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Responsive materials, which can adapt and operate autonomously under dynamic conditions, are a stepping stone towards functional, life-like systems inspired by fueled self-assembly processes in nature. Complex coacervate core micelles (C3Ms) comprising oppositely charged macromolecules constitute a novel class of polymeric micelles ideally suited for use as responsive nanoscopic delivery vehicles of hydrophilic and hydrophobic cargo. To fully exploit their potential, it is important that the C3Ms form and fall apart in an autonomous fashion as orchestrated by dynamic cues in their environment. Herein a means to temporally program the self-regulated C3M coassembly pathway, using a modulated base-catalyzed feedback system, is presented. Incorporated in the C3Ms is a pH responsive polyfluorene-based conjugated polyelectrolyte (CPF) as a building block and trace amounts of a molecular sensor (doxorubicin HCl) as cargo, both of which report on micellar coassembly and disassembly via binding-induced fluorescence quenching. CPF additionally reports on the pH of its microenvironment as its pH-dependent conformational states are mirrored in the transitions of its vibronic bands. This experimental design enables one to monitor solution pH, C3M disassembly and reassembly, as well as cargo release and recapture noninvasively in a closed system with real time florescence experiments.

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect).Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid glands of Wistar rats was performed using 150-MeV protons. To determine suitable (i.e., subtolerance) dose levels for a bath-dose, both whole parotid glands were irradiated with 5 to 25 Gy. Subsequently groups of Wistar rats received 30 Gy to the caudal 50% (shower) and 0 to 10 Gy to the cranial 50% (bath) of both parotid glands. Stimulated saliva flow rate (function) was measured before and up to 240 days after irradiation.Results : Irradiation of both glands up to a dose of 10 Gy did not result in late loss of function and is thus regarded subtolerance. Addition of a dose bath of I to 10 Gy to a high-dose in the caudal 50% of the glands resulted in enhanced function loss.Conclusion: Similar to the spinal cord, the parotid gland demonstrates a bath and shower effect, which may explain the less-than-expected sparing of function after IMRT. (C) 2009 Elsevier Inc.

Currently 1582 HLA-DRB1 alleles have been identified in the IMGT/HLA database (v3.18). Among those alleles, more than 90% have incomplete allele sequences, which complicates the analysis of the functional relevance of polymorphism beyond exon 2. The polymorphic index of each individual exon of the currently known allele sequences, shows that polymorphism is present in all exons, albeit not equally abundant. Full-length HLA-DRB1 RNA sequencing identifies polymorphism of the complete coding region. Here we describe a hemizygous full-length RNA sequence-based typing (SBT) approach based on group-specific HLA-DRB1 amplification and subsequent sequencing. RNA full-length sequences can easily be accessed because of the short amplicon length (801 bp). The RNA-SBT approach was successfully validated on a panel of DRB1 alleles having fully known coding sequences according to the IMGT/HLA database, and cover all serological equivalents. Subsequently, the approach was applied on a panel of 54 alleles with incomplete allele sequences, resulting in full-length coding sequences and the identification of one new and one corrected allele. This study shows the universal applicability of the RNA-based sequencing approach to identify full-length coding sequences and to define the polymorphic content of HLA-DRB1 alleles.

Purpose: To detect volume effects and possible regional differences in radiosensitivity of the rat parotid gland.Methods and Materials: Parotid glands of male albino Wistar rats were locally X-irradiated, with collimators with conformal radiation portals used to supply 100% volume and 50% cranial/caudal partial volumes. High-resolution magnetic resonance imaging was used to provide the outlines of the parotid glands. Single doses of up to 40 Gy were applied, and the effects on saliva secretion, measured with the aid of miniaturized Lashley cups, were followed up to 365 days after the irradiation.Results: Under conditions of equal mean absorbed doses and small variations in dose distribution, a pertinent volume effect was observed for late but not for early radiation damage. The late effects were different for the cranial part as compared with the caudal part of the parotid gland. The reduction in flow rate was much more severe after irradiation in the cranial part. After a single dose of 30 Gy, the reductions in flow rates were approximately 65% and 25% for the cranial and caudal parts, respectively. At that dose, no saliva flow was observed after irradiation of 100% of the gland.Conclusion: From the rat model studies presented, it is concluded that late radiation damage after partial irradiation of parotid glands shows region-dependent volume effects. This finding is expected to be relevant to the radiosensitivity of human salivary glands, and it implies that the predictive power of the mean dose concept in radiotherapeutic practice is limited. The finding of region-dependent late radiation damage also challenges the basic assumptions of most current normal tissue complication probability models for parotid gland function. (c) 2005 Elsevier Inc.

