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Clinical Issue: Disease severity and mortality in patients with cystic fibrosis (CF) is mainly determined by (progressive) pulmonary lung disease. Early diagnosis and therapy are important and of prognostic value to conserve lung function., Standard Radiological Methods: Primary imaging techniques for lung imaging are x‑ray and computed tomography (CT) to monitor disease severity and regional distribution., Methodical Innovations: Radiation-free imaging techniques such as magnetic resonance imaging (MRI) have gained interest over the last decade in order to prevent radiation damage., Performance: The main findings of CF lung disease are airway wall thickening, bronchiectasis, and mucus plugging, which are found in up to 60% of preschool age children. Pleural abnormalities and consolidations are often associated with pulmonary exacerbation. Young CF patients often show a mosaic pattern as functional changes and also perfusion defects can be seen from birth in 50% of CF patients by contrast-enhanced perfusion imaging, and in up to 90% of adult patients, with varying degrees of severity. Dilated bronchial arteries indicate an increased risk for hemoptysis., Achievements: Proton MRI is the sole imaging technique that can show structural and functional lung changes in one examination. Structured assessment using a scoring system helps to systematically grade the extent and severity of all CF-associated changes., Conclusions: Lung MRI for cystic fibrosis has been recently established as a clinical standard examination and is routinely performed at experienced centers. More recently, it has also been used as an endpoint within the framework of clinical studies.

With its high detail of morphological changes in lung parenchyma and airways as well as the possibilities for three-dimensional reconstruction, computed tomography (CT) represents a solid tool for the diagnosis and follow-up in patients suffering from cystic fibrosis (CF). Guidelines for standardized CT image acquisition in CF patients are still missing. In the mostly younger CF patients, an important issue is the well-considered use of radiation in CT imaging. The use of intravenous contrast agent is mainly restricted to acute emergency diagnostics. Typical morphological findings in CF lung disease are bronchiectasis, mucus plugging, or signs of decreased ventilation (air trapping) which can be detected with CT even in early stages. Various scoring systems that have become established over time are used to grade disease severity and for structured follow-up, e.g., in clinical research studies. With the technical development of CT, a number of postprocessing software tools were developed to help clinical reporting and overcome interreader differences for a standardized quantification. As an imaging modality free of ionizing radiation, magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of CF patients and is already frequently a substitute for CT for long-term follow-up at numerous specialized centers.

Conventional projection radiography (chest x‑ray) is one of the most frequently requested procedures in radiology. Even though chest x‑ray imaging is frequently performed in asymptomatic patients for preoperative assessment, clinically relevant incidental findings are relatively scarce. This is due to the relatively low sensitivity of chest x‑rays where few clinically relevant incidental findings are to be expected, as any detectable pathologies will as a rule already be clinically symptomatic. Recommendations from relevant societies for the management of incidental findings, apart from the clarification of incidental nodules, do not exist. This review article therefore describes the most frequent and typical incidental findings of lung parenchyma (apart from pulmonary nodules), mediastinal structures including the hilum of the lungs, pleura, chest wall and major vessels. Also described are those findings which can be diagnosed with sufficient certainty from chest x‑rays so that further clarification is not necessary and those which must be further clarified by multislice imaging procedures or other techniques.

The onset and spontaneous development of cystic fibrosis (CF) lung disease remain poorly understood. In the present study, we used volumetric computed tomography (VCT) as a new method for longitudinal in vivo monitoring of early lesions and disease progression in CF-like lung disease in β-epithelial Na(+) channel (ENaC)-transgenic (TG) mice. Using a VCT scanner prototype (80 kV, 50 mA·s, scan time 19 s and spatial resolution 200 μm), βENaC-TG mice and wild-type (WT) littermates were examined longitudinally at 10 time-points from neonatal to adult ages, and VCT images were assessed by qualitative and quantitative morphological parameters. We demonstrate that VCT detected early-onset airway mucus obstruction, diffuse infiltrates, atelectasis and air trapping as characteristic abnormalities in βENaC-TG mice. Furthermore, we show that early tracheal mucus obstruction predicted mortality in βENaC-TG mice and that the density of lung parenchyma was significantly reduced at all time-points in βENaC-TG compared with WT mice (median ± sem -558 ± 8 HU in WT versus -686 ± 16 HU in βENaC-TG at 6 weeks of age; p < 0.005). Our study demonstrates that VCT is a sensitive, noninvasive technique for early detection and longitudinal monitoring of morphological abnormalities of CF-like lung disease in mice, and may thus provide a useful tool for pre-clinical in vivo evaluation of novel treatment strategies for CF.

To compare the image quality of dynamic lung MRI with variations of steady-state free-precession (SSFP) and gradient echo (GRE) cine techniques at 1.5 T and 3 T. Ventilated porcine lungs with simulated lesions inside a chest phantom and four healthy human subjects were assessed with SSFP (TR/TE=2.9/1.22 ms; 3 ima/s) and GRE sequences (TR/TE=2.34/0.96 ms; 8 ima/s) as baseline at 1.5 and 3 T. Modified SSFPs were performed with nine to ten images/s (parallel imaging factors 2 and 3). Image quality for representative structures and artifacts was ranked by three observers independently. At 1.5 T, standard SSFP achieved the best image quality with superior spatial resolution and signal, but equal temporal resolution to GRE. SSFP with improved temporal resolution was ranked second best. Further acceleration (PI factor 3) was of no benefit, but increased artifacts. At 3 T, GRE outranged SSFP imaging with high lesion signal intensity, while artifacts on SSFP images increased visibly. At 1.5 T, a modified SSFP with moderate parallel imaging (PI factor 2) was considered the best compromise of temporal and spatial resolution. At 3 T, GRE sequences remain the best choice for dynamic lung MRI.

Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

The technology of multislice X-ray computed tomography (MSCT) provides volume data sets with approximately isotropic resolution, which permits a noninvasive 3-D measurement and quantification of airway geometry. In different diseases, like emphysema, chronic obstructive pulmonary disease (COPD), or cystic fribrosis, changes in lung parenchyma are associated with an increase in airway wall thickness. In this paper, we describe an objective measuring method of the airway geometry in the 3-D space. The limited spatial resolution of clinical CT scanners in comparison to thin structures like airway walls causes difficulties in the measurement of the density and the thickness of these structures. Initially, these difficulties will be addressed and then a new method is introduced to circumvent the problems. Therefore the wall thickness is approximated by an integral based closed-form solution, based on the volume conservation property of convolution. We evaluated the method with a phantom containing 10 silicone tubes and proved the repeatability in datasets of eight pigs scanned twice. Furthermore, a comparison of CT datasets of 16 smokers and 15 nonsmokers was done. Further medical studies are ongoing.

Since many pulmonary diseases present with a variable regional involvement, modalities for assessment of regional lung function gained increasing attention over the last years. Together with lung perfusion and gas exchange, ventilation, as a result of the interaction of the respiratory pump and the lungs, is an indispensable component of lung function. So far, this complex mechanism is still mainly assessed indirectly and globally. A differentiation between the individual determining factors of ventilation would be crucial for precise diagnostics and adequate treatment. By dynamic imaging of the respiratory pump, the mechanical components of ventilation can be assessed regionally. Amongst imaging modalities applicable to this topic, magnetic resonance imaging (MRI), as a tool not relying on ionising radiation, is the most attractive. Recent advances in MRI technology have made it possible to assess diaphragmatic and chest wall motion, static and dynamic lung volumes, as well as regional lung function. Even though existing studies show large heterogeneity in design and applied methods, it becomes evident that MRI is capable to visualise pulmonary function as well as diaphragmatic and thoracic wall movement, providing new insights into lung physiology. Partly contradictory results and conclusions are most likely caused by technical limitations, limited number of studies and small sample size. Existing studies mainly evaluate possible imaging techniques and concentrate on normal physiology. The few studies in patients with lung cancer and emphysema already give a promising outlook for these techniques from which an increasing impact on improved and quantitative disease characterization as well as better patient management can be expected.

Recently it has been shown that regional lung perfusion can be assessed using time-resolved contrast-enhanced magnetic resonance (MR) imaging. Quantification of the perfusion images has been attempted, based on definition of small regions of interest (ROIs). Use of complete lung segmentations instead of ROIs could possibly increase quantification accuracy. Due to the low signal-to-noise ratio, automatic segmentation algorithms cannot be applied. On the other hand, manual segmentation of the lung tissue is very time consuming and can become inaccurate, as the borders of the lung to adjacent tissues are not always clearly visible. We propose a new workflow for semi-automatic segmentation of the lung from additionally acquired morphological HASTE MR images. First the lung is delineated semi-automatically in the HASTE image. Next the HASTE image is automatically registered with the perfusion images. Finally, the transformation resulting from the registration is used to align the lung segmentation from the morphological dataset with the perfusion images. We evaluated rigid, affine and locally elastic transformations, suitable optimizers and different implementations of mutual information (MI) metrics to determine the best possible registration algorithm. We located the shortcomings of the registration procedure and under which conditions automatic registration will succeed or fail. Segmentation results were evaluated using overlap and distance measures. Integration of the new workflow reduces the time needed for post-processing of the data, simplifies the perfusion quantification and reduces interobserver variability in the segmentation process. In addition, the matched morphological data set can be used to identify morphologic changes as the source for the perfusion abnormalities.

Purpose: To develop a model for exactly reproducible respiration motion simulations of animal lung explants inside an MR-compatible chest phantom., Materials and Methods: The materials included a piston pump and a flexible silicone reconstruction of a porcine diaphragm and were used in combination with an established MR-compatible chest phantom for porcine heart-lung preparations. The rhythmic inflation and deflation of the diaphragm at the bottom of the artificial thorax with water (1 - 1.5 L) induced lung tissue displacement resembling diaphragmatic breathing. This system was tested on five porcine heart-lung preparations using 1.5T MRI with transverse and coronal 3D-GRE (TR/TE = 3.63/1.58, 256 x 256 matrix, 350 mm FOV, 4 mm slices) and half Fourier T2-FSE (TR/TE = 545/29, 256 x 192, 350 mm, 6 mm) as well as multiple row detector CT (16 x 1 mm collimation, pitch 1.5, FOV 400 mm, 120 mAs) acquired at five fixed inspiration levels. Dynamic CT scans and coronal MRI with dynamic 2D-GRE and 2D-SS-GRE sequences (image frequencies of 10/sec and 3/sec, respectively) were acquired during continuous "breathing" (7/minute). The position of the piston pump was visually correlated with the respiratory motion visible through the transparent wall of the phantom and with dynamic displays of CT and MR images. An elastic body splines analysis of the respiratory motion was performed using CT data., Results: Visual evaluation of MRI and CT showed three-dimensional movement of the lung tissue throughout the respiration cycle. Local tissue displacement inside the lung explants was documented with motion maps calculated from CT. The maximum displacement at the top of the diaphragm (mean 26.26 [SD 1.9] mm on CT and 27.16 [SD 1.5] mm on MRI, respectively [p = 0.25; Wilcoxon test]) was in the range of tidal breathing in human patients., Conclusion: The chest phantom with a diaphragmatic pump is a promising platform for multi-modality imaging studies of the effects of respiratory lung motion.

