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Functional Magnetic Resonance Imaging of the Lung C. P. Heussel, MD2,4
M. Puderbach, MD2,4
1 Department of Diagnostic and Interventional Radiology, Section of
Pulmonary Imaging, University of Heidelberg, Heidelberg, Germany 2 Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany 3 Department of Radiology, German Cancer Research Center, Heidelberg, Germany 4 Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany
M. O. Wielpuetz, MD1,2
Address for correspondence J. Biederer, MD, Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany (e-mail: [email protected]).
Semin Respir Crit Care Med 2014;35:74–82.
Abstract
Keywords
► ► ► ►
functional MRI lung ventilation perfusion respiratory mechanics
Beyond being a substitute for X-ray, computed tomography, and scintigraphy, magnetic resonance imaging (MRI) inherently combines morphologic and functional information more than any other technology. Lung perfusion: The most established method is firstpass contrast-enhanced imaging with bolus injection of gadolinium chelates and timeresolved gradient-echo (GRE) sequences covering the whole lung (1 volume/s). Images are evaluated visually or semiquantitatively, while absolute quantification remains challenging due to the nonlinear relation of T1-shortening and contrast material concentration. Noncontrast-enhanced perfusion imaging is still experimental, either based on arterial spin labeling or Fourier decomposition. The latter is used to separate high- and low-frequency oscillations of lung signal related to the effects of pulsatile blood flow. Lung ventilation: Using contrast-enhanced first-pass perfusion, lung ventilation deficits are indirectly identified by hypoxic vasoconstriction. More direct but still experimental approaches use either inhalation of pure oxygen, an aerosolized contrast agent, or hyperpolarized noble gases. Fourier decomposition MRI based on the lowfrequency lung signal oscillation allows for visualization of ventilation without any contrast agent. Respiratory mechanics: Time-resolved series with high background signal such as GRE or steady-state free precession visualize the movement of chest wall, diaphragm, mediastinum, lung tissue, tracheal wall, and tumor. The assessment of volume changes allows drawing conclusions on regional ventilation. With this arsenal of functional imaging capabilities at high spatial and temporal resolution but without radiation burden, MRI will find its role in regional functional lung analysis and will therefore overcome the sensitivity of global lung function analysis for repeated shortterm treatment monitoring.
Among the imaging modalities available for the lung, magnetic resonance imaging (MRI) was the latest that has been introduced into clinical practice.1 Its value as an alternative imaging modality to X-ray, computed tomography (CT), or
Issue Theme Thoracic Imaging; Guest Editor, Martine Remy-Jardin, MD, PhD
scintigraphy is well acknowledged for several pathologies such as pulmonary embolism, bronchiectasis, pneumonia, etc., in cases when radiation exposure plays a relevant role or the administration of iodinated contrast material is
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1363453. ISSN 1069-3424.
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J. Biederer, MD1,2,3
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availability of 3He make hyperpolarized gas MRI (HP-MRI) a sophisticated tool restricted to specialized research sites and trials.
Magnetic Resonance Imaging of Lung Perfusion Lung perfusion studies to be performed with 1H-MRI are based on either first-pass perfusion contrast-enhanced imaging, arterial spin labeling (ASL), or Fourier decomposition. The first uses the clinically established contrast materials based on gadolinium chelates.5,10–12 Dynamic first-pass perfusion MRI is performed with an intravenous bolus injection of the contrast agent during continuous T1-weighted ultrashort TR and TE gradient-echo (GRE) imaging.13 For optimum contrast, it has been recommended to use a power injector and selected injection protocols.14 Limited to one plane, the socalled two-dimensional (2D) dynamic perfusion MRI covering selected lung sections reaches a temporal resolution of up to 10 images/s with reasonable spatial resolution.15 However, coverage of the complete lung volume needs multiple series and contrast injections, which are usually not feasible. Therefore, the representative imaging planes have to be carefully selected. Dynamic acquisitions of three-dimensional (3D) GRE perfusion MRI with series of full volumes and complete coverage of the lung are realized at the cost of temporal and in-plane resolution.16,17 Parallel imaging and view sharing technology allow for dynamic volume studies around one full lung volume per second. The visual evaluation of the image sets is facilitated by subtraction of the nonenhanced from the contrast-enhanced image signal, which results in a bright display of the contrast-enhanced lung vessels and parenchyma (►Fig. 1). Semiquantitative analysis of contrast-enhanced studies is based on the calculation of signal-time curves, signal-to-noise ratios, and contrast-to-noise ratios with region-of-interest analysis of lung tissue signal. An example outlining the clinical value of lung perfusion studies with
Fig. 1 Contrast-enhanced MRI perfusion study of the lung in a 47-year-old female patient with Osler disease who had recently received arteriovenous malformation embolization of the right lower lobe. (A) On the left, a coronal T2-weighted breath hold image demonstrating tortuous, enlarged vessels in segment 10 of the right lung (circled). (B) The subtracted image of the dynamic perfusion study at 1.4 volumes per second showing a perfusion deficit of the embolized segment. (C, D) Sagittal and coronal reconstructions were obtained from a 20s breath hold 3D high spatial resolution angiogram with bolus time set to peak in the pulmonary vasculature. MRI, magnetic resonance imaging; 3D, threedimensional.