Purpose: The purpose of this study was to explore regional differences in radiosensitivity of rat lung Using lung function and computed tomography (CT) density as endpoints.Methods: At first, CT scans were used to determine rat lung, volumes. The data obtained enabled the design of accurate collimators to irradiate 50% of the total lung volume for the apex, base, left, right, mediastinal and lateral part of the lung. Male Wistar rats were irradiated with a single (lose of 18 Gy of orthovoltage X-rays. Further rat thorax CT scans were made before and 4, 16, 26, and 52 weeks after irradiation to measure ill Vivo lung density changes indicative of lung damage. To evaluate overall lung function, breathing frequencies were measured biweekly starting 1 week before irradiation.Results: Qualitative analysis of the CT scans showed clear density changes for all irradiated lung volumes, with the most prominent changes present in the mediastinal and left group at 26 weeks after radiation. Quantitative analysis using average density changes of whole lungs did not adequately describe the differences in radiation response between the treated groups. However. analysis of the density changes of the irradiated and non-irradiated regions of interest (ROI) more closely matched with the qualitative observations. Breathing frequencies (BF) were only increased after 50% left lung irradiation, indicating that the hypersensitivity of the mediastinal part as assessed by CT analysis, does not result in functional changes.Conclusions: For both BF and CT (best described by ROI analysis), differences in regional lung radiosensitivity were observed. The presentation Of lung damage either as function loss or density changes do not necessarily coincide, meaning that for each endpoint the regional sensitivity may be different. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Purpose: To investigate dose distributions in partial-volume irradiation experiments in small experimental animals, in particular the parotid gland of rat.Materials and methods: High-resolution magnetic resonance imaging images were made that provided the outlines of the parotid glands, which were used to design collimators with conformal radiation ports for 100 and 50% cranial/caudal partial-volume irradiation. A protocol for absolute dosimetry was designed and relative dose measurements were performed. From the three-dimensional topographical data and the three-dimensional dose distribution, dose-volume histograms were determined.Results: The standard uncertainty of absorbed entrance dose was within 3%. Radiochromic film, thermoluminescence dosemeters and ionization chamber dose measurements revealed that the relative doses measured were in good agreement. The 20-80% penumbra of the beam across the 50% field edge was only 0.4 mm at a 6 mm depth. The gradient of the percentage depth dose from the skin of the rat to a depth of 12 mm was 1.5% mm(-1). The absorbed doses in the cranial 50% and the caudal 50% partial volumes were comparable. This finding was reflected in the calculated dose-volume histograms of the different regions, which were similar. The dose in the shielded area between the left and right ports was about 14% of the dose near the centres of the beams.Conclusion: The designed set-up showed that irradiation of small volumes could be performed with high accuracy allowing the study of differences in radiation damage. Similar doses were given to the 50% cranial and 50% caudal gland volumes and, therefore, a possible difference in radiosensitivity in these volumes was not a dose effect. The approach used was also applicable for the irradiation of small volumes of other tissues.

It was studied whether differences in acute radiosensitivity exist between parotid and submandibular/sublingual glands. The results revealed that salivary flow rates decreased dramatically during the first 2 weeks of radiotherapy. Neither recovery nor significant differences were observed between the production of saliva from the parotid and submandibular/sublingual glands during the 13 weeks observation period. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

We monitored 10 patients with unresected (9) or partially resected (1) supratentorial gliomas with 11C-tyrosine position emission tomography (TYR-PET) before and after radiotherapy. TYR-PET tumour volumes were measured using a threshold technique. In seven patients the tumour volume decreased after radiotherapy, although all gliomas persisted on TYR-PET images. In eight patients the tumour protein synthesis rate (PSR) was calculated using a dynamic study protocol in combination with a PATLAK analysis. There were no changes in PSR after radiotherapy, but the PSR was calculated on the remaining tumour volume using the same threshold technique as before therapy, i.e. the decrease in tumour volume was not taken into account. In eight patients the PET data were compared with magnetic resonance spectroscopic imaging (1H-MRSI) performed simultaneously. Although there was no statistically significant correlation between TYR-PET volume changes and 1H-MRSI choline level we observed a simultaneous decrease in volume and choline in four patients.

