Neue Entwicklungen in der MRT des Thorax

MRI was not used often for lung imaging due to technical and physical limitations. Recent developments have considerably improved anatomical MR imaging, and at the same time new perspectives for functional imaging emerged. They consist of functional investigations of pulmonary perfusion (contrast agents, MR angiography) and ventilation (inhaled contrast aerosols, oxygen, hyperpolarized noble gases [He-3, Xe-129] and fluorinated gases [SF6]). New parameters can be measured: homogeneity of ventilation, lung volumes, airspace size, intrapulmonary oxygen partial pressure, dynamic ventilation distribution and ventilation/perfusion ratios. MRI-inherent advantages are: lack of radiation, high spatial and temporal resolution, and a broad range of functional information. MRI of lung ventilation seems to be more sensitive in the detection of ventilation defects than scintigraphy, CT or pulmonary function tests. By combining the new strategies the radiologist will be capable to improve specificity of the investigations and to characterize lung function impairments. The joint assessment of ventilation and perfusion will play a major role in this development.     

Contrast-enhanced MRI of the lung

The lung has long been neglected by MR imaging. This is due to unique intrinsic difficulties: (1) signal loss due to cardiac pulsation and respiration; (2) susceptibility artifacts caused by multiple air-tissue interfaces; (3) low proton density. There are many MR strategies to overcome these problems. They consist of breath-hold imaging, respiratory and cardiac gating procedures, use of short repetition and echo times, increase of the relaxivity of existing spins by administration of intravenous contrast agents, and enrichment of spin density by hyperpolarized noble gases or oxygen. Improvements in scanner performance and frequent use of contrast media have increased the interest in MR imaging and MR angiography of the lung. They can be used on a routine basis for the following indications: characterization of pulmonary nodules, staging of bronchogenic carcinoma, in particular assessment of chest wall invasion; evaluation of inflammatory activity in interstitial lung disease; acute pulmonary embolism, chronic thromboembolic pulmonary hypertension, vascular involvement in malignant disease; vascular abnormalities. Future perspectives include perfusion imaging using extracellular or intravascular (blood pool) contrast agents and ventilation imaging using inhalation of hyperpolarized noble gases, of paramagnetic oxygen or of aerosolized contrast agents. These techniques represent new approaches to functional lung imaging. The combination of visualization of morphology and functional assessment of ventilation and perfusion is unequalled by any other technique.     

MRI of the pulmonary parenchyma

Imaging of the pulmonary parenchyma represents a unique challenge for MRI. Limited signal is caused by low proton density, susceptibility artifacts, and physiological motion (cardiac pulsation, respiration). Recently, further improvements in MRI techniques have widened the potential for investigations of pulmonary parenchymal disease. These include very short echo times, ultrafast turbo-spin-echo acquisitions, projection reconstruction technique, breathhold imaging, ECG triggering, contrast agents (perfusion imaging, aerosols), sodium imaging, hyperpolarized noble gas imaging, and oxygen enhancement. By using widely available techniques, MRI is helpful in the assessment of (a) acute alveolitic processes in chronic infiltrative lung disease, (b) detection and characterization of pulmonary nodules, (c) detection, characterization, and follow-up of pneumonia, (d) differentiation of obstructive atelectasis from non-obstructive atelectasis and infarctions, and (e) measurements of lung water content. Chronic bronchitis, bronchiectasis, and emphysema are not readily assessable by routine MRI techniques. More sophisticated techniques are under investigation for MR imaging of pulmonary ventilation and perfusion. They represent the beginning of functional MR imaging of the lung which will be established in the future.     

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.     

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.     

Functional imaging of the lungs with gas agents

This review focuses on the state‐of‐the‐art of the three major classes of gas contrast agents used in magnetic resonance imaging (MRI)—hyperpolarized (HP) gas, molecular oxygen, and fluorinated gas—and their application to clinical pulmonary research. During the past several years there has been accelerated development of pulmonary MRI. This has been driven in part by concerns regarding ionizing radiation using multidetector computed tomography (CT). However, MRI also offers capabilities for fast multispectral and functional imaging using gas agents that are not technically feasible with CT. Recent improvements in gradient performance and radial acquisition methods using ultrashort echo time (UTE) have contributed to advances in these functional pulmonary MRI techniques. The relative strengths and weaknesses of the main functional imaging methods and gas agents are compared and applications to measures of ventilation, diffusion, and gas exchange are presented. Functional lung MRI methods using these gas agents are improving our understanding of a wide range of chronic lung diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis in both adults and children. J. Magn. Reson. Imaging 2016;43:295–315.     