Cystic fibrosis (CF) is a multi-systemic disease with major impact on the lungs. Pulmonary manifestation is crucial for the prognosis and life expectancy of patients. Imaging modalities and lung function tests reflect the pulmonary status in these patients. The standard imaging modality for diagnosis and follow-up of pulmonary changes is chest x-ray. The gold standard for the detection of parenchymal lung changes remains high resolution computed tomography (HRCT), but this is not used routinely for CF-patients due to radiation exposure. Magnetic resonance imaging (MRI) used to be of no importance in monitoring cystic fibrosis lung disease, as shown in studies from the 1980s and early 1990 s. The continuing improvement of MRI techniques, however, has allowed for an adequate application of this non-radiation method in diagnosing the major pulmonary findings in CF, in addition to the assessment of lung function.

Lung perfusion is a crucial prerequisite for effective gas exchange. Quantification of pulmonary perfusion is important for diagnostic considerations and treatment planning in various diseases of the lungs. Besides disorders of pulmonary vessels such as acute pulmonary embolism and pulmonary hypertension, these also include diseases of the respiratory tract and lung tissue as well as pulmonary tumors. This contribution presents the possibilities and technical requirements of MRI for diagnostic work-up of pulmonary perfusion.

Current imaging methods of the lung concentrate on morphology as well as on the depiction of the pulmonary parenchyma. The need of an advanced and more subtle imaging technology compared to conventional radiography is met by computed topography as the method of choice. Nevertheless, computed tomography yields very limited functional information. This is to be derived from arterial blood gas analysis, spirometry and body plethysmography. These methods, however, lack the scope for regional allocation of any pathology. Magnetic resonance imaging of the lung has been advanced by the use of hyperpolarised (3)Helium as an inhaled gaseous contrast agent. The inhalation of the gas provides functional data by distribution, diffusion and relaxation of its hyperpolarised state. Because anatomical landmarks of the lung can be visualised as well, functional information can be linked with regional information. Furthermore, the method provides high spatial and temporal resolution and lacks the potential side-effects of ionising radiation. Four different modalities have been established: 1. Spin density imaging studies the distribution of gas, normally after a single inhalation of contrast gas in inspiratory breath hold. 2. Dynamic cine imaging studies the distribution of gas with respect to regional time constants of pulmonary gas inflow. 3. Diffusion weighted imaging can exhibit the presence and severity of pulmonary airspace enlargement, as in pulmonary emphysema. 4. Oxygen sensitive imaging displays intrapulmonary oxygen partial pressure and its distribution. Currently, the method is limited by comparably high costs and limited availability. As there have been recent developments which might bring this modality closer to clinical use, this review article will comprise the methodology as well as the current state of the art and standard of knowledge of magnetic resonance imaging of the lung using hyperpolarised (3)Helium.

Purpose: Introduction of a novel software tool (YACTA -- yet another CT analyzer) for detection and quantification of pulmonary emphysema in thin-slice chest MDCT data sets., Materials and Methods: Consisting of grey-level threshold-based algorithms (e. g., region-growing), expert rules and morphological image postprocessing YACTA segments the tracheobronchial tree prior to the detection and quantification of pulmonary emphysema. In addition to general parameters, such as the mean lung density (MLD) and the emphysema index (EI -- also described as pixel index PI), the previously described bullae index (BI) is transformed into a three-dimensional parameter for a morphological description of emphysema. A first evaluation of chest MDCT data sets of 11 patients was performed as well as a comparison of MLD, lung volume (LV), emphysema volume (EV) and PI calculated with two established commercial tools of Siemens Medical Solutions (Volume and Pulmo). Furthermore, the BI was calculated with YACTA., Results: YACTA processed the image data without manual interaction and demonstrated more user-comfort than Volume and Pulmo software, which require manual correction especially for lung segmentation at the hilar regions to separate central airways from lung parenchyma. MLD, LV, and EV values calculated with YACTA were systematically higher (Pulmo: + 50 HU/+ 597 ml/+ 159 ml; Volume: + 32 HU/+ 110 ml/+ 155 ml). Different segmentation algorithms are responsible for this: YACTA includes areas not assessed by mere threshold-based techniques. Constantly lowered LV values of Pulmo are caused by a missing dilatation algorithm. The error correction as a special feature of YACTA results in increased emphysema volumes and indices. The segmentation of the tracheobronchial tree lowers the part of airways falsely classified as emphysema., Conclusion: The new developed software shows higher user comfort as established by semi-automated tools., Results: of LV, EV, MLD and PI are comparable or moderately different. Automatic calculation of a BI is possible, providing information about bullous morphology of pulmonary emphysema. Further studies are necessary to correlate data with clinical or pathological parameters.

