, respectively). Following baseline fractional ventilation measurements, one representative rat was challenged with methacholine and fractional ventilation measurements were performed over a time course of 10 min. A reduction and subsequent recovery in whole-lung r values were detected using the FAVOR method. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

Pulmonary magnetic resonance imaging using hyperpolarised129Xe gas (XeMRI) can quantify ventilation inhomogeneity by measuring the percentage of unventilated lung volume (ventilation defect per cent (VDP)). While previous studies have demonstrated its sensitivity for detecting early cystic fibrosis (CF) lung disease, the utility of XeMRI to monitor response to therapy in CF is unknown. The aim of this study was to assess the ability of XeMRI to capture treatment response in paediatric CF patients undergoing inpatient antibiotic treatment for a pulmonary exacerbation.15 CF patients aged 8–18 years underwent XeMRI, spirometry, plethysmography and multiple-breath nitrogen washout at the beginning and end of inpatient treatment of a pulmonary exacerbation. VDP was calculated from XeMRI images obtained during a static breath hold using semi-automated k-means clustering and linear binning approaches.XeMRI was well tolerated. VDP, lung clearance index and the forced expiratory volume in 1 s all improved with treatment; however, response was not uniform in individual patients. Of all outcome measures, VDP showed the largest relative improvement (−42.1%, 95% CI −52.1–−31.9%, pThese data support further investigation of XeMRI as a tool to capture treatment response in CF lung disease.

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 © 2011 John Wiley & Sons, Ltd.

This paper explores the combination of cone beam optical computed tomography with an N-isopropylacrylamide (NIPAM)-based polymer gel dosimeter for three-dimensional dose imaging of small field deliveries. Initial investigations indicate that cone beam optical imaging of polymer gels is complicated by scattered stray light perturbation. This can lead to significant dosimetry failures in comparison to dose readout by magnetic resonance imaging (MRI). For example, only 60% of the voxels from an optical CT dose readout of a 1 l dosimeter passed a two-dimensional Low′s gamma test (at a 3%, 3 mm criteria, relative to a treatment plan for a well-characterized pencil beam delivery). When the same dosimeter was probed by MRI, a 93% pass rate was observed. The optical dose measurement was improved after modifications to the dosimeter preparation, matching its performance with the imaging capabilities of the scanner. With the new dosimeter preparation, 99.7% of the optical CT voxels passed a Low′s gamma test at the 3%, 3 mm criteria and 92.7% at a 2%, 2 mm criteria. The fitted interjar dose responses of a small sample set of modified dosimeters prepared (a) from the same gel batch and (b) from different gel batches prepared on the same day were found to be in agreement to within 3.6% and 3.8%, respectively, over the full dose range. Without drawing any statistical conclusions, this experiment gives a preliminary indication that intrabatch or interbatch NIPAM dosimeters prepared on the same day should be suitable for dose sensitivity calibration.

Rationale and Objectives We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using 3He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the 3He apparent diffusion coefficient (ADC) and center coronal slice 3He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons. Materials and Methods Twenty-four subjects who provided written informed consent (15 males; mean age 67 ±7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 ± 2 minutes (same-day rescan) and again 7 ± 2 days later (7-day rescan). 3He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lin's concordance correlation coefficients (CCC). Results ADC reproducibility was high for same-day rescan (r2 = 0.934) and 7-day rescan (r2 = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r2 = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r2 = 0.576, P Conclusions Hyperpolarized 3He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV.

