Scott H. Robertson

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.

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 129Xe 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).

3D MRI of impaired hyperpolarized 129Xe uptake in a rat model of pulmonary fibrosis

A variety of pulmonary pathologies, in particular interstitial lung diseases, are characterized by thickening of the pulmonary blood–gas barrier, and this thickening results in reduced gas exchange. Such diffusive impairment is challenging to quantify spatially, because the distributions of the metabolically relevant gases (CO2 and O2) cannot be detected directly within the lungs. Hyperpolarized (HP) 129Xe is a promising surrogate for these metabolic gases, because MR spectroscopy and imaging allow gaseous alveolar 129Xe to be detected separately from 129Xe dissolved in the red blood cells (RBCs) and the adjacent tissues, which comprise blood plasma and lung interstitium. Because 129Xe reaches the RBCs by diffusing across the same barrier tissues (blood plasma and interstitium) as O2, barrier thickening will delay 129Xe transit and, thus, reduce RBC‐specific 129Xe MR signal. Here we have exploited these properties to generate 3D, MR images of 129Xe uptake by the RBCs in two groups of rats. In the experimental group, unilateral fibrotic injury was generated prior to imaging by instilling bleomycin into one lung. In the control group, a unilateral sham instillation of saline was performed. Uptake of 129Xe by the RBCs, quantified as the fraction of RBC signal relative to total dissolved 129Xe signal, was significantly reduced (P = 0.03) in the injured lungs of bleomycin‐treated animals. In contrast, no significant difference (P = 0.56) was observed between the saline‐treated and untreated lungs of control animals. Together, these results indicate that 3D MRI of HP 129Xe dissolved in the pulmonary tissues can provide useful biomarkers of impaired diffusive gas exchange resulting from fibrotic thickening. Copyright

Dose and pulse sequence considerations for hyperpolarized 129Xe 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.

Using hyperpolarized 129Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis

Background Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized 129Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to red blood cells (RBCs). This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores, and its spatial distribution reflects known physiology and patterns of disease. Methods 13 healthy individuals (33.6±15.7 years) and 12 patients with IPF (66.0±6.4 years) underwent 129Xe MRI to generate three-dimensional quantitative maps depicting the 129Xe ventilation distribution, its uptake in interstitial barrier tissues and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores, and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung and to detect the known basal and peripheral predominance of disease in IPF. Results 129Xe MRI depicted functional impairment in patients with IPF, whose mean barrier uptake increased by 188% compared with the healthy reference population. 129Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores but strongly with PFTs. Barrier uptake and RBC transfer both correlated significantly with diffusing capacity of the lungs for carbon monoxide (r=−0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated most strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and subpleural (p<0.01) lung. Conclusions Hyperpolarized129Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in patients with IPF, sensitively and non-invasively.

