Diagnostic performance of whole-body [18F]FDG PET/MR in cancer M staging: A systematic review and meta-analysis.

OBJECTIVES: To calculate the pooled diagnostic performances of whole-body [18F]FDG PET/MR in M staging of [18F]FDG-avid cancer entities. METHODS: A diagnostic meta-analysis was conducted on the [18F]FDG PET/MR in M staging, including studies: (1) evaluated [18F]FDG PET/MR in detecting distant metastasis; (2) compared[ 18F]FDG PET/MR with histopathology, follow-up, or asynchronous multimodality imaging as the reference standard; (3) provided data for the whole-body evaluation; (4) provided adequate data to calculate the meta-analytic performances. Pooled performances were calculated with their confidence interval. In addition, forest plots, SROC curves, and likelihood ratio scatterplots were drawn. All analyses were performed using STATA 16. RESULTS: From 52 eligible studies, 2289 patients and 2072 metastases were entered in the meta-analysis. The whole-body pooled sensitivities were 0.95 (95%CI: 0.91-0.97) and 0.97 (95%CI: 0.91-0.99) at the patient and lesion levels, respectively. The pooled specificities were 0.99 (95%CI: 0.97-1.00) and 0.97 (95%CI: 0.90-0.99), respectively. Additionally, subgroup analyses were performed. The calculated pooled sensitivities for lung, gastrointestinal, breast, and gynecological cancers were 0.90, 0.93, 1.00, and 0.97, respectively. The pooled specificities were 1.00, 0.98, 0.97, and 1.00, respectively. Furthermore, the pooled sensitivities for non-small cell lung, colorectal, and cervical cancers were 0.92, 0.96, and 0.86, respectively. The pooled specificities were 1.00, 0.95, and 1.00, respectively. CONCLUSION: [18F]FDG PET/MR was a highly accurate modality in M staging in the reported [18F]FDG-avid malignancies. The results showed high sensitivity and specificity in each reviewed malignancy type. Thus, our findings may help clinicians and patients to be confident about the performance of [18F]FDG PET/MR in the clinic. CLINICAL RELEVANCE STATEMENT: Although [18F]FDG PET/MR is not a routine imaging technique in current guidelines, mostly due to its availability and logistic issues, our findings might add to the limited evidence regarding its performance, showing a sensitivity of 0.95 and specificity of 0.97. KEY POINTS: • The whole-body [18F]FDG PET/MR showed high accuracy in detecting distant metastases at both patient and lesion levels. • The pooled sensitivities were 95% and 97% and pooled specificities were 99% and 97% at patient and lesion levels, respectively. • The results suggested that 18F-FDG PET/MR was a strong modality in the exclusion and confirmation of distant metastases.

Current Applications of PET/MR: Part I: Technical Basics and Preclinical/Clinical Applications.

Positron emission tomography/magnetic resonance (PET/MR) imaging has gone through major hardware improvements in recent years, making it a reliable state-of-the-art hybrid modality in clinical practice. At the same time, image reconstruction, attenuation correction, and motion correction algorithms have significantly evolved to provide high-quality images. Part I of the current review discusses technical basics, pre-clinical applications, and clinical applications of PET/MR in radiation oncology and head and neck imaging. PET/MR offers a broad range of advantages in preclinical and clinical imaging. In the preclinic, small and large animal-dedicated devices were developed, making PET/MR capable of delivering new insight into animal models in diseases and facilitating the development of methods that inform clinical PET/MR. Regarding PET/MR's clinical applications in radiation medicine, PET and MR already play crucial roles in the radiotherapy process. Their combination is particularly significant as it can provide molecular and morphological characteristics that are not achievable with other modalities. In addition, the integration of PET/MR information for therapy planning with linear accelerators is expected to provide potentially unique biomarkers for treatment guidance. Furthermore, in clinical applications in the head and neck region, it has been shown that PET/MR can be an accurate modality in head and neck malignancies for staging and resectability assessment. Also, it can play a crucial role in diagnosing residual or recurrent diseases, reliably distinguishing from oedema and fibrosis. PET/MR can furthermore help with tumour characterization and patient prognostication. Lastly, in head and neck carcinoma of unknown origin, PET/MR, with its diagnostic potential, may obviate multiple imaging sessions in the near future.

