A novel, end-to-end framework for avoiding collisions between the patient's body and gantry in proton therapy.

BACKGROUND: Administration of external radiation therapy via proton therapy systems carries a risk of occasional collisions between the patient's body and gantry, which is increased by the snout placed near the patient for better dose distribution. Although treatment planning software (TPS) can simulate controlled collisions, the computed tomography (CT) data used for treatment planning are insufficient given that collisions can occur outside the CT imaging region. Thus, imaging the three-dimensional (3D) surface outside the CT range and combining the data with those obtained by CT are essential for avoiding collisions. PURPOSE: To construct a prototype for 3D surface imaging and an end-to-end framework for preventing collisions between the patient's body and the gantry. METHODS: We obtained 3D surface data using a light sectioning method (LSM). By installing only cameras in front of the CT, we achieved LSM using the CT couch motion and preinstalled patient-positioning lasers. The camera image contained both sagittal and coronal lines, which are unnecessary for LSM and were removed by deep learning. We combined LSM 3D surface data and original CT data to create synthetic Digital Imaging and Communications in Medicine (DICOM) data. Subsequently, we compared the TPS snout auto-optimization using the original CT data with the synthetic DICOM data. RESULTS: The mean positional error for LSM of the arms and head was 0.7 ± 0.8  and 0.8 ± 0.8 mm for axial and sagittal imaging, respectively. The TPS snout auto-optimization indicated that the original CT data would cause collisions; however, the synthetic DICOM data prevented these collisions. CONCLUSIONS: The prototype system's acquisition accuracy for 3D surface data was approximately 1 mm, which was sufficient for the collision simulation. The use of a TPS with collision avoidance can help optimize the snout position using synthetic DICOM data. Our proposed method requires no external software for collision simulation and can be integrated into the clinical workflow to improve treatment planning efficiency.

Characterization and clinical utility of different collimator shapes in accelerator-based BNCT systems for head and neck cancer.

NeuCure® is the only accelerator-based boron neutron capture therapy (BNCT) system in the world with pharmaceutical approval. Until now, only flat collimators (FCs) on the patient side have been installed. However, in some cases of head and neck cancer patients, positioning the patient close enough to the collimator when using FCs was difficult. Thus, there are concerns about the prolongation of the irradiation time and overdose to normal tissues. To address these issues, a collimator with a convex-extended section on the patient side (extended collimators [ECs]) was developed, and its pharmaceutical approval was obtained in February 2022. This study evaluated the physical characterization and usefulness of each collimator using a simple geometry water phantom model and human model. In the water phantom model, the thermal neutron fluxes at 2 cm depth on the central axis were 5.13 × 108, 6.79 × 108, 1.02 × 109, and 1.17 × 109n/cm2/s for FC(120), FC(150), EC50(120), and EC100(120), respectively, when the distance from the irradiation aperture was kept constant at 18 cm. With ECs, the relative off-axis thermal neutron flux decreased steeply. In the hypopharyngeal cancer human model, the tumor dose changes were within <2%, but the maximum oral mucosa doses were 7.79, 8.51, 6.76, and 4.57 Gy-Eq, respectively. The irradiation times were 54.3, 41.3, 29.2, and 24.8 min, respectively. In cases where positioning the patient close to the collimator is difficult, the use of ECs may reduce the dose to normal tissues and shorten the irradiation time.

Dosimetric effects of the ipsilateral shoulder position variations in the sitting-positioned boron neutron capture therapy for lower neck tumor.

We aimed to evaluate dosimetric effects of ipsilateral shoulder position variations (ISPVs) in sitting-positioned boron neutron capture therapy (BNCT) for lower neck tumor. The ISPVs were simulated using deformed shoulder images that can simulate arbitrary shape. The dose-volume parameters for the tumor in the rotated shoulder plans considerably varied compared with that for the mucosa. Even in a small number of cases, these differences were clearly observed among patients. The ISPVs in lower neck BNCT have great dosimetric effects.

Determining a methodology of dosimetric quality assurance for commercially available accelerator-based boron neutron capture therapy system.