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contraindicated. However, beyond being a substitute for other imaging modalities, MRI combines morphologic and functional information inherently and more consequently than any other technology.2 Currently, functional MRI of the lung is being transformed from a powerful research tool into clinical routine application. Basically, MRI of lung morphology uses the resonant high-frequency signal of protons in tissues and liquids. With the recent technical advances, the inherent limitations of lung MRI have been tackled, as they are defined by the low 1H-density in the lung and the fast signal decay related to susceptibility artifacts at air-tissue interfaces.3 Beyond imaging lung morphology, the currently recommended standard protocols already comprise elements that enhance the scope of the study by volumetric physiological information. Some of the more sophisticated techniques for research can be readily applied with state-of-the-art clinical MRI scanners; others require significant investments into additional hardware and skilled personnel. 1 H-MRI with paramagnetic contrast agents is being increasingly used on a routine basis. Gadolinium-containing chelates are applied to increase the signal of blood and are particularly useful for perfusion imaging.4,5 Perfusion, ventilation (including ventilation/perfusion [V/Q] ratio),6 gas diffusion for the assessment of lung microstructure (apparent diffusion coefficient [ADC]),7 oxygen concentration,8 and respiratory mechanics can be assessed regionally with specific modifications of contrast-enhanced as well as noncontrast-enhanced 1H-MRI.9 This potential holds great advantages over spirometric pulmonary function testing, which can only provide information on global lung function. Beyond this, scanners with appropriate hardware can be tuned to other nuclei of uneven atomic number than 1H using different resonance frequencies. Gases and liquids with high fluorine content (19F), for example, the inert gas SF6, can be visualized within the airspace directly. Imaging based on hyperpolarized 3He and 129Xe gas provides fascinating insights into pulmonary ventilation, gas exchange, and diffusion—however, hardware investments as well as the limited
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visual and semiquantitative evaluation is the assessment of lung perfusion deficits in cystic fibrosis (CF) patients who suffer from mucus retention and hypoxic vasoconstriction.4,18,19 For quantitative perfusion analysis, it was suggested to use the indicator dilution principle.20 Unfortunately, the relationship between signal intensity and the concentration of the contrast agent in MRI is not linear, which makes the exact calculation of quantitative indices, such as relative regional transit time, blood volume, and blood flow far more difficult than with CT.21 Changes in lung perfusion within a short time scale cannot be monitored with contrast-enhanced studies, since the injectable amount of contrast material is limited and recirculation of the material after the first-pass biases following measurements. Currently, semiquantitative measures based on subtracted perfusion datasets yield easy application and good inter-reader reproducibility.22 For this and other reasons, noncontrast-enhanced techniques are most welcome.
Arterial Spin Labeling ASL is based on intrinsic contrast of magnetized, inflowing blood into the imaging plane or volume. The robustness of the technique against artifacts, spatial resolution, and signal to noise is inferior to contrast-enhanced dynamic perfusion imaging, but the technology has specific advantages: Since ASL does not need application of contrast materials, it allows for prolonged studies with virtually unlimited repetition of measurements.23 For instance, ASL has been successfully applied to study the effects of inhaled oxygen concentration and physical exercise on ventilation–perfusion heterogeneity of the lungs in healthy human subjects.24–26 Despite its successful implementation for scientific studies, ASL of the lungs has not yet made its way into clinical applications. Fourier decomposition MRI—another noncontrast-dependent technique—translates periodic signal alterations recorded with a 2D steady-state free-precession sequence into perfusion- and ventilation-weighted images.27 This technique will be described in more detail in a dedicated section below.
Magnetic Resonance Imaging of Lung Ventilation Since air has no signal in 1H-MRI, lung ventilation can be either estimated from regional signal changes dependent on gas, tissue, and blood content, from signal changes after inhalation of gases (e.g., pure oxygen, hyperpolarized noble, or fluorinated gases), or an aerosol of a paramagnetic contrast agent. Indirectly, hypoxic vasoconstriction in hypoventilated areas of the lung would result in a secondary perfusion deficit that can be detected by contrast-enhanced first-pass perfusion imaging. However, based on the perfusion techniques alone, it might be difficult to distinguish secondary from primary perfusion deficits.
Estimating Regional Lung Ventilation by Volume Changes Principally, fast 2D and 3D imaging techniques should allow estimates of regional ventilation from regional lung volume Seminars in Respiratory and Critical Care Medicine
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changes.28 This would require full lung coverage with adequate spatial and temporal resolution for computer-aided segmentation of lung subvolumes, but this has not been realized so far. Further developments in scanner technology may be needed to make this approach more easily applicable.29
O2 Magnetic Resonance Imaging Oxygen-enhanced MRI is based on the changes in T1-signal by physically resolved O2 in tissues and liquids (i.e., blood). By subtraction of images obtained during inhalation of different concentrations of O2 (i.e., room air and 100% of O2), ventilated parts of the lung show signal changes related to a combination of ventilation, membrane function, and perfusion effects30 (►Fig. 2). However, it remains difficult to separate the superimposing contributions of the respective effects. A key technology to reduce respiratory displacement artifacts is motion compensation, for example, per respiration belt or navigator technique.31 Ohno et al have shown the potential of dynamic oxygen-enhanced MRI for local pulmonary functional loss assessment and clinical stage classification of smoking-related chronic obstructive pulmonary disease (COPD) (►Fig. 3).32
Gaseous and Aerosolized Contrast Agents Inhalation of appropriately aerosolized Gd-contrast material results in bright T1-signal of the lung where the material is retained. The feasibility of this has been evaluated in large animals and human volunteers showing homogeneous distribution of the signal in healthy subjects after several minutes of inhalation.33 In a large animal model, Gd-contrast aerosol in combination with first-pass CE-MR perfusion imaging has been successfully used to demonstrate homogeneous, but gravity-dependent aerosol deposition and perfusion. Regionally matched perfusion–ventilation deficits due to hypoxic vasoconstriction after occlusion of bronchi and regionally mismatched perfusion–ventilation after pulmonary arterial embolization could be distinguished.34 However, further evaluation is required to define the potential of the method for clinical application. Imaging the fluorine signal, for example, of inhaled SF6- or C2F6-gases (mixture of 70% gas—30% O2) or liquids35 has been used to directly visualize pulmonary airspace in animals and volunteers.36,37 Beyond simple visualization of the ventilated airspace, the dependence of the fluorine T1-signal on the local SF6 partial pressure has been used to calculate high-resolution V/Q maps in a rat model for hypoxic vasoconstriction with 2 mm isotropic resolution.38 Experience in patients is so far not available. One disadvantage of fluorine MRI is the necessary development of software and eventually investment into hardware to enable the MR system for multinuclear imaging. A fascinating success was the introduction of positive ventilated airspace contrast with hyperpolarized noble gases. Hyperpolarization can be achieved by optical pumping which results in a higher degree (by orders of magnitude) of alignment of magnetically active nuclei in the gas. This can be exploited to produce a positive image of the gas volume, for example, the ventilated airspace after inhalation39
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Fig. 2 Respiration-triggered oxygen-enhanced 1H-MRI of the lung in a healthy volunteer (A, B) and a patient with idiopathic pulmonary fibrosis (C, D). Proton-density–based images of lung morphology (A, C) and quantitative evaluation of signal intensity change after inhalation of pure O2 (B, D). Areas of diminished signal changes are indicative of ventilation defects in idiopathic pulmonary fibrosis (D). MRI, magnetic resonance imaging. (Image courtesy of Francesco Molinari, Catholic University of Rome, Gemelli Hospital, Rome, Italy.)
