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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 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.

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/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.