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Purpose To determine the reproducibility of several parameters of the ADC measurement by calculating the scan-to-scan intrasubject variability. Materials and Methods Measurements were performed using a gradient-echo sequence with a bipolar gradient for diffusion weighting (b = 3.89 sec/cm2). Five patients with pulmonary emphysema, and six healthy-lung volunteers were included in the study. Images were acquired after inspiration of 3He during a single inspiratory breath-hold. To assess the reproducibility, the measurement was performed twice (time between measurements = 20 minutes) without repositioning the subjects. Analysis was performed on the basis of region-of-interest (ROI) analysis and global lung ADC histograms. Results The mean ADC of a ROI varied by 5.1% between two measurements for volunteers and by 6.1% for patients. In the global evaluation, the 75th percentile demonstrated the best reproducibility (2%), while other parameters showed variations up to 12%. Only the variation of the standard deviation (SD) and the measure of homogeneity of the ADC map showed a significant difference between patients and volunteers. Conclusion Diffusion-weighted imaging (DWI) is a well-reproducible method for assessing the lung microstructure. J. Magn. Reson. Imaging 2005;21:765–774. © 2005 Wiley-Liss, Inc.

The purpose of this study was to use cine-MRI during continuous respiration to measure the respiratory lumenal diameter change in the pharynx and at an upper tracheal level. Fifteen non-smokers and 23 chronic obstructive pulmonary disease (COPD) patients with smoking history (median 50 pack-years) were included. Cine-MRI with seven frames/s was performed during continuous respiration. Minimal and maximal cross-sectional lumenal diameters within the pharynx and the upper tracheal lumen area were measured. The median diameter change in the pharynx (tracheal area) was 70% (1.4 cm(2)) in volunteers and 76% (1.7 cm(2)) in smokers (P=0.98, P=0.04). Tracheal lumenal collapse was a median of 43% in volunteers and 64% in smokers (P=0.011). No clear disease-related difference of the pharynx-lumen was found. The maximal cross-sectional area of the upper trachea lumen as well as the respiratory collapse was larger in COPD patients than in normal subjects. This information is important for the modelling of ventilation and prediction of drug deposition, which are influenced by the airway diameter.

Rationale and objectives Introduction of combination of the segmentation tool SegoMeTex and the virtual endoscopy system VIVENDI to perform virtual endoscopic inspections of the human lung. This virtual bronchoscopy system enables visualization of the tracheobronchial tree down to seventh generation. Furthermore, the modified virtual system visualizes hidden structures such as segmented vascular system or tumors. Materials and methods The segmentation is based on image data acquired by a multislice computed tomography scanner. SegoMeTex is used to segment the tracheobronchial tree by a hybrid system with minimal user action. Similarly, the complementary pulmonary arterial can be segmented, whereas additional structures such as tumors are marked manually. On this dataset, subsequently, data structures of the inner surface for virtual endoscopy are generated. Finally, the dataset can be explored by a virtual bronchoscopy procedure using the VIVENDI system. Results The segmentation method was successfully tested on 22 patients. The hybrid segmentation system identified bronchi up to the sixth generation with a sensitivity of more than 58%, and a positive predictive value of more than 90%. After the segmentation, the datasets are explored interactively (>30 fps on a standard personal computer platform in real-time rendering) using the virtual endoscopy software. The exploration exposed a high-quality reconstruction, even of small structures throughout the dataset. Conclusion Virtual bronchoscopy in combining with a highly sensitive segmentation is a valuable tool for the localization and measurement of stenosis for resection planning.

Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.

The tracheobronchial tree as part of the lung is part of one of the most important organs of the human body. Inhaled air is distributed to the alveolus where oxygen and carbon dioxide exchange between air and blood takes place. In this paper, we introduce the virtual endoscopy system VIVENDI to perform virtual inspections of tracheobronchial trees based on their segmentation and of the complementing blood vessels. It is based on a hybrid segmentation pipeline which enables the segmentation of vascular and tracheobronchial structures down to the seventh generation of the bronchi.

