Harm Meertens

Parotid and submandibular/sublingual salivary flow during high dose radiotherapy

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.

Fast 2D phantom dosimetry for scanning proton beams

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/1 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.

3D Variation in delineation of head and neck organs at risk

BackgroundConsistent 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.MethodsInterobserver 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).ResultsAll 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.ConclusionsVariation 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.

Radiation damage to the heart enhances early radiation-induced lung function loss

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.

Bath and Shower Effects in the Rat Parotid Gland Explain Increased Relative Risk of Parotid Gland Dysfunction After Intensity-Modulated Radiotherapy

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 1 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.

Loco-regional differences in pulmonary function and density after partial rat lung irradiation

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 dose 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 in 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.

The effects of computed tomography image characteristics and knot spacing on the spatial accuracy of B-spline deformable image registration in the head and neck geometry

ObjectivesTo explore the effects of computed tomography (CT) image characteristics and B-spline knot spacing (BKS) on the spatial accuracy of a B-spline deformable image registration (DIR) in the head-and-neck geometry.MethodsThe effect of image feature content, image contrast, noise, and BKS on the spatial accuracy of a B-spline DIR was studied. Phantom images were created with varying feature content and varying contrast-to-noise ratio (CNR), and deformed using a known smooth B-spline deformation. Subsequently, the deformed images were repeatedly registered with the original images using different BKSs. The quality of the DIR was expressed as the mean residual displacement (MRD) between the known imposed deformation and the result of the B-spline DIR.Finally, for three patients, head-and-neck planning CT scans were deformed with a realistic deformation field derived from a rescan CT of the same patient, resulting in a simulated deformed image and an a-priori known deformation field. Hence, a B-spline DIR was performed between the simulated image and the planning CT at different BKSs. Similar to the phantom cases, the DIR accuracy was evaluated by means of MRD.ResultsIn total, 162 phantom registrations were performed with varying CNR and BKSs. MRD-values < 1.0 mm were observed with a BKS between 10–20 mm for image contrast ≥ ± 250 HU and noise < ± 200 HU. Decreasing the image feature content resulted in increased MRD-values at all BKSs. Using BKS = 15 mm for the three clinical cases resulted in an average MRD < 1.0 mm.ConclusionsFor synthetically generated phantoms and three real CT cases the highest DIR accuracy was obtained for a BKS between 10–20 mm. The accuracy decreased with decreasing image feature content, decreasing image contrast, and higher noise levels. Our results indicate that DIR accuracy in clinical CT images (typical noise levels < ± 100 HU) will not be effected by the amount of image noise.

SU-FF-I-105: Positional Accuracy of a B-Spline Based Method for Image Registration in the H&N Area: Effect of Noise, Contrast and Registration Parameters

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.

SU‐FF‐T‐365: Measurement of Radiation Induced Lung Damage in the Rat by CT Image Analysis

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.