The irradiation field of boron neutron capture therapy (BNCT) consists of multiple dose components including thermal, epithermal and fast neutron, and gamma. The objective of this work was to establish a methodology of dosimetric quality assurance (QA), using the most standard and reliable measurement methods, and to determine tolerance level for each QA measurement for a commercially available accelerator-based BNCT system. In order to establish a system of dosimetric QA suitable for BNCT, the following steps were taken. First, standard measurement points based on tissue-administered doses in BNCT for brain tumors were defined, and clinical tolerances of dosimetric QA measurements were derived from the contribution to total tissue relative biological effectiveness factor-weighted dose for each dose component. Next, a QA program was proposed based on TG-142 and TG-198, and confirmed that it could be assessed whether constancy of each dose component was assured within the limits of tolerances or not by measurements of the proposed QA program. Finally, the validity of the BNCT QA program as an evaluation system was confirmed in a demonstration experiment for long-term measurement over 1 year. These results offer an easy, reliable QA method that is clinically applicable with dosimetric validity for the mixed irradiation field of accelerator-based BNCT.

Dosimetric effect of set-up error in accelerator-based boron neutron capture therapy for head and neck cancer.

The dosimetric effect of set-up error in boron neutron capture therapy (BNCT) for head and neck cancer remains unclear. In this study, we analyzed the tendency of dose error by treatment location when simulating the set-up error of patients. We also determined the tolerance level of the set-up error in BNCT for head and neck cancer. As a method, the distal direction was shifted with an interval of 2.5 mm, from 0.0 mm to +20.0 mm and compared with the dose at the reference position. Similarly, the horizontal direction and vertical direction were shifted, with an interval of 5.0 mm, from -20.0 mm to +20.0 mm. In addition, cases with 3.0 mm and 5.0 mm simultaneous shifts in all directions were analyzed as the worst-case scenario. The dose metrics of the minimum dose of the tumor and the maximum dose of the mucosa were evaluated. From unidirectional set-up error analysis, in most cases, the set-up errors with dose errors within ±5% were Δdistal < +2.5 mm, Δhorizontal < ±5.0 mm and Δvertical < ±5.0 mm. In the simulation of 3.0 mm shifts in all directions, the errors in the minimum tumor dose and maximum mucosal dose were -3.6% ±1.4% (range, -5.4% to -0.6%) and 2% ±1.4% (range, 0.4% to 4.5%), respectively. From these results, if the set-up error was within ±3.0 mm in each direction, the dose errors of the tumor and mucosa could be suppressed within approximately ±5%, which is suggested as a tolerance level.

Trend analysis of the dosimetric impact of anatomical changes during proton therapy for maxillary sinus carcinoma.

PURPOSE: Anatomical changes, such as shrinkage and aeration, can affect dose distribution in proton therapy (PT) for maxillary sinus carcinoma (MSC). These changes can affect the dose to the target and organs at risk (OARs); however, when these changes occur during PT is unclear. This study aimed to investigate the dosimetric impact of anatomical changes during PT. MATERIALS AND METHODS: Fifteen patients with MSC were enrolled in this study. Initial PT plans were generated based on initial computed tomography (CT) images. Several repeat CT images were obtained to confirm anatomical changes during PT. Evaluation PT plans were generated by copying initial PT plans to repeat CT images. The dose differences of the target and OARs were evaluated by comparing both the plans. RESULTS: At 3-4 weeks after the initiation of PT, the target volume reduced by approximately 10% as compared with the initial volume. Consequently, the target volumes gradually varied until the end of treatment. The value of V95 (volume that received 95% of the prescription dose) in the clinical target volume of the evaluation PT plan was similar to that of the initial PT plan. However, the dose to OARs, such as the contralateral optic nerve, contralateral eyeball, brainstem, and optic chiasm, increased significantly from the middle to the later phases of the treatment course. In contrast, there was a slight dose difference in the ipsilateral optic apparatus. CONCLUSION: The trend analysis in this study showed that anatomical changes appeared 3-4 weeks after the start of PT, and the dose to the OARs tended to increase. Therefore, it is recommended to check the status of tumor 3-4 weeks after the start of treatment to avoid the deterioration of dose distribution due to these changes.

The impact of different setup methods on the dose distribution in proton therapy for hepatocellular carcinoma.