Quantitative analysis of hyperpolarized 129Xe gas transfer MRI

Purpose Hyperpolarized 129Xe magnetic resonance imaging (MRI) using Dixon‐based decomposition enables single‐breath imaging of 129Xe in the airspaces, interstitial barrier tissues, and red blood cells (RBCs). However, methods to quantitatively visualize information from these images of pulmonary gas transfer are lacking. Here, we introduce a novel method to transform these data into quantitative maps of pulmonary ventilation, and 129Xe gas transfer to barrier and RBC compartments. Methods A total of 13 healthy subjects and 12 idiopathic pulmonary fibrosis (IPF) subjects underwent thoracic 1H MRI and hyperpolarized 129Xe MRI with one‐point Dixon decomposition to obtain images of 129Xe in airspaces, barrier and red blood cells (RBCs). 129Xe images were processed into quantitative binning maps of all three compartments using thresholds based on the mean and standard deviations of distributions derived from the healthy reference cohort. Binning maps were analyzed to derive quantitative measures of ventilation, barrier uptake, and RBC transfer. This method was also used to illustrate different ventilation and gas transfer patterns in a patient with emphysema and one with pulmonary arterial hypertension (PAH). Results In the healthy reference cohort, the mean normalized signals were 0.51 ± 0.19 for ventilation, 4.9 ± 1.5 x 10‐3 for barrier uptake and 2.6 ± 1.0 × 10‐3 for RBC (transfer). In IPF patients, ventilation was similarly homogenous to healthy subjects, although shifted toward slightly lower values (0.43 ± 0.19). However, mean barrier uptake in IPF patients was nearly 2× higher than in healthy subjects, with 47% of voxels classified as high, compared to 3% in healthy controls. Moreover, in IPF, RBC transfer was reduced, mainly in the basal lung with 41% of voxels classified as low. In healthy volunteers, only 15% of RBC transfer was classified as low and these voxels were typically in the anterior, gravitationally nondependent lung. Conclusions This study demonstrates a straightforward means to generate semiquantitative binning maps depicting 129Xe ventilation and gas transfer to barrier and RBC compartments. These initial results suggest that the method could be valuable for characterizing both normal physiology and pathophysiology associated with a wide range of pulmonary disorders.

Uncovering a third dissolved‐phase 129Xe resonance in the human lung: Quantifying spectroscopic features in healthy subjects and patients with idiopathic pulmonary fibrosis

The purpose of this work was to accurately characterize the spectral properties of hyperpolarized 129Xe in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy volunteers.PURPOSE The purpose of this work was to accurately characterize the spectral properties of hyperpolarized 129 Xe in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy volunteers. METHODS Subjects underwent hyperpolarized 129 Xe breath-hold spectroscopy, during which 38 dissolved-phase free induction decays (FIDs) were acquired after reaching steady state (echo time/repetition time = 0.875/50 ms; bandwidth = 8.06 kHz; flip angle≈22 °). FIDs were averaged and then decomposed into multiple spectral components using time-domain curve fitting. The resulting amplitudes, frequencies, line widths, and starting phases of each component were compared among groups using a Mann-Whitney-Wilcoxon U test. RESULTS Three dissolved-phase resonances, consisting of red blood cells (RBCs) and two barrier compartments, were consistently identified in all subjects. In subjects with IPF relative to healthy volunteers, the RBC frequency was 0.70 parts per million (ppm) more negative (P = 0.05), the chemical shift of barrier 2 was 0.6 ppm more negative (P = 0.009), the line widths of both barrier peaks were ∼2 ppm narrower (P < 0.001), and the starting phase of barrier 1 was 20.3 ° higher (P =  0.01). Moreover, the ratio RBC:barriers was reduced by 52.9% in IPF (P < 0.001). CONCLUSIONS The accurate decomposition of 129 Xe spectra not only has merit for developing a global metric of pulmonary function, but also provides necessary insights to optimize phase-sensitive methods for imaging 129 Xe gas transfer. Magn Reson Med 78:1306-1315, 2017.

Establishing an accurate gas phase reference frequency to quantify 129Xe chemical shifts in vivo

129Xe interacts with biological media to exhibit chemical shifts exceeding 200 ppm that report on physiology and pathology. Extracting this functional information requires shifts to be measured precisely. Historically, shifts have been reported relative to the gas‐phase resonance originating from pulmonary airspaces. However, this frequency is not fixed—it is affected by bulk magnetic susceptibility, as well as Xe–N2, Xe–Xe, and Xe–O2 interactions. In this study, we addressed this by introducing a robust method to determine the 0 ppm 129Xe reference from in vivo data.

