Postacute COVID-19 Syndrome: 129Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (129Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers. 129Xe MRI VDP, diffusing capacity of lung for carbon monoxide (Dlco), spirometry, oscillometry, 6-minute walk distance (6MWD), and St George Respiratory Questionnaire (SGRQ) scores were evaluated 3 months and 15 months after COVID-19 infection. Differences between time points were evaluated using the paired t test. Multivariable models were generated to explain exercise capacity and quality-of-life improvement. Odds ratios (ORs) were used to evaluate potential treatment influences. Results Overall, 53 participants (mean age, 55 years ± 18 [SD]; 27 women) attended both 3- and 15-month visits and were included in the analysis. The mean values for 129Xe MRI VDP (5.8% and 4.2%; P = .003), forced expiratory volume in the 1st second of expiration percent predicted (84% and 90%; P = .001), Dlco percent predicted (86% and 99%; P = .002), and SGRQ score (35 and 25; P < .001) improved between the 3- and 15-month visit. VDP measured 3 months after COVID-19 infection predicted the change in 6MWD (ß = -0.643, P = .006), while treatment with respiratory medication at 3 months predicted an improved quality-of-life score at 15 months (OR, 4.0; 95% CI: 1.2, 13.8; P = .03). Conclusion Pulmonary function, gas exchange, exercise capacity, quality of life, and 129Xe MRI ventilation defect percent (VDP) improved in participants with postacute COVID-19 syndrome at 15 months compared with 3 months after infection. VDP measured at 3 months after infection correlated with improved exercise capacity, while treatment with respiratory medication was associated with an improved quality-of-life score 15 months after infection. ClinicalTrials.gov registration no. NCT05014516 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Vogel-Claussen in this issue.

Persistent 129Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome.

BACKGROUND: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood. PURPOSE: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 (129Xe) MRI and CT pulmonary vascular measurements in individuals with PACS. MATERIALS AND METHODS: In this prospective study, patients with PACS aged 18-80 years with a positive polymerase chain reaction COVID-19 test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLco), 129Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 and underwent spirometry, DLco, and 129Xe MRI. The 129Xe MRI red blood cell (RBC) to alveolar-barrier signal ratio, RBC area under the receiver operating characteristic curve (AUC), CT volume of pulmonary vessels with cross-sectional area 5 mm2 or smaller (BV5), and total blood volume were quantified. St George's Respiratory Questionnaire, International Physical Activity Questionnaire, and modified Borg Dyspnea Scale measured quality of life, exercise limitation, and dyspnea. Differences between groups were compared with use of Welch t-tests or Welch analysis of variance. Relationships were evaluated with use of Pearson (r) and Spearman (ρ) correlations. RESULTS: Forty participants were evaluated, including six controls (mean age ± SD, 35 years ± 15, three women) and 34 participants with PACS (mean age, 53 years ± 13, 18 women), of whom 22 were never hospitalized. The 129Xe MRI RBC:barrier ratio was lower in ever-hospitalized participants (P = .04) compared to controls. BV5 correlated with RBC AUC (ρ = .44, P = .03). The 129Xe MRI RBC:barrier ratio was related to DLco (r = .57, P = .002) and forced expiratory volume in 1 second (ρ = .35, P = .03); RBC AUC was related to dyspnea (ρ = -.35, P = .04) and International Physical Activity Questionnaire score (ρ = .45, P = .02). CONCLUSION: Xenon 129 (129Xe) MRI measurements were lower in participants previously infected with COVID-19 who were admitted to in-patient treatment in hospital with post-acute COVID-19 syndrome, 34 weeks ± 25 after infection compared to controls. The 129Xe MRI measures were associated with CT pulmonary vascular density, diffusing capacity of the lung for carbon monoxide, exercise capacity, and dyspnea. Clinical trial registration no.: NCT04584671 © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Wild and Collier in this issue.

Protocols for multi-site trials using hyperpolarized 129 Xe MRI for imaging of ventilation, alveolar-airspace size, and gas exchange: A position paper from the 129 Xe MRI clinical trials consortium.

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.

Hyperpolarized 129 Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept study using superparamagnetic iron oxide nanoparticles.

