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Biomedical subjects

U A van der Heide

Publications and source records attributed to U A van der Heide.

12 recordsLinked to original sources

Influence of the linac design on intensity-modulated radiotherapy of head-and-neck plans.

In this study, we quantify the impact of linac/MLC design parameters on IMRT treatment plans. The investigated parameters were leaf width in the MLC, leaf transmission, related to the thickness of the leaves, and penumbra related primarily to the source size. Seven head-and-neck patients with stage T1-T3N0-N2cM0 oropharyngeal cancer were studied. For each patient nine plans were made with a different set of linac/MLC parameters. The plans were optimized in Pinnacle(3) v7.6c and PLATO RTS v2.6.4, ITP v1.1.8. A hypothetical ideal linac/MLC was introduced to investigate the influence of one parameter at a time without interaction of other parameters. When any of the three parameters was increased from the ideal set-up values (leaf width 2.5 mm, transmission 0%, penumbra 3 mm), the mean dose to the parotid glands increased, given the same tumour coverage. The largest increase was found for increasing leaf transmission. The investigation showed that by changing more than one parameter of the ideal linac/MLC set-up, the increase in the mean dose was smaller than the sum of dose increments for each parameter separately. As a reference to clinical practice, we also optimized the plans of the seven patients with the clinically used Elekta SLi 15, equipped with a standard MLC with a leaf width of 10 mm. As compared to the ideal linac, this resulted in an increase of the average dose to the parotid glands of 5.8 Gy.

Dose-Response Relationship, Radiation↗

Patient position verification using small IMRT fields.

A commonly used approach to quantify and minimize patient setup errors is by using electronic portal imaging devices (EPIDs). The position of the tumor can be verified indirectly by matching the bony anatomy to a reference image containing the same structures. In this paper we present two off-line methods for detecting the position of the bony anatomy automatically, even if every single portal image of each segment of an IMRT treatment beam contains insufficient matching information. Extra position verification fields will no longer be necessary, which reduces the total dose to the patient. The first method, the stack matching method (SMM), stacks the portal image of each segment of a beam to a three dimensional (3D) volume, and this volume is subsequently used during the matching phase. The second method [the averaged projection matching method (APMM)], is a simplification of the first one, since the initially created volume is reduced again to a 2D artificial image, which speeds up the matching procedure considerably, without a significant loss of accuracy. Matching is based on normalized mutual information. We demonstrate our methods by comparing them to existing matching routines, such as matching based on the largest segment. Both phantom and patient experiments show that our methods are comparable with the results obtained from standard position verification methods. The matches are verified by means of visual inspection. Furthermore, we show that when a distinct area of 40-60 cm2 of the EPID is exposed during one treatment beam, both SMM and APMM are able to deliver a good matching result.

Humans↗

Assessment of rigid multi-modality image registration consistency using the multiple sub-volume registration (MSR) method.

Registration of different imaging modalities such as CT, MRI, functional MRI (fMRI), positron (PET) and single photon (SPECT) emission tomography is used in many clinical applications. Determining the quality of any automatic registration procedure has been a challenging part because no gold standard is available to evaluate the registration. In this note we present a method, called the 'multiple sub-volume registration' (MSR) method, for assessing the consistency of a rigid registration. This is done by registering sub-images of one data set on the other data set, performing a crude non-rigid registration. By analysing the deviations (local deformations) of the sub-volume registrations from the full registration we get a measure of the consistency of the rigid registration. Registration of 15 data sets which include CT, MR and PET images for brain, head and neck, cervix, prostate and lung was performed utilizing a rigid body registration with normalized mutual information as the similarity measure. The resulting registrations were classified as good or bad by visual inspection. The resulting registrations were also classified using our MSR method. The results of our MSR method agree with the classification obtained from visual inspection for all cases (p < 0.02 based on ANOVA of the good and bad groups). The proposed method is independent of the registration algorithm and similarity measure. It can be used for multi-modality image data sets and different anatomic sites of the patient.

Algorithms↗

IMRT sequencing for a six-bank multi-leaf system.

In this study, we present a sequencer for delivering step-and-shoot IMRT using a six-bank multi-leaf system. Such a system was proposed earlier and combines a high-resolution field-shaping ability with a large field size. It consists of three layers of two opposing leaf banks with 1 cm leaves. The layers are rotated relative to each other at 60 degrees . A low-resolution mode of sequencing is achieved by using one layer of leaves as primary MLC, while the other two are used to improve back-up collimation. For high-resolution sequencing, an algorithm is presented that creates segments shaped by all six banks. Compared to a hypothetical mini-MLC with 0.4 cm leaves, a similar performance can be achieved, but a trade-off has to be made between accuracy and the number of segments.

Algorithms↗

A six-bank multi-leaf system for high precision shaping of large fields.

