Adaptive prediction of internal target motion using external marker motion: a technical study

An adaptive prediction approach was developed to infer internal target position by external marker positions. First, a prediction model (or adaptive neural network) is developed to infer target position from its former positions. For both internal target and external marker motion, two networks with the same type are created. Next, a linear model is established to correlate the prediction errors of both neural networks. Based on this, the prediction error of an internal target position can be reconstructed by the linear combination of the prediction errors of the external markers. Finally, the next position of the internal target is estimated by the network and subsequently corrected by the reconstructed prediction error. In a similar way, future positions are inferred as their previous positions are predicted and corrected. This method was examined by clinical data. The results demonstrated that an improvement (10% on average) of correlation between predicted signal and real internal motion was achieved, in comparison with the correlation between external markers and internal target motion. Based on the clinical data (with correlation coefficient 0.75 on average) observed between external marker and internal target motions, a prediction error (23% on average) of internal target position was achieved. The preliminary results indicated that this method is helpful to improve the predictability of internal target motion with the additional information of external marker signals. A consistent correlation between external and internal signals is important for prediction accuracy.     

Dynamic modeling of lung tumor motion during respiration

A dynamic finite element model of the lung that incorporates a simplified geometry with realistic lung material properties has been developed. Observations of lung motion from respiratory-gated computed tomography were used to provide a database against which the predictions of the model are assessed. Data from six patients presenting with lung tumors were processed to give sagittal sections of the lung containing the tumor as a function of the breathing phase. Statistical shape modeling was used to outline the diaphragm, the tumor volume and the thoracic wall at each breathing phase. The motion of the tumor in the superior-inferior direction was plotted against the diaphragm displacement. The finite element model employed a simplified geometry in which the lung material fills a rectangular volume enabling two-dimensional coordinates to be used. The diaphragm is represented as a piston, driving the motion. Plots of lung displacement against diaphragm displacement form hysteresis loops that are a sensitive indicator of the characteristics of the motion. The key parameters of lung material that determine the motion are the density and elastic properties of lung material and the airway permeability. The model predictions of the hysteresis behavior agreed well with observation only when lung material is modeled as viscoelastic. The key material parameters are suggested for use as prognostic indicators of the progression of disease and of changes arising from the response of the lung to radiation treatment.     

Peculiarities of external respiration as a marker of activity of cell respiratory enzymes in rat brain

Rats with catatonic freezing are characterized by low motor and explorative activity in the open field test and specific pattern of external respiration, so-called strenuous respiration, which is accompanied by a higher activity of the respiratory enzymes succinate dehydrogenase and NADH dehydrogenase in the hippocampus and motor cortex. No dependencies on the brain structure and animal age are noted. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 8, pp. 138–140, August, 1997     

Quantifying the effect of intrafraction motion during breast IMRT planning and dose delivery

Respiratory motion during intensity modulated radiation therapy (IMRT) causes two types of problems. First, the clinical target volume (CTV) to planning target volume (PTV) margin needed to account for respiratory motion means that the lung and heart dose is higher than would occur in the absence of such motion. Second, because respiratory motion is not synchronized with multileaf collimator (MLC) motion, the delivered dose is not the same as the planned dose. The aims of this work were to evaluate these problems to determine (a) the effects of respiratory motion and setup error during breast IMRT treatment planning, (b) the effects of the interplay between respiratory motion and multileaf collimator (MLC) motion during breast IMRT delivery, and (c) the potential benefits of breast IMRT using breath-hold, respiratory gated, and 4D techniques. Seven early stage breast cancer patient data sets were planned for IMRT delivered with a dynamic MLC (DMLC). For each patient case, eight IMRT plans with varying respiratory motion magnitudes and setup errors (and hence CTV to PTV margins) were created. The effects of respiratory motion and setup error on the treatment plan were determined by comparing the eight dose distributions. For each fraction of these plans, the effect of the interplay between respiratory motion and MLC motion during IMRT delivery was simulated by superimposing the respiratory trace on the planned DMLC leaf motion, facilitating comparisons between the planned and expected dose distributions. When considering respiratory motion in the CTV-PTV expansion during breast IMRT planning, our results show that PTV dose heterogeneity increases with respiratory motion. Lung and heart doses also increase with respiratory motion. Due to the interplay between respiratory motion and MLC motion during IMRT delivery, the planned and expected dose distributions differ. This difference increases with respiratory motion. The expected dose varies from fraction to fraction. However, for the seven patients studied and respiratory trace used, for no breathing, shallow breathing, and normal breathing, there were no statistically significant differences between the planned and expected dose distributions. Thus, for breast IMRT, intrafraction motion degrades treatment plans predominantly by the necessary addition of a larger CTV to PTV margin than would be required in the absence of such motion. This motion can be limited by breath-hold, respiratory gated, or 4D techniques.     

