S. Sivaram Kaushik

Diffusion-Weighted Hyperpolarized 129Xe MRI in Healthy Volunteers and Subjects with Chronic Obstructive Pulmonary Disease

Given its greater availability and lower cost, 129Xe apparent diffusion coefficient (ADC) MRI offers an alternative to 3He ADC MRI. To demonstrate the feasibility of hyperpolarized 129Xe 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 cm2 sec−1 for HV, 0.043 ± 0.006 cm2 sec−1 for AMC, and 0.056 ± 0.008 cm2 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 (VA), r = −0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm2 sec−1 year−1 (r = 0.56, P = 0.02). This study shows that 129Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age‐ and posture‐dependent changes. Magn Reson Med, 2010.

Hyperpolarized 129Xe 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) 129Xe to probe the regional uptake of alveolar gases by directly imaging HP 129Xe 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 129Xe magnetization is rapidly replenished by diffusive exchange with alveolar 129Xe. The dissolved HP 129Xe 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 129Xe 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 129Xe imaging reports on pulmonary function at a fundamental level.

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).

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

In this study, hyperpolarized 129Xe MR ventilation and 1H 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, 1H anatomical images and 129Xe 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 129Xe 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. Copyright

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

The capability to use high‐resolution 3He 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 (R2 = 0.89). This method of analysis is shown to be more sensitive than simple threshold‐based detection of gross ventilation defects. Magn Reson Med 63:658–666, 2010.

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.

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.

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 Gas MRI: 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.

Hyperpolarized Gas MR Imaging

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.