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The in-room laser which is used for patient positioning in radiotherapy is generally projected on the radiation isocenter determined by the Winston-Lutz test and so on. In this study, a couch-mounted verification device was developed that could evaluate all in-room lasers' alignment including the horizontality and verticality at one time. The device has the function to perform the light/radiation field coincidence test and the Winston-Lutz test at the same time. The aim of this report was to introduce the verification procedure for two tests, using the newly developed software and device, and to present the tuning flow of the in-room laser. Moreover, the analysis accuracy of the developed software was evaluated in comparison with commercial software.First, the light/radiation field was evaluated by using tungsten markers on the central surface of the device. Next, after aligning the long-carved lines on the front and sides of the device with the in-room lasers, the Winston-Lutz test was carried out by using the tungsten sphere in the center of the device. The acquired images were collectively analyzed using the developed software equipped with the reporting function. Additionally, the result of this Winston-Lutz test was compared with the result from commercial software.A series of the light/radiation field coincidence test and the Winston-Lutz test were analyzed using the developed device and software. The results could be easily confirmed using the reporting function of the software. Regarding the result of the Winston-Lutz test, most of the analysis differences between the developed software and commercially available software were within the pixel size (0.22 mm).Since the accuracy of the radiation field affects the result of the Winston-Lutz test, the presented procedure of performing the light/radiation coincidence field test in advance facilitates the interpretation of the error of the Winston-Lutz test. Based on the results of the Winston-Lutz test, we were able to demonstrate the tuning flow of all in-room lasers including the horizontality and verticality by using the developed device.We have developed a couch-mounted verification device and software that can evaluate the light/radiation coincidence field test and the alignment including the horizontality and verticality of the in-room laser used for patient positioning in radiotherapy, and reported its usefulness. The analysis accuracy of the developed software was comparable to that of commercially available software. The use of this device and the developed software would contribute to not only the efficiency of adjusting all in-room lasers' alignment including the horizontality and verticality but also reflect accurately the result of the Winston-Lutz test.

Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups— WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)—since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap—that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

Purpose: The accumulated dose distributions during the course of radiation treatment are substantially important for verifying whether treatmentdose distributions are produced according to planned dose distributions. The purpose of this study was to develop a computer‐assisted verification method of accumulated dose distribution during the irradiation of a tumor based on estimation of four‐dimensional (4D) dose distribution using an electronic portal imaging device(EPID).Methods: The 4D ‘treatment’ computed tomography(CT)images during the irradiation were estimated based on affine transformations including respiratory motions, which were derived by registration between a planning portal doseimage and treatment portal dose dynamic image. Planning portal doseimages were calculated from planning CTimages and an algorithm for calculation of dose spatial distribution. Treatment portal doseimages were estimated from EPID dynamic images obtained during a treatment time. The planning portal doseimages were registered to the treatment portal doseimages to obtain the affine transformation, which could include respiratory motion in a patient body. The CTimages at a treatment time were determined by deforming the planning CTimages using the affine transformation matrix. 4D dose distributions during a treatment delivery were obtained by applying a dose calculation algorithm to the 4D treatmentCTimages. Finally, accumulated dose distributions during the course of radiation treatment were verified with planned dose distributions. Results: We applied the proposed method to EPID dynamic images of 2 lungcancer patients, and evaluated the difference in accumulated dose distribution between the plan and treatment using a gamma evaluation (3mm/3%). The average pass rate for 2 cases was 78.2%. Conclusions: The proposed method can be used for adaptively modifying the plan based on the dose discrepancy between the plan and treatment. This work was partially supported by Grant‐in‐Aid for Scientific Research (C) (22611011) and Okawa Foundation for Information and Telecommunications.

Temozolomide (TMZ), used to treat glioblastoma and malignant glioma, induces autophagy, apoptosis and senescence in cancer cells. We investigated fibrin glue (FG) as a drug delivery system for the local administration of high-concentration TMZ aimed at preventing glioma recurrence. Our high-power liquid chromatography studies indicated that FG containing TMZ (TMZ-FG) manifested a sustained drug release potential. We prepared a subcutaneous tumor model by injecting groups of mice with three malignant glioma cell lines and examined the antitumor effect of TMZ-FG. We estimated the tumor volume and performed immunostaining and immunoblotting using antibodies to Ki-67, cleaved caspase 3, LC3 and p16. When FG sheets containing TMZ (TMZ-FGS) were inserted beneath the tumors, their growth was significantly suppressed. In mice treated with peroral TMZ plus TMZ-FGS the tumors tended to be smaller than in mice whose tumors were treated with TMZ-FGS or peroral TMZ alone. The TMZ-FGS induced autophagy, apoptosis and senescence in subcutaneous glioma tumor cells. To assess the safety of TMZ-FG for normal brain, we placed it directly on the brain of living mice and stained tissue sections obtained in the acute and chronic phase immunohistochemically. In both phases, TMZ-FG failed to severely damage normal brain tissue. TMZ-FG may represent a safe new drug delivery system with sustained drug release potential to treat malignant glioma.