Computed tomography (CT) is the method of choice for the morphological assessment of pulmonary structure. Airways. pulmonary parenchyma and their pathologies are shown with high spatial resolution. Airway diseases exhibit bronchial dilatation, wall thickening and an increased visibility in the lung periphery. CT is also the imaging gold standard for the detection and the characterisation of emphysema because a high degree of concordance with histopathological studies. Centrilobular, panlobular and paraseptal emphysema can be differentiated. CT can also provide functional information. Paired inspiratory and expiratory scans with or without spirometric triggering allow to evaluate obstruction of the small airways (airtrapping). On the basis of CT-data lung volumes can be semented. Cine-CT allows to visualise motion of the central airways. e.g. in tracheomalacia, to assess regional ventilation to calculate pulmonary time constants. and to display the co-ordinated or dissociated motion of the thoracic wall and the diaphragm. Beyond the mere high-resolution visualisation of the structure of the lung the application of these CT-strategies makes a regional assessment of pulmonary function possible.

Objectives Quantitative multidetector computed tomography (MDCT) as a potential biomarker is increasingly used for severity assessment of emphysema in chronic obstructive pulmonary disease (COPD). Aim of this study was to evaluate the user-independent measurement variability between five different fully-automatic densitometry software tools. Material and Methods MDCT and full-body plethysmography incl. forced expiratory volume in 1s and total lung capacity were available for 49 patients with advanced COPD (age = 64±9 years, forced expiratory volume in 1s = 31±6% predicted). Measurement variation regarding lung volume, emphysema volume, emphysema index, and mean lung density was evaluated for two scientific and three commercially available lung densitometry software tools designed to analyze MDCT from different scanner types. Results One scientific tool and one commercial tool failed to process most or all datasets, respectively, and were excluded. One scientific and another commercial tool analyzed 49, the remaining commercial tool 30 datasets. Lung volume, emphysema volume, emphysema index and mean lung density were significantly different amongst these three tools (p

To evaluate retrospectively the self-expanding nitinol Sinus-XL stent (OptiMed, Ettlingen, Germany) for the treatment of superior vena cava (SVC) obstruction caused by non-small cell lung cancer (NSCLC).Between October 2009 and December 2012, 23 patients (7 women and 16 men; age, 62.5 y ± 8.5) with stage IIIA (1 patient), IIIB (4 patients) or IV (18 patients) NSCLC and acute SVC obstruction were scheduled for urgent stent implantation. The primary study endpoints were technical success (defined as accurate stent placement with complete coverage of the obstructed SVC), residual stenosis30%, and clinical efficacy. Complications were assessed as a secondary study endpoint.There were 26 stents implanted in 23 patients. The technical success was 100%. Stent dilation was performed after deployment in 18 cases (78%). Stent migration into the right atrium occurred immediately after deployment in one patient; however, this stent was successfully repositioned and stabilized by a second stent. The clinical symptoms improved at least one category according to the International Consensus Committee on Chronic Venous Disease after stent implantation in all but one patient. The mean clinical follow-up was 66 days ± 83 (range, 1-305 d). Three minor complications (13%) and one major complication (4%) occurred.Implantation of the self-expanding Sinus-XL stent for treatment of SVC obstruction caused by NSCLC is a safe and effective urgent treatment in this palliative setting.

A method for in vivo measurement of oxygen partial pressure (pO2) in porcine lungs during partial liquid ventilation (PLV) with perflubron (PFOB) was developed. A pulse sequence for high-resolution MRI of the distribution of PFOB in the lung after intratracheal administration was developed as well. Moreover, quantitative measurements of longitudinal relaxation time T(1) of (19)F resonances for assessment of regional pO2 are described. Due to the need to acquire data during a single expiratory breathhold, only low SNRs were achieved in vivo. Therefore, simulations were performed to investigate the influence of background noise on T(1) values calculated from data with low SNR. Based on these simulations, a postprocessing strategy was developed to correct for systematic errors by background noise prior to quantitative analysis. Results of a pilot study in pigs under conditions of PLV are presented.

A new method for dynamic imaging of pulmonary wash-in and wash-out kinetics of inhaled sulfur hexafluoride (SF6) 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 SF6 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 SF6 gas is feasible in large animals. Moreover, regional wash-in and wash-out kinetics of SF6 can be determined noninvasively with this new method. Potential human applications are discussed. Magn Reson Med 45:605–613, 2001. © 2001 Wiley-Liss, Inc.

