Dosimetric and biologic intercomparison between electron and proton FLASH beams.

BACKGROUND AND PURPOSE: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at an average dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by eFLASHvs. pFLASH has yet been performed and constitutes the aim of the present study. MATERIALS AND METHODS: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥110 Gy/s eFLASH and pFLASH) dose rates. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed using previously validated dosimetric approaches and experimental murine models. RESULTS: The difference between the average absorbed dose measured at Gantry 1 with PSI reference dosimeters and with CHUV/IRA dosimeters was -1.9 % (0.1 Gy/s) and + 2.5 % (110 Gy/s). The neurocognitive capacity of eFLASH and pFLASH irradiated mice was indistinguishable from the control, while both eCONV and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained after an ablative dose of 20 Gy delivered with the two beams at CONV and FLASH dose rates. Tumor rejection upon rechallenge indicates that anti-tumor immunity was activated independently of the beam-type and the dose-rate. CONCLUSION: Despite major differences in the temporal microstructure of proton and electron beams, this study shows that dosimetric standards can be established. Normal brain protection and tumor control were produced by the two beams. More specifically, normal brain protection was achieved when a single dose of 10 Gy was delivered in 90 ms or less, suggesting that the most important physical parameter driving the FLASH sparing effect might be the mean dose rate. In addition, a systemic anti-tumor immunological memory response was observed in mice exposed to high ablative dose of electron and proton delivered at CONV and FLASH dose rate.

Dosimetric and biologic intercomparison between electron and proton FLASH beams.

Background and purpose: The FLASH effect has been validated in different preclinical experiments with electrons (eFLASH) and protons (pFLASH) operating at a mean dose rate above 40 Gy/s. However, no systematic intercomparison of the FLASH effect produced by e vs. pFLASH has yet been performed and constitutes the aim of the present study. Materials and methods: The electron eRT6/Oriatron/CHUV/5.5 MeV and proton Gantry1/PSI/170 MeV were used to deliver conventional (0.1 Gy/s eCONV and pCONV) and FLASH (≥100 Gy/s eFLASH and pFLASH) irradiation. Protons were delivered in transmission. Dosimetric and biologic intercomparisons were performed with previously validated models. Results: Doses measured at Gantry1 were in agreement (± 2.5%) with reference dosimeters calibrated at CHUV/IRA. The neurocognitive capacity of e and pFLASH irradiated mice was indistinguishable from the control while both e and pCONV irradiated cohorts showed cognitive decrements. Complete tumor response was obtained with the two beams and was similar between e and pFLASH vs. e and pCONV. Tumor rejection was similar indicating that T-cell memory response is beam-type and dose-rate independent. Conclusion: Despite major differences in the temporal microstructure, this study shows that dosimetric standards can be established. The sparing of brain function and tumor control produced by the two beams were similar, suggesting that the most important physical parameter driving the FLASH effect is the overall time of exposure which should be in the range of hundreds of milliseconds for WBI in mice. In addition, we observed that immunological memory response is similar between electron and proton beams and is independent off the dose rate.

Caracterización de la Lámpara Flash-LED: EBNeuro Usada para Adquirir Potenciales Evocados Visuales en Ratas / Characterization of the Flash-LED Lamp: EBNeuro Used to Acquired Visual Evoked Potentials in Rats

Resumen: La señal de la amplitud en análisis de Potenciales Evocados Visuales (PEVs) es una variable que depende del tipo y posición de los electrodos, de la fuente, del estímulo y por consecuente, de la intensidad luminosa por lo que es fundamental reportarla para cada diseño experimental y así, garantizar su reproducibilidad. El objetivo de este trabajo es caracterizar una lámpara con 96 LEDs para la adquisición de PEVs en ratas. Se midió la iluminancia y la intensidad luminosa promedio en un sistema espacial XYZ de 8 cm3 aplicable a un sistema estereotáxico para la fijación de ratas. Se realizaron desplazamientos cada 2 cm en cada plano. Se observó que debido a la distribución geométrica de los LEDs la distribución de la iluminancia no sigue la ley del inverso cuadrado, ya que aumenta conforme la lámpara se aleja. Finalmente, se seleccionó una coordenada para la colocación del ojo de la rata empleando una intensidad luminosa promedio para la adquisición del PEV de 1.043 cd e iluminancia de 128.77 luxes a una distancia ojo-lámpara de 9 cm. Una vez caracterizada la intensidad luminosa y de acuerdo con los PEVs obtenidos, esta lámpara puede utilizarse para estudios PEV en ratas en investigaciones posteriores.

Abstract: Signal amplitude for recordings of Visual Evoked Potentials (VEPs) is a variable dependent on the type and position of the electrodes, the source, the stimulus and consequently the luminous intensity; therefore, it is relevant to report it to assure experimental reproducibility. The objective of this work is to characterize flash lamp with 96 LEDs in order to perform the acquisition of VEPs in rats. We measure the illuminance and mean light intensity on space system XYZ of 8 cm3 corresponding to a stereotaxic frame for rodents. Displacements were performed every 2 cm in each plane. Because of the geometric distribution of the LEDs in the EBNeuro lamp the spatial distribution of illuminance does not follow the law of the inverse square, because the illuminance increases as the lamp goes away. Finally a spatial coordinate was selected for the rat eye positioning were the mean luminous intensity was 1.043 cd and 128.77 luxes of illuminance at an eye-lamp distance of 9 cm. According to the obtained VEPs and spatial characterization this lamp can be used for acquire of recordings PEV in rats for further investigations.