The purpose of this study is to develop an experimental model to measure localized radiation-induced lung injury using multiple end-points including breathing frequency, high-resolution computed tomography (CT), and radionuclide perfusion. The rats were anesthetized and the right lung irradiated with a single dose of 18 Gy using 200-kVp x-rays. The lung function of the animals was measured every 2 weeks after irradiation with the breathing rate assay. CT scanning and radionuclide lung perfusion assay were performed prior to and 2, 4, 10, 16, and 34 weeks after irradiation. Significant elevation in breathing rate occurred after 16 weeks, with a maximal increase between 22 and 28 weeks. An increase in the right lung density started 4 weeks after irradiation. Regional measurements indicated a relatively uniform increase in density at 4 and 10 weeks, while foci of high-density areas were observed at the later time points. Changes in rat lung volume indicated shrinkage of the irradiated right lung and accompanying compensatory hypertrophy of the shielded left lung. Radionuclide perfusion assay showed significant decrease in relative blood flow in the irradiated right lung 4 weeks after hemithoracic irradiation. Changes in breathing rate provide an index of overall lung function while changes in lung density, volume, and perfusion are of particular importance for evaluating loco-regional differences in lung sensitivity. This study is the first demonstration that CT can be used to measure volume changes after thoracic irradiation in rats.

In many thoracic cancers, the radiation dose that can safely be delivered to the target volume is limited by the tolerance dose of the surrounding lung tissue. It has been hypothesized that irradiation of the heart may be an additional risk factor for the development of early radiation-induced lung morbidity. In the current study, the dependence of lung tolerance dose on heart irradiation is determined. Fifty percent of the rat lungs were irradiated either including or excluding the heart. Proton beams were used to allow very accurate and conformal dose delivery. Lung function toxicity was scored using a breathing rate assay. We confirmed that the tolerance dose for early lung function damage depends not only on the lung region that is irradiated but also that concomitant irradiation of the heart severely reduces the tolerance of the lung. This study for the first time shows that the response of an organ to irradiation does not necessarily depend on the dose distribution in that organ alone.

The usefulness of the Themes Concerning Blacks (TCB) as a measure of racial identification was explored among African American, African Dutch, and African Surinamese samples. Generally, most of the characters on the TCB cards were perceived by all three groups in ways parallel to the objective description of the cards, the highest number of recorded themes was given to the same cards by all groups, the emotional tone of most of the stories was moderately sad, the outcome of most stories was neutral, and Afrotypic (race-specific) content was significantly absentfrom stories. The absence may be due to the adverse effects of oppression on identity, guarded behavior in the testing situation, and the crudeness of the scoring system. Recommendations forfuture studies using the TCB are given.

Background Consistent delineation of patient anatomy becomes increasingly important with the growing use of highly conformal and adaptive radiotherapy techniques. This study investigates the magnitude and 3D localization of interobserver variability of organs at risk (OARs) in the head and neck area with application of delineation guidelines, to establish measures to reduce current redundant variability in delineation practice. Methods Interobserver variability among five experienced radiation oncologists was studied in a set of 12 head and neck patient CT scans for the spinal cord, parotid and submandibular glands, thyroid cartilage, and glottic larynx. For all OARs, three endpoints were calculated: the Intraclass Correlation Coefficient (ICC), the Concordance Index (CI) and a 3D measure of variation (3D SD). Results All endpoints showed largest interobserver variability for the glottic larynx (ICC = 0.27, mean CI = 0.37 and 3D SD = 3.9 mm). Better agreement in delineations was observed for the other OARs (range, ICC = 0.32-0.83, mean CI = 0.64-0.71 and 3D SD = 0.9-2.6 mm). Cranial, caudal, and medial regions of the OARs showed largest variations. All endpoints provided support for improvement of delineation practice. Conclusions Variation in delineation is traced to several regional causes. Measures to reduce this variation can be: (1) guideline development, (2) joint delineation review sessions and (3) application of multimodality imaging. Improvement of delineation practice is needed to standardize patient treatments.