Rationale and Objectives Hyperpolarized 3 He magnetic resonance imaging ventilation defects have been observed in subjects with respiratory disorders. We quantified 3 He ventilation defects in elderly and middle-aged subjects who had no history of smoking, respiratory, or cardiovascular disorders. Materials and Methods Hyperpolarized 3 He magnetic resonance imaging ventilation defect volume (VDV) and ventilation defect score (VDS) were assessed in eight elderly healthy volunteers (mean 67 ± 6 years) scanned twice within 7 ± 2 minutes and again 7 ± 2 days later. A younger cohort of 24 subjects (mean 44 ± 10 years) was also scanned for direct comparison. Four observers blinded to scan timepoint and subject identity scored VDS and manually segmented VDV in all center coronal slices. Results Center coronal slice ventilation defects were observed in six of eight elderly subjects (ages 63–74 years, 5 males) in all scans acquired and in no middle-aged subjects. At the scan timepoint, mean VDS was 2.7 (mean VDV 52 ± 34 cm 3 ), whereas for same-day rescan, mean VDS was 2.5 (mean VDV 53 ± 35 cm 3 ) and at 7-day rescan, mean VDS was 3.6 (mean VDV 48 ± 39 cm 3 ). Interscan coefficients of variation (COV) for mean VDV was 1.8% (same-day rescan) and 5.3% (7-day rescan) and interobserver COV ranged from 10–12%. Conclusion Elderly subjects have ventilation defects that are reproducible in same-day scanning and 7-day scanning visits. The observation of reproducible pulmonary ventilation defects in otherwise healthy elderly volunteers suggests caution must be used in interpreting results from 3 He studies of elderly subjects.

The Look-Locker (LL) imaging method provides an accurate and efficient approach for mapping the spin-lattice relaxation time, T(1). However, the same recovery of signal during LL image acquisition required to estimate T(1) also results in unwanted modulation of k-space. This is particularly problematic with 3D LL imaging as the number of phase-encoding steps during the recovery interval (e.g., 16) increases in an effort to reduce imaging times. This modulation of k-space has the effect of introducing a point spread function (PSF), which can lead to either image blurring (if the earlier tip angles are assigned to the centre of k-space) or edge enhancement (if the earlier tip angles are assigned to the edges of k-space), thus corrupting T(1) estimation, particularly for small objects. In this study, the PSF and its effect on the acquired images for four different interleaved phase-encode schemes (centric-in, centric-out, sequential and hybrid-sequential) are simulated for a range of T(1), tip angle and 3D LL acquisition parameters expected in practice. It is shown by simulation and confirmed experimentally in phantoms that a hybrid sequential phase-encoding scheme reduces image blurring while maintaining T(1) accuracy ( approximately 2%) and precision (2%) over a range of object sizes down to 2 pixels (2 mm).

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: He 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.

The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T-2*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE = 3 ms, the relationship between changes in 1/T-2* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be similar to 19 s(-1) mM(-1), while that between phase and [Gd] was similar to 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2) = .34 vs. r(2)= .17, respectively). This is likely due to the fact that the estimated change in 1/T2* is more sensitive than the phase to a variety of factors such as partial volume effects and T, weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T2*-weighted magnitude imaging. (c) 2005 Elsevier Inc. All rights reserved.

Hyperpolarized noble gases (HNGs) provide exciting possibilities for MR imaging at ultra-low magnetic field strengths (

A 73-year-old exsmoker with Global initiative for chronic Obstructive Lung Disease stage III chronic obstructive pulmonary disease underwent airway bypass (AB) as part of the Exhale Airway Stents for Emphysema (EASE) trial, and was the only EASE subject to undergo hyperpolarized3He magnetic resonance imaging for evaluation of lung function pre- and post-AB.3He magnetic resonance imaging was acquired twice previously (32 and eight months pre-AB) and twice post-AB (six and 12 months post-AB). Six months post-AB, his increase in forced vital capacity was 3He gas distribution in the regions of stent placement. Given the complex relationship between well-established pulmonary function and quality of life measurements, the present case provides evidence of the value-added information functional imaging may provide in chronic obstructive pulmonary disease interventional studies.