Wegen technischer und physikalischer Einschrankungen wurde die MRT bisher nur selten zur Darstellung der Lunge eingesetzt. Neue Entwicklungen haben allerdings die Moglichkeiten der anatomischen Darstellung mittels MRT erheblich verbessert und gleichzeitig neue Perspektiven fur funktionelle Darstellungen eroffnet. Dazu gehoren Techniken zur funktionellen Untersuchung der Perfusion (Kontrastmittel, MR-Angiographie) und der Ventilation der Lunge (inhalierte aerosolierte Kontrastmittel, Sauerstoff, hochpolarisierte Edelgase [He-3, Xe-129] und fluorinierte Gase [SF6]). Die Gleichmasigkeit der Ventilation, Bestimmung von Lungenvolumina, Grose der Luftraume, intrapulmonale Sauerstoffkonzentration, dynamische Verteilung der Ventilation und regionale Ventilations-Perfusions-Verhaltnisse werden messbar. Die MRT vereinigt im Gegensatz zu den alternativen Untersuchungstechniken eine Vielzahl von Vorteilen: fehlende Strahlenexposition, hohe raumliche und zeitliche Auflosung und ein breites Spektrum funktioneller Informationen. Insbesondere in der Detektion von Ventilationsdefekten erscheint die MRT sensitiver als die Szintigraphie, die CT oder die Lungenfunktionsprufung. Durch die Kombination der neuen Strategien wird der Radiologe die Moglichkeit besitzen, die Spezifitat der Untersuchungen deutlich zu steigern und Storungen der Lungenfunktion zu charakterisieren. Der gemeinsamen Untersuchung von Ventilation und Perfusion kommt dabei eine zentrale Rolle zu.

In tracheo- and bronchomalacia, localisation and determination of collapse is necessary for planning of surgical procedure. We compared inspiratory and expiratory spiral CT, cine CT, bronchoscopy, exemplary cine MR, and evaluated the clinical relevance. Twenty-nine patients (2 follow-ups; mean age 61 years, age range 27-85 years) with suspected or verified tracheal stenosis or collapse (post-tracheotomy: n = 17; neoplasm: n = 5; other: n = 7) underwent paired breath-hold inspiratory and expiratory spiral CT. Forty-five additional cine CT were performed at 1-4 levels (mean 1.5) during continuous respiration (increment 100 ms) to clarify respiratory collapse. The tracheal cross-sectional diameters of both techniques were calculated. Comparison with bronchoscopy, follow-up, and influence upon therapy were evaluated retrospectively. Exemplary comparison with cine MR (8 frames/s) was done in 3 cases. In addition to bronchoscopy, further information concerning localisation, extent, collapse, stability of the tracheal wall, distal portions of the stenosis and extraluminal compressions were obtained. A significantly higher degree and more pathological collapses (50%) were seen using cine CT (38%) compared with paired spiral CT (13%; degree: p0.0001; number: p0.001). The findings changed the further therapeutic procedure in 16 of 29 patients. Further stenoses were excluded and bronchoscopy was verified in another 13 of 29. Temporal resolution of cine CT and cine MR is sufficient; however, spatial resolution of cine MR is inferior. Paired inspiratory and expiratory spiral CT localises tracheal stenoses and demonstrates relevant extraluminal compression. Significantly improved evaluation of respiratory collapse and further information of localised tracheal instability is obtained by cine CT. Cine MR promises more functional information especially due to free choice of imaging plane.

