Detection of respiratory motion in fluoroscopic images for adaptive radiotherapy.

Respiratory motion limits the potential of modern high-precision radiotherapy techniques such as IMRT and particle therapy. Due to the uncertainty of tumour localization, the ability of achieving dose conformation often cannot be exploited sufficiently, especially in the case of lung tumours. Various methods have been proposed to track the position of tumours using external signals, e.g. with the help of a respiratory belt or by observing external markers. Retrospectively gated time-resolved x-ray computed tomography (4D CT) studies prior to therapy can be used to register the external signals with the tumour motion. However, during treatment the actual motion of internal structures may be different. Direct control of tissue motion by online imaging during treatment promises more precise information. On the other hand, it is more complex, since a larger amount of data must be processed in order to determine the motion. Three major questions arise from this issue. Firstly, can the motion that has occurred be precisely determined in the images? Secondly, how large must, respectively how small can, the observed region be chosen to get a reliable signal? Finally, is it possible to predict the proximate tumour location within sufficiently short acquisition times to make this information available for gating irradiation? Based on multiple studies on a porcine lung phantom, we have tried to examine these questions carefully. We found a basic characteristic of the breathing cycle in images using the image similarity method normalized mutual information. Moreover, we examined the performance of the calculations and proposed an image-based gating technique. In this paper, we present the results and validation performed with a real patient data set. This allows for the conclusion that it is possible to build up a gating system based on image data, solely, or (at least in avoidance of an exceeding exposure dose) to verify gates proposed by the various external systems.

Four-dimensional magnetic resonance imaging for the determination of tumour movement and its evaluation using a dynamic porcine lung phantom.

A method of four-dimensional (4D) magnetic resonance imaging (MRI) has been implemented and evaluated. It consists of retrospective sorting and slice stacking of two-dimensional (2D) images using an external signal for motion monitoring of the object to be imaged. The presented method aims to determine the tumour trajectories based on a signal that is appropriate for monitoring the movement of the target volume during radiotherapy such that the radiation delivery can be adapted to the movement. For evaluation of the 4D-MRI method, it has been applied to a dynamic lung phantom, which exhibits periodic respiratory movement of a porcine heart-lung explant with artificial pulmonary nodules. Anatomic changes of the lung phantom caused by respiratory motion have been quantified, revealing hysteresis. The results demonstrate the feasibility of the presented method of 4D-MRI. In particular, it enables the determination of trajectories of periodically moving objects with an uncertainty in the order of 1 mm.

Blood lymphocyte subpopulations in extrinsic and intrinsic asthmatics.

Blood leukocyte numbers and proportions of T lymphocyte subsets were studied in extrinsic asthmatics (EA), intrinsic asthmatics (IA), IA systemically treated with corticosteroids (IA + C), and in age-matched control subjects. The EA and IA showed an increased number of eosinophils. During corticosteroid therapy of IA, the eosinophil number remained elevated, whereas there was a slight decrease in the number of circulating lymphocytes. The proportion of T cells of the suppressor/cytotoxic phenotype carrying the Leu-2a antigen was significantly lower in the IA than in all other groups. In the IA + C group, the proportions of Leu-3a/3b and Leu-2a positive T lymphocytes returned to normal, although the patients still exhibited asthmatic symptoms. These findings suggest that cellular immunologic factors might be involved in the pathogenesis of intrinsic asthma.

mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours.

BACKGROUND: Insulin-like growth factors (IGF) and their corresponding receptors and binding proteins are important in carcinogenesis for several tumours, but their expression pattern in the functionally and biologically heterogeneous human neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown. MATERIALS AND METHODS: This study searched for the mRNA expression patterns of components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF-2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours associated with carcinoid syndrome and functionally inactive tumours) employing reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the 37 tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP-2 was found in all tumour samples while the IGFBP-1 was expressed only at low frequency (10-22%) among the four tumour types. The IGF-2R was predominantly expressed in gastrinomas. Among the four tumour types the expression of IGF-1R, IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <--> IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <--> IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <--> IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6). CONCLUSIONS: The described differences of the expression patterns of the IGF system components in neuroendocrine tumour subtypes suggest tumour type-dependent different pathways in tumour growth control by IGF system components.