Lung MRI for experimental drug research

Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal. Thus, a significant reduction in the number of animals used for experimentation is achieved, as well as minimal interference with their well-being and physiological status. In addition, under certain circumstances the duration of the observation period after disease onset can be shortened since the technique is able to detect changes before these are reflected in parameters of inflammation determined using invasive procedures. The objective of this article is to briefly address MRI techniques that are being used in experimental lung research, with special emphasis on applications. Following an introduction on proton techniques and MRI of hyperpolarized gases, the attention is shifted to the MRI analysis of several aspects of lung disease models, including inflammation, ventilation, emphysema, fibrosis and sensory nerve activation. The next subject concerns the use of MRI in pharmacological studies within the context of experimental lung research. A final discussion points towards advantages and limitations of MRI in this area.     

Lung MRI for experimental drug research

Current techniques to evaluate the efficacy of potential treatments for airways diseases in preclinical models are generally invasive and terminal. In the past few years, the flexibility of magnetic resonance imaging (MRI) to obtain anatomical and functional information of the lung has been explored with the scope of developing a non-invasive approach for the routine testing of drugs in models of airways diseases in small rodents. With MRI, the disease progression can be followed in the same animal. Thus, a significant reduction in the number of animals used for experimentation is achieved, as well as minimal interference with their well-being and physiological status. In addition, under certain circumstances the duration of the observation period after disease onset can be shortened since the technique is able to detect changes before these are reflected in parameters of inflammation determined using invasive procedures. The objective of this article is to briefly address MRI techniques that are being used in experimental lung research, with special emphasis on applications. Following an introduction on proton techniques and MRI of hyperpolarized gases, the attention is shifted to the MRI analysis of several aspects of lung disease models, including inflammation, ventilation, emphysema, fibrosis and sensory nerve activation. The next subject concerns the use of MRI in pharmacological studies within the context of experimental lung research. A final discussion points towards advantages and limitations of MRI in this area.     

Laser-polarized (3)He as a probe for dynamic regional measurements of lung perfusion and ventilation using magnetic resonance imaging.

Magnetic resonance imaging (MRI) using laser-polarized noble gases, such as (129)Xe and (3)He, allows unparalleled noninvasive information on gas distribution in lung airways and distal spaces. In addition to pulmonary ventilation, lung perfusion assessment is crucial for proper diagnosis of pathological conditions, such as pulmonary embolism. Magnetic resonance perfusion imaging usually can be performed using techniques based on the detection of water protons in tissues. However, lung proton imaging is extremely difficult due to the low proton density and the magnetically inhomogeneous structure of the lung parenchyma. Here we show that laser-polarized (3)He can be used as a noninvasive probe to image, in a single MRI experiment, not only the ventilation but also the perfusion state of the lungs. Blood volume maps of the lungs were generated based on the (3)He signal depletion during the first pass of a superparamagnetic contrast agent bolus. The combined and simultaneous lung ventilation and perfusion assessments are demonstrated in normal rat lungs and are applied to an experimental animal model of pulmonary embolism. Magn Reson Med 44:1-4, 2000.     

The role of hyperpolarized 129xenon in MR imaging of pulmonary function

In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (³He) and xenon (¹²⁹Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available ¹²⁹Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP ¹²⁹Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP ¹²⁹Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP ¹²⁹Xe MRI, and (4) propose clinical applications.     