(►Fig. 4). Unfortunately, spin polarization of the gas volume is finite and decays quantitatively with each radio frequency (RF) pulse of the MR system.40 This RF depletion decay has to be taken in account for quantitative studies. Of the available gases, 3He and 129Xe both have specific advantages and
disadvantages. 3He allows for a higher polarization, can be stored more easily, and has a very attractive safety profile,41 but worldwide resources are physically limited. Large quantities have been reserved by US authorities for the construction of specific detectors for radioactive materials at border
Fig. 3 O 2-enhanced MRI in a 62-year-old male patient with cigarette smoke-related COPD (FEV1% of 65%). Color-coded maps of the T1 time of the lung parenchyma when breathing room air (A) and 15 L of pure O2 supplemented by a mask over 10 minutes (B). An inhomogeneous distribution of T1 relaxation times is clearly visible (A), and areas with short T1 with room air and missing T1 shortening after O 2 inhalation (B) may represent hypoventilated lung, that is, emphysema in this case. COPD, chronic obstructive pulmonary disease. (Image courtesy of Simon Triphan, Heidelberg, Germany.)
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Fig. 4 (A–C) Examples of imaging ventilated lung airspace with hyperpolarized 3He MRI. Coronal images acquired at the level of the carina. (A) A 21-year-old healthy female patient, FEV1% ¼ 111%. (B) A 52-year-old female COPD patient, FEV1% ¼ 30%. (C) A 16-year-old female cystic fibrosis patient, FEV1% ¼ 74%. COPD, chronic obstructive pulmonary disease. (Image courtesy of Tallisa Altes, University of Virginia, VA.)
controls. 129Xe is instead more easily available and compact systems for hyperpolarization are offered, but maximal hyperpolarization is lower and larger fractions of Xe in the inhaled air have anesthetic effects.42 A very interesting property of Xe is its solubility in blood. This potentially allows for further applications such as assessment of gas exchange.43
HP-MRI can be used not only to visualize the ventilated air space but also its potential for quantification of regional lung function.44 First of all, regional fractional ventilation can be calculated based on the dependence of MR signal on the volumes and the degree of hyperpolarization of the inhaled gas. Like in
Fig. 5 Noncontrast-enhanced ventilation–perfusion MRI of the lung in a patient with acute pulmonary embolism. (A–C) The upper row of images was taken for clinical diagnosis, (D–F) the lower for follow-up after 6 months. (A, D) The coronal image acquired with a steady-state freeprecession sequence demonstrates a thrombus in the right lower lobe artery (circled) (A). Sagittal ventilation (B, E) and perfusion maps (C, F) show a clear ventilation–perfusion mismatch with normal ventilation signal (B) but absent perfusion signal inside the right lower lobe (C) at the time point of diagnosis (position of the diaphragm marked with dotted line). The clot (D) as well as the ventilation–perfusion mismatch (E, F) has dissolved at follow-up. (Image courtesy of Grzegorz Bauman, Heidelberg, Germany.) Seminars in Respiratory and Critical Care Medicine
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ventilation imaging as used in nuclear medicine, regional differences in airspace signal during inhalation of the gas are directly correlated with ventilation.45 Second, HP-MRI allows drawing conclusions on the microstructure of the lung. Since Brownian random motion of He atoms in free air encompasses distances larger than the diameter of an alveolus, diffusion-weighted HP-MRI can detected different signal characteristics of 3He in free space and inside intact lung tissue. From this baseline, changes in alveolar space (e.g., confluent loss of alveoli in emphysema patients) can be quantified resulting in the ADC.7,46 Third, the decay kinetics of 3He and 129Xe hyperpolarization can be correlated with oxygen concentration. Due to its paramagnetic properties, the signal loss is proportional to absolute oxygen concentration. Therefore, analysis of signal decay allows for an estimation of the local oxygen concentration,47 which would be of high interest in acute lung injury.35,48 Further advanced analysis, for example, calculation of regional V/Q can be derived from these measurements.49
NonContrast-Enhanced Ventilation–Perfusion Scanning—Poor Man’s “Have It All”? One of the latest developments in the field appears to be extremely promising: Noncontrast-enhanced ventilation– perfusion scanning is based on lung signal changes with inspiration depth (highest signal with lowest pulmonary air content in expiration) and heart action (lowest signal with
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maximum blood flow in systole).50 Both result in periodic changes of parenchyma signal that could be separated by means of Fourier decomposition—given that a registration step corrects for lung volume changes.27 Further image postprocessing produces ventilation- and perfusion-weighted maps for regional assessment of lung function (►Figs. 5 and 6). Principally, the Fourier-decomposed MRI has the potential to completely replace V/Q scintigraphy. Thus, the technology has recently been validated against single-photon emission CT perfusion and ventilation imaging,51 and against hyperpolarized 3He- and perfusion MRI.52 Preliminary results from examinations in children with CF are already available.53 Because this technique is neither dependent on the application of intravenous (or intra-alveolar) contrast nor on the patient’s compliance or radiation exposure, it appears to be an ideal candidate for serial examinations in interventional trials.
Magnetic Resonance Imaging of Respiratory Mechanics Time-resolved MRI of lung morphology became feasible with the latest technical advances, that is, parallel imaging and echo sharing which reduced the acquisition times for dynamic MRI. The technical options and limitations are the same as for contrast-enhanced perfusion imaging which is based on similar sequence techniques. Temporal resolutions of up to 10
Fig. 6 Deterioration of lung function in a female patient with cystic fibrosis lung disease documented by annual follow-up Fourier decomposition MRI. The top row (A, C, E) displays ventilation-weighted, the bottom row perfusion-weighted images (B, D, F). The initial examination (A, B) was acquired after diagnosis at the age of 2 years and 5 months. Only apical ventilation defects with mild corresponding hypoperfusion were evident. With disease progression ventilation and matching perfusion defects gradually increased. MRI, magnetic resonance imaging. (Image courtesy of Grzegorz Bauman, Heidelberg, Germany.) Seminars in Respiratory and Critical Care Medicine
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images/s in single slice studies (2D þ time) or 1 volume/s in volumetric technique (3D þ time) allow for respiratory motion analysis of the lung, chest wall, diaphragm, and eventually tumors.54,55 2D series with free breathing or respiratory instructions are used, for example, to verify chest wall adhesion by a tumor indicating eventually invasion or for analysis of respiratory mechanics.56 For example, the dynamic collapse of the large airways in tracheobronchomalacia may be examined with cine-MRI.57 Grid tagging techniques allow to visualize not only displacement but also 3D distortion of lung parenchyma; however, this requires very fast imaging since signal decay in the lung is very fast with short T2. Therefore, this technique has been proven to be most effective when combined with hyperpolarized gas imaging.58 Time-resolved 3D series are used to analyze spatial displacement. The potential overestimation of tumor size with motion-correlated partial volume effects and an underestimation of displacement due to temporal under-sampling are directly related to temporal resolution and will improve with further technical development.55 One of the most promising clinical applications will be radiotherapy planning for organs with respiration-correlated motion.59
resolution while the particular strength of MRI is the application without radiation exposure, allowing for repeated and prolonged measurements in healthy subjects and patients. With the range of technologies described above, MRI is a valuable method for a broad spectrum of clinical and scientific applications. For clinical use, it can be speculated that preferably the cheap, fast, robust, and easily to perform technologies will find broad acceptance. On the contrary, disease-specific protocols for extensive functional assessment of the cardiopulmonary system will be set up in specialized centers. So far, first-pass perfusion imaging has arrived in routine application. However, among the available techniques, Fourier decomposition MRI combines the capacity to show both, lung perfusion and ventilation, with the advantages of being cheap (no contrast material needed) and easy to acquire (free breathing). It, therefore, appears to be one of the most promising candidates for the near future.