Assessment of an image-guided neurosurgery system using a head phantom.

OBJECTIVE: To acknowledge the challenges and limitations of image-guided neurosurgery systems, we compared the application accuracy of two different image registration methods for one commercial system. (VectorVision, BrainLab, Germany). METHODS: We used an anthropomorphic head phantom for radiosurgery and a custom built add-on to simulate surgical targets inside the brain during an image-guided neurosurgery. We used two image registration methods, fiducial registration using attachable surface markers for computed tomography (CT) and surface registration using infrared laser face scanning. After simulation, we calculated the three-dimensional (3D) distance between the predicted position of a target, and its actual position using a registered pointer and an infrared camera. Deviations were measured for both superficial fiducial markers and internal surgical targets by five different users. RESULTS: Deviations from the location of fiducial markers after each registration method were 2.15 ± 0.93 mm after CT surface marker registration and 1.25 ± 0.64 mm after infrared face scanner registration. The mean target registration errors were 2.95 ± 1.4 mm using fiducial registration and 2.90 ± 1.3 mm using surface registration. The largest deviations (6.2 mm) were found for the targets in the skull base and posterior cranial fossa. Fiducial deviations and target registration errors were statistically uncorrelated. The total application accuracy was 4.87 ± 0.97 mm after CT surface marker registration and 4.14 ± 0.64 mm after infrared face scanner registration. CONCLUSIONS: Despite others have reported differences, we did not find significant variations between both registration methods for the target registration error, although application accuracy was slightly better after surface face registration. Superficial registration errors, but not the target registration error, can be routinely evaluated in the operating room. Since both errors were uncorrelated, surgeons may neglect the achievable accuracy of the procedure. The described method is recommended to assess application accuracy in the operating room.

Stereotactic radiosurgery for pediatric patients with intracranial arteriovenous malformations: variables that may affect obliteration time and probability.

INTRODUCTION: It is debatable whether pediatric patients diagnosed with arteriovenous malformations (AVMs) should be treated as adults. Several indexes to classify AVMs have been proposed in the literature, and most try to predict the outcome for each specific treatment. The indexes differ in the variables considered, but they are all based in adult populations. In this study, we analyzed the variables that influence the obliteration time and probability of occurrence in a Mexican pediatric population diagnosed with an AVM and treated with stereotactic radiosurgery (SRS). METHODS: We analyzed 45 pediatric patients (<18 years) with a minimum follow-up of 10 months and a maximum of 112 months. We used logistic regression analysis and Kaplan-Meier curves to evaluate the influence of age, AVM volume, prescribed dose, minimum dose, maximum dose, time of follow-up, sex, previous hemorrhage, venous drainage, treatment technique, previous treatment and location. We also evaluated the predictive power of the following indexes: Spetzler-Martin, RBAS, or K index dose deviation. RESULTS: We found that the radiation technique used may influence the obliteration occurrence (p=0.057). The data suggests that circular arcs are a more efficient treatment technique than dynamic arcs. However, no relationship of dose or volume with treatment technique could be found. Obliteration was also dependent on follow-up time and after three years of follow-up, the obliteration probability decreases (p=0.024). According to Kaplan-Meier analysis, the nidus obliteration time was related with the location according to the Spetzler-Martin index. If the nidus was located in a non-eloquent region, there was a tendency of a shorter obliteration time (p=0.071). CONCLUSION: None of the previously proposed indexes for adults predict obliteration in this pediatric population. Treatment technique, eloquence and follow up time were the only variables that showed influence in obliteration. Since the highest probability of obliteration occurs during the first three years, if the nidus has not been obliterated after this time then another treatment option could be considered.

Comparative analysis of several detectors for the measurement of radiation transmission and leakage from a multileaf collimator.

The multileaf collimator (MLC) is the standard device used to shape radiation beams for 3-d conformal and intensity-modulated radiation therapy (IMRT). Due to the inherent properties of MLC, there is a small amount of radiation transmitted through the leaves, called radiation transmission (RT). Accurate measurements of this radiation are required to commission and validate IMRT-capable treatment planning systems because this radiation may impact the dosimetry of IMRT-calculated dose distributions. This work compares several detectors in the measurement of RT for a micro-multileaf collimation system. The results show that there are statistically significant differences in the measured RT values between detectors from 3.5 to 12.5% for the same MLC model and less than 0.2% relative to the isocentre dose for an open reference field. However, although small in magnitude, these differences may impact the dosimetry of IMRT treatment planning by up to 1.78 Gy to the healthy tissue surrounding the target for a treatment of 60 Gy in 30 fractions. By the later, these differences must be included as a source of uncertainty in IMRT dose delivery. Also, it must be established which detector offers the most reliable results in the measurement of the RT by using Monte Carlo simulation methods.