The purpose of this study was to evaluate the usefulness of thin-section CT for early detection of pneumonia in neutropenic patients with an unknown site of infection and normal or nonspecific findings on chest radiographs.Eighty-seven patients with febrile neutropenia that persisted for more than 2 days despite empiric antibiotic treatment underwent 146 prospective examinations. If findings on chest radiographs were normal (n = 126) or nonspecific (n = 20), thin-section CT (1-mm collimation, 10-mm increment) was done. If thin-section CT scans showed opacities, bronchoalveolar lavage was recommended.Findings on chest radiographs were nonspecific for pneumonia in 20 (14%) of 146 cases, and CT findings in those cases were suggestive of pneumonia. Microorganisms were detected in 11 of those 20 cases. Seven of the 11 cases were not optimally treated before CT diagnosis, the other four were sufficiently treated. Findings on chest radiographs and thin-section CT scans were normal in 56 (38%) of 146 cases. In 70 (48%) of 146 cases, findings on chest radiographs were normal, whereas findings on thin-section CT scans were suggestive of pneumonia. Microorganisms were detected in 30 of the 70 cases. Nineteen of 30 cases were not optimally treated before CT, whereas the other 11 cases were sufficiently treated before CT. In 22 (31%) of these 70 cases, an opacity was observed on the chest radiograph during the 7 days after the CT study. Only three (5%) of 56 pneumonias occurred during the first 7 days after thin-section CT studies with normal findings (p.005). Additional risk factors for pneumonia occurring later that were detectable on chest radiographs were poorly defined nodules (p.05), consolidation (p.05), and younger age (p.05).Thin-section CT scans show findings suggestive of pneumonia about 5 days earlier than chest radiographs show suggestive findings. When thin-section CT scans show findings suggestive of pneumonia, the probability of pneumonia being detected on chest radiographs during the 7-day follow-up is 31%, whereas the probability is only 5% when the findings on the prior thin-section CT scan were normal (p.005). All neutropenic patients with fever of unknown origin and normal findings on chest radiographs should be examined with thin-section CT.

PURPOSE Evaluation of clinical relevance of coronary calcifications detected by helical CT. Evaluation of congruence with fluoroscopy (FS) and coronary angiography. Comparison with studies reporting on application of ultrafast computed tomography. MATERIALS AND METHODS 40 patients underwent helical CT (2 mm slice thickness, table-feed 3 mm/s). Coronary angiography and FS were performed in usual technique. Stenosis and calcifications were evaluated semiquantitatively. RESULTS 28 of 28 stenoses > or = 75% were detected via helical CT by evaluation of calcification (FS: 19). One non-detected solitary stenosis was calculated as 40%. FS did not detect 4 cases with 2-vessel and 3-vessel disease each one case with 1-vessel disease, and one case with a main stem stenosis. Sensitivity of helical CT was 97% (FS: 66%). For the evaluation of stenosis III degree (> or = 75%), sensitivity was 100% (FS: 58%), specificity was 77% (FS: 48%). CONCLUSION Helical CT is more sensitive for haemodynamically relevant stenoses than FS. Helical CT is suitable as a substantial non-invasive diagnostic procedure in coronary heart disease. In certain cases, e.g. if the patient suffers from additional risks, helical CT should be done prior to coronary angiography. Coronary calcifications found incidentally in symptomatic patients at chest CT warrant further cardiological investigation.

Background: Central airway obstruction (CAO) is a life-threatening situation. Stent insertion re-establishes patency of the central airways. Self-expanding metallic Y stents have been available since 2005, widening the spectrum of interventional bronchoscopic techniques. Methods: Retrospective analysis of all patients treated for CAO with a self-expanding metallic Y stent at the Thoraxklinik Heidelberg between May 2005 and January 2009. Results: A total of 43 patients aged 26–81 had a metallic Y stent inserted endoscopically for the treatment of CAO; 39 of these patients (90.7%) had CAO due to malignant disease, four patients (9.3%) due to benign disease. In all 43 patients, the Y stent was deployed without any complications. A longitudinal follow up was possible in 32 of the 43 patients. The stents remained in situ for an average of 107.1 days (range 1–640 days). In 29 patients with malignant CAO the stenosis was successfully overcome with a Y stent; 11 of these patients died within 6 weeks following stent insertion. On follow up the remaining 18 patients showed immediate improvement of dyspnoea. Eight out of the 18 patients (44.4%) tolerated the stent without problems, two (11.1%) required further stenting, six (33.3%) had complications such as increased secretions, cough, dyspnoea or granulation tissue formation. The stent was removed in one patient (5.6%) due to increased secretions, and in another (5.6%) as the stent was no longer required due to successful tumour-specific therapy. Conclusion: Placement of Y stents in symptomatic CAO allows for quick relief of symptoms. Severe complications are rare. Stent removal is possible after successful treatment of the primary tumour. However, the prognostic indicator for survival is the underlying malignancy.