Characterization of clinical human prostate cancer lesions using 3.0-T sodium MRI registered to Gleason-graded whole-mount histopathology.

BACKGROUND: Overtreatment of prostate cancer (PCa) is a healthcare issue. Development of noninvasive imaging tools for improved characterization of prostate lesions might reduce overtreatment. PURPOSE: To measure the distribution of tissue sodium concentration (TSC), proton T2 -weighted signal, and apparent diffusion coefficient (ADC) values in human PCa and to test the presence of a correlation between regional differences in imaging metrics and the Gleason grade of lesions determined from histopathology. STUDY TYPE: Cross-sectional. SUBJECTS: Ten men with biopsy-proven PCa. SEQUENCES/FIELD STRENGTH: Sodium, proton T2 -weighted, and diffusion-weighted MRI data were acquired using Broad-Band 3D-Fast-Gradient-Recalled, 3D Cube (Isotropic 3D-Fast-Turbo-Spin-Echo acquisition) and 2D Spin-Echo sequences, respectively, with a 3.0T MR scanner. ASSESSMENT: All imaging data were coregistered to Gleason-graded postprostatectomy histology, as the standard for prostate cancer lesion characterization. Regional TSC and T2 data were assessed using percent changes from healthy tissue of the same patient (denoted ΔTSC, ΔT2 ). STATISTICS: Differences in ΔTSC, ADC, and ΔT2 as a function of Gleason score were analyzed for each imaging contrast using a one-way analysis of variance or a nonparametric t-test. Correlations between imaging data measures and Gleason score were assessed using a Spearman's ranked correlation. RESULTS: Evaluation of the correlation of ΔTSC, ADC, and ΔT2 datasets with Gleason scoring revealed that only the correlation between ΔTSC and Gleason score was statistically significant (rs = 0.791, p < 0.01), whereas the correlations of ADC and ΔT2 with Gleason score were not (rs = -0.306, p = 0.079 and r s = -0.069, p = 0.699, respectively). In addition, all individual patients showed monotonically increasing ΔTSC with Gleason score. DATA CONCLUSION: The results of this preliminary study suggest that changes in TSC, assessed by sodium MRI, has utility as a noninvasive imaging assay to accurately characterize PCa lesions. Sodium MRI may provide useful complementary information on mpMRI, which may assist the decision-making of men choosing either active surveillance or treatment. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1409-1419.

Unshielded asymmetric transmit-only and endorectal receive-only radiofrequency coil for (23) Na MRI of the prostate at 3 tesla.

BACKGROUND: To develop and optimize radiofrequency (RF) hardware for the detection of endogenous sodium ((23) Na) by 3.0 Tesla (T) MRI in the human prostate. METHODS: A transmit-only receive-only (TORO) RF system of resonators consisting of an unshielded, asymmetric, quadrature birdcage (transmit), and an endorectal (ER), linear, surface (receive) coil were developed and tested on a 3T MRI scanner. Two different ER receivers were constructed; a single-tuned ((23) Na) and a dual-tuned ((1) H/(23) Na). Both receivers were evaluated by the measurements of signal-to-noise ratio (SNR) and B1 homogeneity. For tissue sodium concentration (TSC) quantification, vials containing known sodium concentrations were incorporated into the ER. The system was used to measure the prostate TSC of three men (age 55 ± 5 years) with biopsy-proven prostate cancer. RESULTS: B1 field inhomogeneity of the asymmetric transmitter was estimated to be less than 5%. The mean SNR measured in a region of interest within the prostate using the single-tuned ER coil was 54.0 ± 4.6. The mean TSC in the central gland was 60.2 ± 5.7 mmol/L and in the peripheral gland was 70.5 ± 9.0 mmol/L. CONCLUSION: A TORO system was developed and optimized for (23) Na MRI of the human prostate which showed good sensitivity throughout the prostate for quantitative measurement of TSC.

Gastro-Esophageal Cancer: Can Radiomic Parameters from Baseline 18F-FDG-PET/CT Predict the Development of Distant Metastatic Disease?

