Eduard E. de Lange

MRI of the lungs using hyperpolarized noble gases

The nuclear spin polarization of the noble gas isotopes 3He and 129Xe can be increased using optical pumping methods by four to five orders of magnitude. This extraordinary gain in polarization translates directly into a gain in signal strength for MRI. The new technology of hyperpolarized (HP) gas MRI holds enormous potential for enhancing sensitivity and contrast in pulmonary imaging. This review outlines the physics underlying the optical pumping process, imaging strategies coping with the nonequilibrium polarization, and effects of the alveolar microstructure on relaxation and diffusion of the noble gases. It presents recent progress in HP gas MRI and applications ranging from MR microscopy of airspaces to imaging pulmonary function in patients and suggests potential directions for future developments. Magn Reson Med 47:1029–1051, 2002.

Hyperpolarized 3He MR lung ventilation imaging in asthmatics: Preliminary findings

Asthma is a disease characterized by chronic inflammation and reversible obstruction of the small airways resulting in impaired pulmonary ventilation. Hyperpolarized 3He magnetic resonance (MR) lung imaging is a new technology that provides a detailed image of lung ventilation. Hyperpolarized 3He lung imaging was performed in 10 asthmatics and 10 healthy subjects. Seven asthmatics had ventilation defects distributed throughout the lungs compared with none of the normal subjects. These ventilation defects were more numerous and larger in the two symptomatic asthmatics who had abnormal spirometry. Ventilation defects studied over time demonstrated no change in appearance over 30–60 minutes. One asthmatic subject was studied twice in a three‐week period and had ventilation defects which resolved and appeared in that time. This same subject was studied before and after bronchodilator therapy, and all ventilation defects resolved after therapy. Hyperpolarized 3He lung imaging can detect the small, reversible ventilation defects that characterize asthma. The ability to visualize lung ventilation offers a direct method of assessing asthmatics and their response to therapy. J. Magn. Reson. Imaging 2001;13:378–384.

Functional MRI of the lung using hyperpolarized 3‐helium gas

Lung imaging has traditionally relied on x‐ray methods, since proton MRI is limited to some extent by low proton density in the lung parenchyma and static field inhomogeneities in the chest. The relatively recent introduction of MRI of hyperpolarized noble gases has led to a rapidly evolving field of pulmonary MRI, revealing functional information of the lungs, which were hitherto unattainable. This review article briefly describes the physical background of the technology, and subsequently focuses on its clinical applications. Four different techniques that have been used in various human investigations are discussed: ventilation distribution, ventilation dynamics, and small airway evaluation using diffusion imaging and oxygen uptake assessment. J. Magn. Reson. Imaging 2004;20:540–554.

Dynamic spiral MRI of pulmonary gas flow using hyperpolarized 3He: Preliminary studies in healthy and diseased lungs

An optimized interleaved‐spiral pulse sequence, providing high spatial and temporal resolution, was developed for dynamic imaging of pulmonary ventilation with hyperpolarized 3He, and tested in healthy volunteers and patients with lung disease. Off‐resonance artifacts were minimized by using a short data‐sampling period per interleaf, and gradient‐fidelity errors were compensated for by using measured k‐space trajectories for image reconstruction. A nonsequential acquisition order was implemented to improve image quality during periods of rapid signal change, such as early inspiration. Using a sliding‐window reconstruction, cine‐movies with a frame rate of 100 images per second were generated. Dynamic images demonstrating minimal susceptibility‐ and motion‐induced artifacts were obtained in sagittal, coronal, and axial orientations. The pulse sequence had the flexibility to image multiple slices almost simultaneously. Our initial experience in healthy volunteers and subjects with lung pathology demonstrated the potential of this new tool for capturing the features of lung gas‐flow dynamics. Magn Reson Med 4:667–677, 2001.

Changes in Regional Airflow Obstruction over Time in the Lungs of Patients with Asthma: Evaluation with 3He MR Imaging