Acknowledgments This publication was supported by grants from the Bundesministerium für Bildung und Forschung (BMBF) to the German Center for Lung Research (DZL; 82DZL00401, 82DZL00402, 82DZL00404) and the German Research Foundation (DFG; BI 1297/2–1 and 1297/2–2).
The Bigger Picture—Cardiopulmonary Imaging Lung function and cardiac function are inseparably connected, with many diseases commencing in one and affecting the other organ system with disease progression. In diseases such as pulmonary arterial hypertension (PAH), for example, MRI has already shown to have significant clinical impact, as it can be employed to detect pathologies which may lead to or may be secondary to PAH, in a combined approach assessing lung parenchyma and heart function.60 In the subgroup of chronic-thromboembolic pulmonary hypertension, MRI angiography has been shown to effectively display thrombi for surgery planning and to predict outcome after surgical thrombectomy.61 Pulmonary hypertension may also develop in patients with COPD, and it is known that right ventricular hypertrophy is among the earliest sign of a pressure increase in the pulmonary circulation.62 It is this understanding of COPD as a systemic disease, for example, that further emphasizes MRI’s potential for “one-stop-shop” functional assessment. Further studies are needed to customize and establish disease-specific MRI protocols to harvest MRI’s potential for regional assessment of lung function in routine patient care. Currently, a substudy within the multicenter trial “COSYCONET” is being conducted to assess the potential clinical value of functional MRI techniques compared with CT in up to 675 COPD patients.63
Conclusions
1 Biederer J, Beer M, Hirsch W, et al. MRI of the lung (2/3). Why …
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In conclusion, MRI is far more than just a valuable adjunct to CT and X-ray. Helical CT (i.e., with multiple row detector systems) remains the benchmark modality for clinical imaging of lung morphology with respect to spatial and temporal Seminars in Respiratory and Critical Care Medicine
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enhanced MRI with simultaneous cardiac and respiratory synchronization for the assessment of interstitial lung disease. J Magn Reson Imaging 2007;26(6):1523–1529 Ohno Y, Koyama H, Nogami M, et al. Dynamic oxygen-enhanced MRI versus quantitative CT: pulmonary functional loss assessment and clinical stage classification of smoking-related COPD. AJR Am J Roentgenol 2008;190(2):W93-9 Haage P, Karaagac S, Spüntrup E, Truong HT, Schmidt T, Günther RW. Feasibility of pulmonary ventilation visualization with aerosolized magnetic resonance contrast media. Invest Radiol 2005; 40(2):85–88 Suga K, Ogasawara N, Tsukuda T, Matsunaga N. Assessment of regional lung ventilation in dog lungs with Gd-DTPA aerosol ventilation MR imaging. Acta Radiol 2002;43(3):282–291 Heussel CP, Scholz A, Schmittner M, et al. Measurements of alveolar pO2 using 19F-MRI in partial liquid ventilation. Invest Radiol 2003;38(10):635–641 Wolf U, Scholz A, Heussel CP, Markstaller K, Schreiber WG. Subsecond fluorine-19 MRI of the lung. Magn Reson Med 2006;55(4): 948–951 Scholz A-W, Wolf U, Fabel M, et al. Comparison of magnetic resonance imaging of inhaled SF6 with respiratory gas analysis. Magn Reson Imaging 2009;27(4):549–556 Adolphi NL, Kuethe DO. Quantitative mapping of ventilationperfusion ratios in lungs by 19F MR imaging of T1 of inert fluorinated gases. Magn Reson Med 2008;59(4):739–746 Matsuoka S, Patz S, Albert MS, et al. Hyperpolarized gas MR Imaging of the lung: current status as a research tool. J Thorac Imaging 2009;24(3):181–188 van Beek EJR, Wild JM, Kauczor H-U, Schreiber W, Mugler JP III, de Lange EE. Functional MRI of the lung using hyperpolarized 3helium gas. J Magn Reson Imaging 2004;20(4):540–554 Lutey BA, Lefrak SS, Woods JC, et al. Hyperpolarized 3He MR imaging: physiologic monitoring observations and safety considerations in 100 consecutive subjects. Radiology 2008;248(2): 655–661 Hersman FW, Ruset IC, Ketel S, et al. Large production system for hyperpolarized 129Xe for human lung imaging studies. Acad Radiol 2008;15(6):683–692 Driehuys B, Möller HE, Cleveland ZI, Pollaro J, Hedlund LW. Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe. Radiology 2009;252(2):386–393 van Beek EJR, Dahmen AM, Stavngaard T, et al. Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial. Eur Respir J 2009;34(6):1311–1321 Haczku A, Emami K, Fischer MC, et al. Hyperpolarized 3He MRI in asthma measurements of regional ventilation following allergic sensitization and challenge in mice—preliminary results. Acad Radiol 2005;12(11):1362–1370 Mata JF, Altes TA, Cai J, et al. Evaluation of emphysema severity and progression in a rabbit model: comparison of hyperpolarized 3He and 129Xe diffusion MRI with lung morphometry. J Appl Physiol (1985) 2007;102(3):1273–1280 Eberle B, Markstaller K, Schreiber WG, Kauczor HU. Hyperpolarised gases in magnetic resonance: a new tool for functional imaging of the lung. Swiss Med Wkly 2001;131(35-36):503–509 Bruells CS, Rossaint R, Dembinski R. [Ventilation in acute respiratory distress. Lung-protective strategies]. Med Klin Intensivmed Notfmed 2012;107(8):596–602 Rizi RR, Baumgardner JE, Ishii M, et al. Determination of regional VA/Q by hyperpolarized 3He MRI. Magn Reson Med 2004;52(1): 65–72 Suga K, Ogasawara N, Okada M, Tsukuda T, Matsunaga N, Miyazaki M. Lung perfusion impairments in pulmonary embolic and airway obstruction with noncontrast MR imaging. J Appl Physiol (1985) 2002;92(6):2439–2451