Noble gas pulmonary magnetic resonance imaging (MRI) is transitioning away from 3He to 129Xe gas, but the physiological/clinical relevance of 129Xe apparent diffusion coefficient (ADC) parenchyma measurements is not well understood. Therefore, our objective was to generate 129Xe MRI ADC for comparison with 3He ADC and with well‐established measurements of alveolar structure and function in older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In four never‐smokers and 10 COPD ex‐smokers, 3He (b = 1.6 sec/cm2) and 129Xe (b = 12, 20, and 30 sec/cm2) ADC, computed tomography (CT) density‐threshold measurements, and the diffusing capacity for carbon monoxide (DLCO) were measured. To understand regional differences, the anterior–posterior (APG) and superior–inferior (∆SI) ADC differences were evaluated. Compared to never‐smokers, COPD ex‐smokers showed greater 3He ADC (P = 0.006), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.006), but not for ADCb30 (P > 0.05). Never‐smokers and COPD ex‐smokers had significantly different APG for 3He ADC (P = 0.02), 129Xe ADCb12 (P = 0.006), and ADCb20 (P = 0.01), but not for ADCb30 (P > 0.05). ∆SI for never‐ and ex‐smokers was significantly different for 3He ADC (P = 0.046), but not for 129Xe ADC (P > 0.05). There were strong correlations for DLCO with 3He ADC and 129Xe ADCb12 (both r = −0.95, P < 0.05); in a multivariate model 129Xe ADCb12 was the only significant predictor of DLCO (P = 0.049). For COPD ex‐smokers, CT relative area, We aimed to better understand how 129Xe MRI measurements might explain well‐established measurements of emphysema, and explored different 129Xe MRI apparent diffusion coefficients (ADCs) in a small group of older never‐smokers and ex‐smokers with chronic obstructive pulmonary disease (COPD). In the same visit, 3He ADC, the diffusing capacity of carbon monoxide and computed tomography (CT) emphysema measurements were acquired. In this small group of older never‐smokers and ex‐smokers with COPD, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.

Both benign and malignant breast lesions may exhibit intense contrast enhancement when imaged using gadolinium-enhanced MRI. We propose a quantitative approach for fitting dynamic signal intensity (SI) data that may distinguish benign from malignant lesions. We studied 78 lesions in 75 women (18 malignancies, 16 fibroadenomas, and 44 other benign breast lesions) to determine the potential of this model for decreasing false-positive MR results. Twenty-eight lesions showed no enhancement; all were benign. One lesion showed a complex pattern not amenable to region-of-interest analysis and was considered a false positive. SI versus time data for the remaining 49 lesions were fit to the proposed model. We found that one parameter, M, the normalized slope of the SI enhancement profile evaluated at half the maximal signal intensity, seemed to be highly correlated with malignancy and offered improved discrimination between malignant and benign lesions compared to a previously published two-point slope method.

In subjects with chronic obstructive pulmonary disease (COPD), hyperpolarized xenon-129 (129Xe) magnetic resonance imaging (MRI) reveals significantly greater ventilation defects than hyperpolarized helium-3 (3He) MRI. The physiological and/or morphological determinants of ventilation defects and the differences observed between hyperpolarized 3He and 129Xe MRI are not yet understood. Here we aimed to determine the structural basis for the differences in ventilation observed between 3He and 129Xe MRI in subjects with COPD using apparent diffusion coefficients (ADC) and computed tomography (CT). Ten COPD ex-smokers provided written, informed consent and underwent MRI, CT, spirometry, and plethysmography. 3He and 129Xe MRI ventilation volume was generated using semiautomated segmentation, and ADC maps were registered to generate ADC values for lung regions of interest ventilated by both gases (ADCHX) and by 3He gas only (ADCHO). CT wall area percentage and the lowest 15th percentile point of the CT lung density histogram (HU15%) were also evaluated. For lung regions accessed by 3He gas only, mean 3He ADCHO was significantly greater than for regions accessed by both gases (ADCHO = 0.503 ± 0.119 cm2/s, ADCHX = 0.470 ± 0.125 cm2/s, P < 0.0001). The difference between 3He and 129Xe ventilation volume was significantly correlated with CT HU15% ( r = −65, P = 0.04) and 3He ADCHO ( r = 0.70, P = 0.02), but not CT wall area percentage ( r = −0.34, P = 0.33). In conclusion, in this small study in COPD subjects, we observed significantly decreased 129Xe MRI ventilation compared with 3He MRI, and these regions of decreased 129Xe ventilation were spatially and significantly correlated with regions of increased pulmonary emphysema, but not airway wall thickness.

To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography.This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements.129Xe VDP was significantly greater than 3He VDP for patients with COPD (P.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P.0001) and 129Xe VDP (r=-0.89, P.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001).In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD.