Novel Magnetic Resonance Imaging for Assessment of Bronchial Stenosis in Lung Transplant Recipients

Bronchial stenosis in lung transplant recipients is a common disorder that adversely affects clinical outcomes. It is evaluated by spirometry, CT scanning, and bronchoscopy with significant limitations. We hypothesize that MRI using both ultrashort echo time (UTE) scans and hyperpolarized (HP) 129Xe gas can offer structural and functional assessment of bronchial stenosis seen after lung transplantation. Six patients with lung transplantation–related bronchial stenosis underwent HP 129Xe MRI and UTE MRI in the same session. Three patients subsequently underwent airway stent placement and had repeated MRI at 4‐week follow‐up. HP 129Xe MRI depicted decreased ventilation distal to the stenotic airway. After airway stent placement, MRI showed that low‐ventilation regions had decreased (35% vs. 27.6%, p = 0.006) and normal‐ventilation regions had increased (17.9% vs. 27.6%, p = 0.04) in the stented lung. Improved gas transfer was also seen on 129Xe MRI. There was a good correlation between UTE MRI and independent bronchoscopic airway diameter assessment (Pearson correlation coefficient = 0.92). This pilot study shows that UTE and HP 129Xe MRI are feasible in patients with bronchial stenosis related to lung transplantation and may provide structural and functional airway assessment to guide treatment. These conclusions need to be confirmed with larger studies.

TH-EF-BRA-10: High Spatiotemporal Resolution Self-Sorted 4D MRI

PURPOSE To describe a novel method for self-sorted 4D-MRI and to characterize the output image quality as measured by signal-to-noise ratio (SNR), spatiotemporal resolution, and level of artifact. METHODS A three-dimensional radial sampling function with a quasi-random distribution of polar/azimuthal k-space angles was implemented in a standard pulse sequence. Acquisition time was approximately 2 minutes. The DC component of the k-space signal was used to estimate and sort the breathing cycle into ten respiratory phases. For a given respiratory phase, the k-space data were combined with the periphery of the k-space data from all phases and reconstructed with the re-gridding algorithm onto a 1283 matrix. The extent of data sharing was controlled by the average breathing curve. The sampling and reconstruction technique were tested and validated in simulation, dynamic phantom, animal, and human studies with varying breathing periods/amplitudes. RESULTS The signal at the k-space center accurately measures respiratory motion over a large range of breathing periods (0.5-7.0 seconds) and amplitudes (5-30% of FOV). Sharing of high frequency k-space data driven by the average breathing curve improves spatial resolution and artifact level at a cost of an increase in noise floor. Although equal sharing of k-space data improves resolution and SNR, phases with large temporal changes accumulate considerable distortion artifacts. In the absence of view-sharing, no distortion artifacts are observed while spatial resolution is degraded. CONCLUSION The use of a quasi-random sampling function and view-sharing driven by the average breathing curve provide a feasible method for self-sorted 4D MRI at reduced acquisition times. This approach allows for the extent of data sharing to be inversely-proportional to the average breathing motion hence improving resolution and decreasing artifact levels. NIH-1R21CA165384.

Three-dimensional echo-planar cine imaging of cerebral blood supply using arterial spin labeling

ObjectiveEcho-planar imaging (EPI) with CYlindrical Center-out spatiaL Encoding (EPICYCLE) is introduced as a novel hybrid three-dimensional (3D) EPI technique. Its suitability for the tracking of a short bolus created by pseudo-continuous arterial spin labeling (pCASL) through the cerebral vasculature is demonstrated.Materials and methodsEPICYCLE acquires two-dimensional planes of k-space along center-out trajectories. These “spokes” are rotated from shot to shot about a common axis to encode a k-space cylinder. To track a bolus of labeled blood, the same subset of evenly distributed spokes is acquired in a cine fashion after a short period of pCASL. This process is repeated for all subsets to fill the whole 3D k-space of each time frame.ResultsThe passage of short pCASL boluses through the vasculature of a 3D imaging slab was successfully imaged using EPICYCLE. By choosing suitable sequence parameters, the impact of slab excitation on the bolus shape could be minimized. Parametric maps of signal amplitude, transit time, and bolus width reflected typical features of blood transport in large vessels.ConclusionThe EPICYCLE technique was successfully applied to track a short bolus of labeled arterial blood during its passage through the cerebral vasculature.