Multispectral diffusion-weighted MRI of the instrumented cervical spinal cord: a preliminary study of 5 cases.

PURPOSE: Diffusion-weighted imaging has undergone substantial investigation as a potential tool for advanced assessment of spinal cord health. Unfortunately, commonly encountered surgically implanted spinal hardware has historically disrupted these studies. This preliminary investigation applies the recently developed multispectral diffusion-weighted PROPELLER technique to quantitative assessment of the spinal cord immediately adjacent to metallic spinal fusion instrumentation. METHODS: Morphological and diffusion-weighted MRI of the spinal cord was collected from 5 subjects with implanted cervical spinal fusion hardware. Conventional and multispectral diffusion-weighted images were also collected on a normative non-instrumented control cohort and utilized for methodological stability analysis. Variance of the ADC values derived from the normative control group was then analyzed on a subject-by-subject basis and qualitatively correlated with clinical morphological interpretations. RESULTS: Normative control ADC values within the spinal cord were stable across DWI methods for a b value of 600 s/mm2, though this stability degraded at lower b value levels. Susceptibility artifacts precluded conventional DWI analysis of the cord in subjects with spinal fusion hardware in 4 of the 5 test cases. On the contrary, multispectral PROPELLER DWI produced viable ADC measurements within the cord of all 5 instrumented subjects. Instrumented cord regions without obvious pathology (N = 4) showed ADC values that were lower than expected, whereas one subject with diagnosed myelomalacia showed abnormally elevated ADC. CONCLUSIONS: In the absence of instrumentation, multispectral DWI provides quantitative capabilities that match with those of conventional DWI approaches. In a preliminary instrumented subject analysis, cord ADC values showed both expected and unexpected variations from the normative cohort. These slides can be retrieved under Electronic Supplementary Material.

MRI of Hip Arthroplasties: Comparison of Isotropic Multiacquisition Variable-Resonance Image Combination Selective (MAVRIC SL) Acquisitions With a Conventional MAVRIC SL Acquisition.

OBJECTIVE. The objective of our study was to compare the quality and diagnostic utility of the following three metal artifact reduction sequences in evaluating hip arthroplasties: conventional multiacquisition variable-resonance image combination selective (MAVRIC SL), isotropic MAVRIC SL, and reduced-TR isotropic MAVRIC SL. SUBJECTS AND METHODS. Ninety-three hip arthroplasties (85 total hip replacements and eight hip resurfacings [nine bilateral hips]) in 84 patients (38 men and 46 women; mean age ± SD, 69.1 ± 9.7 years old) were imaged and evaluated. A calibration scan determined the number of spectral bins needed for each implant, and isotropic and conventional MAVRIC SL images were acquired. Reduced-TR isotropic MAVRIC SL scans were acquired for 40 arthroplasties. Two board-certified radiologists blinded to MRI acquisition evaluated images for clinical and image quality features and compared images using a mixed-effects ordinal logistic regression model and odds ratios. Rater agreement was assessed with Gwet agreement coefficients. Scanning times were compared using mixed-effects linear regression. Significance was set at p < 0.05. RESULTS. Calibration scans decreased the number of bins needed (median, 12 bins; interquartile range, 10-16 bins). Isotropic MAVRIC SL (mean scanning time, 7 minutes 16 seconds; 95% CI, 7 minutes 7 seconds-7 minutes 25 seconds) acquisitions had the longest scanning time, and conventional (mean, 5 minutes 46 seconds; 95% CI, 5 minutes 37 seconds-5 minutes 55 seconds) and reduced-TR isotropic (5 minutes 28 seconds; 95% CI, 5 minutes 15 seconds-5 minutes 41 seconds) MAVRIC SL acquisitions had scanning times that were similar. Both isotropic and reduced-TR isotropic MAVRIC SL images showed decreased blurring and improved visualization of the synovium and periprosthetic bone compared with conventional MAVRIC SL images (p < 0.001). Isotropic MAVRIC SL acquisitions more effectively improved signal-to-noise ratio (SNR), visualization of the synovium and periprosthetic bone, and lesion conspicuity and decreased blurring compared with reduced-TR isotropic MAVRIC SL acquisitions (p < 0.032). CONCLUSION. Isotropic MAVRIC SL acquisitions improve SNR, conspicuity of lesions, and visualization of synovium and periprosthetic bone and decrease blurring compared with conventional MAVRIC SL acquisitions.