The purpose of this study is to evaluate the real-time respiratory motion of the prostate and surrounding tissues/organs in the supine and prone positions and to investigate, using cine-MRI, whether a belly board can reduce respiratory-induced motion in the prone position. Cine-MRI scans were made of 13 volunteers in the supine and prone positions on a flat board and in two different prone positions using a belly board. Images in cine mode were recorded for 20 seconds. For each session, the points of interest (POIs) were located at the apex, base, mid-anterior surface and mid-posterior surface of the prostate; the tip of the seminal vesicle; the pubic symphysis; and the sacrum. The maximum range and standard deviation (SD) of the displacement from the mean value were calculated. The SDs for each of the four different positions were compared using a paired t-test. Respiratory-induced prostate motion was significantly larger in the prone position than in the supine position. However, when a belly board was used in the prone position, motion in the prostate and surrounding tissues/organs was significantly reduced. There were no significant differences between the two different positions using a belly board in any of the POIs.

Glioblastoma multiforme (GBM) harbors are not only rapidly dividing cells but also small populations of slowly dividing and dormant cells with tumorigenesity, self-renewal, and multi-lineage differentiation capabilities. Known as glioblastoma stem cells (GSCs), they are resistant to conventional chemo- and radiotherapy and may be a causative factor in recurrence. The treatment outcome in patients with GBM remains unsatisfactory and their mean survival time has not improved sufficiently. We studied clinical evidence and basic research findings to assess the possibility of new treatment strategies that target GSCs and their specific microenvironments (GBM niches) and raise the possibility of adding new treatments to eradicate GSCs and GBM niches.

We have developed a computerized method for estimating patient setup errors in portal images based on localized pelvic templates for prostate cancer radiotherapy. The patient setup errors were estimated based on a template-matching technique that compared the portal image and a localized pelvic template image with a clinical target volume produced from a digitally reconstructed radiography (DRR) image of each patient. We evaluated the proposed method by calculating the residual error between the patient setup error obtained by the proposed method and the gold standard setup error determined by consensus between two radiation oncologists. Eleven training cases with prostate cancer were used for development of the proposed method, and then we applied the method to 10 test cases as a validation test. As a result, the residual errors in the anterior–posterior, superior–inferior and left–right directions were smaller than 2 mm for the validation test. The mean residual error was 2.65 ± 1.21 mm in the Euclidean distance for training cases, and 3.10 ± 1.49 mm for the validation test. There was no statistically significant difference in the residual error between the test for training cases and the validation test (P = 0.438). The proposed method appears to be robust for detecting patient setup error in the treatment of prostate cancer radiotherapy.

The X-ray source or focal radiation is one of the factors that can degrade the conformal field edge in stereotactic body radiotherapy. For that reason, it is very important to estimate the total focal radiation profiles of linear accelerators, which consists of X-ray focal-spot radiation and extra-focal radiation profiles. Our purpose in this study was to propose an experimental method for estimating the focal-spot and extra-focal radiation profiles of linear accelerators based on triple Gaussian functions. We measured the total X-ray focal radiation profiles of the accelerators by moving a slit in conjunction with a photon field p-type silicon diode. The slit width was changed so that the extra-focal radiation could be optimally included in the total focal radiation. The total focal radiation profiles of an accelerator at 4-MV and 10-MV energies were approximated with a combination of triple Gaussian functions, which correspond to the focal-spot radiation, extra-focal radiation, and radiation transmitted through the slit assembly. As a result, the ratios of the Gaussian peak value of the extra-focal radiation to that of the focal spot for 4 and 10 MV were 0.077 and 0.159, respectively. The peak widths of the focal-spot and extra-focal radiation profiles were 0.57 and 25.0 mm for 4 MV, respectively, and 0.60 and 22.0 mm for 10 MV, respectively. We concluded that the proposed focal radiation profile model based on the triple Gaussian functions may be feasible for estimating the X-ray focal-spot and extra-focal radiation profiles.

