Patient-specific quality assurance for intracranial cases in robotic radiosurgery system.

PURPOSE: The purpose of this study was to perform pretreatment patient-specific quality assurance (QA) for intracranial irradiation using CyberKnife with an ion chamber. METHODS: Twenty-five intracranial plans created using the ray-tracing algorithm were used for this study. Computed tomography (CT) images of the water-equivalent RW3 slab phantom with PinPoint ionization chamber were acquired with 1-mm slice thickness and transferred to the MultiPlan treatment planning system (TPS). Four gold fiducial markers embedded into two different plates were used to tracking during the irradiation. Intracranial plans were transferred to CT images of the RW3 phantom. The isodose curves and sensitive volume of ion chamber were overlapped. Point dose measurements were performed three times and the mean point doses were calculated for each plan. The mean doses measured by the PinPoint ion chamber were compared with those of the calculated by MultiPlan TPS in the sensitive volume of PinPoint. RESULTS: The mean percentage difference (MPD) in point dose measurements was -2.44±1.97 for 25 plans. The maximum and minimum percentage differences between the measured and calculated absolute point doses were -7.14 and 0.23, respectively. The MPD was -1.70±1.90 for 12 plans using a fixed collimator and -3.11±1.86 for 13 plans using an IRIS cone. CONCLUSIONS: Point dose measurement is a reliable and functional method for pre-treatment patient-specific QA in intracranial CyberKnife plans. Point dose verification should be performed to correct any possible errors prior to patient treatment. It is recommended for use in patient-specific QA process in the CyberKnife plans.

Absolute dose verification of static intensity modulated radiation therapy (IMRT) with ion chambers of various volumes and TLD detectors.

AIM: This study aims at examining absolute dose verification of step-and-shoot intensity modulated radiation treatment (IMRT) of prostate and brain patients by use of ion chambers of two different volumes and thermoluminescent detectors (TLD). BACKGROUND: The volume of the ion chamber (IC) is very important for absolute dose verification of IMRT plans since the IC has a volume average effect. With TLD detectors absolute dose verification can be done measuring the dose of multiple points simultaneously. MATERIALS AND METHODS: Ion chambers FC65-P of volume 0.65 cc and semiflex of volume 0.125 cc as well as TLDs were used to measure the central axis absolute dose of IMRT quality assurance (QA) plans. The results were compared with doses calculated by a treatment planning system (TPS). The absolute doses of off axis points located 2 cm and 4 cm away from the isocenter were measured with TLDs. RESULTS: The measurements of the 0.125 cc ion chamber were found to be closer to TPS calculations compared to the 0.65 cc ion chamber, for both patient groups. For both groups the root mean square (RMS) differences between doses of the TPS and the TLD detectors are within 3.0% for the central axis and points 2 cm away from the isocenter of each axis. Larger deviations were found at the field edges, which have steep dose gradient. CONCLUSIONS: The 0.125 cc ion chamber measures the absolute dose of the isocenter more accurately compared to the 0.65 cc chamber. TLDs have good accuracy (within 3.0%) for absolute dose measurements of in-field points.

Does partial expander deflation exacerbate the adverse effects of radiotherapy in two-stage breast reconstruction?

BACKGROUND: The optimum protocol for expander volume adjustment with respect to the timing and application of radiotherapy remains controversial. METHODS: Eighteen New Zealand rabbits were divided into three groups. Metallic port integrated anatomic breast expanders of 250 cc were implanted on the back of each animal and controlled expansion was performed. Group I underwent radiotherapy with full expanders while in Group II, expanders were partially deflated immediately prior to radiotherapy. Control group did not receive radiotherapy.The changes in blood flow at different volume adjustments were investigated in Group II by laser Doppler flowmetry. Variations in the histopathologic properties of the irradiated tissues including the skin, capsule and the pocket floor, were compared in the biopsy specimens taken from different locations in each group. RESULTS: A significant increase in skin blood flow was detected in Group II with partial expander deflation. Overall, histopathologic exam revealed aggravated findings of chronic radiodermatitis (epidermal atrophy, dermal inflammation and fibrosis, neovascularisation and vascular changes as well as increased capsule thickness) especially around the lower expander pole, in Group II. CONCLUSIONS: Expander deflation immediately prior to radiotherapy, may augment the adverse effects, especially in the lower expander pole, possibly via enhanced radiosensitization due to a relative increase in the blood flow and tissue oxygenation.

