Alexei Ouriadov

Hyperpolarized 3He magnetic resonance imaging of chronic obstructive pulmonary disease: reproducibility at 3.0 tesla.

RATIONALE AND OBJECTIVES We assessed subjects with stage II and stage III chronic obstructive pulmonary disease (COPD) and age-matched healthy volunteers at a single center using (3)He magnetic resonance imaging (MRI) at 3.0 T. Measurements of the (3)He apparent diffusion coefficient (ADC) and center coronal slice (3)He ventilation defect volume (VDV) were examined for same-day and 7-day reproducibility as well as subgroup comparisons. MATERIALS AND METHODS Twenty-four subjects who provided written informed consent (15 males; mean age 67 +/-7 years) with stage II (n = 9), stage III COPD (n = 7), and age-matched healthy volunteers (n = 8) were enrolled based on their age and pulmonary function test results. All subjects underwent plethysmography, spirometry, and MRI at 3.0 T. The time frame between scans was 7 +/- 2 minutes (same-day rescan) and again 7 +/- 2 days later (7-day rescan). (3)He ADC and VDV reproducibility was evaluated using linear regression, intraclass correlation coefficients (ICC) and Lins concordance correlation coefficients (CCC). RESULTS ADC reproducibility was high for same-day rescan (r(2) = 0.934) and 7-day rescan (r(2) = 0.960, ICC and CCC of 0.96 and 0.98, respectively). Same-day rescan VDV reproducibility evaluated using the ICC and CCC (0.97 and 0.98, respectively) as well as linear regression (r(2) = 0.941) was also high, but VDV 7-day rescan reproducibility was lower and significantly different (r(2) = 0.576, P < .001, ICC 0.74, CCC 0.75, P < .01). CONCLUSIONS Hyperpolarized (3)He MRI was well-tolerated in subjects with stage II and stage III COPD. Seven-day repeated scanning was highly reproducible for ADC and moderately reproducible for VDV.

Anatomical distribution of He-3 apparent diffusion coefficients in severe chronic obstructive pulmonary disease

To evaluate the anatomical distribution of apparent diffusion coefficients (ADC) using hyperpolarized helium‐3 (3He) MRI in chronic obstructive pulmonary disease (COPD).

Rapid and efficient mapping of regional ventilation in the rat lung using hyperpolarized 3He with Flip angle variation for offset of RF and relaxation (FAVOR)

A novel imaging method is presented, Flip Angle Variation for Offset of RF and Relaxation (FAVOR), for rapid and efficient measurement of rat lung ventilation using hyperpolarized helium‐3 (3He) gas. The FAVOR technique utilizes variable flip angles to remove the cumulative effect of RF pulses and T1 relaxation on the hyperpolarized gas signal and thereby eliminates the need for intervening air wash‐out breaths and multiple cycles of 3He wash‐in breaths before each image. The former allows an improvement in speed (by a factor of ≈30) while the latter reduces the cost of each measurement (by a factor of ≈5). The FAVOR and conventional ventilation methods were performed on six healthy male Brown Norway rats (190–270 g). Lobar measurements of ventilation, r, obtained with the FAVOR method were not significantly different from those obtained with the conventional method for the right middle and caudal and left lobes (P > 0.05 by a Wilcoxon matched pairs test). A methacholine challenge test was also administered to an animal and reduction and recovery of r was detected by the FAVOR method. The reduced 3He consumption and the improvement in speed provided by FAVOR suggest that it may allow measurement of ventilation in human subjects not previously possible. Magn Reson Med 59:1304–1310, 2008.

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. Magn Reson Med, 2012.

Hyperpolarized noble gas magnetic resonance imaging of the animal lung: Approaches and applications

Hyperpolarized noble gas (HNG) magnetic resonance (MR) imaging is a very promising noninvasive tool for the investigation of animal models of lung disease, particularly to follow longitudinal changes in lung function and anatomy without the accumulated radiation dose associated with x rays. The two most common noble gases for this purpose are H3e (helium 3) and X129e (xenon 129), the latter providing a cost-effective approach for clinical applications. Hyperpolarization is typically achieved using spin-exchange optical pumping techniques resulting in ∼10 000-fold improvement in available magnetization compared to conventional Boltzmann polarizations. This substantial increase in polarization allows high spatial resolution (<1 mm) single-slice images of the lung to be obtained with excellent temporal resolution (<1 s). Complete three-dimensional images of the lungs with 1 mm slice thickness can be obtained within reasonable breath-hold intervals (<20 s). This article provides an overview of the current met...

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

Hyperpolarized 3He 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 3He 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 3He apparent diffusion coefficient is studied in a rat model of emphysema, based on elastase instillation, specifically for δ values less than one millisecond. Longitudinal (DL) and transverse (DT) 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 (Lm). Whole‐lung mean DT measured at δ = 360 μs in the elastase‐instilled rat lungs (0.14 ± 0.09 cm2/s) demonstrated the most significant increase (p = 0.00195) compared to the sham‐instilled cohort (0.06 ± 0.06 cm2/s) and had a strong linear correlation with Lm (Pearsons correlation coefficient of 0.9). These results suggest that measurement of 3He apparent diffusion coefficient anisotropy, specifically DT, can provide a sensitive indicator of emphysema, particularly at very short diffusion times (δ = 360 μs). Magn Reson Med, 2011.

Pulmonary Hyperpolarized 129 Xe Morphometry for Mapping Xenon Gas Concentrations and Alveolar Oxygen Partial Pressure: Proof-of-Concept Demonstration in Healthy and COPD Subjects

Diffusion‐weighted (DW) hyperpolarized 129Xe morphometry magnetic resonance imaging (MRI) can be used to map regional differences in lung tissue micro‐structure. We aimed to generate absolute xenon concentration ([Xe]) and alveolar oxygen partial pressure (pAO2) maps by extracting the unrestricted diffusion coefficient (D0) of xenon as a morphometric parameter.

Theoretical prediction and experimental measurement of the field dependence of the apparent transverse relaxation of hyperpolarized noble gases in lungs.

In this work, computer modeling based on a finite element method is used to simulate the T2* relaxation of hyperpolarized noble gases (HNG) in the lungs. A physical model of lung airways consisting of a phantom constructed from micro-capillary fibers of diameters similar to the size of lung airways with semi-permeable walls is also presented. The fibers are surrounded by a liquid medium (water) of magnetic susceptibility similar to lung tissue. Theoretical predictions of the field strength dependence of T2* for 129Xe in the phantom and in vivo rat lung are presented. These predictions are in good agreement with experimental T2* values obtained from the phantoms and in vivo rat lungs (160, 19 and 8 ms) at three different field strengths (0.074, 1.89 and 3T, respectively) using hyperpolarized 129Xe. The strong dependence of T2* on field strength is consistent with the theoretical prediction that low fields may be optimal for HNG MR imaging of the lungs as the decreased T2* at high fields necessitates an increase in bandwidth for conventional MR imaging.

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

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

MRI using hyperpolarized noble gases, 3He and 129Xe, provides noninvasive assessments of lung structure and function. Previous work demonstrated that absolute ventilated lung volumes (aVLV) measured in rats using hyperpolarized 3He agree well with micro‐CT.