Multispectral diffusion-weighted imaging near metal implants.

PURPOSE: The need for diffusion-weighted-imaging (DWI) near metallic implants is becoming increasingly relevant for a variety of clinical diagnostic applications. Conventional DWI methods are significantly hindered by metal-induced image artifacts. A novel approach relying on multispectral susceptibility artifact reduction techniques is presented to address this unmet need. METHODS: DWI near metal implants is achieved through a combination of several advanced MRI acquisition technologies. Previously described approaches to Carr-Purcell-Meiboom-Gill spin-echo train DWI sequences using the periodically rotated overlapping parallel lines with enhanced reconstruction are combined with multispectral-imaging metal artifact reduction principles to provide DWI with substantially reduced artifact levels. The presented methods are applied to limited sets of slices over areas of sarcoma risk near six implanted devices. RESULTS: Using the presented methods, DWI assessment without bulk image distortions is demonstrated in the immediate vicinity of metallic interfaces. In one subject, the apparent diffusion coefficient was reduced in a region of suspected sarcoma directly adjacent to fixation hardware. CONCLUSIONS: An initial demonstration of minimal-artifact multispectral DWI in the near vicinity of metallic hardware is described and successfully demonstrated on clinical subjects. Magn Reson Med 79:987-993, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Quantifying metal-induced susceptibility artifacts of the instrumented spine at 1.5T using fast-spin echo and 3D-multispectral MRI.

PURPOSE: To evaluate magnetic resonance imaging (MRI) artifacts near metallic spinal instrumentation using both conventional metal artifact reduction sequences (MARS) and 3D multispectral imaging sequences (3D-MSI). MATERIALS AND METHODS: Both MARS and 3D-MSI images were acquired in 10 subjects with titanium spinal hardware on a 1.5T GE 450W scanner. Clinical computed tomography (CT) images were used to measure the volume of the implant using seed-based region growing. Using 30-40 landmarks, the MARS and 3D-MSI images were coregistered to the CT images. Three independent users manually segmented the artifact volume from both MR sequences. For five L-spine subjects, one user independently segmented the nerve root in both MARS and 3D-MSI images. RESULTS: For all 10 subjects, the measured artifact volume for the 3D-MSI images closely matched that of the CT implant volume (absolute error: 4.3 ± 2.0 cm3 ). The MARS artifact volume was ∼8-fold higher than that of the 3D-MSI images (30.7 ± 20.2, P = 0.002). The average nerve root volume for the MARS images was 24 ± 7.3% lower than the 3D-MSI images (P = 0.06). CONCLUSION: Compared to 3D-MSI images, the higher-resolution MARS images may help study features farther away from the implant surface. However, the MARS images retained substantial artifacts in the slice-dimension that result in a larger artifact volume. These artifacts have the potential to obscure physiologically relevant features, and can be mitigated with 3D-MSI sequences. Hence, MR study protocols may benefit with the inclusion both MARS and 3D-MSI sequences to accurately study pathology near the spine. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:51-58.

External calibration of the spectral coverage for three-dimensional multispectral MRI.