Does hyperbaric oxygen administration before or after irradiation decrease side effects of irradiation on implant sites?

BACKGROUND: One of the main limitations of implant-based breast reconstruction is the high rate of complications such as capsular contracture and poor aesthetic outcome, due to adjuvant radiotherapy. Hyperbaric oxygen treatment (HBOT) has been used to assist wound healing in the prevention and treatment of the side effects of irradiation. We aimed to investigate this effect of HBOT on the capsule reaction and skin, applied before and after irradiation, following the placement of an implant under the dorsal skin of the rat. METHODS: Fifteen Wistar rats were randomly divided into 3 groups. A 18-mL smooth testicular implant was introduced into a subcutaneous pocket located on the dorsum of each rat. A single dose of 17-Gy irradiation was given to the implanted area of each rat at the third week. HBOT which lasted 3 weeks was administered to group I before irradiation, group II after irradiation. The control group did not receive HBOT. All of the rats were killed at the ninth week (6 weeks after irradiation). The dorsal skin with the capsule overlying the implant were excised for histopathological processing. The thickness of the capsule reaction of each group was evaluated statistically. RESULTS: Our histopathological examination revealed changes due to radiation in the control group. Many of these findings were found to be more subtle in group I and nearly absent in the group II. There was not any statistical difference between the thickness of the capsule reactions of the control group and group I, or group I and group II, but the capsular thickness of the control group was statistically higher than group II. CONCLUSION: It can be predicted that the use of HBOT following irradiation is an effective tool to reduce the capsule reaction of the implanted area and the tissue damage seen in radiodermatitis.

Morphological and functional changes of blood-brain barrier in kindled rats with cortical dysplasia.

Cortical dysplasia (CD) is one of the major causes contributing to epileptogenesis associated with blood-brain-barrier (BBB) disturbances. The current study investigated the functional and ultrastructural changes of BBB in pentylenetetrazole (PTZ)-kindled rats with CD. Pregnant rats on E17 were exposed to 145 cGy of gamma-irradiation and offspring were used for experiments. The rats were given PTZ three times per week to induce kindling. The permeability of BBB was determined by using sodium fluorescein (NaFlu). Immunohistochemistry for occludin, GFAP and c-fos, western-blot analysis for occludin and electron microscopy for the ultrastructural alterations in BBB were performed. The brain level of NaFlu did not increase in rats with CD and/or kindling. Following administration of a convulsive dose of PTZ, a significant increase in BBB permeability was observed in kindled rats with CD. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Slightly enhanced immunoreactivity for GFAP was observed in all groups except control. c-fos immunoreactivity in brain sections of kindled rats with CD displayed a striking increase by convulsive PTZ challenge. Tight junctions were ultrastructurally intact, whereas markedly increased number of pinocytotic vesicles was noted in brain endothelium of kindled rats with CD by convulsive dose of PTZ. The present study showed that epileptic seizures induced by convulsive PTZ challenge during kindling-mediated epileptogenesis in the presence of CD changed both functional and ultrastructural properties of the BBB and considerably enhanced transendothelial vesicular transport, while paracellular pathway was apparently not involved in this setting.

Effect of a carbon fiber tabletop on the surface dose and attenuation for high-energy photon beams.