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imaging: qualitative comparison of Fourier decomposition MR imaging with SPECT/CT in porcine lung. Radiology 2011;260(2): 551–559 Bauman G, Scholz A, Rivoire J, et al. Lung ventilation- and perfusion-weighted Fourier decomposition magnetic resonance imaging: in vivo validation with hyperpolarized 3He and dynamic contrast-enhanced MRI. Magn Reson Med 2013;69(1):229–237 Bauman G, Eichinger M, Deimling M. Non-contrast-enhanced lung perfusion MRI in comparison to contrast-enhanced MRI perfusion in young cystic fibrosis patients. Insights into Imaging 2010;1(1):S301 Fabel M, Wintersperger BJ, Dietrich O, et al. MRI of respiratory dynamics with 2D steady-state free-precession and 2D gradient echo sequences at 1.5 and 3. Tesla: an observer preference study. Eur Radiol 2009;19(2):391–399 Biederer J, Dinkel J, Remmert G, et al. 4D-Imaging of the lung: reproducibility of lesion size and displacement on helical CT, MRI, and cone beam CT in a ventilated ex vivo system. Int J Radiat Oncol Biol Phys 2009;73(3):919–926 Dinkel J, Hintze C, Tetzlaff R, et al. 4D-MRI analysis of lung tumor motion in patients with hemidiaphragmatic paralysis. Radiother Oncol 2009;91(3):449–454
of the pharynx and trachea in normal subjects and COPD patients: assessment by cine-MRI. Eur Radiol 2004;14(12):2188–2197 Cai J, Sheng K, Benedict SH, et al. Dynamic MRI of grid-tagged hyperpolarized helium-3 for the assessment of lung motion during breathing. Int J Radiat Oncol Biol Phys 2009;75(1):276–284 Cai J, McLawhorn R, Read PW, et al. Effects of breathing variation on gating window internal target volume in respiratory gated radiation therapy. Med Phys 2010;37(8):3927–3934 Nagendran J, Michelakis E. MRI: one-stop shop for the comprehensive assessment of pulmonary arterial hypertension? Chest 2007;132(1):2–5 Kreitner K-FJ, Ley S, Kauczor H-U, et al. Chronic thromboembolic pulmonary hypertension: pre- and postoperative assessment with breath-hold MR imaging techniques. Radiology 2004;232(2): 535–543 Vonk-Noordegraaf A, Marcus JT, Holverda S, Roseboom B, Postmus PE. Early changes of cardiac structure and function in COPD patients with mild hypoxemia. Chest 2005;127(6):1898–1903 Lorenz J, Bals R, Kauczor H-U, et al. [Meeting of experts on obstructive airway diseases: targets and methods]. Pneumologie 2012;66(9):526–538l
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Functional Magnetic Resonance Imaging of the Lung C. P. Heussel, MD2,4
M. Puderbach, MD2,4
1 Department of Diagnostic and Interventional Radiology, Section of
Pulmonary Imaging, University of Heidelberg, Heidelberg, Germany 2 Translational Lung Research Center (TLRC) Heidelberg, Member of the German Center for Lung Research (DZL), Heidelberg, Germany 3 Department of Radiology, German Cancer Research Center, Heidelberg, Germany 4 Department of Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik at University of Heidelberg, Heidelberg, Germany
M. O. Wielpuetz, MD1,2
Address for correspondence J. Biederer, MD, Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, D-69120 Heidelberg, Germany (e-mail: [email protected]).
Semin Respir Crit Care Med 2014;35:74–82.
Abstract
Keywords
► ► ► ►
functional MRI lung ventilation perfusion respiratory mechanics
Beyond being a substitute for X-ray, computed tomography, and scintigraphy, magnetic resonance imaging (MRI) inherently combines morphologic and functional information more than any other technology. Lung perfusion: The most established method is firstpass contrast-enhanced imaging with bolus injection of gadolinium chelates and timeresolved gradient-echo (GRE) sequences covering the whole lung (1 volume/s). Images are evaluated visually or semiquantitatively, while absolute quantification remains challenging due to the nonlinear relation of T1-shortening and contrast material concentration. Noncontrast-enhanced perfusion imaging is still experimental, either based on arterial spin labeling or Fourier decomposition. The latter is used to separate high- and low-frequency oscillations of lung signal related to the effects of pulsatile blood flow. Lung ventilation: Using contrast-enhanced first-pass perfusion, lung ventilation deficits are indirectly identified by hypoxic vasoconstriction. More direct but still experimental approaches use either inhalation of pure oxygen, an aerosolized contrast agent, or hyperpolarized noble gases. Fourier decomposition MRI based on the lowfrequency lung signal oscillation allows for visualization of ventilation without any contrast agent. Respiratory mechanics: Time-resolved series with high background signal such as GRE or steady-state free precession visualize the movement of chest wall, diaphragm, mediastinum, lung tissue, tracheal wall, and tumor. The assessment of volume changes allows drawing conclusions on regional ventilation. With this arsenal of functional imaging capabilities at high spatial and temporal resolution but without radiation burden, MRI will find its role in regional functional lung analysis and will therefore overcome the sensitivity of global lung function analysis for repeated shortterm treatment monitoring.
Among the imaging modalities available for the lung, magnetic resonance imaging (MRI) was the latest that has been introduced into clinical practice.1 Its value as an alternative imaging modality to X-ray, computed tomography (CT), or
Issue Theme Thoracic Imaging; Guest Editor, Martine Remy-Jardin, MD, PhD
scintigraphy is well acknowledged for several pathologies such as pulmonary embolism, bronchiectasis, pneumonia, etc., in cases when radiation exposure plays a relevant role or the administration of iodinated contrast material is
Copyright © 2014 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662.
DOI http://dx.doi.org/ 10.1055/s-0033-1363453. ISSN 1069-3424.
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J. Biederer, MD1,2,3
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availability of 3He make hyperpolarized gas MRI (HP-MRI) a sophisticated tool restricted to specialized research sites and trials.
