Probing of chain conformations in conjugated polymer nanoparticles by electron spin resonance spectroscopy.

In the case of conjugated polymer chains usually considered as rigid or stiff, it is an open question how the individual chains adopt their conformation inside nanoparticles. Here, the conformation of such a rigid conjugated polymer chain is elucidated for the first time. For this purpose, electron paramagnetic resonance spectroscopy as a method allowing for a direct observation is established.

Inter-observer reproducibility of semi-automatic tumor diameter measurement and volumetric analysis in patients with lung cancer.

OBJECTIVES: Therapy monitoring in oncologic patient requires precise measurement methods. In order to improve the precision of measurements, we used a semi-automated generic segmentation algorithm to measure the size of large lung cancer tumors. The reproducibility of computer-assisted measurements were assessed and compared with manual measurements. METHODS: CT scans of 24 consecutive lung cancer patients who were referred to our hospital over a period of 6 months were analyzed. The tumor sizes were measured manually by 3 independent radiologists, according to World Health Organization (WHO) and the Revised Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. At least 10 months later, measurements were repeated semi-automatically on the same scans by the same radiologists. The inter-observer reproducibility of all measurements was assessed and compared between manual and semi-automated measurements. RESULTS: Manual measurements of the tumor longest diameter were significantly (p < 0.05) smaller compared with the semi-automated measurements. The intra-rater correlations coefficients were significantly higher for measurements of longest diameter (intra-class correlation coefficients: 0.998 vs. 0.986; p < 0.001) and area (0.995 vs. 0.988; p = 0.032) using semi-automated compared with manual method. The variation coefficient for manual measurement of the tumor area (WHO guideline, 15.7% vs. 7.3%) and the longest diameter (RECIST guideline, 7.7% vs. 2.7%) was 2-3 times that of semi-automated measurement. CONCLUSIONS: By using computer-assisted size assessment in primary lung tumor, interobserver-variability can be reduced to about half to one-third compared to standard manual measurements. This indicates a high potential value for therapy monitoring in lung cancer patients.

MRI of the lung (3/3)-current applications and future perspectives.

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations.

[Lung cancer staging]. / Staging des Lungenkarzinoms.

Lung cancer is the third most frequent new cancer diagnosis in Germany. An elaborate clinical diagnosis is essential for successful therapy planning. The necessary examinations are defined in the current S3 guideline on lung cancer diagnosis and therapy. A compilation of diagnostic reports has led to the current 7th edition of the TNM system. According to this update staging is carried out in terms of tumor extent, lymph node status and distant metastases. The resultant tumor stage forms the basis for individual therapy planning. Current guidelines as well as the current TNM system are presented. The usefulness of modern cross-sectional imaging and the possible modalities in this system is reported.

[New procedures. Comprehensive staging of lung cancer by MRI]. / Neue Verfahren. Umfassendes Staging des Lungenkarzinoms mit der MRT.

Lung cancer staging according to the TNM system is based on morphological assessment of the primary cancer, lymph nodes and metastases. All aspects of this important oncological classification are measurable with MRI. Pulmonary nodules can be detected at the clinically relevant size of 4-5 mm in diameter. The extent of mediastinal, hilar and supraclavicular lymph node affection can be assessed at the same time. The predominant metastatic spread to the adrenal glands and spine can be detected in coronal orientation during dedicated MRI of the lungs. Search focused whole body MRI completes the staging. Various additional MR imaging techniques provide further functional and clinically relevant information during a single examination. In the oncological context the most important techniques are imaging of perfusion and tumor motion. Functional MRI of the lungs complements the pure staging and improves surgical approaches and radiotherapy planning.

A hybrid breath hold and continued respiration-triggered technique for time-resolved 3D MRI perfusion studies in lung cancer.