PURPOSE: The dose changes in the buildup region and beam attenuation by a carbon fiber tabletop were investigated for 6-and 18-MV photon beams. MATERIALS AND METHODS: Measurements were performed for 2 x 2 cm to 40 x 40 cm field sizes. The surface dose and percentage depth doses (PDD) were measured by a Markus parallel plate chamber. Attenuation measurements were made at the cylindrical phantom for 180 degrees rotation of the beam. RESULTS: A carbon fiber tabletop increases the surface dose from 7.5% to 63.0% and from 4% to 43% for small fields at 6 and 18 MV, respectively. The increase was nearly fivefold for the 10 x 10 cm field and nearly twofold for the 40 x 40 cm field. Beam attenuation of the tabletop varies from 3.0% to 5.6% for 180 degrees and 120 degrees gantry angles for 6 MV. CONCLUSION: The carbon fiber tabletop significantly decreases the skin-sparing effect. The dosimetric effect of the tabletop may be higher, especially for the intensity-modulated radiation therapy depending on the beam orientation. Attenuation should be considered and corrected such as any material under the patient at the treatment planning stage.

Effects of lipopolysaccharide on the radiation-induced changes in the blood-brain barrier and the astrocytes.

The use of radiation to improve the efficacy of chemotherapy on malignant brain tumors is also known to cause side effects on vascular endothelial cells and astrocytes in normal parts of the brain. We investigated the effects of lipopolysaccharide (LPS) on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during whole-brain irradiation in rats. The permeability of the BBB to Evans blue (EB) dye significantly increased in the cerebral cortex, diencephalon and cerebellum regions of rats exposed to irradiation (P<0.01). In contrast, the BBB permeability in irradiated rats was significantly reduced by LPS (P<0.05). Tumor necrosis factor-alpha (TNF-alpha) levels were increased following LPS, irradiation and irradiation plus LPS (P<0.05, P<0.01). Irradiated brain vessels showed a considerable loss of staining intensity of tight junction proteins Zonula occludens-1 (ZO-1) and occludin. Staining for Zonula occludens-1 and occludin was intensive in animals treated with LPS and irradiation plus LPS. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in very few astrocytes of irradiated brains. However, this staining showed an increased positive intensity in the brain sections of LPS-treated as well as of irradiation plus LPS-treated animals. These results indicate that LPS reduces the passage of exogenous vascular tracer EB-binding albumin into the brain, at least partly, by increasing the expression of tight junction proteins and GFAP, following the irradiation. We suggest that irradiation may affect paracellular permeability through disruption of tight junction proteins, Zonula occludens-1 and occludin, and LPS could provide beneficial effects on the BBB integrity and the astrocytes against irradiation damage.

Determination of surface dose and the effect of bolus to surface dose in electron beams.

When treating tumors from surface to a certain depth (<5 cm), electron beams are preferred in radiotherapy. To increase the surface doses of lower electron beams, tissue-equivalent bolus materials are often used. We observed that the surface doses increased with increasing field sizes and electron energies. At the same time, we also observed that all electron parameters were shifted toward the skin as much as the thickness of the bolus used. The effect of bolus to the surface doses was more significant at low electron energies than at higher electron energies. Rando phantom measurements at 6-, 7.5-, and 9-MeV were slightly lower than the solid phantom measurements, which could only be explained by the inverse square law effect and the Rando phantom contour irregularity.

A comparative study of the peripheral doses from a linear accelerator with a multileaf collimator system.

This study presents a comparison of peripheral doses (PDs) measured using an ionisation chamber with treatment planning system (TPS) data and a Monte Carlo (MC) simulation of a 6-MV photon beam. The ion chamber measurements and MC simulation produced similar results for all out-of-field distances and field sizes considered in this study. For the 0° and 90° collimation angles, the average local per cent dose differences between the MC and TPS calculations were 2.7 % (range: -2.4, +22.6) and -1.7 % (range: -12.2, +10.8), respectively. The corresponding differences between the MC calculations and the ion chamber measurements were 2.2 % (range: -2.4, 24.7) and -1.8 % (range: -17, 15.2) for all field sizes and depths, respectively. Whereas the PDs increased with field sizes, the variations with depth were negligible at large distances. The TPS calculations usually yielded higher PDs than ion chamber measurements at distances close to the field edge. In contrast, at the farther distances, the TPS results indicated lower doses than both the ion chamber and the MC data. TPS data are not sufficient for use in calculating the out-of-field doses. These results can be used to estimate non-target organ doses to patients.