In this study, we present the design for an alternative MLC system that allows high precision shaping of large fields. The MLC system consists of three layers of two opposing leaf banks. The layers are rotated 60 degrees relative to each other. The leaves in each bank have a standard width of 1 cm projected at the isocentre. Because of the symmetry of the collimator set-up it is expected that collimator rotation will not be required, thus simplifying the construction considerably. A 3D ray tracing computer program was developed in order to simulate the fluence profile for a given collimator and used to optimize the design and investigate its performance. The simulations show that a six-bank collimator will afford field shaping of fields of about 40 cm diameter with a precision comparable to that of existing mini MLCs with a leaf width of 4 mm.

Computer Simulation↗

Partial boosting of prostate tumours.

BACKGROUND AND PURPOSE: In this planning study we propose a class solution for partial boosting of prostate tumours. Treatment margins and rectum dose are similar to that of the conventional treatment and are supposed to have no direct link to the level of dose escalation. We also study the robustness of our class solution in the presence of geometrical deviations. METHODS AND MATERIALS: To study the specifications of the class solution ten patients with histologically confirmed prostate cancer were replanned. Besides a conventional plan for each patient, different partial boost plans were produced with an inverse treatment-planning tool. We also simulated treatment geometrical deviations to estimate their effect on partial boost plans. RESULTS: In our class solution we use three contours in our inverse treatment planning, which are based on the classical CTV. A three beam arrangement appeared to produce a dose distribution, which is comparable to that of a five or seven beam geometry. Comparison of partial boost plans and conventional plans indicated that all conditions for a partial boost plan could be satisfied with the proposed class solution. Simulation of treatment geometrical deviations showed that large random deviations have a minor effect on the overall dose distributions, while systematic deviations may decrease the boost dose and increase the rectal dose. CONCLUSIONS: We presented a class solution for partial boosting of prostate tumours in which the level of dose escalation is dealt with separately from the margin size and the nominal rectum dose. The framework put forward in this study allows practical introduction of intensity modulated radiotherapy in routine clinical practice using current standards of imaging and position verification.

Humans↗

A maximum entropy analysis of protein orientations using fluorescence polarization data from multiple probes.

Techniques have recently become available to label protein subunits with fluorescent probes at predetermined orientation relative to the protein coordinates. The known local orientation enables quantitative interpretation of fluorescence polarization experiments in terms of orientation and motions of the protein within a larger macromolecular assembly. Combining data obtained from probes placed at several distinct orientations relative to the protein structure reveals functionally relevant information about the axial and azimuthal orientation of the labeled protein segment relative to its surroundings. Here we present an analytical method to determine the protein orientational distribution from such data. The method produces the broadest distribution compatible with the data by maximizing its informational entropy. The key advantages of this approach are that no a priori assumptions are required about the shape of the distribution and that a unique, exact fit to the data is obtained. The relative orientations of the probes used for the experiments have great influence on information content of the maximum entropy distribution. Therefore, the choice of probe orientations is crucial. In particular, the probes must access independent aspects of the protein orientation, and two-fold rotational symmetries must be avoided. For a set of probes, a "figure of merit" is proposed, based on the independence among the probe orientations. With simulated fluorescence polarization data, we tested the capacity of maximum entropy analysis to recover specific protein orientational distributions and found that it is capable of recovering orientational distributions with one and two peaks. The similarity between the maximum entropy distribution and the test distribution improves gradually as the number of independent probe orientations increases. As a practical example, ME distributions were determined with experimental data from muscle fibers labeled with bifunctional rhodamine at known orientations with respect to the myosin regulatory light chain (RLC). These distributions show a complex relationship between the axial orientation of the RLC relative to the fiber axis and the azimuthal orientation of the RLC about its own axis. Maximum entropy analysis reveals limitations in available experimental data and supports the design of further probe angles to resolve details of the orientational distribution.

Biophysical Phenomena↗

Dynamic measurement of myosin light-chain-domain tilt and twist in muscle contraction.

A new method is described for measuring motions of protein domains in their native environment on the physiological timescale. Pairs of cysteines are introduced into the domain at sites chosen from its static structure and are crosslinked by a bifunctional rhodamine. Domain orientation in a reconstituted macromolecular complex is determined by combining fluorescence polarization data from a small number of such labelled cysteine pairs. This approach bridges the gap between in vitro studies of protein structure and cellular studies of protein function and is used here to measure the tilt and twist of the myosin light-chain domain with respect to actin filaments in single muscle cells. The results reveal the structural basis for the lever-arm action of the light-chain domain of the myosin motor during force generation in muscle.

Animals↗

The effect of actin filament compliance on the interpretation of the elastic properties of skeletal muscle fibres.