PURPOSE: Assessment of lung cancer perfusion is impaired by respiratory motion. Imaging times for contrast agent wash-out studies often exceed breath hold capabilities, and respiration triggering reduces temporal resolution. Temporally resolved volume acquisition of entire tumors is required to assess heterogeneity. Therefore, we developed and evaluated an MR measurement technique that exceeds a single breath hold, and provides a variable temporal resolution during acquisition while suspending breath-dependent motion. MATERIALS AND METHODS: 20 patients with suspected lung cancer were subjected to perfusion studies using a spoiled 3D gradient echo sequence after bolus injection of 0.07 mmol/kg body weight of Gd-DTPA. 10 acquisitions in expiratory breath hold were followed by 50 navigator-triggered acquisitions under free breathing. Post-processing allowed for co-registration of the 3D data sets. An ROI-based visualization of the signal-time curves was performed. RESULTS: In all cases motion-suspended, time-resolved volume data sets (40 x 33 x 10 cm(3), voxel size: 2.1 x 2.1 x 5.0 mm(3)) were generated with a variable, initially high temporal resolution (2.25 sec) that was synchronized with the breath pattern and covered up to 8 1/2 min. In 7 / 20 cases a remaining offset could be reduced by rigid co-registration. The tumors showed fast wash-in, followed by rapid signal decay (8 / 20) or a plateau. CONCLUSION: The feasibility of a perfusion study with hybrid breath hold and navigator-triggered time-resolved 3D MRI which combines high initial temporal resolution during breath hold with a long wash-out period under free breathing was demonstrated.

[Investigation of respiratory-dependent movements of pulmonary space-occupying lesions with MRI]. / Untersuchung der atemabhängigen Bewegungen pulmonaler Raumforderungen mit der MRT.

Parallel imaging and echo sharing techniques have markedly reduced the acquisition times for MRI of large volumes. Dynamic 2 and 3-dimensional data sets of the chest with high temporal resolution (up to 10 images/s with single slice and 2 volume/s) allow an analysis of respiratory motion of the lungs and tumors. Time-resolved 2D series in preselected planes can be used to observe respiratory motion during free breathing or after respiratory commands, e.g. to exclude chest wall invasion by a tumor or for diagnosing impairment of respiratory mechanics. Time-resolved 3D-series (4D-MRI) allow monitoring of the spatial displacement of the lungs and tumors as a whole volume. Present limitations such as an overestimation of tumor size and an underestimation of displacement due to a limited temporal resolution are expected to be overcome with further technical developments. However, 4D-MRI already appears to be the appropriate tool to select patients for motion-adapted radiotherapy. In addition 4D-MRI is available for a broad spectrum of scientific applications, as it allows repeated and prolonged series of measurements without radiation exposure.

[Computed tomography of the lungs. A step into the fourth dimension]. / Computertomographie der Lunge. Ein Schritt in die vierte Dimension.

PURPOSE: To discuss the techniques for four dimensional computed tomography of the lungs in tumour patients. METHOD: The image acquisition in CT can be done using respiratory gating in two different ways: the helical or cine mode. In the helical mode, the couch moves continuously during image and respiratory signal acquisition. In the cine mode, the couch remains in the same position during at least one complete respiratory cycle and then moves to next position. The 4D images are either acquired prospectively or reconstructed retrospectively with dedicated algorithms in a freely selectable respiratory phase. RESULTS: The time information required for motion depiction in 4D imaging can be obtained with tolerable motion artefacts. Partial projection and stepladder-artifacts are occurring predominantly close to the diaphragm, where the displacement is most prominent. Due to the long exposure times, radiation exposure is significantly higher compared to a simple breathhold helical acquisition. Therefore, the use of 4D-CT is restricted to only specific indications (i.e. radiotherapy planning). CONCLUSION: 4D-CT of the lung allows evaluating the respiration-correlated displacement of lungs and tumours in space for radiotherapy planning.

MR imaging of the chest: a practical approach at 1.5T.

Magnetic resonance imaging (MRI) is capable of imaging infiltrative lung diseases as well as solid lung pathologies with high sensitivity. The broad use of lung MRI was limited by the long study time as well as its sensitivity to motion and susceptibility artifacts. These disadvantages were overcome by the utilisation of new techniques such as parallel imaging. This article aims to propose a standard MR imaging protocol at 1.5T and presents a spectrum of indications. The standard protocol comprises non-contrast-enhanced sequences. Following a GRE localizer (2D-FLASH), a coronal T2w single-shot half-Fourier TSE (HASTE) sequence with a high sensitivity for infiltrates and a transversal T1w 3D-GRE (VIBE) sequence with a high sensitivity for small lesions are acquired in a single breath hold. Afterwards, a coronal steady-state free precession sequence (TrueFISP) in free breathing is obtained. This sequence has a high sensitivity for central pulmonary embolism. Distinct cardiac dysfunctions as well as an impairment of the breathing mechanism are visible. The last step of the basic protocol is a transversal T2w-STIR (T2-TIRM) in a multi-breath holds technique to visualize enlarged lymph nodes as well as skeletal lesions. The in-room time is approximately 15min. The extended protocol comprises contrast-enhanced sequences (3D-GRE sequence (VIBE) after contrast media; about five additional minutes). Indications are tumorous lesions, unclear (malignant) pleural effusions and inflammatory diseases (vaskulitis). A perfusion analysis can be achieved using a 3D-GRE in shared echo-technique (TREAT) with a high temporal resolution. This protocol can be completed using a MR-angiography (3D-FLASH) with high spatial resolution. The in-room time for the complete protocol is approximately 30min.

