We present a full-scale clinical prototype system for in vivo range verification of proton pencil-beams using the prompt gamma-ray spectroscopy method. The detection system consists of eight LaBr scintillators and a tungsten collimator, mounted on a rotating frame. Custom electronics and calibration algorithms have been developed for the measurement of energy- and time-resolved gamma-ray spectra during proton irradiation at a clinical dose rate. Using experimentally determined nuclear reaction cross sections and a GPU-accelerated Monte Carlo simulation, a detailed model of the expected gamma-ray emissions is created for each individual pencil-beam. The absolute range of the proton pencil-beams is determined by minimizing the discrepancy between the measurement and this model, leaving the absolute range of the beam and the elemental concentrations of the irradiated matter as free parameters. The system was characterized in a clinical-like situation by irradiating different phantoms with a scanning pencil-beam. A dose of 0.9 Gy was delivered to a [Formula: see text] cm target with a beam current of 2 nA incident on the phantom. Different range shifters and materials were used to test the robustness of the verification method and to calculate the accuracy of the detected range. The absolute proton range was determined for each spot of the distal energy layer with a mean statistical precision of 1.1 mm at a 95% confidence level and a mean systematic deviation of 0.5 mm, when aggregating pencil-beam spots within a cylindrical region of 10 mm radius and 10 mm depth. Small range errors that we introduced were successfully detected and even large differences in the elemental composition do not affect the range verification accuracy. These results show that our system is suitable for range verification during patient treatments in our upcoming clinical study.
Purpose Quantify the accuracy of a clinical proton treatment planning system (TPS) as well as Monte Carlo (MC) based dose calculation through measurements. Assess the clinical impact in a cohort of patients with tumors located in the lung. Methods A lung phantom and ion chamber array were used to measure the dose to a plane through a tumor embedded in lung and to determine the distal fall-off of the proton beam. Results were compared with TPS and MC calculations. Dose distributions in 19 patients (54 fields total) were simulated using MC and compared to the TPS algorithm. Results MC increases dose calculation accuracy in lung tissue compared to the TPS and reproduces dose measurements in the target to within ±2%. The average difference between measured and predicted dose in a plane through the center of the target is 5.6% for the TPS and 1.6% for MC. MC recalculations in patients show a mean dose to the clinical target volume on average 3.4% lower than the TPS, exceeding 5% for small fields. For large tumors MC also predicts consistently higher V5 and V10 to the normal lung, due to a wider lateral penumbra, which was also observed experimentally. Critical structures located distal to the target can show large deviations, though this effect is very patient-specific. Range measurements show that MC can reduce range uncertainty by a factor ~2: the average(maximum) difference to the measured range is 3.9mm(7.5mm) for MC and 7mm(17mm) for the TPS in lung tissue. Conclusion Integration of Monte Carlo dose calculation techniques into the clinic would improve treatment quality in proton therapy for lung cancer by avoiding systematic overestimation of target dose and underestimation of dose to normal lung. Additionally, the ability to confidently reduce range margins would benefit all patients through potentially lower toxicity.
Chronic imaging windows in mice have been developed to allow intravital microscopy of many different organs and have proven to be of paramount importance in advancing our knowledge of normal and disease processes. A model system that allows long-term intravital imaging of lymph nodes would facilitate the study of cell behavior in lymph nodes during the generation of immune responses in a variety of disease settings and during the formation of metastatic lesions in cancer-bearing mice. We describe a chronic lymph node window (CLNW) surgical preparation that allows intravital imaging of the inguinal lymph node in mice. The CLNW is custom-made from titanium and incorporates a standard coverslip. It allows stable longitudinal imaging without the need for serial surgeries while preserving lymph node blood and lymph flow. We also describe how to build and use an imaging stage specifically designed for the CLNW to prevent (large) rotational changes as well as respiratory movement during imaging. The entire procedure takes approximately half an hour per mouse, and subsequently allows for longitudinal intravital imaging of the murine lymph node and surrounding structures for up to 14 d. Small-animal surgery experience is required to successfully carry out the protocol.
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