To study adjacent tissue damage after delivery of holmium, thulium and excimer laser pulses, porcine thoracic aortas were irradiated in vivo. After 3 days, microscopic analysis of 67 craters produced by all three lasers demonstrated large dissections extending from the craters. The mean diameter of the dissections was smaller for excimer-induced craters (1.38 +/- 0.42 mm; n = 22) than for holmium-induced (2.7 +/- 0.87 mm; n = 22) and thulium-induced (2.37 +/- 0.42 mm; n = 14) craters (p less than 0.01 vs. mid-infrared dissections). In addition, microscopic analysis demonstrated necrosis adjacent to the crater. The lateral necrotic zones of the thulium-induced craters were smaller than the holmium- and excimer-induced necrotic zones (p less than 0.01). To identify the origin of the excessive tissue tearing, laser-saline and laser-tissue interaction were compared in vitro by time-resolved flash photography. In saline solution, the mid-infrared lasers showed bubble formation on a microsecond time scale. The excimer laser produced similar bubbles in the vicinity of tissue. For all three lasers, elevation of the tissue surface was shown during in vitro ablation. Dimension (diameter up to 4 mm) and time course (rise time of 100 to 300 microseconds) of bubble formation and tissue elevation were strikingly similar. Thus, tissue dissections are caused by the expansion of a vapor bubble within the target tissue. Coronary dissections after excimer and mid-infrared laser angioplasty might be related to the forceful bubble expansion.

SUMMARY The spatial distribution of species in boundary situations between heathland communities and adjacent vegetation types in the subalpine zone of the Monts du Forez was studied. Ten transects were analysed, four dealing with the transition between heathland and ombrotrophic peatland, and six dealing with the transition between heathland and communities characterized by tall forbs. Species cover and the composition of vascular plants in each square metre were studied in detail. The distribution pattern of the species along the transects is interpreted ecologically and discussed phytosociologically. The similarity between the heathland and adjacent vegetation was calculated and a number of quantitative characteristics of the boundary situations (species diversity, floristic fall, dissimilarity) were analysed. The four methods applied for measurement of alteration in the floristic composition were compared with each other, and their usefulness is discussed here.

A 37-year-old woman was admitted to the emergency room because of an autointoxication with hydroxychloroquine, leading to haemodynamic instability. Treatment consisted of the rapid administration of intravenous diazepam, after which the hypotension recovered rapidly even though no vasoactive medication was given. Treatment with diazepam has been advised in the Netherlands for many years in case of severe hydroxychloroquine intoxication, despite the fact that convincing evidence for its use is lacking. On the basis of the experience with the relevant cases, the administration of diazepam, 2 mg/kg initially followed by 2 mg/kg/24 hours as a continuous infusion, should certainly be considered for supportive treatment in the ICU in case of severe haemodynamic instability.

PURPOSE: To assess the association between the dose distributions in the rectum and late Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer (RTOG/EORTC), Late Effects of Normal Tissue SOMA, and Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 graded rectal toxicity among patients with prostate cancer treated with RT.METHODS AND MATERIALS: Included in the study were 124 patients who received three-dimensional conformal RT for prostate cancer to a total dose of 70 Gy in 2-Gy fractions. All patients completed questionnaires regarding rectum complaints before RT and during long-term follow-up. Late rectum Grade 2 or worse toxicity, according to RTOG/EORTC, LENT SOMA, and CTCAE v3.0 criteria, was analyzed in relation to rectal dose and volume parameters.RESULTS: Dose-volume thresholds (V40>or=65%, V50>or=55%, V65>or=45%, V70>or=20%, and a rectum volumeor=70 Gy (V70) was most predictive for late Grade 2 or worse rectal toxicity with each of the grading systems. The associations were strongest, however, with use of the LENT SOMA system.CONCLUSIONS: Volume effects for late radiation-induced rectal toxicity are present, but their clinical significance depends on the grading system used. This should be taken into account in the interpretation of studies reporting on radiation-induced rectal toxicity.