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s(-1) by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 +/- 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Currently, unruptured cerebral aneurysms (U-Ans) are positively treated in conformity with the guideline for the Japanese Society for Detection of Asymptomatic Brain Diseases. Direct operations are performed after informed consent is obtained in U-Ans cases. However, unfortunate outcomes have occurred even if safe surgery was done. Therefore we examined the characteristics of U-Ans and report surgical treatment in our hospital. Consecutive operations (n=45) on 43 patients between January 2005 and October 2007 were included in this study. Surgical neck clipping was performed on all patients. The mean age was 67 years. U-Ans were discovered in medical check-ups in 24 cases (56%), during close examinations of headache and dizziness in 10 cases, examination of oculomotor palsy in 5 cases and examination of ruptured cerebral aneurysm in 2 cases, respectively. The mean U-Ans sizes were 6.1 mm in the internal carotid artery, 6.4 mm in the anterior cerebral artery and 6.4 mm in the middle cerebral artery (MCA), respectively. One basilar top aneurysm 7 mm in size was included. Surgical morbidity was recognized in 2 patients (4%). One patient, a 75 year-old male, suffered a left temporal cerebral infarction due to mechanical vasospasm. Another patient, a 67 year-old female, developed a cerebral infarction in the territory of the right MCA due to the compression for MCA during approach for basilar-top UAn. We experienced 2 cases with unfortunate outcomes. Surgical complications caused by mechanical damage and vessel compression occurred. These complications in clipping for aneurysms are preventable. More care in performing operative procedures is needed.

The aim of this study was to present the technical aspects of the breath-hold technique with respiratory monitoring and visual feedback and to evaluate the feasibility of this system in healthy volunteers.To monitor respiration, the vertical position of the fiducial marker placed on the patient's abdomen was tracked by a machine vision system with a charge-coupled device camera. A monocular head-mounted display was used to provide the patient with visual feedback about the breathing trace. Five healthy male volunteers were enrolled in this study. They held their breath at the end-inspiration and the end-expiration phases. They performed five repetitions of the same type of 15-s breath-holds with and without a head-mounted display, respectively. A standard deviation of five mean positions of the fiducial marker during a 15-s breath-hold in each breath-hold type was used as the reproducibility value of breath-hold.All five volunteers well tolerated the breath-hold maneuver. For the inspiration breath-hold, the standard deviations with and without visual feedback were 1.74 mm and 0.84 mm, respectively (P = 0.20). For the expiration breath-hold, the standard deviations with and without visual feedback were 0.63 mm and 0.96 mm, respectively (P = 0.025).Our newly developed system might help the patient achieve improved breath-hold reproducibility.

Purpose: The voluntary breath-hold (BH) technique is a simple method to control the respiration-related motion of a tumor during irradiation. However, the abdominal and chest wall position may not be accurately reproduced using the BH technique. The purpose of this study was to examine whether visual feedback can reduce the fluctuation in wall motion during BH using a new respiratory monitoring device. Methods and Materials: We developed a laser-based BH monitoring and visual feedback system. For this study, five healthy volunteers were enrolled. The volunteers, practicing abdominal breathing, performed shallow end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end-inspiration BH (DIBH) with or without visual feedback. The abdominal and chest wall positions were measured at 80-ms intervals during BHs. Results: The fluctuation in the chest wall position was smaller than that of the abdominal wall position. The reproducibility of the wall position was improved by visual feedback. With a monitoring device, visual feedback reduced the mean deviation of the abdominal wall from 2.1 ± 1.3 mm to 1.5 ± 0.5 mm, 2.5 ± 1.9 mm to 1.1 ± 0.4 mm, and 6.6 ± 2.4 mm to 2.6 ± 1.4 mm in SEBH, SIBH, and DIBH, respectively. Conclusions: Volunteers can perform the BH maneuver in a highly reproducible fashion when informed about the position of the wall, although in the case of DIBH, the deviation in the wall position remained substantial.