Magnetic Resonance Imaging of Lung Perfusion Lung perfusion studies to be performed with 1H-MRI are based on either first-pass perfusion contrast-enhanced imaging, arterial spin labeling (ASL), or Fourier decomposition. The first uses the clinically established contrast materials based on gadolinium chelates.5,10–12 Dynamic first-pass perfusion MRI is performed with an intravenous bolus injection of the contrast agent during continuous T1-weighted ultrashort TR and TE gradient-echo (GRE) imaging.13 For optimum contrast, it has been recommended to use a power injector and selected injection protocols.14 Limited to one plane, the socalled two-dimensional (2D) dynamic perfusion MRI covering selected lung sections reaches a temporal resolution of up to 10 images/s with reasonable spatial resolution.15 However, coverage of the complete lung volume needs multiple series and contrast injections, which are usually not feasible. Therefore, the representative imaging planes have to be carefully selected. Dynamic acquisitions of three-dimensional (3D) GRE perfusion MRI with series of full volumes and complete coverage of the lung are realized at the cost of temporal and in-plane resolution.16,17 Parallel imaging and view sharing technology allow for dynamic volume studies around one full lung volume per second. The visual evaluation of the image sets is facilitated by subtraction of the nonenhanced from the contrast-enhanced image signal, which results in a bright display of the contrast-enhanced lung vessels and parenchyma (►Fig. 1). Semiquantitative analysis of contrast-enhanced studies is based on the calculation of signal-time curves, signal-to-noise ratios, and contrast-to-noise ratios with region-of-interest analysis of lung tissue signal. An example outlining the clinical value of lung perfusion studies with
Fig. 1 Contrast-enhanced MRI perfusion study of the lung in a 47-year-old female patient with Osler disease who had recently received arteriovenous malformation embolization of the right lower lobe. (A) On the left, a coronal T2-weighted breath hold image demonstrating tortuous, enlarged vessels in segment 10 of the right lung (circled). (B) The subtracted image of the dynamic perfusion study at 1.4 volumes per second showing a perfusion deficit of the embolized segment. (C, D) Sagittal and coronal reconstructions were obtained from a 20s breath hold 3D high spatial resolution angiogram with bolus time set to peak in the pulmonary vasculature. MRI, magnetic resonance imaging; 3D, threedimensional.
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contraindicated. However, beyond being a substitute for other imaging modalities, MRI combines morphologic and functional information inherently and more consequently than any other technology.2 Currently, functional MRI of the lung is being transformed from a powerful research tool into clinical routine application. Basically, MRI of lung morphology uses the resonant high-frequency signal of protons in tissues and liquids. With the recent technical advances, the inherent limitations of lung MRI have been tackled, as they are defined by the low 1H-density in the lung and the fast signal decay related to susceptibility artifacts at air-tissue interfaces.3 Beyond imaging lung morphology, the currently recommended standard protocols already comprise elements that enhance the scope of the study by volumetric physiological information. Some of the more sophisticated techniques for research can be readily applied with state-of-the-art clinical MRI scanners; others require significant investments into additional hardware and skilled personnel. 1 H-MRI with paramagnetic contrast agents is being increasingly used on a routine basis. Gadolinium-containing chelates are applied to increase the signal of blood and are particularly useful for perfusion imaging.4,5 Perfusion, ventilation (including ventilation/perfusion [V/Q] ratio),6 gas diffusion for the assessment of lung microstructure (apparent diffusion coefficient [ADC]),7 oxygen concentration,8 and respiratory mechanics can be assessed regionally with specific modifications of contrast-enhanced as well as noncontrast-enhanced 1H-MRI.9 This potential holds great advantages over spirometric pulmonary function testing, which can only provide information on global lung function. Beyond this, scanners with appropriate hardware can be tuned to other nuclei of uneven atomic number than 1H using different resonance frequencies. Gases and liquids with high fluorine content (19F), for example, the inert gas SF6, can be visualized within the airspace directly. Imaging based on hyperpolarized 3He and 129Xe gas provides fascinating insights into pulmonary ventilation, gas exchange, and diffusion—however, hardware investments as well as the limited
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visual and semiquantitative evaluation is the assessment of lung perfusion deficits in cystic fibrosis (CF) patients who suffer from mucus retention and hypoxic vasoconstriction.4,18,19 For quantitative perfusion analysis, it was suggested to use the indicator dilution principle.20 Unfortunately, the relationship between signal intensity and the concentration of the contrast agent in MRI is not linear, which makes the exact calculation of quantitative indices, such as relative regional transit time, blood volume, and blood flow far more difficult than with CT.21 Changes in lung perfusion within a short time scale cannot be monitored with contrast-enhanced studies, since the injectable amount of contrast material is limited and recirculation of the material after the first-pass biases following measurements. Currently, semiquantitative measures based on subtracted perfusion datasets yield easy application and good inter-reader reproducibility.22 For this and other reasons, noncontrast-enhanced techniques are most welcome.
Arterial Spin Labeling ASL is based on intrinsic contrast of magnetized, inflowing blood into the imaging plane or volume. The robustness of the technique against artifacts, spatial resolution, and signal to noise is inferior to contrast-enhanced dynamic perfusion imaging, but the technology has specific advantages: Since ASL does not need application of contrast materials, it allows for prolonged studies with virtually unlimited repetition of measurements.23 For instance, ASL has been successfully applied to study the effects of inhaled oxygen concentration and physical exercise on ventilation–perfusion heterogeneity of the lungs in healthy human subjects.24–26 Despite its successful implementation for scientific studies, ASL of the lungs has not yet made its way into clinical applications. Fourier decomposition MRI—another noncontrast-dependent technique—translates periodic signal alterations recorded with a 2D steady-state free-precession sequence into perfusion- and ventilation-weighted images.27 This technique will be described in more detail in a dedicated section below.
Magnetic Resonance Imaging of Lung Ventilation Since air has no signal in 1H-MRI, lung ventilation can be either estimated from regional signal changes dependent on gas, tissue, and blood content, from signal changes after inhalation of gases (e.g., pure oxygen, hyperpolarized noble, or fluorinated gases), or an aerosol of a paramagnetic contrast agent. Indirectly, hypoxic vasoconstriction in hypoventilated areas of the lung would result in a secondary perfusion deficit that can be detected by contrast-enhanced first-pass perfusion imaging. However, based on the perfusion techniques alone, it might be difficult to distinguish secondary from primary perfusion deficits.