PURPOSE: To investigate the impact of different setup methods, vertebral body matching (VM), diaphragm matching (DM), and marker matching (MM), on the dose distribution in proton therapy (PT) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-eight HCC lesions were studied retrospectively to assess changes in the dose distribution on two computed tomography (CT) scans. One was for treatment planning (1st-CT), and the other was for dose confirmation acquired during the course of PT (2nd-CT). The dose coverage of the clinical target volume (CTV-D98 ) and normal liver volume that received 30 Gy relative biological effectiveness (RBE) (liver-V30 ) were evaluated under each condition. Initial treatment planning on the 1st-CT was defined as reference, and three dose distributions recalculated using VM, DM, and MM on the 2nd-CT, were compared to it, respectively. In addition, the relationship between the CTV-D98 of each method and the distance between the center of mass (COM) of the CTV and the right diaphragm top was evaluated. RESULTS: For CTV-D98 , significant differences were observed between the reference and VM and DM, respectively (P = 0.013, P = 0.015). There were also significant differences between MM and VM and DM, respectively (P = 0.018, P = 0.036). Regarding liver-V30 , there was no significant difference in any of the methods, and there were no discernable difference due to the different setup methods. In DM, only two out of 34 cases with a distance from right diaphragm top to COM of CTV of 90 mm or less that CTV-D98 difference was 5% or more and CTV-D98 was worse than VM were confirmed. CONCLUSION: Although MM is obviously the most effective method, it is suggested that DM may be particularly effective in cases where the distance from right diaphragm top to COM of CTV of 90 mm or less.

End-to-end test to evaluate the comprehensive geometric accuracy of a proton rotating gantry using a cone-shaped scintillator screen detector.

In this study, we aim to evaluate the comprehensive geometric accuracy of proton rotating gantries by performing an end-to-end test using a cone-shaped scintillator screen detector, known as XRV-124. The XRV-124 comprises a cone-shaped sheet-like scintillator and charge-coupled device camera that detects the scintillation light. First, the results of the Winston-Lutz and end-to-end XRV-124 tests performed on a conventional linear accelerator were compared to confirm the reliability of the XRV-124, and the snout position dependency of the geometric accuracy was evaluated for the proton rotating gantry as a pre-verification process. Thereafter, an end-to-end test including computed tomography imaging and irradiation in 30° steps from 0° to 330° for two proton rotating gantries, which have the same specifications, was performed. The results of the pre-verification indicated that sufficient accuracy was obtained for the end-to-end test of the proton rotating gantry. The end-to-end test results showed a peak-to-peak deviation of up to 2 mm for some of the coordinate axes. The two gantries exhibited almost similar results in terms of the absolute quantity; however, a few trends were different. Thus, the beam axis deviations were confirmed to be within the safety margin, as expected in clinical practice. Based on the results of this study, the XRV-124 can be used as a comprehensive end-to-end constancy test tool, as it enables a comparative verification of multiple rotating gantries and geometric accuracy verification of different treatment modalities.

A new concept for verifying the isocentric alignment of the proton-rotational gantry for radiation control.

The purpose of this study was to introduce the modified Winston-Lutz (mWL) test and to evaluate its feasibility. This is a new method to completely absorb the proton beam around the isocenter inside a phantom for radiation control. The mWL test was performed using a 14-cm-diameter acrylic Lucy 3D QA Phantom for a passive-scattering proton beam gantry. The energy of the unmodulated proton beam was adjusted such that the residual range was < 130 mm, and the energy of the proton beam was completely lost around the isocenter. The radiation field was formed with a multi-leaf collimator at 8.6 × 8.6 mm2 in the isocenter plane. The phantom was loaded with a 4-mm-diameter tungsten ball, and the EBT3 was set up at the isocenter. The proton beam was irradiated at gantry angles with 45° steps, and the isocenter deviation of the proton beam was measured and subsequently analyzed. Although the radiation field penumbra was blurred under the influence of scattered radiation due to placement in the phantom compared to the traditional WL test placed in the air, evaluation of the beam axis accuracy was possible. The results confirmed that the maximum total displacement was less than 0.9 mm, and the specifications of the device were met. The mWL test is feasible and effective to reduce the building activation in proton beam treatment facilities. Thus, it can be considered a useful method that sufficiently satisfies the shielding calculation conditions.

Patient-specific quality assurance for proton depth dose distribution using a multi-layer ionization chamber in a single-ring wobbling method.