To determine positioning accuracy of a machine vision system in radiotherapy.The machine vision system was composed of 640 x 480 pixel CCD cameras and computerized control systems. For image acquisition, the phantom was set up for the reference position and a single CCD camera was positioned 1.5 m from the isocenter. The image data of the fiducial marker with 1.5 mm lead pellet on the lateral surface of the phantom was captured onto the CCD, and then the position of the marker was accurately calculated. The phantom was moved 0.25, 0.50, 0.75, 1.00, 2.00, and 3.00 mm from the reference position, using a micrometer head. The position of the fiducial marker was analyzed using a kilo-voltage fluoroscopic imaging system and a machine vision system.Using fluoroscopic images, the discrepancy between the actual movement of the phantom by micrometer heads and the measurement was found to be 0.12 +/- 0.05 mm (mean +/- standard deviation). In contrast, the detection of the movement by the machine vision system coincided with the discrepancy of 0.0067 +/- 0.0048 mm.This study suggests that the machine vision system can be used to measure small changes in patient position with a resolution of less than 0.1 mm.

To evaluate the feasibility and treatment outcomes of stereotactic radiotherapy (SRT) using a newly developed simple body cast system for lung and liver tumors.From April 2003 to July 2004, 20 patients were treated with SRT at the Kyushu University Hospital. Thirteen patients had primary lung cancer, 5 had metastatic lung cancer, and 2 had hepatocellular carcinoma. All patients were fixed with a thermoplastic body cast combined with a vacuum pillow, arm and leg support, and a carbon plate. SRT was given in 5-8 fields with an isocenter dose of 48-60 Gy in 4-10 fractions. Target verification was performed by computed tomography (CT) during the first session, and by anterior-posterior (A-P) and lateral portal images during the second and subsequent sessions.The average setup errors and deviation in the first treatment session were 1.4 +/- 1.2, 1.1 +/- 1.0, and 3.3 +/- 2.8 mm in the lateral, A-P, and cranio-caudal (C-C) directions, respectively. The setup errors in the second and subsequent sessions were 2.4 +/- 0.5, 1.4 +/- 1.8, and 3.7 +/- 2.6 mm in the lateral, A-P, and C-C directions, respectively. The patient's movement during a treatment session was within 5 mm in any direction. Despite the short follow-up periods (1-15 months), complete response was shown in 4 lesions, and partial response was shown in 15 lesions. Neither local progression nor serious complication was observed in any patient.SRT using our body cast system was a safe and reliable treatment method for extracranial tumors.

Purpose: We developed a novel automated estimation method for patient setup errors based on simulated and real portal images for prostate cancerradiotherapy.Methods: The estimation of patient setup errors in this study was based on a template matching technique with a cross‐correlation coefficient and Sobel filter between the real portal image and localized pelvic template of reference image, which were DRR (digitally reconstructedradiography)images and simulated portal images. The simulated portal image was derived by projecting a CTimage according to an inverse exponential power law of x‐ray attenuation for a water‐equivalent path length of each voxel of the CTimage on each ray from a source to each pixel on the EPID (electric portal imaging device). A localized pelvic template of each patient in AP (anterior‐posterior) or lateral view was automatically extracted from the DRR or simulated portal images by cropping a rectangular region, which was determined by using the mean pelvic template and four anatomical feature points. We applied the proposed method to three prostate cancer cases, and evaluated it using the residual error between the patient setup error obtained by proposed method and the gold standard setup error determined by two radiation oncologists.Results: The average residual errors of the patient setup error for the DRR and simulated portal images were 0.79 and 1.26 mm in the left‐right (LR) direction, 3.17 and 2.05 mm in the superior‐inferior (SI) direction, 1.69 and 5.82 mm in the anterior‐posterior (AP) direction, 3.84 and 6.94 mm in Euclidean distance (ED), respectively. If we used the simulated portal image for LR and SI directions and the DRRimage for AP direction, the Euclidean distance was 3.22 mm. Conclusions: The proposed method has a potential to correctly estimate patient setup errors for prostate cancerradiotherapy.

Purpose: Lateral scatter kernels (LSKs) of an electronic portal imaging device(EPID) and a water equivalent phantom are essential data for estimating the three‐dimensional dose distributions in lungcancer patients who receive stereotactic body radiotherapy. The LSKs are used for converting portal images to portal doseimages. The purpose of this study was to investigate a method of estimating LSKs of the EPID and water equivalent phantom, and then compare the LSKs between experimental measurements and the Monte Carlo(MC) method. Method and Materials: The experimental LSKs were derived from the differentiation of the signal (mean pixel value or absorbed dose) as a function of equivalent circular radius of irradiation area. Mean pixel values in a region of interest of the EPID and absorbed doses in the water equivalent phantom were measured for estimating the LSKs of the EPID and water equivalent phantom, respectively, by changing the irradiation area of 3×3 to 20×20 cm2. For evaluation of the experimental method, the theoretical LSKs were obtained based on the Monte Carlo method by simulating the same geometry of the experimental set‐up including the EPID and water equivalent phantom. Two x‐ray energies of 6 and 10 MV were employed respectively, at a medicallinear accelerator in conjunction with an EPID.Results: The experimental method overestimated the LSKs of the EPID and water equivalent phantom compared with those of the Monte Carlo simulation method. The full width half maximum values at 6 and 10 MV of the theoretical LSKs were 0.166 and 0.193 cm for the EPID, respectively, and 0.177 and 0.211 cm for the water equivalent phantom, respectively. Conclusion: We should continue to investigate the experimental and theoretical methods for estimation of LSKs of the EPID and water equivalent phantom for dose verification in stereotactic lungradiotherapy.