PURPOSE: By combining images created at distinct frequency offsets from the Larmor frequency, three-dimensional (3D) multispectral imaging (3D-MSI) sequences help overcome the large spatial frequency dispersion caused by metal implants. This frequency dispersion, however, varies with the implant size, orientation, and composition. Using a MAVRIC 3D-MSI acquisition, we sought to prospectively calibrate the spectral coverage needed for 3D-MSI scans. This calibration should offer a significant improvement to image quality, and reduce the scan time. METHODS: The 24 spectral bins from the calibration scan were used to generate a map of frequency offsets around the implant. The magnitude image was used to remove any outliers in the associated frequency offset map, and this processed map was used to determine the cutoff frequency offset and, hence, number of spectral bins. This approach was tested in 13 subjects, by retrospectively reconstructing MAVRIC-SL images with fewer spectral bins. Subsequently, the spectral coverage for MAVRIC-SL images was prospectively calibrated in six subjects, and based on the cutoff frequency offset, these images were acquired with fewer spectral bins. RESULTS: With fewer spectral bins, both retrospectively and prospectively calibrated MAVRIC-SL images adequately delineated the implant boundary. CONCLUSION: Incorporating this calibration procedure into future 3D-MSI exams will help improve image signal-to-noise ratio, reduce scan time, and significantly improve clinical workflow when imaging near orthopedic implants. Magn Reson Med 76:1494-1503, 2016. © 2015 International Society for Magnetic Resonance in Medicine.

Single-breath clinical imaging of hyperpolarized (129)Xe in the airspaces, barrier, and red blood cells using an interleaved 3D radial 1-point Dixon acquisition.

PURPOSE: We sought to develop and test a clinically feasible 1-point Dixon, three-dimensional (3D) radial acquisition strategy to create isotropic 3D MR images of (129)Xe in the airspaces, barrier, and red blood cells (RBCs) in a single breath. The approach was evaluated in healthy volunteers and subjects with idiopathic pulmonary fibrosis (IPF). METHODS: A calibration scan determined the echo time at which (129)Xe in RBCs and barrier were 90° out of phase. At this TE, interleaved dissolved and gas-phase images were acquired using a 3D radial acquisition and were reconstructed separately using the NUFFT algorithm. The dissolved-phase image was phase-shifted to cast RBC and barrier signal into the real and imaginary channels such that the image-derived RBC:barrier ratio matched that from spectroscopy. The RBC and barrier images were further corrected for regional field inhomogeneity using a phase map created from the gas-phase (129)Xe image. RESULTS: Healthy volunteers exhibited largely uniform (129)Xe-barrier and (129)Xe-RBC images. By contrast, (129)Xe-RBC images in IPF subjects exhibited significant signal voids. These voids correlated qualitatively with regions of fibrosis visible on CT. CONCLUSIONS: This study illustrates the feasibility of acquiring single-breath, 3D isotropic images of (129)Xe in the airspaces, barrier, and RBCs using a 1-point Dixon 3D radial acquisition.

Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease.

In this study, hyperpolarized (129) Xe MR ventilation and (1) H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age-matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader-based ventilation defect score percentage (VDS%) and a semi-automated segmentation-based ventilation defect percentage (VDP). Reader-based values were assigned by two experienced radiologists and resolved by consensus. In the semi-automated analysis, (1) H anatomical images and (129) Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader-based VDS% correlated strongly with the semi-automatically generated VDP (r = 0.97, p < 0.0001) and with CV (r = 0.82, p < 0.0001). Both (129) Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1 s (FEV1 ) (VDS%: r = -0.78, p = 0.0002; VDP: r = -0.79, p = 0.0003; CV: r = -0.66, p = 0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r = 0.61, p = 0.0002; VDP: r = 0.63, p = 0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns.

Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients.

PURPOSE: To evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 ((129)Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years ± 18.8 [standard deviation]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized (129)Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects' serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after (129)Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a χ(2) test and to subject age by using logistic regression. Changes in vital signs were tested for significance across subject group and time by using a repeated-measures multivariate analysis of variance test. RESULTS: The 44 subjects tolerated all xenon inhalations, no subjects withdrew, and no serious adverse events occurred. No significant changes in vital signs (P > .27) were observed, and no subjects exhibited changes in laboratory test or ECG results at follow-up that were deemed clinically important or required intervention. Most subjects (91%) did experience transient xenon-related symptoms, most commonly dizziness (59%), paresthesia (34%), euphoria (30%), and hypoesthesia (30%). All symptoms resolved without clinical intervention in 1.6 minutes ± 0.9. CONCLUSION: Inhalation of hyperpolarized (129)Xe is well tolerated in healthy subjects and in those with mild or moderate COPD. Subjects do experience mild, transient, xenon-related symptoms, consistent with its known anesthetic properties.

