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Technical Developments |
1 Departments of Radiology (E.E.d.L., J.P.M., J.R.B., J.K.S., C.D.T.)
2 Internal Medicine (J.D.T.)
3 Surgery (T.M.D.), University of Virginia Health Sciences Center, Box 170, 1000 Lee St, Charlottesville, VA 22908
4 Magnetic Imaging Technologies, Durham, NC (P.L.B.)
5 Department of Physics, Princeton University, Princeton, NJ (G.D.C.).
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Abstract |
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Index terms: Helium • Lung, MR, 60.12143 • Magnetic resonance (MR), contrast enhancement, 60.121412, 60.12143 • Magnetic resonance (MR), nuclei other than H, 60.121412, 60.12147
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Introduction |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In this study, we evaluated the potential application of lung MR imaging with hyperpolarized 3He. Helium was used because it has a much greater magnetic moment than 129Xe and depolarizes more slowly. In addition, 3He can be inhaled in relatively large quantities without substantial risk as it is not absorbed by the tissues of the lung. Furthermore, there are no known serious side effects associated with inhalation of helium gas, on the basis of experience in deep-sea divers who typically use much larger volumes and concentrations than are used with MR imaging of the lungs (6). The promising initial imaging results and inherent safety of 3He coupled with an emerging commercial supply of polarized 3He gas for the clinical environment makes further investigation of this contrast agent a desirable endeavor.
The purpose of our study was twofold. First, we assessed the ability to manage and operate a prototypic 3He gas polarizer in a clinical environment to routinely and reliably deliver polarized gas for imaging subjects in a 1.5-T MR imager. The MR imager included a broad-band spectroscopy option modified, in a straightforward manner, to operate at the resonant frequency of 48 MHz for 3He. Second, we investigated the application of hyperpolarized 3He MR imaging in a variety of subjects to assess the range of typical image features and variants that can be expected, as a foundation for developing an understanding of the capabilities of 3He imaging for depiction and evaluation of lung air space anatomy, ventilatory function, and pathologic conditions.
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Materials and Methods |
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Gas Preparation and Delivery
Polarization of the 3He gas was performed with a prototypic system (Magnetic Imaging Technologies, Durham, NC) with use of the method of collisional spin exchange between 3He and an optically pumped rubidium vapor (2). For this process, 3He is enclosed in a cylindrical glass chamber, which is in a low magnetic field (approximately 10 G), at a pressure of approximately 8 atm. At this pressure, the rubidium absorption profile is broadened to provide an improved match to the broad-beam profile of the diode-array laser, thereby giving an increased light absorption efficiency. This glass chamber also contains trace amounts of rubidium and molecular nitrogen (N2 serves as a buffer gas to reduce optical deexcitation of the rubidium). Circularly polarized laser light, tuned to the D1 resonance of rubidium, illuminates the glass chamber which is heated to 200°C to produce a rubidium vapor density of roughly 1 ppm of the 3He density. Absorption of the laser light produces a high electronic polarization in the rubidium atoms by means of optical pumping (Fig 1). Subsequent gas collisions between the rubidium and 3He atoms then transfer some of this polarization to the 3He nuclei. The collisional spin exchange is very slow, with a typical time constant on the order of hours. After polarizing for 6–8 hours, the chamber is cooled to room temperature, which causes most of the vapor to condense out onto the walls of the cell so that an infinitesimal amount (<0.01 µg) of rubidium is introduced into the subject breathing the hyperpolarized 3He gas. As an additional precaution, the 3He gas is passed through a 0.2-µm filter (Gelman Sciences, Ann Arbor, Mich) to ensure removal of any rubidium droplets from the gas stream. The prototypic polarization system is relatively compact, requiring approximately 30 sq ft (2.8 m2) for siting, including access for operation and service. The only special requirements for operation include a 220-V power source and compressed air.
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Imaging Equipment
The studies were performed by using a commercial 1.5-T whole-body imager (Magnetom Vision; Siemens Medical Systems, Iselin, NJ) modified to operate at 48 MHz by the addition of a broad-band radio-frequency amplifier. A prototypic, close-fitting, 48-MHz radio-frequency coil was used for data acquisition (Fig 2). This coil was a Helmholtz pair with an element diameter of 28.5 cm, which was large enough to cover the extent of the lungs in most subjects. The coil operated in a transmit-receive mode and was positioned with one coil element beneath the subject and the other coil element above. The separation between the elements was adjusted for the chest size of the subject.
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The MR protocols were approved by our institutional review board, and informed consent was obtained from all participants. Throughout each study, the subject's heart rate and blood oxygen saturation level were monitored. All procedures were supervised by a physician.