Correct placement of radiation fields relative to patient anatomy is essential in radiotherapy in order to minimise serious side effects to reduce the probability of recurrence of the tumour. One way to determine patient setup accuracy is to analyse portal images obtained in the therapy beam distal to the patient. A field placement analysis (FPA) method has been developed for detailed evaluation of patient setup by comparing positions of corresponding radiation field edges in digitised simulator and portal images. A simulator image is matched to a portal image using similar anatomical landmarks in both images and mapping these landmarks against each other applying a least squares minimisation approach. Discrepancies between the simulator field edge (reference) and a portal field edge are determined by comparing the distances between the central axis of the beam and corresponding edge segments and the angles of these segments with a reference line. Uncertainties in these distances and angles are to a large extent determined by the magnification, rotation and translation procedure. Uncertainties due to the FPA method itself are of about 1.0 mm and 0.5 degrees in portal images of head and neck fields. These FPA uncertainties are in general smaller than the variations due to patient setups. Matching of simulator and portal images of lateral pelvic fields revealed larger uncertainties: 1.7 mm and 1.1 degrees. Setup variations in this kind of pelvic radiation field are usually also larger, and therefore meaningful results can be obtained with the new FPA method.

Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung.Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test.Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILE Finally, a modified CV model is described that is consistent to all data.Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung. (c) 2007 Elsevier Inc.

Purpose: In this study we investigated whether the position of head and neck cancer patients during radiotherapy could be determined from portal images of oblique radiation beams. Currently applied additional anterior posterior (AP) and lateral verification beams could then be abandoned.Method: The patient position was determined from portal images of the oblique radiation beams and compared with that determined from AP and lateral verification beams. Seven hundred and fifty-one portal images of 18 different patients were analyzed.Results: The set-up errors of patients that were treated with oblique gantry angles could be determined with the same accuracy from the oblique beams as from the AP and lateral verification beams in the ventrodorsal and craniocaudal direction. An additional AP beam was necessary to obtain the same accuracy in the lateral direction, because the used beam directions were relatively close to lateral. The position verification of patients treated with both oblique gantry angles and isocentric table rotations was more accurate if AP and lateral verification beams were used.Conclusions: For patients treated with an irradiation technique with oblique gantry angles (and no isocentric table rotations) position verification can be performed by using these oblique radiation beams. (c) 2007 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 85 (2007) 126-131.

The aim of this study was to estimate the accuracy and reproducibility of citric-acid-stimulated parotid saliva sampling. In healthy volunteers a strong correlation (r(2) = 0.79) between flow rates from the left and right parotid gland was observed. In patients with Sjogren's syndrome this correlation (r(2) = 0.90) was even stronger. The intraindividual variation in healthy volunteers was 23.3 +/- 5.9%. Increasing the number of collections did not reduce this variation significantly. In head and neck cancer patients, to estimate whether repeated measurements result in more reliable baseline values for use in clinical studies, repeated collections did not result in a significant reduction of intrapatient variation, similar to the results with the healthy volunteers. Thus, notwithstanding the good agreement between left and right flow rates, a high variation in parotid flow rates has to be considered when planning clinical trials evaluating the effects of treatment on salivary gland functioning.

Purpose: Usually, models that predict normal tissue complication probability (NTCP) are fitted to clinical data with the maximum likelihood (ML) method. This method inevitably causes a loss of information contained in the data. In this study, an alternative method is investigated that calculates the parameter probability distribution (PD), and, thus, conserves all information. The PD method also allows the calculation of the uncertainty in the NTCP, which is an (often-neglected) prerequisite for the intercomparison of both treatment plans and NTCP models. The PD and ML methods are applied to parotid gland data, and the results are compared. Methods and Materials: The drop in salivary flow due to radiotherapy was measured in 25 parotid glands of 15 patients. Together with the parotid gland dose-volume histograms (DVH), this enabled the calculation of the parameter PDs for three different NTCP models (Lyman, relative seriality, and critical volume). From these PDs, the NTCP and its uncertainty could be calculated for arbitrary parotid gland DVHs. ML parameters and resulting NTCP values were calculated also. Results: All models fitted equally well. The parameter PDs turned out to have nonnormal shapes and long tails. The NTCP predictions of the ML and PD method usually differed considerably, depending on the NTCP model and the nature of irradiation, NTCP curves and ML parameters suggested a highly parallel organization of the parotid gland, Conclusions: Considering the substantial differences between the NTCP predictions of the ML and PD method, the use of the PD method is preferred, because this is the only method that takes all information contained in the clinical data into account. Furthermore, PD method gives a true measure of the uncertainty in the NTCP, (C) 2001 Elsevier Science Inc.