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.

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.

Background The aim of this retrospective analysis, was to evaluate the safety and efficacy of Lung Volume Reduction with coils (LVR-Coil) treatment in a single-centre setting in patients with severe heterogeneous emphysema and bilaterally incomplete fissures Methods In this retrospective analysis 86 patients with severe COPD (m/f:40/46, age: 64 ± 7 years) and bilateral incomplete fissures were included. A total of 10 coils were unilaterally implanted in a single lobe. 28 patients received additional treatment of a contralateral lobe. At 90, 180 and 365 days’ follow-up changes in pulmonary function tests, 6-Minute-Walk-Test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications were recorded. Results FEV1 improved significantly at the 90-day follow up (p:0.001) but the improvement was not sustained at 180 and 365 days (0.71 ± 0.21 L vs 0.76 ± 0.23 L vs 0.73 ± 0.22 L vs 0.69 ± 0.18 L). FEV1 improved more than 12% (minimal clinically significant change, MCID) in 30 patients (38%). Vital Capacity improved significantly at the 90- (p Conclusions LVR-coil improved PFT, 6MWT and mMRC initially but improvement was lost after 365 days. However, this improvement came at a cost of significant complications and with a 3.5% mortality rate.

The authors wish to determine the extent to which the Response Evaluation Criteria in Solid Tumors (RECIST) and the criteria of the World Health Organization (WHO) can predict tumor volumes and changes in volume using clinical data.The data presented are a reanalysis of data acquired in other studies, including the public database from the Lung Image Database Consortium (LIDC) and from a study of liver tumors.The principal result is that a given RECIST diameter predicts volume to a factor of 16 or 10 for the two data sets, respectively, by examining 95% prediction bounds and that changes in volume are predicted only little better: to within a factor of 7 for the liver data. The WHO criteria reduce the prediction bounds by a factor of 1.3 in all cases. Also, the RECIST threshold of 10 mm to measure a nodule corresponds to a transition zone width of a factor of more than 2 in volume for the nodules in the LIDC database.While the RECIST diameter is certainly correlated with the volume, and similarly for changes in these quantities, the use of the diameter introduces additional variation assuming volume is the quantity of interest. Exactly how much this reduces the statistical power of clinical drug trials is a key open question for future research.

Invasive fungal infections (IFIs) are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of IFI in immunocompromised patients is particularly challenging and time consuming, but delayed initiation of antifungal treatment increases mortality. The limited overall outcome has led to the strategy of initiating either 'empirical' or 'preemptive' antifungal therapy before the final diagnosis. However, diagnostic procedures have been vastly improved in recent years. Particularly noteworthy is the introduction of newer imaging techniques and non-culture methods, including antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples. Though varying widely in cancer patients, the risk of IFI is highest in those with allogeneic stem cell transplantation and those with acute leukemia. The AGIHO presents recommendations for the diagnosis of IFIs with risk-adapted screening concepts for febrile episodes in patients with haemato-oncological disorders.

The authors investigate the extent to which Response Evaluation Criteria in Solid Tumors (RECIST) can predict tumor volumes in ideal geometric settings and using clinical data.The authors consider a hierarchy of models including uniaxial ellipsoids, general ellipsoids, and composites of ellipsoids, using both analytical and numerical techniques to show how well RECIST can predict tumor volumes in each case. The models have certain features that are compared to clinical data.The principal conclusion is that a change in the reported RECIST value needs to be a factor of at least 1.2 to achieve a 95% confidence that one ellipsoid is larger than another assuming the ratio of maximum to minimum diameters is no more than 2, an assumption that is reasonable for some classes of tumors. There is a significant probability that RECIST will select a tumor other than the largest due to orientation effects of nonspherical tumors: in previously reported malignoma data, RECIST would have selected a tumor other than the largest in 9% of the cases. Also, the widely used spherical model connecting RECIST values for a single tumor to volumes overestimates these volumes.RECIST imposes a limit on the ability to determine tumor volumes, which is greater than the limit imposed by modem medical computed tomography machines. It is also likely the RECIST limit is above natural biological variability of stable lesions. The authors recommend the study of such natural variability as a fruitful avenue for further study.