Purpose: (3)He-MRI is able to visualize the regional distribution of lung ventilation with a temporal and spatial resolution so far unmatched by any other technique. The aim of the study was the development of a new software tool for quantification of dynamic ventilation parameters in absolute physical units., Materials and Methods: During continuous breathing, a bolus of hyperpolarized (3)He (300 ml) was applied at inspiration and a series of 168 coronal projection images simultaneously acquired using a 2D FLASH-sequence. Postprocessing software was developed to analyze the (3)He distribution in the lung. After correction for lung motion, several ventilation parameters (rise time, delay time, (3)He amount and (3)He peak flow) were calculated. Due to normalization of signal intensities, these parameters are presented in absolute physical units. The data sets were analyzed on a ROI basis as well as on a pixel-by-pixel basis., Results: Using the developed software, the measurements were analyzed in 6 lung-healthy volunteers, in one patient after lung transplantation, and in one patient with lung emphysema. The volunteers' parameter maps of the pixel-based analysis showed an almost homogeneous distribution of the ventilation parameters within the lung. In the parameter maps of both patients, regions with poor ventilation were observed., Conclusion: The developed software permits an objective and quantitative analysis of regional lung ventilation in absolute physical units. The clinical significance of the parameters, however, has to be determined in larger clinical studies. The software may become valuable in grading and following pulmonary function as well as in monitoring any therapy.

Purpose: To develop a software tool for quantitative analysis of alveolar oxygen partial pressure (p(A)O(2)) as well as its time course during apnea., Material and Methods: T (1)-relaxation times of hyperpolarized (3)He are reduced by paramagnetic oxygen rendering (3)He-MRI sensitive to oxygen and thus allowing the assessment of the local oxygen partial pressure in the pulmonary airspaces. Oxygen-related relaxation and loss of polarization by RF-excitation can be discriminated by acquiring two image series with varying interscan delay and/or flip angles. Software was developed to calculate the p(A)O(2) and the decay rate in user-defined regions of interest (ROIs) automatically. Moreover, parameter maps can be calculated. In addition to the analysis of 2-dimensional data sets, the software allows the evaluation of 3-dimensional measurements for the first time. Artifacts due to lung motion were reduced by implementing a motion correction algorithm., Results: The software was successfully applied to data sets from healthy volunteers and from patients with various lung diseases. The parameter maps demonstrated a more homogeneous distribution of p(A)O(2) for the volunteers than for the patients. A regional increase in p(A)O(2) was found in a few patients., Conclusion: The described software allows the absolute quantification of p(A)O(2) as well as its variation over time. In the future, therefore, the software may gain importance for detecting mismatches between ventilation and perfusion, e. g., in patients with pulmonary embolism or chronic obstructive lung diseases.

Purpose: Evaluation of lung perfusion by contrast-enhanced 3D MRI using partial parallel imaging techniques., Materials and Methods: Eight healthy volunteers were examined using a contrast-enhanced dynamic FLASH 3D sequence with partial parallel imaging technique at 1.5 T MRI with a TA of 1.5 sec. The whole lung was covered by 36 coronal slices. A ventral, middle and dorsal slice of each lung was manually segmented and signal-to-time curves were computed. For absolute quantification of blood flow through the right and left pulmonary artery, phase-contrast flow measurements were performed., Results: No significant difference was found between the signal intensity in the right (8.9 +/- 2.6) and left (8.0 +/- 3.5) lung, corresponding to a left-to-right signal intensity ratio of 0.9. A significantly higher signal intensity was found in the dorsal regions of the lungs (p = 0.01) compared to the ventral regions. The time to peak of the signal intensity was significantly shorter in the dorsal (15.3 sec) and middle (15.7 sec) regions of the lungs (p = 0.03 and p = 0.04, respectively) than in the ventral regions (16.3 sec). The ratio between blood flow through the left (2.2 L/min) and right (2.7 L/min) lung was 0.84., Conclusion: Partial parallel image acquisition can assess the perfusion of the lungs at high temporal resolution. The perfusion is slightly higher on the right than on the left. The signal increases faster and has a higher peak in the dorsal lung regions.

Purpose: Dynamic CT (dCT) allows visualization and quantification of ventilated lung and atelectases with high temporal resolution during continuous ventilation. This study compares a quantitative image analysis in a subcarinal single slice dCT series versus a whole lung spiral-CT, in order to analyze, whether the distribution of atelectasis of a single dCT series is representative for the whole lung., Materials and Methods: dCT in sliding windows technique (slice thickness 1 mm, temporal increment 100 ms) was performed in 8 healthy pigs 3 cm caudal to the carina during continuous mechanical ventilation. Subsequently, a spiral-CT of the whole lung (slice thickness 2 mm; pitch 1.5; increment 2 mm) was acquired during inspiratory breath hold (airway pressure 20 mbar). Lung segmentation and planimetry of predefined density ranges were achieved using a dedicated software tool in both data-sets. Thus, the fractions of the following functional lung compartments were averaged over time: hyperinflated lung (- 1024 to - 910 HE), normal ventilated lung -900 to -300 HE) and atelectasis (-300 to +200 HE)., Results: Quantitative analysis of dCT-series during continuous respiration correlated with the density analysis in spiral-CT as follows: hyperinflated lung r = 0.56; normal ventilated lung r = 0.83 and atelectases r = 0.84. Analysis of spiral-CT showed the following distribution of functional lung compartments: hyperinflated lung 3.1% normal ventilated lung 77.9% and atelectasis 19.0%. In dCT, hyperinflated lung represented 6.4%, normal ventilated lung 65.2% and atelectasis 28.4% of total the lung area., Conclusion: The results of our study demonstrate that dCT allows monitoring of atelectasis formation in response to different ventilatory strategies. However, a deviation between dCT and spiral-CT has to be taken into account. In subcarinal dCT series, hyperinflated lung areas and atelectases were overestimated due to a craniocaudal gradient of atelectases, whereas normal ventilated lung was underestimated.