Purpose: Evaluation of the B‐Spline based Registration Method (BSRM) and the effect of contrast, signal to noise ratio and registration parameter settings on the accuracy of the restored voxel displacements in deformed H&N images.Method and Materials:CTimages of a 8×15×25 cm3 phantom were constructed. The phantom contained spherical and elliptical structures simulating a tumor and several H&N organs. From this set, additional CT sets were constructed by: 1) affine transformation, 2) imposing shaped deformations up to 20 mm and 3) addition of noise of 10 HU up to 300 HU (1SD). The BSRM of the Insight Toolkit combined with Elastix was used to register the various distorted phantoms to the original phantom. The effect of different parameter settings of the registration has been investigated (number of iterations, spacing of the B‐ spline grid, number of resolution levels). Displacement vectors calculated in the deformable registration were compared with the imposed deformations. Average residual voxel displacement and other similarity measures were calculated. Results: Satisfactory convergence of the average residual displacement is reached after 64, 64 and 128 iterations for 3 levels of resolution. A grid spacing of 8–12 mm gives good results, although for sharp deformations a 6 mm grid is better in most cases. The increase in noise has a minor influence on the accuracy. An average tracking accuracy of better than 2 mm for parotid gland edges seems feasible. In some areas, however residual displacement errors up to 6–8 mm are observed. Conclusions: The BSRM seems to be suitable for intensity based deformable image registration of structures like the parotid and submandibular glands in the H&N region. Careful tuning of parameter values is important to obtain reliable results. References: ITK: www.itk.org, Elastix: www.isi.uu.nl/Elastix.

A quality control system especially designed for dosimetry in scanning proton beams has been designed and tested. The system consists of a scintillating screen (Gd2O2S:Tb), mounted at the beam-exit side of a phantom, and observed by a low noise CCD camera with a long integration time. The purpose of the instrument is to make a fast and accurate two-dimensional image of the dose distribution at the screen position in the phantom. The linearity of the signal with the dose, the noise in the signal, the influence of the ionization density on the signal, and the influence of the field size on the signal have been investigated. The spatial resolution is 1.3 mm (1 s.d.), which is sufficiently smaller than typical penumbras in dose distributions, The measured yield depends linearly on the dose and agrees within 5% with the calculations. In the images a signal to noise ration (signal/l s.d.) of 10(2) has been found, which is in the same order of magnitude as expected from the calculations. At locations in the dose distribution possessing a strong contribution of high ionization densities (i.e., in the Bragg peak), we found some quenching of the light output, which can be described well by existing models if the beam characteristics are known. For clinically used beam characteristics such as a Spread Out Bragg peak, there is at most 8% deviation from the NACP ionization chamber measurements. The conclusion is that this instrument is a useful tool for quick and reliable quality control of proton beams. The long integration-time capabilities of the system make it worthwhile to investigate its applicability in scanning proton beams and other dynamic treatment modalities. (C) 1998 American Association of Physicists in Medicine. [S0094-2405(98)02104-X].

Purpose: To design a method to quantify morphological changes in irradiated lung tissue, assessed by CT. Method and Materials: CT images were made at different time points after administration of varying doses to different regions of the rat lung. The experiment included irradiation of 100%, 50% (6 different regions) and 25% (2 regions) of the total lung volume. The applied doses were: 9,10,11 and 12 Gy for the 100% lung volume, 16,18,20 and 22 Gy for the 50% volumes and 27,30,33 and 36 Gy for the 25% volumes. A computerized contouring method was developed to automatically delineate the lungs in the CT images. For each irradiated region the average CT-value (ACV) of its pixels and its standard deviation (SD) were determined. The changes in ACV and its SD with respect to the same region in controls were combined in a vector M. The length and orientation of M was used to characterize the changes in the CT image pattern, i.e. the morphology of the lung tissue. The total lung volume of all animals and M were measured at 8, 26 and 38 weeks for all irradiated regions, averaged over all dose values. After normalization, M was also measured as a function of dose. Results: About 13.000 contours in lung volume studies of 374 rats were automatically drawn. With respect to the controls, a decrease in total lung volume in time was observed. Significant changes in radiation responses M were found in all irradiated regions. The largest radiation response was found for lateral lung volumes. Conclusion: The auto-contouring method is very robust and can easily be applied to process large amounts of CT-slices of irradiated rat lung. The method showed significant changes in average lung CT pixel values and their variation for sub volumes of irradiated lung tissue.