Image Review
The images were reviewed in consensus by two experienced radiologists (E.E.d.L., C.D.T.) who were blinded to any information about the subjects with respect to their age, sex, and clinical data, if any. One of the observers had considerable experience in MR imaging and relatively little experience in scintigraphy, and the second observer had considerable experience in ventilation scintigraphy and relatively little experience in MR imaging. They assessed together (at the same time) whether the distribution of the inhaled 3He gas in the lungs, the visualization of the trachea and first degree bronchi, the coverage of the two lungs by the radio-frequency coil, and the overall diagnostic quality of the images was good, moderate, or poor. In addition, assessments were made whether the lung fissures were visualized over their entire extent, partially, or not at all, and whether there were large, moderate, or small ventilation defects. Assessments were also made as to whether there were artifacts caused by motion of the heart or great vessels that were substantial enough to interfere with image interpretation or whether these artifacts were mild or absent. The reviewers also evaluated in consensus whether there were any apparent differences in image quality and depiction of the lungs between the two-dimensional FLASH and interleaved echo-planar sequences. Subsequently, to test the ability to assess pathologic findings in a reproducible manner on hyperpolarized 3He images, the two reviewers were asked, several weeks after the consensus review, to score independently the severity of lung abnormalities (ie, ventilation defects) for each of the 32 studies. Grading was performed with a continuous 10-point scale in which the score of 1 represented no disease and the score of 10 represented severe disease.
Statistical Analysis
The degree of association between the two independent evaluations of the severity of lung defects was assessed with the Spearman rank correlation. This correlation measures the degree to which the reviewers agree on the ordering of the images from the least to the most severe lung defects.
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Results |
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Imaging Studies
The distribution of the gas was rated as good in 24 of the 32 studies (Fig 3), moderate in six, and poor in two. The lung fissures were seen over their entire extent in six cases, over a large extent in 12, and over a small extent in six. The fissures could not be identified in the remaining eight studies. The trachea and first bronchi were visualized well in one case, relatively well in eight cases, and poorly in 13, and were not seen in 10. Defects were large in three studies, moderate in four, and small in three (Fig 4). The defects were most extensive in the patient with severe emphysema and corresponded to defects seen at xenon 133 ventilation (wash-in) scintigraphy several months earlier (Fig 5). In one of the healthy subjects, a few small defects were seen (Fig 6a); at 3He imaging 1 week later, the defects had disappeared but several new defects, including a large one, were seen in different areas of the lungs (Fig 6b). Upon further questioning, the volunteer indicated that she had a history of asthma and had been experiencing mild seasonal allergies without noticeable pulmonary symptoms. At repeat follow-up 3He MR examination 1 week after the second study, the defects had disappeared and all symptoms had subsided (Fig 6c). In all healthy subjects, the gas was noted to be present in all areas of the lungs including those most peripheral, Iin all cases with ventilation defects, the noninvolved portions of the lungs were well visualized. This indicates that the single breath hold of the hyperpolarized gas was sufficient to fill all functioning lung spaces. Motion artifacts (pulsation artifacts from the heart or great vessels against the lung) that interfered with image interpretation were substantial in three studies, mild in two, and absent in the remaining 27. Coverage of the 28.5-cm Helmholtz coil was good in 24 studies, moderate in seven, and poor in one study. The overall diagnostic quality was rated as good for 28 studies, moderate for three, and poor for one study, which was performed at the beginning of our experiments. No apparent differences in image quality and lung depiction were noted with the two-dimensional FLASH versus the interleaved echo-planar sequences (Fig 7).
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Discussion |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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In this study, we found that there was good alveolar distribution of the gas in the majority of cases after a single inhalation and breath hold of the hyperpolarized 3He gas. The images were believed to be of diagnostic quality with good visualization of the air spaces and lung fissures and with very few artifacts from cardiac motion or the pulsating great vessels. Even in the cases with patchy and wedge-shaped ventilation defects, signal intensity from the gas was noted in the periphery of the remaining areas of the lung, indicating that the gas penetration into those areas of the lung was sufficient after a single inhalation. This is not unexpected as helium gas diffuses quickly (approximately 1 mm/msec). In the majority of our studies, imaging was performed with 1 L of 10%–25% hyperpolarized gas; however, no substantial differences in gas distribution were noted in the few cases in which the volume of gas was varied. Although none of our participants experienced any problems inhaling the gas in the volumes provided, it is possible that problems may occur in patients with breathing difficulties. With higher polarizations, however, it is expected that smaller volumes of gas can be used to provide the same imaging results.
In our study, we used a prototypic 28.5-cm Helmholtz coil. For some subjects, this coil was too small, resulting in incomplete coverage of the lungs (Fig 4a). Also, in some cases there was increased signal intensity in the anterior or posterior portions of the lungs due to the proximity of the coil elements to the chest wall or the back (Figs 3b, 3c, 4b). Similar artifacts are also observed frequently with commercial body phased-array coils. Additional limitations of the coil are that it has a linearly polarized design, which does not take advantage of state-of-the-art coil technology such as circularly polarized or phased-array designs.