We aimed to determine if clinical parameters and radiomics combined with sarcopenia status derived from baseline 18F-FDG-PET/CT could predict developing metastatic disease and overall survival (OS) in gastroesophageal cancer (GEC). Patients referred for primary staging who underwent 18F-FDG-PET/CT from 2008 to 2019 were evaluated retrospectively. Overall, 243 GEC patients (mean age = 64) were enrolled. Clinical, histopathology, and sarcopenia data were obtained, and primary tumor radiomics features were extracted. For classification (early-stage vs. advanced disease), the association of the studied parameters was evaluated. Various clinical and radiomics models were developed and assessed. Accuracy and area under the curve (AUC) were calculated. For OS prediction, univariable and multivariable Cox analyses were performed. The best model included PET/CT radiomics features, clinical data, and sarcopenia score (accuracy = 80%; AUC = 88%). For OS prediction, various clinical, CT, and PET features entered the multivariable analysis. Three clinical factors (advanced disease, age ≥ 70 and ECOG ≥ 2), along with one CT-derived and one PET-derived radiomics feature, retained their significance. Overall, 18F-FDG PET/CT radiomics seems to have a potential added value in identifying GEC patients with advanced disease and may enhance the performance of baseline clinical parameters. These features may also have a prognostic value for OS, improving the decision-making for GEC patients.

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.

Evaluation of MR anatomically-guided PET reconstruction using a convolutional neural network in PSMA patients.

Background. Recently, approaches have utilized the superior anatomical information provided by magnetic resonance imaging (MRI) to guide the reconstruction of positron emission tomography (PET). One of those approaches is the Bowsher's prior, which has been accelerated lately with a convolutional neural network (CNN) to reconstruct MR-guided PET in the imaging domain in routine clinical imaging. Two differently trained Bowsher-CNN methods (B-CNN0 and B-CNN) have been trained and tested on brain PET/MR images with non-PSMA tracers, but so far, have not been evaluated in other anatomical regions yet.Methods. A NEMA phantom with five of its six spheres filled with the same, calibrated concentration of 18F-DCFPyL-PSMA, and thirty-two patients (mean age 64 ± 7 years) with biopsy-confirmed PCa were used in this study. Reconstruction with either of the two available Bowsher-CNN methods were performed on the conventional MR-based attenuation correction (MRAC) and T1-MR images in the imaging domain. Detectable volume of the spheres and tumors, relative contrast recovery (CR), and background variation (BV) were measured for the MRAC and the Bowsher-CNN images, and qualitative assessment was conducted by ranking the image sharpness and quality by two experienced readers.Results. For the phantom study, the B-CNN produced 12.7% better CR compared to conventional reconstruction. The small sphere volume (<1.8 ml) detectability improved from MRAC to B-CNN by nearly 13%, while measured activity was higher than the ground-truth by 8%. The signal-to-noise ratio, CR, and BV were significantly improved (p< 0.05) in B-CNN images of the tumor. The qualitative analysis determined that tumor sharpness was excellent in 76% of the PET images reconstructed with the B-CNN method, compared to conventional reconstruction.Conclusions. Applying the MR-guided B-CNN in clinical prostate PET/MR imaging improves some quantitative, as well as qualitative imaging measures. The measured improvements in the phantom are also clearly translated into clinical application.

Respiratory and cardiac motion correction in positron emission tomography using elastic motion approach for simultaneous abdomen and thorax positron emission tomography-magnetic resonance imaging.

Background: Cardiac and respiratory motions in clinical positron emission tomography (PET) are a major contributor to inaccurate PET quantification and lesion characterisation. In this study, an elastic motion-correction (eMOCO) technique based on mass preservation optical flow is adapted and investigated for positron emission tomography-magnetic resonance imaging (PET-MRI) applications. Methods: The eMOCO technique was investigated in a motion management QA phantom and in twenty-four patients who underwent PET-MRI for dedicated liver imaging and nine patients for cardiac PET-MRI evaluation. Acquired data were reconstructed with eMOCO and gated motion correction techniques at cardiac, respiratory and dual gating modes, and compared to static images. Standardized uptake value (SUV), signal-to-noise ratio (SNR) of lesion activities from each gating mode and correction technique were measured and their means/standard deviation (SD) were compared using 2-ways ANOVA analysis and post-hoc Tukey's test. Results: Lesions' SNR are highly recovered from phantom and patient studies. The SD of the SUV resulted from the eMOCO technique was statistically significantly less (P<0.01) than the SD resulted from conventional gated and static SUVs at the liver, lung and heart. Conclusions: The eMOCO technique was successfully implemented in PET-MRI in a clinical setting and produced the lowest SD compared to gated and static images, and hence provided the least noisy PET images. Therefore, the eMOCO technique can potentially be used on PET-MRI for improved respiratory and cardiac motion correction.