The aim of our study was to demonstrate, in vivo, bubble expansion in blood and to assess any damage to the arterial wall after 1 - 10 excimer laser pulses (55 mJ/mm2). Time resolved flash photography demonstrated the expansion and implosion of a vapor bubble, which induced a 50% diameter increase of the artery within 75 microsecond(s) and a subsequent invagination (150 - 500 microsecond(s) ). This microsecond dilation and invagination caused extensive wall damage (up to 1.9 mm) far beyond the penetration depth of 308 nm laser light (< 100 micrometers ). The damage, which increased with the number of laser pulses, may be related to the dissections observed after excimer laser coronary angioplasty.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

BACKGROUND Previous in vitro studies demonstrated that during excimer laser ablation of aortic tissue in saline, a fast-expanding and imploding vapor bubble is formed. The present in vivo study was designed to demonstrate the formation of a fast-expanding intraluminal bubble in flowing blood and to assess any damage to the adjacent arterial wall. METHODS AND RESULTS Excimer laser pulses (one to 10, at 55 mJ/mm2 per pulse) were delivered coaxially in the femoral and iliac arteries of nine normal rabbits. Time-resolved flash photography of dissected arteries in situ demonstrated a 50% diameter increase within 75 microseconds after the laser pulse and a subsequent invagination (150-500 microseconds) that corresponded with the temporal course of the bubble expansion (up to 3.2 mm in diameter) and implosion observed in a hemoglobin solution. One day after laser light delivery, light microscopy (47 arterial segments) showed abrasion of the internal elastic lamina, medial necrosis, and extensive dissection planes filled with red blood cells. The degree (up to 100% medial necrosis) and extent of damage (up to 1.9 mm in length) increased with the number of delivered laser pulses. CONCLUSIONS In blood, each excimer laser pulse generated a fast-expanding and imploding vapor bubble. In vivo, the intraluminal vapor bubble produced microsecond dilation and invagination of the adjacent arterial segment, which induced dissections and extensive wall damage far beyond the penetration depth of 308-nm laser light (< 100 microns). This unique pattern of extensive wall damage observed in the rabbit might explain the mechanism of dissection observed in humans and might have an impact on the acute and chronic outcome after excimer laser coronary angioplasty.

On-line electronic portal imaging devices are beginning to come into clinical service in support of radiotherapy. A variety of technologies are being explored to provide real-time or near real-time images of patient anatomy within x-ray fields during treatment on linear accelerators. The availability of these devices makes it feasible to verify treatment portals with much greater frequency and clarity than with film. This article reviews the physics of high-energy imaging and describes the operation principles of the electronic portal imaging devices that are under development or are beginning to be used clinically.

In fractionated radiation therapy with high energy photon beams, patient set-up is verified by analysing the position of the radiation field relative to the patient anatomy. This analysis is performed in an X-ray film, which has been exposed at the beam exit side of the patient during irradiation. Electronic portal image detectors, such as fluorescent screens, scanning diode arrays, or matrix ionization chambers produce an image within a few seconds, and enable an instantaneous verification of the patient set-up for every treatment session. An approach to detect radiation field edges in portal images using global threshold segmentation and local gradient information is presented.