PURPOSE To determine changes in regional airflow obstruction over time in the lungs of patients with asthma, as demonstrated with hyperpolarized helium 3 ((3)He) magnetic resonance (MR) imaging, and to assess correlations with disease severity and use of asthma medications. MATERIALS AND METHODS Institutional review board approval and written informed consent were obtained for this HIPAA-compliant study. Use of (3)He was approved by the U.S. Food and Drug Administration. Forty-three patients underwent 103 MR imaging studies in total; 26 were imaged twice within 42-82 minutes (same day), and 17 were imaged on 3 days between 1 and 476 days (multiday). Each day, spirometry was performed, disease severity was determined, and the use of asthma medications was recorded. Images were reviewed in a pairwise fashion to determine total ventilation defect number, defects in same location between imaging studies, and size. Parametric and nonparametric statistical methods were used. RESULTS For the same-day examinations, the mean number of defects per image section was similar at baseline and repeat imaging (1.8 +/- 1.9 [standard deviation] vs 1.6 +/- 1.9, respectively; P = .15), with 75% of defects remaining in the same location and 71% of these not changing size. For the multiday examinations, the mean number of defects per section was higher for study 2 (2.4 +/- 1.5) than study 1 (1.7 +/- 0.9, P = .02), was lower for study 3 (1.5 +/- 1.1) than for study 2 (P < .01), and was similar for studies 1 and 3 (P = .56). Time between examinations was not associated with change in mean number of defects per section (median intrasubject correlation [r(m)] = 0.01, P = .64) or change in spirometric values (range of r(m) values: -0.56 to -0.31; range of P values: .09-.71). Defects in the same location decreased with time (r(m) = -0.83, P < .01), with 67% persisting between studies 1 and 2 (median interval, 31 days), 43% persisting between studies 2 and 3 (median interval, 41 days), and 38% persisting between studies 1 and 3 (median interval, 85 days); 46%-58% of defects remained unchanged in size. These trends were the same regardless of disease severity or medication use. CONCLUSION In asthma, focal airflow impediment within the lungs can be markedly persistent over time, regardless of disease severity or treatment.

Hyperpolarized noble gas MR imaging of the lung: potential clinical applications.

Hyperpolarized noble gases are a new class of MR contrast agent. Since the first hyperpolarized gas MR images of the lung were reported, there has been considerable interest in using hyperpolarized gas to obtain high spatial and temporal resolution images of the air spaces of the lung. In addition to static images of lung ventilation, new techniques are being developed using hyperpolarized gas to obtain dynamic, diffusion and oxygen concentration images of the lung. In this article, we review the potential clinical applications of pulmonary hyperpolarized gas MRI and discuss the preliminary findings in a variety of lung diseases. Hyperpolarized gas MRI has the potential to provide a comprehensive morphologic and functional assessment of the lung.

Assessment of lung development using hyperpolarized helium-3 diffusion MR imaging.

To determine whether hyperpolarized helium‐3 (HHe) diffusion MR can detect the expected enlargement of alveoli that occurs with lung growth during childhood.

Assessment of the lung microstructure in patients with asthma using hyperpolarized 3He diffusion MRI at two time scales: comparison with healthy subjects and patients with COPD.

To investigate short‐ and long‐time‐scale 3He diffusion in asthma.

An in vivo evaluation of the reproducibility of intima-media thickness measurements of the carotid artery segments using B-mode ultrasound

B-mode ultrasound may be used to measure the intima-media thickness (IMT) in subjects with a history of atherosclerosis. The variability between measurements depends on the subjective interpretation of ultrasonographers and readers. The two carotid arteries, subdivided in common (CCA), bulbus (BUL) and internal (ICA) of 10 men with proven coronary disease, were scanned twice by two ultrasonographers with a 1-week interval. The IMTs were measured off-line by two readers. The number of IMT measurements was 75 (94%) of 80 in the CCA, 61 (76%) of 80 in the BUL and 43 (54%) of 80 in the ICA segment. In the CCA segment, the agreement between readers (mean = 0.02 mm; limits: -0.26 to +0.3 mm) and between visits for each reader separately (reader 1: mean = 0.01 mm; limits: -0.33 to +0.35 mm and, reader 2: mean = 0.04 mm; limits: -0.36 to +0.44 mm) was better than in the more distal segments. Therefore, it is concluded that IMT measurements are best performed in the CCA segment.

Time dependence of 3He diffusion in the human lung: measurement in the long-time regime using stimulated echoes.

A stimulated‐echo‐based technique was developed to measure the long‐time‐scale apparent diffusion coefficient (ADC) of hyperpolarized 3He during a single breath‐hold acquisition. Computer simulations were used to evaluate the performance of the technique and guide the selection of appropriate parameter values for obtaining accurate ADC values. The technique was used in 10 healthy subjects and two subjects with chronic obstructive pulmonary disease (COPD) to measure the global ADC for diffusion times between a few tenths of a second and several seconds, and to acquire spatial maps of the ADC for a diffusion time of 1.5 s. The reproducibility of the technique and its sensitivity to the direction of diffusion sensitization were also investigated. In healthy subjects, global ADC values decreased by severalfold over the range of diffusion times measured (mean values = 0.039 and 0.023 cm2/s at diffusion times of 0.61 and 1.54 s, respectively). ADC maps were generally uniform, with mean values similar to the corresponding global values. For the two COPD subjects, global ADC values were substantially greater than those of every healthy subject at all diffusion times measured. In addition, regional elevations of ADC values were far more conspicuous on long‐time‐scale ADC maps than on short‐time‐scale ADC maps. Magn Reson Med, 2006.