Estimating Regional Lung Ventilation by Volume Changes Principally, fast 2D and 3D imaging techniques should allow estimates of regional ventilation from regional lung volume Seminars in Respiratory and Critical Care Medicine
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changes.28 This would require full lung coverage with adequate spatial and temporal resolution for computer-aided segmentation of lung subvolumes, but this has not been realized so far. Further developments in scanner technology may be needed to make this approach more easily applicable.29
O2 Magnetic Resonance Imaging Oxygen-enhanced MRI is based on the changes in T1-signal by physically resolved O2 in tissues and liquids (i.e., blood). By subtraction of images obtained during inhalation of different concentrations of O2 (i.e., room air and 100% of O2), ventilated parts of the lung show signal changes related to a combination of ventilation, membrane function, and perfusion effects30 (►Fig. 2). However, it remains difficult to separate the superimposing contributions of the respective effects. A key technology to reduce respiratory displacement artifacts is motion compensation, for example, per respiration belt or navigator technique.31 Ohno et al have shown the potential of dynamic oxygen-enhanced MRI for local pulmonary functional loss assessment and clinical stage classification of smoking-related chronic obstructive pulmonary disease (COPD) (►Fig. 3).32
Gaseous and Aerosolized Contrast Agents Inhalation of appropriately aerosolized Gd-contrast material results in bright T1-signal of the lung where the material is retained. The feasibility of this has been evaluated in large animals and human volunteers showing homogeneous distribution of the signal in healthy subjects after several minutes of inhalation.33 In a large animal model, Gd-contrast aerosol in combination with first-pass CE-MR perfusion imaging has been successfully used to demonstrate homogeneous, but gravity-dependent aerosol deposition and perfusion. Regionally matched perfusion–ventilation deficits due to hypoxic vasoconstriction after occlusion of bronchi and regionally mismatched perfusion–ventilation after pulmonary arterial embolization could be distinguished.34 However, further evaluation is required to define the potential of the method for clinical application. Imaging the fluorine signal, for example, of inhaled SF6- or C2F6-gases (mixture of 70% gas—30% O2) or liquids35 has been used to directly visualize pulmonary airspace in animals and volunteers.36,37 Beyond simple visualization of the ventilated airspace, the dependence of the fluorine T1-signal on the local SF6 partial pressure has been used to calculate high-resolution V/Q maps in a rat model for hypoxic vasoconstriction with 2 mm isotropic resolution.38 Experience in patients is so far not available. One disadvantage of fluorine MRI is the necessary development of software and eventually investment into hardware to enable the MR system for multinuclear imaging. A fascinating success was the introduction of positive ventilated airspace contrast with hyperpolarized noble gases. Hyperpolarization can be achieved by optical pumping which results in a higher degree (by orders of magnitude) of alignment of magnetically active nuclei in the gas. This can be exploited to produce a positive image of the gas volume, for example, the ventilated airspace after inhalation39
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Fig. 2 Respiration-triggered oxygen-enhanced 1H-MRI of the lung in a healthy volunteer (A, B) and a patient with idiopathic pulmonary fibrosis (C, D). Proton-density–based images of lung morphology (A, C) and quantitative evaluation of signal intensity change after inhalation of pure O2 (B, D). Areas of diminished signal changes are indicative of ventilation defects in idiopathic pulmonary fibrosis (D). MRI, magnetic resonance imaging. (Image courtesy of Francesco Molinari, Catholic University of Rome, Gemelli Hospital, Rome, Italy.)
(►Fig. 4). Unfortunately, spin polarization of the gas volume is finite and decays quantitatively with each radio frequency (RF) pulse of the MR system.40 This RF depletion decay has to be taken in account for quantitative studies. Of the available gases, 3He and 129Xe both have specific advantages and
disadvantages. 3He allows for a higher polarization, can be stored more easily, and has a very attractive safety profile,41 but worldwide resources are physically limited. Large quantities have been reserved by US authorities for the construction of specific detectors for radioactive materials at border
Fig. 3 O 2-enhanced MRI in a 62-year-old male patient with cigarette smoke-related COPD (FEV1% of 65%). Color-coded maps of the T1 time of the lung parenchyma when breathing room air (A) and 15 L of pure O2 supplemented by a mask over 10 minutes (B). An inhomogeneous distribution of T1 relaxation times is clearly visible (A), and areas with short T1 with room air and missing T1 shortening after O 2 inhalation (B) may represent hypoventilated lung, that is, emphysema in this case. COPD, chronic obstructive pulmonary disease. (Image courtesy of Simon Triphan, Heidelberg, Germany.)
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Fig. 4 (A–C) Examples of imaging ventilated lung airspace with hyperpolarized 3He MRI. Coronal images acquired at the level of the carina. (A) A 21-year-old healthy female patient, FEV1% ¼ 111%. (B) A 52-year-old female COPD patient, FEV1% ¼ 30%. (C) A 16-year-old female cystic fibrosis patient, FEV1% ¼ 74%. COPD, chronic obstructive pulmonary disease. (Image courtesy of Tallisa Altes, University of Virginia, VA.)