Purpose: Our purpose of this study was to develop a computer‐assisted verification method for lungtumor regions using a Gaussian image enhancement based on second derivatives of Gaussian functions in cine images on an EPID without implanted markers during SBRT.Method and Materials: The localization for a lungtumor was based on a template matching technique between a “tumor template” image obtained from a first EPID cine image and the subsequent image. The irradiation field region was cropped from an original EPID cine image by analyzing the histogram of this image. The “tumor template” image was segmented from the first EPID cine image, i.e., reference portal image, by using a Gaussian image enhancement based on second derivatives of Gaussian functions and a region growing technique. The tumor region was determined within the irradiation field as the position where the tumor template image took the maximum cross‐correlation value within each subsequent cine image. For performance evaluation of the proposed method, we applied the proposed method to EPIDimages acquired from twelve cases (age: 51–83 years old, mean: 72) with a non‐small cell lungcancer, and calculated the following two values: (1) the location error, i.e., the Euclidean distance from “tumor” point to the candidate point and (2) the overlap measure between the target candidate regions obtained by the manual method and our automated segmentation method. Results: The average location deviation between tumor center points obtained by the proposed method and the manual method was 1.80 ± 0.73 mm. The average overlap measure was 66.0 ± 10.0% for 12 cases. Conclusion: The results of this study suggest that the proposed method based on the tumor template matching technique might be feasible for localization of a lungtumor without implanted markers in SBRT.

Purpose/Objective(s): It is very important to monitor the location of a tumor in cine images by using an electronic portal imaging device (EPID) during stereotactic body radiotherapy (SBRT), because it has been unclear whether the internal margin is appropriate for displacements of a tumor due to respiratory motion. Our motivation for this study is a clinical need of a tool for investigating whether the internal margin is appropriate for a moving tumor due to respiration, and tracking the moving tumor in real time without implanted markers, because a majority of conventional methods have used markers implanted adjacent to a tumor, which are invasive approaches for patients. Our goal of the study was to develop an automated method for localization of a lung tumor in cine images on an EPID without implanted markers during the SBRT.

Purpose: The purpose of this study was to estimate beam profiles in lung stereotactic body radiotherapy for acceptance test of radiotherapy planning system (RTP) system. The beam profiles measured by an ionization chamber were approximated by using three Gaussian functions, and compared with profile data calculated by two RTP systems. Method and Materials: X‐ray linear accelerator with 4,6,10MV (Varian 21EX) was used to deliver symmetric beam profile for a field size of 5×5cm2. A lung phantom consisted of a lung equivalent material (thickness : 170 mm) sandwiched by two Solid Waters, whose thickness were 30 mm and 50 mm for anterior and posterior sides, respectively. Measured beam profiles were approximated by manually determining three amplitudes and standard deviations of three Gaussian functions corresponding to three point spread functions of an x‐ray focus, x‐ray or electron scatter, and a detector,and by integrating the composed function. Finally, we evaluated our method by comparing the approximated beam profiles with those calculated by two algorithms in two RTP systems, i.e., Convolution/superposition (CS) (Philips Pinnacle) and analytical anisotropic algorithm (AAA) (Varian Eclipse).Results: Difference between the measured and approximated beam profiles were 4% at 20–80% doses, and 1.5% difference at the other doses. The fringe values (distance between the 50 and 90% levels) of beam profiles approximated by Gaussian functions and calculated by CS and AAA algorithms were 4.7, 6.1, 6.4 mm for 4MV x‐ray, 5.7, 6.9, 7.1 mm for 6MV x‐ray, and 6.8, 7.7, 8.2 mm for 10MV x‐ray, respectively. Conclusion: It was suggested the beam profile model based on the three Gaussian functions may be useful for acceptance test of a RTP system.