PURPOSE: To measure regional changes in hyperpolarized 129 Xe MRI signal and apparent transverse relaxation ( T2∗ ) because of instillation of SPION-labeled alveolar-like macrophages (ALMs) in the lungs of rats and compare to histology. METHODS: MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION-labeled ALMs into either the left or right lung. T2∗ maps were calculated from 2D multi-echo data at each time point and changes in T2∗ were measured and compared to control rats receiving 4 million unlabeled ALMs. Histology of the ex vivo lungs was used to compare the regional MRI findings with the locations of the SPION-labeled ALMs. RESULTS: Regions of signal loss were observed immediately after instillation of unlabeled and SPION-labeled ALMs and persisted at least 1 h in the case of the SPION-labeled ALMs. This was reflected in the measurements of T2∗ . One hour after the instillation of SPION-labeled ALMs, the T2∗ decreased to 54.0 ± 7.0% of the baseline, compared to a full recovery to baseline after the instillation of unlabeled ALMs. Histology confirmed the co-localization of SPION-labeled ALMs with regions of signal loss and T2∗ decreases for each rat. CONCLUSION: Hyperpolarized 129 Xe MRI can detect the presence of SPION-labeled ALMs in the airways 1 h after instillation. This approach is promising for targeting and tracking of stem cells for the treatment of lung disease.

High spatial resolution hyperpolarized 3 He MRI of the rodent lung using a single breath X-centric gradient-recalled echo approach.

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 3 He rodent lung MRI using a centric-out readout scheme (ie, x-centric), allowing high-resolution, density-weighted imaging. METHODS: HP 3 He 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 (<78 µm). In particular, rodent major airways with less restricted diffusion of 3 He could only be visualized with the x-centric method. CONCLUSIONS: The x-centric method significantly reduces diffusion weighting, allowing high spatial and temporal resolution HP 3 He gas density-weighted rodent lung MRI. Magn Reson Med 78:2334-2341, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Early stage radiation-induced lung injury detected using hyperpolarized (129) Xe Morphometry: Proof-of-concept demonstration in a rat model.

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 (129) Xe diffusion-weighted MRI to detect the lung morphological changes associated with early stage RILI. METHODS: Hyperpolarized (129) Xe MRI was performed using eight different diffusion sensitizations (0.0-115 s/cm(2) ) 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 < 0.02) in the irradiated rats (74 ± 17 µm, 43 ± 12 µm, and 54 ± 17 µm, respectively) compared with the control rats (100 ± 12 µm, 67 ± 10 µm, and 79 ± 12 µm, respectively). Changes in measured Lm values were consistent with changes in MLI values observed by histology. CONCLUSIONS: Hyperpolarized (129) Xe MRI provides a way to detect and measure regional microanatomical changes in lung parenchyma in a preclinical model of RILI. Magn Reson Med 75:2421-2431, 2016. © 2015 Wiley Periodicals, Inc.

Hyperpolarized (129) Xe imaging of the rat lung using spiral IDEAL.

PURPOSE: To implement and optimize a single-shot spiral encoding strategy for rapid 2D IDEAL projection imaging of hyperpolarized (Hp) (129) Xe in the gas phase, and in the pulmonary tissue (PT) and red blood cells (RBCs) compartments of the rat lung, respectively. THEORY AND METHODS: A theoretical and experimental point spread function analysis was used to optimize the spiral k-space read-out time in a phantom. Hp (129) Xe IDEAL images from five healthy rats were used to: (i) optimize flip angles by a Bloch equation analysis using measured kinetics of gas exchange and (ii) investigate the feasibility of the approach to characterize the exchange of Hp (129) Xe. RESULTS: A read-out time equal to approximately 1.8 × T2* was found to provide the best trade-off between spatial resolution and signal-to-noise ratio (SNR). Spiral IDEAL approaches that use the entire dissolved phase magnetization should give an SNR improvement of a factor of approximately three compared with Cartesian approaches with similar spatial resolution. The IDEAL strategy allowed imaging of gas, PT, and RBC compartments with sufficient SNR and temporal resolution to permit regional gas exchange measurements in healthy rats. CONCLUSION: Single-shot spiral IDEAL imaging of gas, PT and RBC compartments and gas exchange is feasible in rat lung using Hp (129) Xe. Magn Reson Med 76:566-576, 2016. © 2015 Wiley Periodicals, Inc.

Comparison of hyperpolarized (3)He and (129)Xe MRI for the measurement of absolute ventilated lung volume in rats.