Summary Objectives Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenic patients. The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy. We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML). Methods This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AML patients undergoing remission induction chemotherapy. Oral voriconazole 200mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia. Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy. Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety. Results A total of 25 patients were randomly assigned to receive voriconazole ( N =10) or placebo ( N =15). Incidence of lung infiltrates until day 21 was 0 (0%) in the voriconazole and 5 (33%) in the placebo group ( P =0.06). Average length of stay in hospital was shorter in the voriconazole group (mean 31.9days) than in the placebo group (mean 37.3days, P =0.09). Four patients were diagnosed with hepatosplenic candidiasis until a 4week follow-up, all in the placebo group ( P =0.11). Adverse events and toxicity did not differ between the two treatment groups. The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical. Conclusion In AML patients undergoing induction chemotherapy, prophylactic oral voriconazole 200mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.

Es wird eine Methode zum objektiven Bestimmen der Wanddicke und des Gesamt durchmessers von Bronchien in der 3-dimensionalen Computertomographie vorgestellt. Die Methode wurde erfolgreich an Phantomen evaluiert. Erste Studien sowohl an tierischen als auch an menschlichen Bronchien verliefen erfolgversprechend.

Rationale and Objectives: Partial liquid ventilation using Perfluorcarbon (PFC) is an innovative treatment of acute respiratory distress syndrome. However, the underlying mechanisms are not totally clear. The aim was to investigate the distribution of oxygen partial pressure within the PFC-filled lung (ppO 2 ). Methods: Nine pigs underwent partial liquid ventilation, receiving 20 mL PFC/kg bodyweight (bw). Measurements were obtained by a chemical shift selective TurboFLASH sequence at different axial lung levels. ppO 2 was calculated from 1 9 F-MRI by nonlinear curve T 1 -fitting technique after noise correction. Results: Quantification and distribution of ppO 2 was performed successfully. A narrow relationship of the inspiratory O 2 fraction and ppO 2 , as well as a significant ventral-to-dorsal gradient of ppO 2 (ventral:dependent lung = 1.9:1) were detected in all subjects and slice positions. Conclusions: In vivo measurement of local ppO 2 gains new and clinical important insights into the physiology of PLV. The previously unknown ppO 2 gradient within PFC fits to distribution of perfusion. Dependent lung regions appear to have limited access to O 2 from central airways.

The new technology of the Multislice-CT provides volume data sets with approximately isotropic resolution, which permits a non invasive measurement of diffuse lung diseases like emphysema in the 3D space. The aim of our project is the development of a full automatic 3D CAD (Computer Aided Diagnosis) software tool for detection, quantification and characterization of emphysema in a thoracic CT data set. It should supply independently an analysis of an image data set to support the physician in clinical daily routine. In this paper we describe the developed 3D algorithms for the segmentation of the tracheo-bronchial tree, the lungs and the emphysema regions. We present different emphysema describing indices.

The aim of this study was to evaluate the diagnostic value of contrast-enhanced MR angiography (ce MRA) and helical CT angiography (CTA) of the pulmonary arteries in the preoperative workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH). The ce MRA and CTA studies of 32 patients were included in this retrospective evaluation. Image quality was scored by two independent blinded observers. Data sets were assessed for number of patent segmental, subsegmental arteries, and number of vascular segments with thrombotic wall thickening, intraluminal webs, and abnormal proximal to distal tapering. Image quality for MRA/CTA was scored excellent in 16 of 16, good in 11 of 14, moderate in 2 of 5, and poor in no examinations. The MRA/CTA showed 357 of 366 patent segmental and 627 of 834 patent subsegmental arteries. CTA was superior to MRA in visualization of thrombotic wall thickening (339 vs 164) and of intraluminal webs (257 vs 162). Abnormal proximal to distal tapering was better assessed by MRA than CTA (189 vs 16). In joint assessment of direct and indirect signs, MRA and CTA were equally effective (353 vs 355). MRA and CTA are equally effective in the detection of segmental occlusions of the pulmonary arteries in CTEPH. CTA is superior for the depiction of patent subsegmental arteries, of intraluminal webs, and for the direct demonstration of thrombotic wall thickening.