SUMMARY The development of noninvasive techniques should always be an important goal of diagnostic radiology. Despite the recent excitement regarding intravenous MR imaging contrast agents (e.g., Gd-DTPA), the role of noncontrast MR imaging for the breast should not be overlooked. First, it must be kept in mind that administration of an intravenous contrast material is an invasive procedure that poses some health concern and may not be acceptable to certain patients. Second, injection of intravenous contrast media is an expensive procedure that incurs costs related to the contrast media itself as well as from the personnel required to administer the media and monitor any adverse reactions. Third, there may be specific imaging situations in which a lesion must be located prior to administration of contrast media, for example, when dynamic contrast enhanced imaging is to be performed and temporal resolution limits the volume of coverage to only a few slices. Finally, noncontrast MR imaging techniques also may be useful in their own right for obtaining information not otherwise available from a contrast- enhanced study, particularly quantitative relaxometric and spectroscopic measurements that may be useful for tissue characterization. It should also be noted that optimized noncontrast MR methods also might be used in conjunction with contrast agents to improve overall clinical utility. The heterogeneous nature of the breast and the overlap in Tl and T2 between different normal and abnormal breast tissue types frequently renders conventional noncontrast breast MR images confusing and ambiguous. Hybrid imaging approaches combining Tl weighting, T2 weighting, and fat suppression techniques as well as multivariate image analysis may be helpful for improving the sensitivity of MR imaging to breast disease; however, specificity remains a problem. Recent advances in clinical MR imaging have provided the opportunity to explore other approaches which may shed new light on the characterization of breast disease including NMRD, spin locking, magnetization transfer, and multicomponent relaxation analysis. MR imaging derived morphologic factors (i.e., lesion spiculation, parenchymal patterns) also may have a role to play in breast disease diagnosis and risk assessment. Several avenues of future development of noncontrast breast MR imaging would seem fruitful. NMRD and spin locking results suggest the potential contrast benefit of low field imaging of the breast, particularly, with the probable development of open concept low field MR imaging devices, which will provide improved access and low cost. In vivo relaxation time measurements, particularly multicomponent T2 analysis and incorporation of MTC and chemical shift imaging techniques, may improve breast MR image specificity. Furthermore, multivariate analysis and breast tissue segmentation using relaxation time measurements will help to classify breast tissues and provide 3-D volume measurements and visualization for improved diagnosis (e.g., MR-guided biopsy) and therapy (e.g., stereotactic radiotherapy and laser therapy). Other noncontrast breast MR imaging approaches might also be possible. In particular, techniques that give information about tumor vascularity without the need for intravenous contrast agents (e.g., perfusion/diffusion imaging and MR angiography) need to be investigated.

PURPOSE: To quantitatively evaluate a small pilot group of ex-smokers with chronic obstructive pulmonary disease (COPD) and healthy volunteers during approximately 2 years by using hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging. MATERIALS AND METHODS: All subjects provided written informed consent to the study protocol, which was approved by the local research ethics board and Health Canada and was compliant with the Personal Information Protection and Electronic Documents Act and HIPAA. Hyperpolarized (3)He MR imaging, hydrogen 1 MR imaging, spirometry, and plethysmography were performed in 15 ex-smokers with COPD and five healthy volunteers (with the same mean age and age range) at baseline and 26 months +/- 2 (standard deviation) later. Apparent diffusion coefficients (ADCs) derived from (3)He MR imaging were calculated from diffusion-weighted (3)He MR images, and (3)He ventilation defect volume (VDV) and ventilation defect percentage (VDP) were generated after manual segmentation of (3)He MR spin-density images. RESULTS: For subjects with COPD, significant increases in (3)He MR imaging-derived VDV (P = .03), VDP (P = .006), and ADC (P = .02) were detected, whereas there was no significant change in forced expiratory volume in 1 second (FEV(1)) (P = .97). For healthy never-smokers, there was no significant change in imaging or pulmonary function measurements at follow-up. There was a significant correlation between changes in FEV(1) and changes in VDV (r = -0.70, P = .02) and VDP (r = -0.70, P = .03). CONCLUSION: For this small pilot group of ex-smokers with COPD, (3)He MR imaging-derived VDV, VDP, and ADC measurements worsened significantly, but there was no significant change in FEV(1), suggesting increased sensitivity of hyperpolarized (3)He MR imaging for depicting COPD changes during short time periods.