PURPOSE: MRI using hyperpolarized noble gases, (3)He and (129)Xe, provides noninvasive assessments of lung structure and function. Previous work demonstrated that absolute ventilated lung volumes (aVLV) measured in rats using hyperpolarized (3)He agree well with micro-CT. METHODS: In this work, aVLV measurements were performed in rats using hyperpolarized (129)Xe MRI and compared with hyperpolarized (3)He 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 cm(2)/s and 0.067 ± 0.011 cm(2)/s for (3)He and (129)Xe, respectively. Mean apparent diffusion coefficient of parenchyma was 0.21 ± 0.07 cm(2)/s and 0.027 ± 0.008 cm(2)/s for (3)He and (129)Xe, respectively. Mean transverse relaxation time values were 1.57 ± 0.25 ms and 2.80 ± 0.25 ms for (3)He and (129)Xe, respectively, in a model trachea and 3.18 ± 1.00 ms and 4.88 ± 0.60 ms for (3)He and (129)Xe, 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 (3)He and (129)Xe, respectively, demonstrating good agreement between (129)Xe and (3)He. CONCLUSIONS: (129)Xe offers an important alternative to (3)He for hyperpolarized gas MRI of aVLV in rats.

Measurement of 129Xe gas apparent diffusion coefficient anisotropy in an elastase-instilled rat model of emphysema.

Hyperpolarized noble gas ((3)He and (129)Xe) apparent diffusion coefficient (ADC) measurements have shown remarkable sensitivity to microstructural (i.e., alveolar) changes in the lung, particularly emphysema. The ADC of hyperpolarized noble gases depends strongly on the diffusion time (Δ), and (3)He ADC has been shown to be anisotropic for Δ ranging from a few milliseconds down to a few hundred microseconds. In this study, the anisotropic nature of (129)Xe diffusion and its dependence on Δ were investigated both numerically, in a budded cylinder model, and in vivo, in an elastase-instilled rat model of emphysema. Whole lung longitudinal ADC (D(L)) and transverse ADC (D(T)) were measured for Δ = 6, 50, and 100 ms at 73.5 mT, and correlated with measurements of the mean linear intercept (L(m)) obtained from lung histology. A significant increase (P = 0.0021) in D(T) was measured for Δ = 6 ms between the sham (0.0021 ± 0.0005 cm(2)/s) and elastase-instilled (0.005 ± 0.001 cm(2)/s) cohorts, and a strong correlation was measured between D(T) (Δ = 6 ms) and L(m), with a Pearson's correlation coefficient of 0.90. This study confirms that (129)Xe D(T) increases correlate with alveolar space enlargement due to elastase instillation in rats.

Lung morphometry using hyperpolarized (129) Xe apparent diffusion coefficient anisotropy in chronic obstructive pulmonary disease.

PURPOSE: The goal of this work was to investigate lung morphological changes associated with chronic obstructive pulmonary disease (COPD) using hyperpolarized (129) Xe diffusion-weighted MRI. METHODS: Hyperpolarized (129) Xe MRI was performed at three different nonzero diffusion sensitizations (b-value = 12, 20, and 30 s/cm(2) ) 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 cm(2) /s and 0.072 ± 0.02 cm(2) /s, respectively) compared with the healthy subjects (0.083 ± 0.011 cm(2) /s and 0.046 ± 0.017 cm(2) /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 (3) He MRI in similar subjects. CONCLUSIONS: Diffusion-weighted hyperpolarized (129) Xe MRI is a promising technique for mapping changes in human lung morphology and may be useful for early detection of emphysema associated with COPD.

Hyperpolarized 3He and 129Xe MR imaging in healthy volunteers and patients with chronic obstructive pulmonary disease.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Regional ventilation mapping of the rat lung using hyperpolarized ¹²9Xe magnetic resonance imaging.

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.

Mapping of (3) He apparent diffusion coefficient anisotropy at sub-millisecond diffusion times in an elastase-instilled rat model of emphysema.

Hyperpolarized (3) He gas can provide detailed anatomical maps of the macroscopic airways in the lungs (i.e., ventilation) as well as insight into the lung microstructure through the apparent diffusion coefficient. In particular, the apparent diffusion coefficient of (3) He in the lung exhibits anisotropic effects that depend on diffusion time (δ), and it has been shown to be extraordinarily sensitive to enlargement in terminal airways and alveoli associated with emphysema. In this study, the anisotropic nature of the (3) He apparent diffusion coefficient is studied in a rat model of emphysema, based on elastase instillation, specifically for δ values less than one millisecond. Longitudinal (D(L) ) and transverse (D(T) ) diffusion coefficients were mapped at δ = 360 µs and δ = 800 µs based on a cylinder model of lung structure and correlated with histological measurement of alveolar damage based on mean linear intercept (L(m) ). Whole-lung mean D(T) measured at δ = 360 µs in the elastase-instilled rat lungs (0.14 ± 0.09 cm(2) /s) demonstrated the most significant increase (p = 0.00195) compared to the sham-instilled cohort (0.06 ± 0.06 cm(2) /s) and had a strong linear correlation with L(m) (Pearson's correlation coefficient of 0.9). These results suggest that measurement of (3) He apparent diffusion coefficient anisotropy, specifically D(T) , can provide a sensitive indicator of emphysema, particularly at very short diffusion times (δ = 360 µs).