Background: Fast dynamic computed tomography (dCT) has been used to assess regional dynamics of lung inflation and deflation processes. The aim of this study was to relate ventilation-induced changes in lung density distribution, as measured over several respiratory cycles by dCT, to oxygenation and shunt fraction in a lavage acute respiratory distress syndrome model., Methods: Six anaesthetized pigs underwent pressure-constant ventilation (FIO2=1.0, inspiratory:expiratory ratio=1:1) before and after induction of lung damage by saline lavage. Mean airway pressure (Paw) was varied (8, 13, 18, 23, 28, 33, and 38 cm H2O) in random order. At each Paw level, dCT acquisitions were performed over several respiratory cycles (Somatom Plus4, Siemens; supradiaphragmatic transverse slice; thickness=1 mm; temporal resolution=100 ms). During scanning at each Paw, arterial and mixed venous blood were obtained for blood gas analysis and shunt calculation. In each CT image, fractional areas (FA) of defined density ranges representing ventilated lung and atelectasis were determined by planimetry using dedicated software. The FA data of individual 100 ms scans were averaged over several respiratory cycles, and expressed as mean FA in percentage of total lung area at each Paw. For atelectatic lung parenchyma a quantitative relationship of the respective mean FA to shunt fraction was studied using regression analysis., Results: Under steady-state conditions, mean FA of atelectasis correlated linearly with the calculated shunt fraction (healthy lungs, r=+0.76; lavaged lungs, r=+0.89). There is a non-linear relationship between mean FA of ventilated lung parenchyma and mean FA of atelectasis with PaO2., Conclusions: We conclude that dCT allows assessment of the effects of ventilator adjustments and resultant Paw; changes upon lung aeration and oxygenation rapidly, and with good spatial and temporal resolution. This may benefit patients with acute lung injury, whose ventilatory pattern may be optimized as early as during their first diagnostic workup.

MRI of the lungs using hyperpolarized helium-3 ((3)He) allows the determination of intrapulmonary oxygen partial pressures (p(O2)). The need to separate competing processes of signal loss has hitherto required two different imaging series during two different breathing maneuvers. In this work, a new imaging strategy to measure p(O2) by a single series of consecutive scans is presented. The feasibility of the method is demonstrated in three healthy human volunteers. Maps and histograms of intrapulmonary p(O2) are calculated. Changes in the oxygen concentration of the inhaled gas mixture are well reproduced in the histograms. Monte Carlo (MC) simulations of the temporal evolution of (3)He hyperpolarization within the lungs were performed to evaluate the accuracy of this measurement technique, and its limitations., (Copyright 2002 Wiley-Liss, Inc.)

In magnetic resonance imaging (MRI), nuclear spins are the source of the image signal. In the lung, low-proton spin density in alveolar gas and abundant gas-tissue interfaces substantially impair conventional native 1H-MRI. Spin polarisation can be increased in two non-radioactive noble gas isotopes, 3He and 129Xe, by exposure to polarised laser light. When inhaled, such "magnetized" gases provide high-intensity MR images of the pulmonary airspaces. Thus, hyperpolarised gas (HPG) MRI opens up new routes to a) morphologic imaging of airways and alveolar spaces, and b) analysis of the intrapulmonary distribution of inhaled aliquots of these tracer gases; c) diffusion-sensitive MRI-techniques allow mapping of the "apparent diffusion coefficient" (ADC) of 3He within lung airspaces, where ADC is physically related to local bronchoalveolar dimensions; d) also, 3He magnetisation decays in an oxygen-containing atmosphere at a rate proportional to ambient PO2. This property allows image-based determination of regional broncho-alveolar PO2 and its decrease during a breathhold. Currently, these modalities of functional lung imaging are being assessed by several European and American research groups in animal models, human volunteers and patients. First results show good imaging quality with excellent spatial and unprecedented temporal resolution, and attest to the reproducibility, feasibility and safety of the technique. Regionally impaired ventilation of both structural and functional origin is detected with high sensitivity, e.g. in smokers, asthmatics, patients with COPD or after lung transplantation. Studies into regional ADC and PO2 measurement demonstrate good agreement with reference methods and physiological predictions. The present limitations of HPG-MRI include the HPG production rate and the US and EU health authorities' still pending final approval for clinical use.

We used dynamic CT to identify two different time constants of lung aeration and their individual contribution to the total increase in cross-sectional lung area in healthy and experimentally damaged lungs. In five healthy pigs, inflation and deflation between 0 and 50 cm H2O was imposed during dynamic (250 ms/image) CT acquisition, and repeated after experimental lung injury by saline lavage. The fractional areas of density ranges, which represent aerated lung parenchyma, were determined planimetrically, and their time for expansion during the manoeuvre was fitted using a bi-exponential model. Thus, two compartments, their sizes, i.e. their relative contributions to lung area aerated by the manoeuvre, and their specific time constants (tau) were sought. Healthy lungs were characterized best by a one-compartmental behaviour with one tau only, both during inflation (median tau=0.5 s; range 0.4-0.6 s) and deflation (1.2 s; 1.1-1.3 s). In damaged lungs two compartments were found both during inspiration and expiration, with 86% (78-87%) of the recruitable lung area following a short tau of 0.5 s (0.5-0.6), and 14% (13-22%) following a longer tau of 9.1 s (8-16.8 s) during inflation. During expiration, damaged lungs had a short tau of 0.8 s (0.5-1.0 s) for 94% (84-100%) of deflated lung area, and a longer tau of 26.5 s (7.1-34.3 s) for 6% (0-16%). We conclude that dynamic CT indicates the relative size and temporal behaviour of functional compartments in normal and abnormal lungs. Our findings suggest that after lung damage, cyclic ventilation with inspiratory periods of <10 s duration will not achieve maximum recruitment for a chosen inspiratory pressure. In ARDS, the short expiratory tau predisposes to atelectasis formation if expiratory times are >1 s.