Dosimetric investigation of LDR brachytherapy ¹9²Ir wires by Monte Carlo and TPS calculations.

PURPOSE: The aim of this study was to investigate the dose rate distribution around (192)Ir wires used as radioactive sources in low-dose-rate brachytherapy applications. MATERIALS AND METHODS: Monte Carlo modeling of a 0.3-mm diameter source and its surrounding water medium was performed for five different wire lengths (1-5 cm) using the MCNP software package. RESULTS: The computed dose rates per unit of air kerma at distances from 0.1 up to 10 cm away from the source were first verified with literature data sets. Then, the simulation results were compared with the calculations from the XiO CMS commercial treatment planning system. CONCLUSION: The study results were found to be in concordance with the treatment planning system calculations except for the shorter wires at close distances.

Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with (125)I seeds (model I25.S16).

PURPOSE: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with (125)I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. METHODS: Using EBT film, absolute doses were measured for (125)I seeds (model I25.S16) in COMS eye plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at (125)I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film∕PS Homo) and (film∕PS Hetero) were obtained. RESULTS: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film∕PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film∕PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. CONCLUSIONS: Substantial heterogeneity effect on the (125)I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple (125)I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.

Topiramate reduces blood-brain barrier disruption and inhibits seizure activity in hyperthermia-induced seizures in rats with cortical dysplasia.

We investigated the effects of topiramate (TPM), a novel broad spectrum anticonvulsant, on seizure severity, survival rate and blood-brain barrier (BBB) integrity during hyperthermic seizures in rats with cortical dysplasia (CD). Offsprings of irradiated mothers were used in this study. To show the functional and morphological alterations in BBB integrity, quantitative analysis of Evans blue (EB) extravasation, immunohistochemistry and electron microscopic assessment of horseradish peroxidase (HRP) permeability were performed. Rats with CD exposed to hyperthermia exhibited seizures with mean Racine's scores of 3.92 ± 1.2. Among the rats with CD pretreated with TPM, 21 of 24 rats showed no sign of seizure activity upon exposure to hyperthermia (p<0.01). The immunoreactivity of occludin, a tight junction protein, remained essentially unaltered in capillaries of hippocampus in all groups. In animals with CD exposed to hyperthermia, the significantly increased p-glycoprotein immunoreactivity in hippocampus (p<0.01) was slightly decreased by TPM pretreatment. Hyperthermic seizures increased BBB permeability to EB in animals with CD, but TPM pretreatment decreased the penetration of the tracer into the brain in these animals (p<0.01). Ultrastructurally frequent vesicles containing HRP reaction products were observed in capillary endothelial cells in cerebral cortex and hippocampus of rats with CD subjected to hyperthermia-induced seizures, and TPM pretreatment prevented the development of HRP reaction products in these animals. The results of this study suggest that TPM inhibits seizure activity and maintains BBB integrity in the course of febrile seizures in the setting of CD.

Vagus nerve stimulation inhibits seizure activity and protects blood-brain barrier integrity in kindled rats with cortical dysplasia.

AIMS: This study investigates the effects of vagus nerve stimulation (VNS) on seizure severity and blood-brain barrier (BBB) integrity in kindled rats with cortical dysplasia (CD). MAIN METHODS: Pregnant rats were exposed to 145 cGy of gamma-irradiation on day 17 of pregnancy. In offsprings, kindling was induced by giving subconvulsive doses of pentylenetetrazole. Left VNS was performed for 48 h at output currents of 0.5 or 1 mA. Horseradish peroxidase (HRP) was used to study the BBB permeability. Immunohistochemistry for occludin and P-glycoprotein (P-gp) was also performed. KEY FINDINGS: Kindled rats with CD exhibited seizures with mean Racine's scores of 3.57 ± 1.2 during video EEG recording. Kindled animals with CD receiving VNS at 0.5 and 1.0 mA did not exhibit either clinical or electrophysiological signs of seizure. Immunostaining for occludin, a tight junction protein, in hippocampus remained relatively intact in all groups. VNS-treated and -untreated kindled animals with CD revealed intense immunostaining for P-gp in hippocampal formation (P<0.01). Electron microscopic observations revealed frequent transport vesicles containing electron-dense HRP reaction products in the cytoplasm of brain capillary endothelial cells in both cerebral cortex and hippocampus of kindled animals with CD. Those which were exposed to 1 mA VNS were observed to have brain capillary endothelial cells largely devoid of HRP reaction products in both cerebral cortex and hippocampus. SIGNIFICANCE: The results of this study suggest that VNS therapy at 1 mA inhibits seizure activity and protects BBB integrity by limiting the enhancement of transcellular pathway in kindled animals with CD.