Functional MR imaging of pulmonary ventilation using hyperpolarized noble gases

The current status of experimental and clinical applications for functional MR imaging of pulmonary ventilation using hyperpolarized noble gases are reviewed. 3-helium (3He) and 129-xenon (129Xe) can be hyperpolarized by optical pumping techniques such as spin exchange or metastability exchange in sufficient amounts. This process leads to an artificial, non-equilibrium increase of the density of excited nuclei which represents the source of the MR signal. Those hyperpolarized gases are administered mostly via inhalation, and will fill airways and airspaces allowing for ventilation imaging. Recent human studies concentrate on imaging the airways and airspaces with high spatial resolution. Normal ventilation is reflected by an almost complete and homogeneous distribution of the hyperpolarized gas represented by the signal detected. Loss of signal or inhomogeneous signal distribution represent mass effects and ventilatory abnormalities. Even healthy subjects with seasonal allergies without pulmonary symptoms have been observed to exhibit transient ventilation defects. Real-time imaging of ventilation has become feasible for 3He MR imaging and allows for assessment of ventilation-distribution. Furthermore, functional oxygen-sensitive 3He MR imaging opens the field of non-invasive assessment of regional intrapulmonary oxygen concentrations in vivo. Knowing that the diffusion of gas is affected by the geometry and nature of its environment, diffusion measurements are under investigation as a sensitive marker of diseases that involve structural changes of lung parenchyma, such as emphysema and fibrosis. Whereas 3He is not absorbed and is restricted to the airspaces, 129Xe is soluble in blood and lipid-rich tissue. This presents the opportunity for additional dissolved-phase imaging, providing a step towards simultaneous ventilation-perfusion studies.     

MRI using hyperpolarized noble gases

The aim of this study was to review the physical basis of MRI using hyperpolarized noble gases as well as the present status of preclinical and clinical applications. Non-radioactive noble gases with a nuclear spin 1/2 (He-3, Xe-129) can be hyperpolarized by optical pumping. Polarization is transferred from circularly polarized laser light to the noble-gas atoms via alkali-metal vapors (spin exchange) or metastable atoms (metastability exchange). Hyperpolarization results in a non-equilibrium polarization five orders of magnitude higher than the Boltzmann equilibrium compensating for the several 1000 times lower density of noble gases as compared with liquid state hydrogen concentrations in tissue and allows for short imaging times. Hyperpolarization can be stored sufficiently long (3 h to 6 days) to allow for transport and application. Magnetic resonance systems require a broadband radio-frequency system – which is generally available for MR spectroscopy – and dedicated coils. The hyperpolarized gases are administered as inhalative “contrast agents” allowing for imaging of the airways and airspaces. Besides the known anesthetic effect of xenon, no adverse effects are observed in volunteers or patients. Pulse sequences are optimized to effectively use the non-renewable hyperpolarization before it decays or is destroyed, using fast low-flip-angles strategies to allow for dynamic/breath-hold imaging of highly diffusible (He) or soluble (Xe) gases with in vivo T1-times well below 1 min. Since helium is not absorbed in considerable amounts, its application is restricted to the lung. Xe-129 is also under investigation for imaging of white matter disease and functional studies of cerebral perfusion. Magnetic resonance imaging using hyperpolarized gases is emerging as a technical challenge and opportunity for the MR community. Preliminary experience suggests potential for functional imaging of pulmonary ventilation and cerebral perfusion. Received 10 September 1997; Revision received 24 November 1997; Accepted 1 December 1997     

Noninvasive mapping of regional response to segmental allergen challenge using magnetic resonance imaging and [F-18]fluorodeoxyglucose positron emission tomography.

Magnetic resonance (MR) and positron emission tomography (PET) imaging techniques were coregistered to demonstrate regional ventilation and inflammation in the lung for in vivo, noninvasive evaluation of regional lung function associated with allergic inflammation. Four Brown Norway rats were imaged pre- and post segmental allergen challenge using respiratory-gated He-3 magnetic resonance imaging (MRI) to visualize ventilation, T(1)-weighted proton MRI to depict inflammatory infiltrate, and [F-18]fluorodeoxyglucose-PET to detect regional glucose metabolism by inflammatory cells. Segmental allergen challenges were delivered and the pre- and postchallenge lung as well as the contralateral lung were compared. Coregistration of the imaging results demonstrated that regions of ventilation defects, inflammatory infiltrate, and increased glucose metabolism correlated well with the site of allergen challenge delivery and inflammatory cell recruitment, as confirmed by histology. This method demonstrates that fusion of functional and anatomic PET and MRI image data may be useful to elucidate the functional correlates of inflammatory processes in the lungs.     