Impact of the COVID-19 Pandemic on Staging Oncologic PET/CT Imaging and Patient Outcome in a Public Healthcare Context: Overview and Follow Up of the First Two Years of the Pandemic.

To assess the impact of the COVID-19 pandemic on the diagnosis, staging and outcome of a selected population throughout the first two years of the pandemic, we evaluated oncology patients undergoing PET/CT at our institution. A retrospective population of lung cancer, melanoma, lymphoma and head and neck cancer patients staged using PET/CT during the first 6 months of the years 2019, 2020 and 2021 were included for analysis. The year in which the PET was performed was our exposure variable, and our two main outcomes were stage at the time of the PET/CT and overall survival (OS). A total of 1572 PET/CTs were performed for staging purposes during the first 6 months of 2019, 2020 and 2021. The median age was 66 (IQR 16), and 915 (58%) were males. The most prevalent staged cancer was lung cancer (643, 41%). The univariate analysis of staging at PET/CT and OS by year of PET/CT were not significantly different. The multivariate Cox regression of non-COVID-19 significantly different variables at univariate analysis and the year of PET/CT determined that lung cancer (HR 1.76 CI95 1.23-2.53, p < 0.05), stage III (HR 3.63 CI95 2.21-5.98, p < 0.05), stage IV (HR 11.06 CI95 7.04-17.36, p < 0.05) and age at diagnosis (HR 1.04 CI95 1.02-1.05, p < 0.05) had increased risks of death. We did not find significantly higher stages or reduced OS when assessing the year PET/CT was performed. Furthermore, OS was not significantly modified by the year patients were staged, even when controlled for non-COVID-19 significant variables (age, type of cancer, stage and gender).

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.

Improved PET/MRI accuracy by use of static transmission source in empirically derived hardware attenuation correction.

BACKGROUND: Accurate quantification of radioactivity, measured by an integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) system, is still a challenge. One aspect of such a challenge is to correct for the hardware attenuation, such as the patient table and radio frequency (RF) resonators. For PET/MRI systems, computed tomography (CT) is commonly used to produce hardware attenuation correction (AC) maps, by converting Hounsfield units (HU) to a linear attenuation coefficients (LAC) map at the PET energy level 511 keV, using a bilinear model. The model does not address beam hardening, nor higher density materials, which can lead to inaccurate corrections. PURPOSE: In this study, we introduce a transmission-based (TX-based) AC technique with a static Germanium-68 (Ge-68) transmission source to generate hardware AC maps using the PET/MRI system itself, without the need for PET or medical CT scanners. The AC TX-based maps were generated for a homogeneous cylinder, made of acrylic as a validator. The technique thereafter was applied to the patient table and posterior part of an RF-phased array used in cardiovascular PET/MRI imaging. The proposed TX-based, and the CT-based, hardware maps were used in reconstructing PET images of one cardiac patient, and the results were analysed and compared. RESULTS: The LAC derived by the TX-based method for the acrylic cylinder is estimated to be 0.10851 ± 0.00380 cm-1 compared to the 0.10698 ± 0.00321 cm-1 theoretical value reported in the literature. The PET photon counts were reduced by 8.7 ± 1.1% with the patient table, at the region used in cardiac scans, while the CT-based map, used for correction, over-estimated counts by 4.3 ± 1.3%. Reconstructed in vivo images using TX-based AC hardware maps have shown 4.1 ± 0.9% mean difference compared to those reconstructed images using CT-based AC. CONCLUSIONS: The LAC of the acrylic cylinder measurements using the TX-based technique was in agreement with those in the literature confirming the validity of the technique. The over-estimation of photon counts caused by the CT-based model used for the patient table was improved by the TX-based technique. Therefore, TX-based AC of hardware using the PET/MRI system itself is possible and can produce more accurate images when compared to the CT-based hardware AC in cardiac PET images.