Recently, X-ray diffraction studies provided direct evidence for an appreciable length change in the actin filament upon activation. This finding has profound implications on the interpretation of the elastic properties of skeletal muscle fibre. In this study we determined the compliance of the actin filament during activation, using the data obtained previously from quick stretch and release experiments on skeletal muscle fibres of the frog. The effects of filament compliance are demonstrated clearly in the elastic properties of partially activated fibres. The low-frequency elasticity increases linearly with tension, reflecting an increase in the number of force-producing cross-bridges. At higher frequencies, this linearity is lost. In this study we describe the data consistently in terms of a cross-bridge stiffness increasing linearly with tension and a constant Young's modulus for the actin filament of 44 MN m-2. This corresponds to a compliance of 23 pm microns-1 per kN m-2 tension developed. Using this value for the actin filament Young's modulus, its contribution to the elastic properties of skeletal muscle fibre of the frog is considered in rigor and relaxation. The filament compliance hardly affects the overall elasticity of the muscle fibre in relaxation. In contrast, it contributes to a large extent to the overall elasticity in rigor. Taking account of the filament compliance, we find that the Young's modulus in rigor exhibits an increase from 14 MN m-2 at frequencies below 500 Hz to 55 MN m-2 above 40 kHz.

Actins↗

A computer simulation study of the relation between lipid and probe behaviour in bilayer systems.

Computer simulations are presented of the behaviour of elongated probe molecules anchored to the interface of lipid bilayers above the phase transition of the hydrocarbon chains. The simulations thus mimic the behaviour of the fluorescent probe 1-(4-(trimethylammonio)phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and Cholestane spin label in lipid systems. In contrast to any experimental technique the simulations follow the behaviour of both the lipid molecules and the probe within the bilayer structure. Thus, the relation between the behaviour of the probe molecules and the order and dynamics of the lipid chains can be studied in detail. We find that the presence of probe molecules, at the low concentrations used experimentally, causes only a marginal perturbation in the intrinsic properties of the lipid chains. The simulations presented support the conventional prescription for describing the orientational behaviour of probe molecules in lipid bilayers in terms of a local effective orienting potential. They indicate, however, that the potential arises from the confinement of the probe molecules between long segments of lipid chains in elongated free-volume cavities within the bilayer structure. In this sense the orienting potential concept needs to be refined in order to take into account the combined effect of the restricted free rattling motions of the probes within the free-volume cavities and the orientations of the cavities themselves relative to the normal to the bilayer plane. The time scale of the motions of the cavities within the bilayer is determined by the rotational motions of long segments of the lipid chains. These observations justify the use of rigid probe molecules such as TMA-DPH and Cholestane spin labels for monitoring the orientational order and dynamics in lipid bilayer systems.

1,2-Dipalmitoylphosphatidylcholine↗

A fluorescence depolarization study of the orientational distribution of crossbridges in muscle fibres.

A fluorescence depolarization study of the orientational distribution of crossbridges in dye-labelled muscle fibres is presented. The characterization of this distribution is important since the rotation of crossbridges is a key element in the theory of muscle contraction. In this study we exploited the advantages of angle-resolved experiments to characterize the principal features of the orientational distribution of the crossbridges in the muscle fibre. The directions of the transition dipole moments in the frame of the dye and the orientation and motion of the dye relative to the crossbridge determined previously were explicitly incorporated into the analysis of the experimental data. This afforded the unequivocal determination of all the second and fourth rank order parameters. Moreover, this additional information provided discrimination between different models for the orientational behaviour of the crossbridges. Our results indicate that no change of orientation takes place upon a transition from rigor to relaxation. The experiments, however, do no rule out a conformational change of the myosin S1 during the transition.

Animals↗

The orientation of transition moments of dye molecules used in fluorescence studies of muscle systems.

Fluorescence and phosphorescence depolarization techniques can provide information on orientational order and rotational motion of crossbridges in muscle fibres. However the depolarization experiment monitors the orientation and motion of the crossbridges indirectly. The changes in depolarization arise from a change in the orientation of the transition dipoles of the dye attached to the crossbridge. In order to extract the physiologically relevant orientations from the data it is therefore necessary to characterize the orientation of the dye molecule relative to the crossbridge and the orientation of the transition moments in the frame of the dyes. The dyes 1,5-I-AEDANS and eosin-5-maleimide are commonly used for labelling the crossbridge in muscle fibres. The orientations of the absorption and fluorescence emission dipoles of these two dyes in the molecular frame were determined. Angle resolved fluorescence depolarization experiments on the dyes, macroscopically aligned in a stretched polymer matrix of poly vinyl alcohol, were carried out. The data were analyzed in terms of an orientational distribution of the dye molecules in the film and the orientations of the absorption and emission dipoles in the frame of the dye molecule. Experimental data, obtained from a given sample at different excitation wavelengths, were analyzed simultaneously in a global target approach. This leads to a reduction in the number of independent parameters optimized by the non-linear least squares procedure.

Animals↗