The purpose of this prospective study was to measure lung attenuation at paired HRCT obtained at full inspiratory/expiratory position, to correlate with pulmonary function tests (PFTs) and to characterize different types of ventilatory impairment. One hundred fifty-five patients with and without pulmonary disease underwent paired HRCT obtained at full inspiratory/expiratory position. Three scan pairs were evaluated by densito- and planimetry using dedicated software. The PFTs were available for correlation in all patients (mean interval 5 days). Mean lung density (MLD) at full inspiration was -813 HU, and MLD at full expiration was -736 HU; both, as well as the expiratory attenuation increase, demonstrated significant correlations with static and dynamic lung volumes: up to r=0.68, p0.05 for residual volume. The MLD and emphysema indices correlated markedly better for scans obtained at full expiration than at full inspiration, e.g. correlation with the residual volume: r=0.68 compared with r=0.55. Even better correlations were obtained for the lung area (229 cm(2) at inspiration, 190 cm(2) at expiration), up to r=0.74 for the lung area in expiration and the intrathoracic gas volume. Inspiratory MLD and the expiratory attenuation increase were able to differentiate obstructive and restrictive ventilatory impairment from normal subjects, the best results were obtained from scans obtained at full expiratory position ( p0.05). In conclusion, scans obtained at full expiratory position reveal more functional information than scans obtained at full inspiratory position. Quantitative analysis of CT obtained at full expiratory position provides good estimations of static and dynamic lung volumes as well as significant differences between normal subjects and patients with ventilatory impairment.

A method for in vivo measurement of oxygen partial pressure (pO2) in porcine lungs during partial liquid ventilation (PLV) with perflubron (PFOB) was developed. A pulse sequence for high-resolution MRI of the distribution of PFOB in the lung after intratracheal administration was developed as well. Moreover, quantitative measurements of longitudinal relaxation time T(1) of (19)F resonances for assessment of regional pO2 are described. Due to the need to acquire data during a single expiratory breathhold, only low SNRs were achieved in vivo. Therefore, simulations were performed to investigate the influence of background noise on T(1) values calculated from data with low SNR. Based on these simulations, a postprocessing strategy was developed to correct for systematic errors by background noise prior to quantitative analysis. Results of a pilot study in pigs under conditions of PLV are presented.

PURPOSE: To study the additional benefit from adenoviral p53 gene therapy in patients undergoing first-line chemotherapy for advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Twenty-five patients with nonresectable NSCLC were enrolled in an open-label, multicenter phase II study of three cycles of regimen A, carboplatin (area under the curve, 6; day 1) plus paclitaxel (175 mg/m2, day 1), or regimen B, cisplatin (100 mg/m2, day 1) plus vinorelbine (25 mg/m2, days 1, 8, 15, and 22) in combination with intratumoral injection of 7.5 × 1012 particles of SCH 58500 (rAd/p53, day 1). Responses of individual tumor lesions were assessed after each cycle, and gene transfer was examined in posttreatment tumor biopsies using reverse transcriptase polymerase chain reaction. RESULTS: There was no difference between the response rate of lesions treated with p53 gene therapy in addition to chemotherapy (52% objective responses) and lesions treated with chemotherapy alone (48% objective responses). Subgroup analysis according to the chemotherapy regimens revealed evidence for increased mean local tumor regressions in response to additional p53 gene therapy in patients receiving regimen B, but not in patients receiving regimen A. There was no survival difference between the two chemotherapy regimens, and the median survival of the cohort was 10.5 months (1-year survival, 44%). Transgene expression was confirmed in tumor samples from 68% of patients, and toxicities attributable to gene therapy were mild to moderate. CONCLUSION: Intratumoral adenoviral p53 gene therapy appears to provide no additional benefit in patients receiving an effective first-line chemotherapy for advanced NSCLC.

MRI with hyperpolarized helium-3 (3He) provides high-resolution imaging of ventilated airspaces. The first aim of this 3He-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 3He 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/α = 11 ms/4.2 ms/

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.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.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).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.