Evaluation of 511 keV photon attenuation by a novel 32-channel phased array prospectively designed for cardiovascular hybrid PET/MRI imaging.

BACKGROUND: Simultaneous cardiovascular imaging with positron emission tomography (PET) and magnetic resonance imaging (MRI) requires tools such as radio frequency (RF) phased arrays to achieve high temporal and spatial resolution in the MRI, as well as accurate quantification of PET. Today, high-density phased arrays (> 16 channels) used for cardiovascular PET/MRI are not designed to achieve low PET attenuation, and correcting the PET attenuation they cause requires off-line reconstruction, extra time and resources. PURPOSE: Motivated by previous work assessing the MRI performance of a novel prospectively designed 32-channel phased array, this study assessed the PET image quality with this array in place. Guided by NEMA standards, PET performance was measured using global PET counts, regional background variation (BV), contrast recovery (CR) and contrast-to-noise ratio (CNR) for both the novel array and standard arrays (mMR 12-channel and MRI 32-channel). Nonattenuation-corrected (NAC) data from all arrays (and each part of the array) were processed and compared to no-array, and relative percentage difference (RPD) of the global means was estimated and reported for each part of the arrays. Attenuation correction (AC) of PET images (water in the phantom) using two approaches, MR-based AC map (MRAC) and dual-energy CT-based map (DCTAC), was performed, and RPD compared for each part of the arrays. Percent mean attenuation within regions of interests of the phantom images from each array were compared using a two-way analysis of variance (ANOVA). RESULTS: The NAC data of the anterior part of the novel array recorded the least PET attenuation (≤ 2%); while the full novel array (anterior and posterior together) AC data, produced by MRAC and DCTAC approaches, recorded attenuation of 1.5 ± 2.9% and 0.0 ± 2.5%, respectively. The novel array PET count loss was significantly lower (p = 0.001) than those caused by the standard arrays. CONCLUSIONS: Results of this novel 32-channel cardiac array PET performance evaluation, together with its previously reported MRI performance assessment, suggest the novel array to be a strong alternative to the standard arrays currently used for cardiovascular hybrid PET/MRI imaging. It enables accurate PET quantification and high-temporal and spatial resolution for MR imaging.

Assessment of a novel 32-channel phased array for cardiovascular hybrid PET/MRI imaging: MRI performance.

BACKGROUND: Cardiovascular imaging using hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) requires a radio frequency phased array resonator capable of high acceleration factors in order to achieve the shortest breath-holds while maintaining optimal MRI signal-to-noise ratio (SNR) and minimum PET photon attenuation. To our knowledge, the only two arrays used today for hybrid PET/MRI cardiovascular imaging are either incapable of achieving high acceleration or affect the PET photon count greatly. PURPOSE: This study is focused on the evaluation of the MRI performance of a novel third-party prototype 32-channel phased array designed for simultaneous PET/MRI cardiovascular imaging. The study compares the quality parameters of MRI parallel imaging, such as g-factor, noise correlation coefficients, and SNR, to the conventional arrays (mMR 12-channel and MRI-only 32-channel) currently used with hybrid PET/MRI systems. The quality parameters of parallel imaging were estimated for multiple acceleration factors on a phantom and three healthy volunteers. Using a Germanium-68 (Ge-68) phantom, preliminary measurements of PET photon attenuation caused by the novel array were briefly compared to the photon counts produced from no-array measurements. RESULTS: The global mean of the g-factor and SNRg produced by the novel 32-channel PET/MRI array were better than those produced by the MRI-only 32-channel array by 5% or more. The novel array has resulted in MRI SNR improvements of > 30% at all acceleration factors, in comparison to the mMR12-channel array. Preliminary evaluation of PET transparency showed less than 5% photon attenuation caused by both anterior and posterior parts of the novel array. CONCLUSIONS: The MRI performance of the novel PET/MRI 32-channel array qualifies it to be a viable alternative to the conventional arrays for cardiovascular hybrid PET/MRI. A detailed evaluation of the novel array's PET performance remains to be conducted, but cursory assessment promises significantly reduced attenuation.

Hyperpolarized 129Xe magnetic resonance imaging: tolerability in healthy volunteers and subjects with pulmonary disease.

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 < .001), and both resolved 1 minute later, with no difference between subject groups. 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.