controls. 129Xe is instead more easily available and compact systems for hyperpolarization are offered, but maximal hyperpolarization is lower and larger fractions of Xe in the inhaled air have anesthetic effects.42 A very interesting property of Xe is its solubility in blood. This potentially allows for further applications such as assessment of gas exchange.43
HP-MRI can be used not only to visualize the ventilated air space but also its potential for quantification of regional lung function.44 First of all, regional fractional ventilation can be calculated based on the dependence of MR signal on the volumes and the degree of hyperpolarization of the inhaled gas. Like in
Fig. 5 Noncontrast-enhanced ventilation–perfusion MRI of the lung in a patient with acute pulmonary embolism. (A–C) The upper row of images was taken for clinical diagnosis, (D–F) the lower for follow-up after 6 months. (A, D) The coronal image acquired with a steady-state freeprecession sequence demonstrates a thrombus in the right lower lobe artery (circled) (A). Sagittal ventilation (B, E) and perfusion maps (C, F) show a clear ventilation–perfusion mismatch with normal ventilation signal (B) but absent perfusion signal inside the right lower lobe (C) at the time point of diagnosis (position of the diaphragm marked with dotted line). The clot (D) as well as the ventilation–perfusion mismatch (E, F) has dissolved at follow-up. (Image courtesy of Grzegorz Bauman, Heidelberg, Germany.) Seminars in Respiratory and Critical Care Medicine
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ventilation imaging as used in nuclear medicine, regional differences in airspace signal during inhalation of the gas are directly correlated with ventilation.45 Second, HP-MRI allows drawing conclusions on the microstructure of the lung. Since Brownian random motion of He atoms in free air encompasses distances larger than the diameter of an alveolus, diffusion-weighted HP-MRI can detected different signal characteristics of 3He in free space and inside intact lung tissue. From this baseline, changes in alveolar space (e.g., confluent loss of alveoli in emphysema patients) can be quantified resulting in the ADC.7,46 Third, the decay kinetics of 3He and 129Xe hyperpolarization can be correlated with oxygen concentration. Due to its paramagnetic properties, the signal loss is proportional to absolute oxygen concentration. Therefore, analysis of signal decay allows for an estimation of the local oxygen concentration,47 which would be of high interest in acute lung injury.35,48 Further advanced analysis, for example, calculation of regional V/Q can be derived from these measurements.49
NonContrast-Enhanced Ventilation–Perfusion Scanning—Poor Man’s “Have It All”? One of the latest developments in the field appears to be extremely promising: Noncontrast-enhanced ventilation– perfusion scanning is based on lung signal changes with inspiration depth (highest signal with lowest pulmonary air content in expiration) and heart action (lowest signal with
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maximum blood flow in systole).50 Both result in periodic changes of parenchyma signal that could be separated by means of Fourier decomposition—given that a registration step corrects for lung volume changes.27 Further image postprocessing produces ventilation- and perfusion-weighted maps for regional assessment of lung function (►Figs. 5 and 6). Principally, the Fourier-decomposed MRI has the potential to completely replace V/Q scintigraphy. Thus, the technology has recently been validated against single-photon emission CT perfusion and ventilation imaging,51 and against hyperpolarized 3He- and perfusion MRI.52 Preliminary results from examinations in children with CF are already available.53 Because this technique is neither dependent on the application of intravenous (or intra-alveolar) contrast nor on the patient’s compliance or radiation exposure, it appears to be an ideal candidate for serial examinations in interventional trials.
Magnetic Resonance Imaging of Respiratory Mechanics Time-resolved MRI of lung morphology became feasible with the latest technical advances, that is, parallel imaging and echo sharing which reduced the acquisition times for dynamic MRI. The technical options and limitations are the same as for contrast-enhanced perfusion imaging which is based on similar sequence techniques. Temporal resolutions of up to 10
Fig. 6 Deterioration of lung function in a female patient with cystic fibrosis lung disease documented by annual follow-up Fourier decomposition MRI. The top row (A, C, E) displays ventilation-weighted, the bottom row perfusion-weighted images (B, D, F). The initial examination (A, B) was acquired after diagnosis at the age of 2 years and 5 months. Only apical ventilation defects with mild corresponding hypoperfusion were evident. With disease progression ventilation and matching perfusion defects gradually increased. MRI, magnetic resonance imaging. (Image courtesy of Grzegorz Bauman, Heidelberg, Germany.) Seminars in Respiratory and Critical Care Medicine
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images/s in single slice studies (2D þ time) or 1 volume/s in volumetric technique (3D þ time) allow for respiratory motion analysis of the lung, chest wall, diaphragm, and eventually tumors.54,55 2D series with free breathing or respiratory instructions are used, for example, to verify chest wall adhesion by a tumor indicating eventually invasion or for analysis of respiratory mechanics.56 For example, the dynamic collapse of the large airways in tracheobronchomalacia may be examined with cine-MRI.57 Grid tagging techniques allow to visualize not only displacement but also 3D distortion of lung parenchyma; however, this requires very fast imaging since signal decay in the lung is very fast with short T2. Therefore, this technique has been proven to be most effective when combined with hyperpolarized gas imaging.58 Time-resolved 3D series are used to analyze spatial displacement. The potential overestimation of tumor size with motion-correlated partial volume effects and an underestimation of displacement due to temporal under-sampling are directly related to temporal resolution and will improve with further technical development.55 One of the most promising clinical applications will be radiotherapy planning for organs with respiration-correlated motion.59
resolution while the particular strength of MRI is the application without radiation exposure, allowing for repeated and prolonged measurements in healthy subjects and patients. With the range of technologies described above, MRI is a valuable method for a broad spectrum of clinical and scientific applications. For clinical use, it can be speculated that preferably the cheap, fast, robust, and easily to perform technologies will find broad acceptance. On the contrary, disease-specific protocols for extensive functional assessment of the cardiopulmonary system will be set up in specialized centers. So far, first-pass perfusion imaging has arrived in routine application. However, among the available techniques, Fourier decomposition MRI combines the capacity to show both, lung perfusion and ventilation, with the advantages of being cheap (no contrast material needed) and easy to acquire (free breathing). It, therefore, appears to be one of the most promising candidates for the near future.
Acknowledgments This publication was supported by grants from the Bundesministerium für Bildung und Forschung (BMBF) to the German Center for Lung Research (DZL; 82DZL00401, 82DZL00402, 82DZL00404) and the German Research Foundation (DFG; BI 1297/2–1 and 1297/2–2).
The Bigger Picture—Cardiopulmonary Imaging Lung function and cardiac function are inseparably connected, with many diseases commencing in one and affecting the other organ system with disease progression. In diseases such as pulmonary arterial hypertension (PAH), for example, MRI has already shown to have significant clinical impact, as it can be employed to detect pathologies which may lead to or may be secondary to PAH, in a combined approach assessing lung parenchyma and heart function.60 In the subgroup of chronic-thromboembolic pulmonary hypertension, MRI angiography has been shown to effectively display thrombi for surgery planning and to predict outcome after surgical thrombectomy.61 Pulmonary hypertension may also develop in patients with COPD, and it is known that right ventricular hypertrophy is among the earliest sign of a pressure increase in the pulmonary circulation.62 It is this understanding of COPD as a systemic disease, for example, that further emphasizes MRI’s potential for “one-stop-shop” functional assessment. Further studies are needed to customize and establish disease-specific MRI protocols to harvest MRI’s potential for regional assessment of lung function in routine patient care. Currently, a substudy within the multicenter trial “COSYCONET” is being conducted to assess the potential clinical value of functional MRI techniques compared with CT in up to 675 COPD patients.63
Conclusions
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In conclusion, MRI is far more than just a valuable adjunct to CT and X-ray. Helical CT (i.e., with multiple row detector systems) remains the benchmark modality for clinical imaging of lung morphology with respect to spatial and temporal Seminars in Respiratory and Critical Care Medicine
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