Effects of levetiracetam on blood-brain barrier disturbances following hyperthermia-induced seizures in rats with cortical dysplasia.

AIMS: The mechanisms underlying the changes in blood-brain barrier (BBB) integrity and the generation of seizures in childhood associated with preexisting brain lesions like cortical dysplasia (CD) are poorly understood. We investigated the effects of levetiracetam (LEV) on BBB integrity and the survival during hyperthermic seizures in rats with CD. MAIN METHODS: Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. On postnatal day 28, hyperthermia-induced seizures were evoked in offspring with CD. To show the functional and morphological alterations in BBB integrity, quantitative analysis of sodium fluorescein (NaFlu) extravasation, immunohistochemistry and electron microscopy were performed. KEY FINDINGS: Seizure scores and mortality rates were decreased by LEV during hyperthermia-induced seizures in rats with CD (P<0.01). Increased NaFlu extravasation into brain by hyperthermia-induced seizures in animals with CD was decreased by LEV (P<0.01). While glial fibrillary acidic protein (GFAP) immunoreactivity slightly increased in brain sections of animals with CD during hyperthermia-induced seizures, LEV led to GFAP immunoreactivity comparable to that of controls. Decreased occludin immunoreactivity and expression in CD plus hyperthermia-induced seizures was increased by LEV. Opening of tight junctions and abundance of pinocytotic vesicles representing ultrastructural evidences of BBB impairment and severe perivascular edema were observed in animals with CD exposed to hyperthermia-induced seizures and LEV treatment led to the attenuation of these findings. SIGNIFICANCE: These results indicate that LEV may present a novel approach for the protection of the BBB besides its antiepileptic impact on hyperthermic seizures in the setting of CD.

Levetiracetam decreases the seizure activity and blood-brain barrier permeability in pentylenetetrazole-kindled rats with cortical dysplasia.

This study investigates the effects of levetiracetam (LEV) on the functional and structural properties of blood-brain barrier (BBB) in pentylenetetrazole (PTZ)-kindled rats with cortical dysplasia (CD). Pregnant rats were exposed to 145 cGy of gamma-irradiation on embryonic day 17. In offsprings, kindling was induced by giving subconvulsive doses of PTZ three times per week for 45 days. While all kindled rats with CD died during epileptic seizures evoked by the administration of a convulsive dose of PTZ in 15 to 25 min, one week LEV (80 mg/kg) pretreatment decreased the mortality to 38% in the same setting. LEV caused a remarkable decrease (p<0.01) in extravasation of sodium fluorescein dye into the brain tissue of kindled animals with CD treated with convulsive dose of PTZ. Occludin immunoreactivity and expression remained essentially unchanged in all groups. Immunoreactivity for glial fibrillary acidic protein (GFAP) was observed to be slightly increased by acute convulsive challenge in kindled rats with CD while LEV pretreatment led to GFAP immunoreactivity comparable to that of controls. An increased c-fos immunoreactivity in kindled rats with CD exposed to convulsive PTZ challenge was also observed with LEV pretreatment. Tight junctions were ultrastructurally intact, whereas LEV decreased the increased pinocytotic activity in brain endothelium of kindled rats with CD treated with convulsive dose of PTZ. The present study showed that LEV decreased the increased BBB permeability considerably by diminishing vesicular transport in epileptic seizures induced by convulsive PTZ challenge in kindled animals with CD.