129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome.

BACKGROUND: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised 129Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of 129Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity. Hence, we measured 129Xe MRI ventilation defects, pulmonary function and symptoms in ever-hospitalised and never-hospitalised patients who had COVID-19 with persistent symptoms consistent with post-acute COVID-19 syndrome (PACS). METHODS: Consenting participants with a confirmed diagnosis of PACS completed 129Xe MRI, CT, spirometry, multi-breath inert-gas washout, 6-minute walk test, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnoea scale, modified Borg scale and International Physical Activity Questionnaire. Consenting ever-COVID volunteers completed 129Xe MRI and pulmonary function tests only. RESULTS: Seventy-six post-COVID and nine never-COVID participants were evaluated. Ventilation defect per cent (VDP) was abnormal and significantly greater in ever-COVID as compared with never-COVID participants (p<0.001) and significantly greater in ever-hospitalised compared with never-hospitalised participants who had COVID-19 (p=0.048), in whom diffusing capacity of the lung for carbon-monoxide (p=0.009) and 6-minute walk distance (6MWD) (p=0.005) were also significantly different. 129Xe MRI VDP was also related to the 6MWD (p=0.02) and post-exertional SpO2 (p=0.002). Participants with abnormal VDP (≥4.3%) had significantly worse 6MWD (p=0.003) and post-exertional SpO2 (p=0.03). CONCLUSION: 129Xe MRI VDP was significantly worse in ever-hospitalised as compared with never-hospitalised participants and was related to 6MWD and exertional SpO2 but not SGRQ or mMRC scores. TRIAL REGISTRATION NUMBER: NCT05014516.

Signal-to-noise ratio for hyperpolarized ³He MR imaging of human lungs: a 1.5 T and 3 T comparison.

The signal-to-noise ratio in hyperpolarized noble gas MR imaging is expected to be independent of field strength at frequencies typical of clinical systems (e.g., 1.5 T), where body noise dominates over coil noise. Furthermore, at higher fields (e.g., 3 T), the SNR of lung images may decline due to decreases in T(2) originating from increases in susceptibility-induced field gradients at the air-tissue interface. In this work, the SNR of hyperpolarized (3) He lung imaging at two commonly used clinical field strengths (1.5 T and 3 T) were compared in the same volunteers. Thermally polarized and hyperpolarized (3) He phantoms were used to account for differences in MR imaging system and (3) He polarizer performance, respectively, at the two field strengths. After correcting for T(2) values measured at 1.5 T (16 ± 2 ms) and 3 T (7 ± 1 ms), no significant difference in image SNR between the two field strengths was observed, consistent with theory.

Comparison of hyperpolarized (3)He 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 (3)He MRI and Xe-enhanced computed tomography (Xe-CT) under similar ventilator conditions. Whole-lung measurements of ventilation r obtained with (3)He 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 (3)He 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.

Chronic obstructive pulmonary disease: longitudinal hyperpolarized (3)He MR imaging.

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.

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, (3) He and (129) Xe, in the lungs. Recently, it has been demonstrated that measurements of alveolar oxygen partial pressure can be obtained using the spin-spin relaxation rate (R(2) ) of (3) He at low magnetic field strengths (<0.1 T) in vivo. R(2) 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 R(2) values of hyperpolarized (3) He and (129) Xe 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 (3) He and (129) Xe 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 (3) He in whole rat lung show good agreement (r(2) = 0.973) with predictions based on lung volumes and ventilation parameters. For (129) Xe, multicomponent relaxation was observed with one component exhibiting an increase in R(2) with decreasing alveolar oxygen partial pressure.

Comparison of hyperpolarized (3)He 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 (3)He-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 O(2), alternately with (3)He, 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 (3)He. 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 (3)He-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 (3)He-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.

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.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.