MRI of the lung: state of the art

Magnetic resonance imaging (MRI) of the lung is technically challenging due to the low proton density and fast signal decay of the lung parenchyma itself. Additional challenges consist of tissue loss, hyperinflation, and hypoxic hypoperfusion, e.g., in emphysema, a so-called "minus-pathology". However, pathological changes resulting in an increase of tissue ("plus-pathology"), such as atelectases, nodules, infiltrates, mucus, or pleural effusion, are easily depicted with high diagnostic accuracy. Although MRI is inferior or at best equal to multi-detector computed tomography (MDCT) for the detection of subtle morphological features, MRI now offers an increasing spectrum of functional imaging techniques such as perfusion assessment and measurement of ventilation and respiratory mechanics that are superior to what is possible with MDCT. Without putting patients at risk with ionizing radiation, repeated examinations allow for the evaluation of the course of lung disease and monitoring of the therapeutic response through quantitative imaging, providing a level of functional detail that cannot be obtained by any other single imaging modality. As such, MRI will likely be used for clinical applications beyond morphological imaging for many lung diseases. In this article, we review the technical aspects and protocol suggestions for chest MRI and discuss the role of MRI in the evaluation of nodules and masses, airway disease, respiratory mechanics, ventilation, perfusion and hemodynamics, and pulmonary vasculature.     

Validation of functional imaging as a biomarker for radiation treatment response

Major advances in radiotherapy techniques, increasing knowledge of tumour biology and the ability to translate these advances into new therapeutic approaches are important goals towards more individualized cancer treatment. With the development of non-invasive functional and molecular imaging techniques such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction, for treatment individualization is not only based on morphological criteria but also on biological tumour characteristics. The goal of individualization of radiotherapy is to improve treatment outcome and potentially reduce chronic treatment toxicity. This review gives an overview of the molecular and functional imaging modalities of tumour hypoxia and tumour cell metabolism, proliferation and perfusion as predictive biomarkers for radiation treatment response in head and neck tumours and in lung tumours. The current status of knowledge on integration of PET/CT/MRI into treatment management and bioimage-guided adaptive radiotherapy are discussed.Advances in understanding the molecular biology of cancer and the ability to translate these advances into therapeutic approaches are important achievements towards individualized cancer treatment. With the development of non-invasive functional and molecular imaging modalities such as positron emission tomography (PET)-CT scanning and MRI, there is now a need to evaluate potential new biomarkers for tumour response prediction. It is noteworthy that treatment individualization is not only based on morphological criteria but also on biological tumour characteristics such as metabolic and proliferative activity, and hypoxic tumour status before and during treatment.¹ The validation and integration of imaging biomarkers before and early during therapy are important tasks for further clinical research and may help to individually select, adapt and optimize treatment schedules for patients in order to improve treatment outcomes, that is, to increase tumour control probability and/or to reduce chronic treatment-related toxicity.²The primary aim of a predictive biomarker is to accurately determine the outcome of a given treatment. Therefore, the accurate prediction may help facilitate potential interventions early during the course of treatment. By contrast, prognostic markers show an association with patient outcome independent of a given treatment. The increasing use and availability of PET/CT as well as of MRI in radiotherapy will make it feasible to incorporate imaging predictive tests into clinical practice if validation studies confirm the utility of specific PET tracers or functional MRI or CT parameters. In this review, the capacity to use these functional imaging biomarkers is focused on PET, MRI and CT for radiotherapy response detection in head and neck tumours and in lung tumours.     

Oxygen-enhanced MR imaging of mice lungs.

Inhaled molecular oxygen has been widely used in humans to evaluate pulmonary ventilation using MRI. MR imaging has recently played a greater role in examining the morphologic and physiologic characteristics of mouse models of lung disease where structural changes are highly correlated to abnormalities in respiratory function. The motivation of this work is to develop oxygen-enhanced MR imaging for mice. Conventional human MR techniques cannot be directly applied to mouse imaging due to smaller dimensions and faster cardiac and respiratory physiology. This study examines the development of oxygen-enhanced MR as a noninvasive tool to assess regional ventilation in spontaneously breathing mice. An optimized cardiac-triggered, respiratory-gated fast spin-echo imaging sequence was developed to address demands of attaining adequate signal from the parenchyma, maintaining practical acquisition times, and compensating for rapid physiological motion. On average, a 20% T1-shortening effect was observed in mice breathing 100% oxygen as compared to air. The effect of ventilation was shown as a significant signal intensity increase of 11% to 16% in the mouse parenchyma with 100% oxygen inhalation. This work demonstrates that adequate contrast and resolution can be achieved using oxygen-enhanced MR to visualize ventilation, providing an effective technique to study ventilation defects in mice.     