A new method for dynamic imaging of pulmonary wash-in and wash-out kinetics of inhaled sulfur hexafluoride (SF(6)) gas was developed. Measurements at the fluorine-19 Larmor frequency were performed in pigs using a gradient echo pulse sequence with 0.5 ms echo time and a measurement time of 9.1 s per image. Dynamic MRI was performed during wash-in and wash-out of SF(6) gas in mechanically ventilated porcine lungs. A postprocessing strategy was developed for quantitative determination of wash-out time constants in the presence of noise. Mean wash-out constants were 4.78 +/- 0.48 breaths vs. 4.33 +/- 0.76 breaths for left and right lung when ventilation was performed with low tidal volume, and 1.73 +/- 0.16 breaths vs. 1.85 +/- 0.11 breaths with high tidal volume ventilation. In conclusion, breath-hold MRI of SF(6) gas is feasible in large animals. Moreover, regional wash-in and wash-out kinetics of SF(6) can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605-613, 2001., (Copyright 2001 Wiley-Liss, Inc.)

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.

Objective: We compared multiple neural networks with a density mask for the automatic detection and quantification of ground-glass opacities on high-resolution CT under clinical conditions., Subjects and Methods: Eighty-four patients (54 men and 30 women; age range, 18-82 years; mean age, 49 years) with a total of 99 consecutive high-resolution CT scans were enrolled in the study. The neural network was designed to detect ground-glass opacities with high sensitivity and to omit air-tissue interfaces to increase specificity. The results of the neural network were compared with those of a density mask (thresholds, -750/-300 H), with a radiologist serving as the gold standard., Results: The neural network classified 6% of the total lung area as ground-glass opacities. The density mask failed to detect 1.3%, and this percentage represented the increase in sensitivity that was achieved by the neural network. The density mask identified another 17.3% of the total lung area to be ground-glass opacities that were not detected by the neural network. This area represented the increase in specificity achieved by the neural network. Related to the extent of the ground-glass opacities as classified by the radiologist, the neural network (density mask) reached a sensitivity of 99% (89%), specificity of 83% (55%), positive predictive value of 78% (18%), negative predictive value of 99% (98%), and accuracy of 89% (58%)., Conclusion: Automatic segmentation and quantification of ground-glass opacities on high-resolution CT by a neural network are sufficiently accurate to be implemented for the preinterpretation of images in a clinical environment; it is superior to a double-threshold density mask.

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.

Radiological cross-sectional imaging modalities, particularly computed tomography (CT) have become the mainstays for diagnosing lung disease in recent years. These enable morphological visualization of pathological processes with the greatest possible spatial resolution. Modern technical developments and complementary strategies have led to new applications and new functional assessments which need to be reviewed together with state-of-the-art techniques in nuclear imaging. The diagnosis of pulmonary embolism using spiral CT angiography and magnetic resonance (MR) angiography certainly belongs in this category. CT has become the an alternative modality of first choice, and it is also challenging pulmonary angiography as the gold standard. Direct visualization of patent pulmonary arteries and thromboembolic material is complemented by that of effects on the pulmonary parenchyma and right heart function; it also provides perfusion studies and MR-based flow measurement to assess hemodynamic compromise. Ventilation studies have long been a domain of nuclear imaging, and new techniques for the direct visualization of ventilation are emerging from recent developments in the field of MR imaging, for example, using hyperpolarized inert gases. New functional parameters of ventilation can be derived from these studies. For the diagnosis of metabolically active disease, such as tumor and pneumonia, CT offers very high sensitivity, for example, in screening for intrapulmonary nodules using low-dose CT and in the early detection of pulmonary infiltrates in high-risk patients. Especially for characterizing pulmonary nodules there is a need to combine nuclear medicine techniques, such as in positron-emission tomography.

MRI with hyperpolarized helium-3 ((3)He) provides high-resolution imaging of ventilated airspaces. The first aim of this (3)He-study was to compare observations of localized signal defects in healthy smokers and non-smokers. A second aim was to describe relationships between parameters of lung function, volume of inspired (3)He and signal-to-noise ratio. With Ethics Committee approval and informed consent, 12 healthy volunteers (seven smokers and five non-smokers) were studied. Imaging was performed in a 1.5 T scanner using a two-dimensional FLASH sequence at 30V transmitter amplitude (TR/TE/alpha = 11 ms/4.2 ms/<10 degrees ). Known amounts of (3)He were inhaled from a microprocessor-controlled delivery device and imaged during single breath-holds. Images were evaluated visually, and scored using a prospectively defined 'defect-index'. Signal-to-noise ratio of the images were correlated with localization, (3)He volumes and static lung volumes. Due to poor image quality studies of two smokers were not eligible for the evaluation. Smokers differed from non-smokers in total number and size of defects: the 'defect-index' of smokers ranged between 0.8 and 6.0 (median = 1.1), that of non-smokers between 0.1 and 0.8 (median = 0.4). Intraindividually, an anteroposterior gradient of signal-to-noise ratio was apparent. Signal-to-noise ratio correlated with the estimated amount of hyperpolarization administered (r = 0. 77), but not with static lung volumes. We conclude that (3)He MRI is a sensitive measure to detect regional abnormalities in the distribution of ventilation in clinically healthy persons with normal pulmonary function tests., (Copyright 2000 John Wiley & Sons, Ltd.)