Diffusion-weighted hyperpolarized 129Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease.

Given its greater availability and lower cost, (129) Xe apparent diffusion coefficient (ADC) MRI offers an alternative to (3) He ADC MRI. To demonstrate the feasibility of hyperpolarized (129) Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age-matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm(2) sec(-1) for HV, 0.043 ± 0.006 cm(2) sec(-1) for AMC, and 0.056 ± 0.008 cm(2) sec(-1) for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior-posterior direction by ∼ 22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity-induced tissue compression. The COPD group exhibited a significantly larger superior-inferior ADC reduction (∼ 28%) than the healthy groups (∼ 24%) (P = 0.00018, HV; P = 3.45 × 10(-5) , AMC), consistent with smoking-related tissue destruction in the superior lung. Superior-inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = -0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = -0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V(A) ), r = -0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm(2) sec(-1) year(-1) (r = 0.56, P = 0.02). This study shows that (129) Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age- and posture-dependent changes.

Analysis and Evaluation of a Deep Learning Reconstruction Approach with Denoising for Orthopedic MRI.

PURPOSE: To evaluate two settings (noise reduction of 50% or 75%) of a deep learning (DL) reconstruction model relative to each other and to conventional MR image reconstructions on clinical orthopedic MRI datasets. MATERIALS AND METHODS: This retrospective study included 54 patients who underwent two-dimensional fast spin-echo MRI for hip (n = 22; mean age, 44 years ± 13 [standard deviation]; nine men) or shoulder (n = 32; mean age, 56 years ± 17; 17 men) conditions between March 2019 and June 2020. MR images were reconstructed with conventional methods and the vendor-provided and commercially available DL model applied with 50% and 75% noise reduction settings (DL 50 and DL 75, respectively). Quantitative analytics, including relative anatomic edge sharpness, relative signal-to-noise ratio (rSNR), and relative contrast-to-noise ratio (rCNR) were computed for each dataset. In addition, the image sets were randomized, blinded, and presented to three board-certified musculoskeletal radiologists for ranking based on overall image quality and diagnostic confidence. Statistical analysis was performed with a nonparametric hypothesis comparing derived quantitative metrics from each reconstruction approach. In addition, inter- and intrarater agreement analysis was performed on the radiologists' rankings. RESULTS: Both denoising settings of the DL reconstruction showed improved edge sharpness, rSNR, and rCNR relative to the conventional reconstructions. The reader rankings demonstrated strong agreement, with both DL reconstructions outperforming the conventional approach (Gwet agreement coefficient = 0.98). However, there was lower agreement between the readers on which DL reconstruction denoising setting produced higher-quality images (Gwet agreement coefficient = 0.31 for DL 50 and 0.35 for DL 75). CONCLUSION: The vendor-provided DL MRI reconstruction showed higher edge sharpness, rSNR, and rCNR in comparison with conventional methods; however, optimal levels of denoising may need to be further assessed.Keywords: MRI Reconstruction Method, Deep Learning, Image Analysis, Signal-to-Noise Ratio, MR-Imaging, Neural Networks, Hip, Shoulder, Physics, Observer Performance, Technology Assessment Supplemental material is available for this article. © RSNA, 2021.

Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine.

The capability to use high-resolution (3)He MRI to depict regional ventilation changes and airway narrowing in mice challenged with methacholine (MCh) offers the opportunity to gain new insights into the study of asthma. However, to fully exploit the value of this novel technique, it is important to move beyond visual inspection of the images toward automated and quantitative analysis. To address this gap, we describe a postprocessing approach to create ventilation difference maps to better visualize and quantify regional ventilation changes before and after MCh challenge. We show that difference maps reveal subtle changes in airway caliber, and highlight both focal and diffuse regional alterations in ventilation. Ventilation changes include both hypoventilation and compensatory areas of hyperventilation. The difference maps can be quantified by a histogram plot of the ventilation changes, in which the standard deviation increases with MCh dose (R(2) = 0.89). This method of analysis is shown to be more sensitive than simple threshold-based detection of gross ventilation defects.