Close localization of DAP-kinase positive tumour-associated macrophages and apoptotic colorectal cancer cells.

The death-associated protein kinase (DAP-kinase) is a cytoskeleton-associated protein crucially involved in the induction of early apoptotic pathways. Aberrant hypermethylation of the DAP-kinase promoter plays a major role in tumorigenesis. We aimed to investigate the inactivation of DAP-kinase and its association with apoptotic cell death in 94 colorectal carcinomas. DAP-kinase promoter hypermethylation and mRNA expression were investigated using methylation-specific PCR and real-time RT-PCR, respectively. The expression of DAP-kinase, Fas, and Fas-ligand (FasL) proteins was studied by immunohistochemistry and immunofluorescence. Apoptosis of tumour cells was investigated using the TUNEL assay. DAP-kinase was expressed in tumour cells and tumour-invading macrophages and was closely associated with high numbers of apoptotic tumour cells. DAP-kinase expression co-localized with FasL overexpression in tumour-associated macrophages, and aberrant promoter hypermethylation was verified in more than 50% of carcinomas. There was a tendency for proximal tumours to show DAP-kinase promoter methylation more frequently (p = 0.07). Promoter methylation resulted in a decrease or loss of DAP-kinase protein expression in tumour cells and tumour-associated macrophages. Simultaneously, a decreased apoptotic count and loss of Fas/FasL expression was observed in tumour cells. Our study is the first to demonstrate DAP-kinase expression in invading tumour-associated macrophages in colorectal cancer. The presence of similar expression levels of DAP-kinase in tumour cells and associated macrophages, and their dependence on the promoter methylation status of the tumour cells, suggests cross talk between these cell types during apoptotic cell death.

[MRI in staging of lung cancer]. / MRT zum Staging des Lungenkarzinoms.

PURPOSE: Overview of magnetic resonance imaging (MRI) in staging of lung cancer. MATERIAL AND METHODS: Currently available methods of imaging lung cancer, lymph node and distant metastases by MRI are explained. At present, MRI is mainly used in the detection of cerebral metastases and assessment of infiltration of the thoracic wall and of the mediastinum. The capabilities of T2-weighted single-shot TSE (HASTE) and T1-weighted 3D gradient echo techniques (VIBE) are demonstrated. RESULTS: With the advent of new fast sequences like HASTE and VIBE the spatial resolution comes close to that of computed tomography but with an outstanding soft tissue contrast and without radiation exposure. The introduction of lymph node specific contrast media will improve sensitivity and specificity in N staging. Additionally, whole-body MRI is capable of detecting distant metastases, in particular in the organs at risk, i.e. brain, upper abdomen and musculoskeletal system. CONCLUSION: MRI is gaining importance as part of a multimodal imaging approach for staging of lung cancer.

[Segmental anatomy of the liver in computed tomography: do we localize the lesion accurately?]. / Segmentanatomie der Leber in der Computertomographie: Lokalisieren wir die Läsionen richtig?

PURPOSE: To evaluate if Couinaud's model using the planes of the major veins is an adequate tool for the presurgical localization of focal liver lesions. METHODS: Biphasic helical CT scans were performed on patients evaluated for liver resection using an increased IV bolus of contrast medium (180 ml lopamidol) and 2 mm image reconstruction increments. During the first evaluation, all liver lesions were localized in the conventional way using the planes of the 3 major hepatic veins and the portal trunks as segmental boundaries. In a second review, all lesions were attributed to the nearest peripheral portal branches. The path and the segmental attribution of the portal branches were analysed. Evaluations were performed using an interactive cine mode as well as three-dimensional reconstructions. RESULTS: 20 of 126 (16%) liver lesions had a different segmental location if the individual anatomy of the peripheral portal branch was used instead of the conventional technique. These different locations were due to the path of the portal trunks or the path of the peripheral portal branches crossing the planes of the major hepatic veins. CONCLUSION: The segmental anatomy of the liver using the planes of hepatic veins and portal trunks according to Couinaud is not an accurate tool for the presurgical localization of liver lesions in many cases.