Objective: Assessment of the temporal and spatial dynamics of hyperpolarized Helium-3 (3He) distribution in the lung with ultrafast gradient-echo magnetic-resonance imaging., Material and Methods: Coronal images of the lung were acquired using ultrafast gradient-echo pulse sequences with TR/TE = 3.3 ms/1.3 ms (slice thickness, 40 mm) and TR/TE = 2.0 ms/0.7 ms (without slice selection). A series of 80 or 160 projection images was obtained with 210 ms or 130 ms temporal resolution, respectively. Imaging was performed during several respiratory cycles after application of a single bolus of 300 mL hyperpolarized 3He. Measurements were performed in six healthy volunteers (spontaneous breathing)., Results: Different phases of in- and expiration could be visualized. During the course of consecutive respiratory cycles the 3He signal decreased due to dilution of 3He in residual alveolar gas and by inspired air, relaxation due to oxygen and the RF pulses, and due to Helium-3 washout. The signal of a single bolus of 3He was detected in the lung for up to four respiratory cycles. Anatomical structures were better visualized on slice selective images than on images without slice selection., Conclusion: Distribution of inspired 3He within the tracheobronchial tree and alveolar space and its washout can be visualized by ultrafast imaging of a single bolus of hyperpolarized 3He gas. This method may allow for regional analysis of lung function with temporal and spatial resolution superior to conventional methods.

Purpose: To obtain statistical data on the use of high-resolution computed tomography (HRCT) for early detection of pneumonia in febrile neutropenic patients with unknown focus of infection., Materials and Methods: One hundred eighty-eight HRCT studies were performed prospectively in 112 neutropenic patients with fever of unknown origin persisting for more than 48 hours despite empiric antibiotic treatment. Fifty-four of these studies were performed in transplant recipients. All patients had normal chest roentgenograms. If pneumonia was detected by HRCT, guided bronchoalveolar lavage was recommended. Evidence of pneumonia on chest roentgenograms during follow-up and micro-organisms detected during follow-up were regarded as documentation of pneumonia., Results: Of the 188 HRCT studies, 112 (60%) showed pneumonia and 76 were normal. Documentation of pneumonia was possible in 61 cases by chest roentgenography or micro-organism detection (54%) (P < 10(-6)). Sensitivity of HRCT was 87% (88% in transplant recipients), specificity was 57% (67%), and the negative predictive value was 88% (97%). A time gain of 5 days was achieved by the additional use of HRCT compared to an exclusive use of chest roentgenography., Conclusion: The high frequency of inflammatory pulmonary disease after a suspicious HRCT scan (> 50%) proves that pneumonia is not excluded by a normal chest roentgenogram. Given the significantly longer duration of febrile episodes in transplant recipients, HRCT findings are particularly relevant in this subgroup. Patients with normal HRCT scans, particularly transplant recipients, have a low risk of pneumonia during follow-up. All neutropenic patients with fever of unknown origin and normal chest roentgenograms should undergo HRCT.

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.

Objective: This study was designed to determine lung volumes using inspiratory and expiratory helical CT with two-dimensional (2D) and three-dimensional (3D) postprocessing and to compare the accuracy of those measurements with pulmonary function test results., Subjects and Methods: Seventy-two patients with suspected pulmonary disease underwent unenhanced helical CT (slice thickness, 8 mm; pitch, 2; increment, 8 mm) at deep inspiration and expiration. Lung volumes were determined using either a 2D approach (semiautomatic segmentation; thresholds, -1024 and -200 H) or a 3D technique (double-threshold seeded volumes of interest; thresholds, -1024 H [lower] and -900, -500, 400, -300, or -200 H [upper]). Pulmonary function tests were available for correlation in all cases., Results: Using inspiratory helical CT, we underestimated total lung capacity by 12%, which had a good correlation (r = .89) with static lung volumes. Volume revealed by expiratory helical CT was equivalent to intrathoracic gas volume, which also exhibited a good correlation (r = .88). However, using expiratory helical CT, we overestimated residual volume by 850 ml with a rather good correlation (r = .77). An emphysema index revealed moderate correlation with the relative forced expiratory volume in 1 sec (inspiration, r = -.66; expiration, r = -.54), whereas the expired volume showed a moderate correlation with the absolute forced expiratory volume in 1 sec (r = .65). The 2D approach showed lower absolute volumes than the 3D technique (mean, 3.6%; r = .99). In the 3D technique, lower upper thresholds led to reduced volumes (170 ml/100 H)., Conclusion: Inspiratory and expiratory helical CT show high correlation with static lung volumes. The 3D technique (-1024 to -200 H) is recommended for absolute estimation of lung volumes.

Magnetic resonance angiography (MRA) has been established as a powerful noninvasive imaging modality. Its applications to the study of the pulmonary vasculature have been hampered by a multitude of factors, such as respiratory and cardiac motion artifacts, saturation problems, long acquisition times, and limited spatial resolution. The recent introduction of contrast-enhanced MRA (CE-MRA) has greatly improved the potential for possible investigation of the pulmonary arteries under clinical conditions. Three-dimensional sequences with minimum TR and TE, a flip angle between 20 degrees and 60 degrees, and minimum slice thickness can be considered an optimal approach for breath-hold imaging combined with the automatic injection of contrast medium. Early studies have demonstrated the superiority of CE-MRA over nonenhanced techniques. The major indication for CE-MRA of the pulmonary vasculature is pulmonary embolism. Here a sensitivity of 85% and specificity of 95% can be obtained. It can be complemented by perfusion imaging, ventilation imaging, functional measurements of the right ventricle, and MR venography of the pelvic and femoral veins. Blood pool contrast agents will open new perspectives in the future. This article reviews the technical aspects of CE-MRA of the pulmonary vasculature, pathologic findings, and their interpretation as well as present and future clinical applications.