MR ventilation-perfusion imaging of human lung using oxygen-enhanced and arterial spin labeling techniques.

Magnetic resonance ventilation-perfusion (V/Q) imaging has been demonstrated using oxygen and arterial spin labeling techniques. Inhaled oxygen is used as a paramagnetic contrast agent in ventilation imaging using a multiple inversion recovery (MIR) approach. Pulmonary perfusion imaging is conducted using a flow-sensitive alternating inversion recovery with an extra radiofrequency pulse (FAIRER) technique. A half Fourier single-short turbo spin echo (HASTE) sequence is used for data acquisition in both techniques. V/Q imaging was performed in ten of the twenty volunteers, while either ventilation or perfusion was imaged in the other ten. This V/Q imaging scheme is completely noninvasive, does not involve ionized radiation, and shows promising potential for clinical use in the diagnosis of lung diseases such as pulmonary embolism.     

Non‐contrast‐enhanced perfusion and ventilation assessment of the human lung by means of fourier decomposition in proton MRI

Assessment of regional lung perfusion and ventilation has significant clinical value for the diagnosis and follow‐up of pulmonary diseases. In this work a new method of non‐contrast‐enhanced functional lung MRI (not dependent on intravenous or inhalative contrast agents) is proposed. A two‐dimensional (2D) true fast imaging with steady precession (TrueFISP) pulse sequence (TR/TE = 1.9 ms/0.8 ms, acquisition time [TA] = 112 ms/image) was implemented on a 1.5T whole‐body MR scanner. The imaging protocol comprised sets of 198 lung images acquired with an imaging rate of 3.33 images/s in coronal and sagittal view. No electrocardiogram (ECG) or respiratory triggering was used. A nonrigid image registration algorithm was applied to compensate for respiratory motion. Rapid data acquisition allowed observing intensity changes in corresponding lung areas with respect to the cardiac and respiratory frequencies. After a Fourier analysis along the time domain, two spectral lines corresponding to both frequencies were used to calculate the perfusion‐ and ventilation‐weighted images. The described method was applied in preliminary studies on volunteers and patients showing clinical relevance to obtain non‐contrast‐enhanced perfusion and ventilation data. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Imaging of lung function using hyperpolarized helium-3 magnetic resonance imaging: Review of current and emerging translational methods and applications

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical research and decision making in pulmonary medicine. Particular attention is given to functional imaging approaches related to ventilation and diffusion-weighted imaging with applications in chronic obstructive pulmonary disease, cystic fibrosis, asthma, and radiation-induced lung injury. The strengths and challenges of the application of (3)He MRI in these indications are discussed along with a comparison to established and emerging imaging techniques.     

MRI of lungs using partial liquid ventilation with water-in-perfluorocarbon emulsions.

A novel (1)H-MRI contrast modality for rat lungs has been developed using water-in-perfluorocarbon (PFC) emulsions for partial liquid ventilation (PLV). The feasibility of the new ventilation protocol for (1)H-MRI studies of lungs has been demonstrated. (1)H-MR images of lungs have been obtained with sensitivity and spatial resolution higher than those of the (19)F-MRI of lungs previously reported. Diffusion-weighted MRI measurements of lungs showed that the results obtained are related to the pulmonary architecture and functional properties of lungs. Although the methodology needs further improvement and evaluation, it appears to have great potential in a wide range of new applications in the field of lung MRI, such as in vivo detection of lung cancer, emphysema, and allograft rejection following lung transplantation. The ability of this technique to achieve high-quality MR images of lungs, together with its technical simplicity, stability, and low cost, makes this method a promising imaging technique for the lungs.