Hyperpolarized Gas MR Imaging: Technique and Applications.

Functional imaging offers information more sensitive to changes in lung structure and function. Hyperpolarized helium ((3)He) and xenon ((129)Xe) MR imaging of the lungs provides sensitive contrast mechanisms to probe changes in pulmonary ventilation, microstructure, and gas exchange. Gas imaging has shifted to the use of (129)Xe. Xenon is well-tolerated. (129)Xe is soluble in pulmonary tissue, which allows exploring specific lung function characteristics involved in gas exchange and alveolar oxygenation. Hyperpolarized gases and (129)Xe in particular stand to be an excellent probe of pulmonary structure and function, and provide sensitive and noninvasive biomarkers for pulmonary diseases.

Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI.

PURPOSE: The aim of this study was to evaluate the effect of hyperpolarized (129)Xe dose on image signal-to-noise ratio (SNR) and ventilation defect conspicuity on both multi-slice gradient echo and isotropic 3D-radially acquired ventilation MRI. MATERIALS AND METHODS: Ten non-smoking older subjects (ages 60.8±7.9years) underwent hyperpolarized (HP) (129)Xe ventilation MRI using both GRE and 3D-radial acquisitions, each tested using a 71ml (high) and 24ml (low) dose equivalent (DE) of fully polarized, fully enriched (129)Xe. For all images SNR and ventilation defect percentage (VDP) were calculated. RESULTS: Normalized SNR (SNRn), obtained by dividing SNR by voxel volume and dose was higher for high-DE GRE acquisitions (SNRn=1.9±0.8ml(-2)) than low-DE GRE scans (SNRn=0.8±0.2ml(-2)). Radially acquired images exhibited a more consistent, albeit lower SNRn (High-DE: SNRn=0.5±0.1ml(-2), low-DE: SNRn=0.5±0.2ml(-2)). VDP was indistinguishable across all scans. CONCLUSIONS: These results suggest that images acquired using the high-DE GRE sequence provided the highest SNRn, which was in agreement with previous reports in the literature. 3D-radial images had lower SNRn, but have advantages for visual display, monitoring magnetization dynamics, and visualizing physiological gradients. By evaluating normalized SNR in the context of dose-equivalent formalism, it should be possible to predict (129)Xe dose requirements and quantify the benefits of more efficient transmit/receive coils, field strengths, and pulse sequences.

Extending semiautomatic ventilation defect analysis for hyperpolarized (129)Xe ventilation MRI.

RATIONALE AND OBJECTIVES: Clinical deployment of hyperpolarized (129)Xe magnetic resonance imaging requires accurate quantification and visualization of the ventilation defect percentage (VDP). Here, we improve the robustness of our previous semiautomated analysis method to reduce operator dependence, correct for B1 inhomogeneity and vascular structures, and extend the analysis to display multiple intensity clusters. MATERIALS AND METHODS: Two segmentation methods were compared-a seeded region-growing method, previously validated by expert reader scoring, and a new linear-binning method that corrects the effects of bias field and vascular structures. The new method removes nearly all operator interventions by rescaling the (129)Xe magnetic resonance images to the 99th percentile of the cumulative distribution and applying fixed thresholds to classify (129)Xe voxels into four clusters: defect, low, medium, and high intensity. The methods were applied to 24 subjects including patients with chronic obstructive pulmonary disease (n = 8), age-matched controls (n = 8), and healthy normal subjects (n = 8). RESULTS: Linear-binning enabled a faster and more reproducible workflow and permitted analysis of an additional 0.25 ± 0.18 L of lung volume by accounting for vasculature. Like region-growing, linear-binning VDP correlated strongly with reader scoring (R(2) = 0.93, P < .0001), but with less systematic bias. Moreover, linear-binning maps clearly depict regions of low and high intensity that may prove useful for phenotyping subjects with chronic obstructive pulmonary disease. CONCLUSIONS: Corrected linear-binning provides a robust means to quantify (129)Xe ventilation images yielding VDP values that are indistinguishable from expert reader scores, while exploiting the entire dynamic range to depict multiple image clusters.