In our institute an electronic portal imaging device (PID) has been developed and it recently became available for routine clinical practice. Images are available within 3 to 6 seconds after the start of irradiation; they are displayed on a video monitor next to the control console of the accelerator. The image quality is similar to the quality of images obtained with films. Because of its cassette-like shape and its low weight, the PID can easily be handled by technicians. An important advantage of the PID over conventional films is its pseudo-real time viewing facility. Typically, 5 to 10 images of each field can be made during one treatment session. In case a high accuracy in setup is demanded, the field edges of the first image, obtained with about 10% of the fraction dose, can be studied for acceptability before the rest of the dose is delivered. Using two prototype PID's first clinical experience has been obtained with patients treated for malignant tumors at various sites. Intra-treatment motion as a result of breathing, swallowing, or patient motion in a cast was seen. Motion of high contrast objects, for example, a field edge during irradiation, can be followed. This feature is important for future applications in computer controlled radiotherapy. Another advantage of the PID over film is that the image is digitally available. Therefore it can be further processed for quality improvement and quantitative analysis. Simple processing is done within seconds on the PID unit. A local network for the transfer of images from the accelerators to the evaluation room, where a detailed analysis of the field placement is performed, is under installation. Simulator film images are digitized in this room and are sent to the PID at the accelerator for a quick comparison with portal images during irradiation. We conclude that our device can replace the conventional film detector for portal imaging, that useful images are obtained within seconds during irradiation, and that the position of the field outline relative to the patient anatomy can be followed during dose delivery.

Source strength measurements were performed for cesium-137 spherical sources of nine Selectron-LDR remote afterloading systems in The Netherlands. The mean reference air kerma rate of a set of sources was obtained from air kerma rate measurements in a phantom at a distance of about 5.5 cm from a large number (24 to 30) of sources. The results were compared with the source strengths specified by the manufacturer. Discrepancies between measured and manufacturers data ranging from − 2.3 % to + 3.9 were observed. The frequency distribution of the strength of the sources within a set was measured by the use of a well-type ionisation chamber. The root mean square deviations of the nine source sets ranged from 1.0 to 3.2%. Application of the in-phantom calibration method would improve the precision of source strength measurements and therefore reduce the differences in dose delivery between institutes. The uncertainty of the in-phantom method, which could be estimated by statistical methods, was 0.3 (one standard deviation). That part of the uncertainty, which could not be evaluated by statistical methods, was estimated to be about 1.2% (one effective standard deviation). This latter part in the uncertainty needs further investigation in order to reduce the overall uncertainty.

It is very important to have a daily verification of patient setup during radiotherapy. Therefore, we have developed an on-line imaging device for high energy photons. It consists of a matrix of 128 x 128 liquid filled ionisation chambers and has a field of view of 320 mm x 320 mm. This device has an extremely flat cassette-like housing for easy handling and for application with existing radiotherapy equipment. A dedicated microcomputer is used to measure the currents of the 16384 ionisation chambers at high speed. The same computer is used to restore and process the images. With an imaging time of 3.1 s, an image quality comparable to film is obtained. Images of high and low contrast phantoms and of patients are presented. With this device, high quality portal images will be available within only a few seconds after the start of the treatment. This allows an almost instantaneous decision on the approval of patient setup. In addition, it enables observation of organ or patient motion during a single treatment. Analysis of these images at high speed will be an interesting new area of research.

An intercomparison was made between dose-rate calculations performed in 10 institutes in The Netherlands for intracavitary applications with the Selectron-LDR remote afterloading machine. The results of 11 computer planning systems of five different manufacturers were compared with reference dose-rate calculations. The difference in clinically relevant dose-points like rectum and bladder, were less than 2% if the values of the coordinates of source and dose-points were given, except for one type of planning system, that showed differences up to 10%. The errors observed for the latter system were probably due to a coarse calculation grid, which becomes important in regions with a high dose gradient. If the reconstruction process of source and dose-point positions from radiographs was included as it usually is in practice, then the accuracy became worse and the planning system that showed large errors before, gave unacceptable errors of 30% to 40% in the rectal area. This is due to additional errors introduced in the reconstruction. The intercomparison showed that it is very important that computer treatment planning systems for brachytherapy calculations are tested before clinical use. The reconstruction technique for source and dose-point positions should be part of this test. Radiographs should be made of a phantom that simulates the cervix application, and the radiography technique should be similar to the one that is clinically employed.

Summary Measurements have been performed of build-up and depth-dose characteristics of photon beams under Hodgkin's disease treatment conditions as applied in two hospitals (AVL, Amsterdam and IGR, Villejuif). Although different types of accelerators, photon energies, field sizes and SSD are employed, similar dose distributions along the beam axis have been obtained in both centers. In order to explain this unexpected good agreement, the influence of the geometrical conditions of irradiation on the build-up and depth-dose distribution has been studied in detail for five photon beams (8 MV-25 MV) of three types of accelerators.