The purpose of this study was to describe the 3He MRI findings of normal pulmonary ventilation in healthy volunteers and to evaluate abnormalities in patients with different lung diseases. Hyperpolarized 3He gas (300 ml, 3 x 10(5) Pa, polarized to 35-45% by optical pumping, provided in special glass cells) was inhaled by 8 healthy volunteers and 10 patients with different lung diseases. Imaging was performed with a three-dimensional fast low-angle shot (FLASH) sequence (TR = 11.8 msec; TE = 5 msec; transmitter amplitude, 5-8 V; corresponding flip angle, < 5 degrees) in a single breath-hold (22-42 seconds). Clinical and radiological examinations were available for correlation. The studies were performed successfully in eight of eight volunteers and in 8 of 10 patients. The lung parenchyma of volunteers with normal ventilatory function exhibited rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease or bronchiectasis presented with severe signal inhomogeneities with patchy or wedge-shaped defects. The mass effect of bronchogenic carcinoma, chronic empyema, lymphadenopathy, or pleural effusion caused large signal defects, representing the lesion and adjacent hypoventilation, the extent of which had not been presumed from chest x-ray or CT. 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its abnormalities. Additional studies are needed to determine its potential clinical role.

To assess the feasibility of helium-3 magnetic resonance (MR) imaging with a three-dimensional fast low-angle shot (FLASH) sequence, He-3 gas (volume, 300 mL; pressure, 3 x 10(5) Pa; polarized up to 45% by means of optimal pumping) was inhaled by five healthy volunteers and five patients with pulmonary diseases. All breath-hold examinations (22-42 seconds) were completed successfully. Normal ventilation was depicted with homogeneous high signal intensity, lesions were depicted as causing defects, and obstructive lung disease was depicted with severely inhomogeneous signal intensity.

After single-lung transplantation in a patient suffering from obstructive emphysema lung function parameters worsened during follow-up. To complement the routine high-resolution CT (HRCT) scans acquired in inspiration, additional scans were obtained to evaluate regional lung function. The comparison of HRCT scans acquired in inspiration and in expiration revealed different ventilation conditions of both lungs, continuous acquisition in a single slice (dynamic multiscan acquisition) in the axial and coronal plane demonstrated mediastinal shifting and the movement of the diaphragm during the whole breathing cycle. Both modalities can provide important information concerning regional differences of ventilation after single-lung transplantation. Expiratory HRCT should be applied on a regular basis in the follow-up of patients after single-lung transplantation. The application of axial and coronal dynamic multiscan acquisitions will be helpful in particular clinical conditions, like increasing hyperinflation, mediastinal shifting or bronchial collapse within the region of the anastomosis.

Purpose: To determine the sensitivity and clinical impact of high-resolution CT (HRCT) of the lung in febrile neutropenic patients under antibiotic therapy., Material and Methods: Chest X-ray and HRCT were prospectively performed to exclude pneumonia in 34 patients (53 examinations) suffering from febrile neutropenia following antitumor therapy. Diagnosis was confirmed by bronchoalveolar lavage or sputum cultures., Results: Chest X-ray showed pneumonia in 13/53 examinations, in 12/13 a micro-organism was found. HRCT demonstrated pneumonia in 39/53, in 31/39 a micro-organism was found. All cases with positive cultures showed suspicious HRCT findings. Changes in antibiotic treatment resulted in findings suspicious for pneumonia and evidence of a new or a just treated micro-organism (chest X-ray 8/53, HRCT 31/53); the search for the source of fever was escalated in cases without evidence of micro-organisms and without suspicion of pneumonia findings 14/53., Conclusion: HRCT of the lung exhibits a higher sensitivity than conventional radiographs. Findings resulted in relevant therapeutic consequences. Hence, HRCT is indicated in neutropenic patients with fever and inconspicuous chest X-ray.

Purpose: To evaluate the role of computed tomography (CT) in diagnosis of chronic thromboembolic pulmonary hypertension, assessment of surgical operability, and follow-up after surgery., Materials and Methods: Seventy-five patients with chronic thromboembolism were examined with CT; 63 underwent thromboendarterectomy, and postoperative CT scans were acquired in 23. CT scans were analyzed for vascular and parenchymal changes, and findings were compared with those on lung scintigrams and with surgical results., Results: CT findings allowed confirmation of the diagnosis of chronic thromboembolism and ensured technical operability (sensitivity, 77%; specificity, 100%; overall accuracy, 80%) by means of direct visualization of thrombi in central pulmonary arteries in 53 patients., Conclusion: CT enables demonstration of pulmonary thromboembolism with criteria pertaining to pulmonary arteries and to lung parenchyma and enables assessment of technical operatibility and confirmation of surgical success.

This is a report on a largely asymptomatic patient with a unilaterally non-functional lung. The differential diagnosis between an acquired, "destroyed" lung and congenital hypoplasia of the lung with secondary inflammatory changes proves difficult. The various imaging procedures that are available, used in conjunction with the histological findings, permit a classification.

Magnetic Resonance Imaging (MRI) of the chest and especially the lung is more and more accepted as a valuable additional imaging modality for several pulmonary diseases. Magnetic Resonance Imaging allows for combined morphological and functional imaging and therefore elucidates perfectly the effect of parenchymal changes and destruction onto pulmonary perfusion and ventilation. This overview presents the current status for the application of pulmonary MRI in chronic obstructive pulmonary disease as well as infectious and neoplastic diseases. [ABSTRACT FROM AUTHOR]