Measuring diffusion limitation with a perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis.

Although xenon is classically taught to be a "perfusion-limited" gas, (129)Xe in its hyperpolarized (HP) form, when detected by magnetic resonance (MR), can probe diffusion limitation. Inhaled HP (129)Xe diffuses across the pulmonary blood-gas barrier, and, depending on its tissue environment, shifts its resonant frequency relative to the gas-phase reference (0 ppm) by 198 ppm in tissue/plasma barrier and 217 ppm in red blood cells (RBCs). In this work, we hypothesized that in patients with idiopathic pulmonary fibrosis (IPF), the ratio of (129)Xe spectroscopic signal in the RBCs vs. barrier would diminish as diffusion-limitation delayed replenishment of (129)Xe magnetization in RBCs. To test this hypothesis, (129)Xe spectra were acquired in 6 IPF subjects as well as 11 healthy volunteers to establish a normal range. The RBC:barrier ratio was 0.55 ± 0.13 in healthy volunteers but was 3.3-fold lower in IPF subjects (0.16 ± 0.03, P = 0.0002). This was caused by a 52% reduction in the RBC signal (P = 0.02) and a 58% increase in the barrier signal (P = 0.01). Furthermore, the RBC:barrier ratio strongly correlated with lung diffusing capacity for carbon monoxide (DLCO) (r = 0.89, P < 0.0001). It exhibited a moderate interscan variability (8.25%), and in healthy volunteers it decreased with greater lung inflation (r = -0.78, P = 0.005). This spectroscopic technique provides a noninvasive, global probe of diffusion limitation and gas-transfer impairment and forms the basis for developing 3D MR imaging of gas exchange.

Probing the regional distribution of pulmonary gas exchange through single-breath gas- and dissolved-phase 129Xe MR imaging.

Although some central aspects of pulmonary function (ventilation and perfusion) are known to be heterogeneous, the distribution of diffusive gas exchange remains poorly characterized. A solution is offered by hyperpolarized 129Xe magnetic resonance (MR) imaging, because this gas can be separately detected in the lung's air spaces and dissolved in its tissues. Early dissolved-phase 129Xe images exhibited intensity gradients that favored the dependent lung. To quantitatively corroborate this finding, we developed an interleaved, three-dimensional radial sequence to image the gaseous and dissolved 129Xe distributions in the same breath. These images were normalized and divided to calculate "129Xe gas-transfer" maps. We hypothesized that, for healthy volunteers, 129Xe gas-transfer maps would retain the previously observed posture-dependent gradients. This was tested in nine subjects: when the subjects were supine, 129Xe gas transfer exhibited a posterior-anterior gradient of -2.00 ± 0.74%/cm; when the subjects were prone, the gradient reversed to 1.94 ± 1.14%/cm (P < 0.001). The 129Xe gas-transfer maps also exhibited significant heterogeneity, as measured by the coefficient of variation, that correlated with subject total lung capacity (r = 0.77, P = 0.015). Gas-transfer intensity varied nonmonotonically with slice position and increased in slices proximal to the main pulmonary arteries. Despite substantial heterogeneity, the mean gas transfer for all subjects was 1.00 ± 0.01 while supine and 1.01 ± 0.01 while prone (P = 0.25), indicating good "matching" between gas- and dissolved-phase distributions. This study demonstrates that single-breath gas- and dissolved-phase 129Xe MR imaging yields 129Xe gas-transfer maps that are sensitive to altered gas exchange caused by differences in lung inflation and posture.

Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model.

The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 µm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance.

Hyperpolarized Xe MR imaging of alveolar gas uptake in humans.

BACKGROUND: One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) (129)Xe to probe the regional uptake of alveolar gases by directly imaging HP (129)Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP (129)Xe magnetization is rapidly replenished by diffusive exchange with alveolar (129)Xe. The dissolved HP (129)Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs. CONCLUSIONS: The features observed in dissolved-phase (129)Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP (129)Xe imaging reports on pulmonary function at a fundamental level.