Abstract 2309 Objectives. Treatment of invasive aspergillosis (IA) fails in up to 50% of all cases and the mortality rate is at least 30%. Antifungal combination treatment has not been proven to be beneficial and dose escalation with liposomal amphotericin B did not improve outcome. New approaches are needed for patients with severe immunosuppression. Methods. Escalating high dosages of caspofungin were investigated in IA defined according to modified EORTC/MSG criteria. The tested cohort of patients received 70mg, 100mg, 150mg or 200mg QD, 8 patients each were to receive caspofungin first-line treatment for proven/probable IA for up to 28 days. Dose limiting toxicity was defined as 2 of 8 patients in the same cohort with the same grade ≥4 non-hematological treatment-related adverse event (TRAE), or 4 of 8 patients with a grade ≥3 non-hematological TRAE. If no dose-limiting toxicity was reached, 12 additional patients were to be enrolled in the 200mg cohort. Patients unevaluable for toxicity or pharmacokinetic analysis were replaced. Results. A total of 46 patients were treated in the 4 cohorts (9, 8, 9, 20 pts). IA was proven in 2.2% and probable in 97.8%. Patient characteristics were as follows: Median age 61 years (min 18.3, max 73.7); 21/46 (45.7%) female. Underlying disease distribution was: AML 50%, ALL 8.7%, lymphoma 19.6%, chronic lymphocytic leukaemia 10.9%, other 10.9%. Median duration of treatment was 24.5 days. Two (4.3%) patients with treatment durations ≤5 days were replaced for pharmacokinetic analysis, but evaluated for safety and efficacy. No dose-limiting toxicity was found by investigator or DSMB assessment. At end of treatment (EOT) complete plus partial response was achieved in the 4 cohorts in 4/9, 3/8, 6/9, 12/20 patients, i.e. 25/46 (54.3%) of the total population. Stable disease was achieved in 4 patients (8.7%), 17 (37%) patients failed treatment. Overall survival at 12 weeks was 76.1%. After a 12 week follow-up attributable mortality was 8.7%. Death due to malignancy occurred in 10.9%, to sepsis in 8.7%. Conclusions. In the first-line treatment of proven or probable invasive aspergillosis no dose-limiting toxicity of caspofungin at doses up to 200 mg QD was found. Complete plus partial response rates at EOT were 54.3% after dose-escalated caspofungin treatment, and thus in the range of the success rates previously reported with voriconazole and liposomal amphotericin B. Twelve weeks after start of treatment the 23.9% overall mortality rate was lower than that found in the literature. Disclosures: Cornely: MSD: Consultancy, Honoraria. Vehreschild: MSD: Honoraria. Rüping: MSD: Honoraria. Silling: MSD: Membership on an entity's Board of Directors or advisory committees. Lehrnbecher: MSD: Membership on an entity's Board of Directors or advisory committees. Ullmann: MSD: Honoraria. Groll: MSD: Membership on an entity's Board of Directors or advisory committees. Karthaus: MSD: Membership on an entity's Board of Directors or advisory committees.

Patients with severe neutropenia lasting for more than 10 days, who develop fever and pulmonary infiltrates, are at high risk of treatment failure and infection-related death, under conventional broad-spectrum antibiotics. Early supplementation by a systemic antifungal therapy active against Aspergillus spp. has been shown to markedly improve their clinical outcome. Prognosis is significantly influenced by early identification of lung infiltrates by means of high-resolution thoracic computed tomography. Non-culture based diagnostic procedures using a highly sensitive Sandwich ELISA assay to detect circulating galactomannan, or PCR techniques to amplify circulating fungal DNA, may facilitate the diagnosis of invasive pulmonary aspergillosis. CT-directed bronchoscopy and bronchoalveolar lavage using standardized procedures are useful in order to identify causative microorganisms such as filamentous fungi or Pneumocystis carinii. The standard antifungal agent in the treatment of these patients, amphotericin B deoxycholate, has been challenged recently by newly developed antifungals such as voriconazole. It seems important to continue antifungal treatment for at least 14 days before first response assessment. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates, to avoid inadequate antimicrobial treatment modification.

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.