Quantifying the effect of respiratory motion on lung tumour dosimetry with the aid of a breathing phantom with deforming lungs

The contribution of organ and tumour motion to the degradation of planned dose distributions during radiotherapy to the breathing lung has been experimentally investigated and quantified. An anthropomorphic, tissue-equivalent breathing phantom with deformable lungs has been built, in which the lung tumour can be driven in any arbitrary 3D trajectory. The trajectory is programmed into a motion controller connected to a high-precision moving platform that is connected to the tumour. The motion controller is connected to the accelerator's dose counter and the speed of motion is scaled to the dose rate. This ensures consistent delivery despite variation in either the dose rate or inter-segment timing. For this study, the phantom was made to breathe by a set of periodic equations representing respiratory motion by an asymmetric, trigonometric function. Several motion amplitudes were selected to be applied in the primary axis of motion. Five three-dimensional, geometrically conformal (3DCRT) fractions with different starting phases (spaced uniformly in the breathing cycle) were delivered to the phantom and compared to a delivery where the phantom was static at the end-expiration position. A set of intensity-modulated radiotherapy plans (IMRT) was subsequently delivered in the same manner. Bigger amplitudes of motion resulted in a higher degree of dose blurring. Severe underdosages were observed when deliberately selecting the PTV wrongly, their extent being correlated with the degree of margin error. IMRT motion-averaged dose distributions exhibited areas of high dose in the gross tumour volume (GTV) which were not present in the static irradiations, arising from booster segments that the optimizer was creating to achieve planning target volume (PTV) homogeneity during the inverse-planning process. 3DCRT, on the other hand, did not demonstrate such effects. It has been concluded that care should be taken to control the delivered fluence when delivering IMRT to the breathing lung, even when the PTV margin has been adequately chosen to include the extent of the breathing motion.     

Effect of prolonged undernutrition on rat diaphragm mitochondrial respiration.

Previous studies have shown that undernutrition induces an impairment of the respiratory muscle function in patients with chronic lung disease. To explain this, we hypothesized that undernutrition could decrease oxidative metabolism in the diaphragm. We therefore examined the effect of prolonged undernutrition on diaphragm mitochondrial oxygen uptake with pyruvate and palmitate as substrates in adult rats. Ten rats served as controls (CTL). Ten nutritionally deprived rats (ND) received 40% of their estimated daily nutrition. Five weeks of undernutrition induced a 33% decrease in state 3 respiration with pyruvate plus malate as substrate (993 +/- 171 versus 1488 +/- 167 nmol atomic O/mg/min, P < 0.01) and a 39% decrease with palmitate plus malate (516 +/- 89 versus 850 +/- 165 nmol atomic O/mg/min, P < 0.05). With succinate plus rotenone, there was no significant difference in the respiratory rate between groups. In the ND group, we found a significant decrease in citrate synthase activity (P < 0.01), and also in reduced nicotinamine adenine dinucleotide (NADH) dehydrogenase activity (P < 0.05), which cannot alone induce such a state 3 respiratory decrease. This showed that undernutrition in rat diaphragm does not induce an alteration in protein complexes I, II, III, and IV, or the F complex containing the mitochondrial ATPase of the electron transport chain. In conclusion, the main result of this study was that prolonged undernutrition induced a decrease in mitochondrial respiration secondary to a significant reduction in NADH generation by the Krebs cycle, which may affect respiratory muscle function with implications for patient care.     

体外膈肌起搏的临床应用及研究进展

体外膈肌起搏器是我国研制的创新技术产品,主要刺激膈神经引起膈肌收缩.体外膈肌起搏技术应用于临床已有30年历史,研究成果较多,应用范围较广,目前主要应用于呼吸系统疾病治疗.