In a number of our studies, particularly in the ones involving the subjects with a history of smoking, patchy and wedge-shaped ventilation defects were seen. These defects were readily depicted and they were most prominent in the patient with the clinical diagnosis of emphysema. It is most likely that the defects in these cases were based on ventilatory disturbances caused by destruction of lung tissue that typically occurs with smoking. These findings, which have also been observed by others (6,7) performing noble gas MR imaging, are likely to be permanent. Since we did not perform repeat MR imaging in the patients with presumed destructive lung disease, we have no proof that the defects were indeed fixed. In the patient with severe emphysema, however, the fact that similar abnormalities were also seen on the 133Xe wash-in scintigraphic image obtained several months earlier supports the permanent character of the lesions (Fig 5). Findings at 133Xe imaging are usually very reproducible on repeat studies in patients with emphysema. Transient ventilation defects were also observed in our study, as in our healthy subject with mild seasonal allergies. Although the cause of these defects is unknown, it is likely that they were due to mucous plugging or bronchospasm, processes that are also transient and typically can occur in patients with asthma. The results of our interobserver correlation testing showed that assessment of abnormalities by the two reviewers was performed with only little variation between observers. This suggests that interpretation of the images was reproducible, which is important if this technique is to become clinically useful.
In imaging with hyperpolarized gas, the available magnetization is determined by the gas polarization achieved by the laser process; therefore, there are particular issues with respect to the choice of pulse sequence technique. In fact, hyperpolarized gas imaging is analogous to the situation with magnetization-preparation sequences since the magnetization is obtained independent of and prior to the actual acquisition. Therefore, the use of a low-flip-angle pulse sequence is one straightforward approach to ensure sufficient magnetization is available for all lines in k space. Use of a conventional spin-echo sequence is not appropriate since each 180° pulse would invert the longitudinal magnetization remaining in the image section for the other k-space lines. In addition, because of the many air-tissue interfaces in the lung, susceptibility effects are potentially large, contributing to a short T2* and strongly influencing the appropriate choice of echo time and bandwidth in the sequence for 3He imaging in the lung. However, rapid diffusion of the 3He gas will tend to average these susceptibility gradients on a local level and, therefore, reduce the severity of this constraint.
In the majority of our studies, we used a low-flip-angle, gradient-echo sequence (FLASH) with section-sequential or section-interleaved acquisition, providing sufficient numbers of image sections to cover the lungs in a single 15–22-second breath hold. (We found that a section-sequential, as opposed to section-interleaved, acquisition was beneficial for minimizing motion artifacts from the heart and great vessels. In contrast to conventional proton imaging, the difference in repetition time [13.3 vs 120 msec] between these acquisition modes is irrelevant due to the nature of the hyperpolarized magnetization.) However, since these imaging times may still be relatively long for individuals with breathing difficulties, implementation of faster techniques is crucial. As demonstrated, we evaluated an interleaved, echo-planar, gradient-echo pulse sequence and found that it provides similar quality and the same number of image sections as does the FLASH sequence, but in a much shorter, 5–10-second breath hold.
Recently, another MR-based technique for depicting lung ventilation has been developed that relies on the paramagnetic properties of molecular oxygen, or O2, to visualize the lung air spaces (11,12). Hyperpolarized 129Xe has also been used to visualize the air spaces in humans (9). Further development and evaluation of these methods, as well as the method with hyperpolarized 3He, will be required to determine the relative merits of each technique.
In conclusion, with use of hyperpolarized 3He, high-quality lung images can be consistently obtained and ventilatory abnormalities readily depicted, making this technique potentially useful for evaluating pulmonary disease. Hyperpolarized 3He, generated with a compact prototypic polarization system, was used in this study to routinely and reliably produce diagnostic-quality MR images of the air spaces of the lung. The images were rapidly obtained and provided better spatial resolution than is generally possible with 133Xe scintigraphy, currently the most often used ventilation imaging technique. Since MR imaging with hyperpolarized 3He gas has the potential to show the acinar units of the lungs, it is likely that the technique will become particularly useful for evaluating small airways disease such as emphysema, asthma, or cystic fibrosis. However, a limitation is that the gas is relatively expensive (about $100 per liter) due to the limited world supply. Recycling of the 3He gas is likely to reduce the cost. Nevertheless, it is expected that substantial improvements will be possible with further optimization of pulse sequence techniques and coils, providing high-resolution MR images of the lung air spaces with use of smaller gas volumes and shorter acquisition times than were possible in the current study.
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Acknowledgments |
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Footnotes |
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Address reprint requests to E.E.d.L.
From the 1998 RSNA scientific assembly.
Abbreviation: FLASH = fast low-angle shot
Author contributions: Guarantors of integrity of entire study, E.E.d.L., J.P.M., J.R.B.; study concepts and design, E.E.d.L., J.P.M., J.R.B., T.M.D.; definition of intellectual content, E.E.d.L.; literature research, E.E.d.L., J.P.M., J.R.B.; clinical studies, E.E.d.L., J.D.T., T.M.D.; experimental studies, J.P.M., J.R.B., P.L.B., J.K.S., G.D.C.; data acquisition, E.E.d.L., J.P.M., J.R.B., C.D.T., P.L.B., J.K.S., G.D.C.; data analysis, E.E.d.L., J.P.M., J.R.B.; manuscript preparation, E.E.d.L.; manuscript editing, E.E.d.L., J.P.M., J.R.B.; manuscript review, J.D.T., C.D.T., T.M.D.
Received February 25, 1998;
revision requested April 27, 1998; revision received July 21, 1998;
accepted September 28, 1998.
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References |
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TOPAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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