The use of a multi-layer ionization chamber, Zebra, in patient-specific quality assurance (QA) for proton depth dose distributions in a single-ring wobbling method is investigated. The depth dose distributions measured using Zebra are compared with those calculated using the treatment planning system (TPS), XiO-M, and measured using an ionization chamber with a motorized water phantom system. Because the TPS only provides point doses, the average doses are calculated using in-house software. The detector size-corrected depth dose distributions are obtained by determining the average of the dose distributions from the TPS over a cylindrical region similar to the size of the Zebra detectors. The calculated depth dose distributions from the cases with a simple compensator shape are in good agreement with those obtained from the TPS without performing volume averaging; however, a 15% difference was shown when compared with those from the cases with a complex compensator shape. Then, the measurements are compared with the detector size-corrected depth dose distributions, showing an improved agreement within 3% for the highly steep dose gradient regions. Although there are some field size limitations, the Zebra system is a useful device for the fast measurement of patient-specific QA for depth dose distributions in wobbled proton beams. However, careful consideration is required for complex dose distribution fields, because the measurements obtained using Zebra cannot be directly compared to the depth dose distributions from the TPS owing to the finite detector size of the Zebra chamber.

Impact of Nicotine Transport across the Blood-Brain Barrier: Carrier-Mediated Transport of Nicotine and Interaction with Central Nervous System Drugs.

Nicotine, an addictive substance, is absorbed from the lungs following inhalation of tobacco smoke, and distributed to various tissues such as liver, brain, and retina. Recent in vivo and in vitro studies suggest the involvement of a carrier-mediated transport process in nicotine transport in the lung, liver, and inner blood-retinal barrier. In addition, in vivo studies of influx and efflux transport of nicotine across the blood-brain barrier (BBB) revealed that blood-to-brain influx transport of nicotine is more dominant than brain-to-blood efflux transport of nicotine. Uptake studies in TR-BBB13 cells, which are an in vitro model cell line of the BBB, suggest the involvement of H+/organic cation antiporter, which is distinct from typical organic cation transporters, in nicotine transport at the BBB. Moreover, inhibition studies in TR-BBB13 cells showed that nicotine uptake was significantly reduced by central nervous system (CNS) drugs, such as antidepressants, anti-Alzheimer's disease drugs, and anti-Parkinson's disease drugs, suggesting that the nicotine transport system can recognize these molecules. The cumulative evidence would be helpful to improve our understanding of smoking-CNS drug interaction for providing appropriate medication.

Role of cationic drug-sensitive transport systems at the blood-cerebrospinal fluid barrier in para-tyramine elimination from rat brain.

BACKGROUND: para-Tyramine (p-TA) is a biogenic amine which is involved in multiple neuronal signal transductions. Since the concentration of p-TA in dog cerebrospinal fluid (CSF) has been reported to be greater than that in plasma, it is proposed that clearance of cerebral p-TA is important for normal function. The purpose of this study was to examine the role of the blood-brain barrier and blood-cerebrospinal fluid barrier (BCSFB) in p-TA clearance from the brain. METHODS: In vivo [3H]p-TA elimination from rat cerebral cortex and from CSF was examined after intracerebral and intracerebroventricular administration, respectively. To evaluate BCSFB-mediated p-TA transport, [3H]p-TA uptake by isolated rat choroid plexus and conditionally immortalized rat choroid plexus epithelial cells, TR-CSFB3 cells, was performed. RESULTS: The half-life of [3H]p-TA elimination from rat CSF was found to be 2.9 min, which is 62-fold faster than that from rat cerebral cortex. In addition, this [3H]p-TA elimination from the CSF was significantly inhibited by co-injection of excess unlabeled p-TA. Thus, carrier-mediated p-TA transport process(es) are assumed to take part in p-TA elimination from the CSF. Since it is known that transporters at the BCSFB participate in compound elimination from the CSF, [3H]p-TA transport in ex vivo and in vitro models of rat BCSFB was examined. The [3H]p-TA uptake by isolated rat choroid plexus and TR-CSFB3 cells was time-dependent and was inhibited by unlabeled p-TA, indicating carrier-mediated p-TA transport at the BCSFB. The p-TA uptake by isolated choroid plexus and TR-CSFB3 cells was not reduced in the absence of extracellular Na+ and Cl-, and in the presence of substrates of typical organic cation transporters. However, this p-TA uptake was significantly inhibited by cationic drugs such as propranolol, imipramine, amantadine, verapamil, and pyrilamine. Moreover, p-TA uptake by TR-CSFB3 cells took place in an oppositely-directed H+ gradient manner. Therefore, this suggested that p-TA transport at the BCSFB involves cationic drug-sensitive transport systems which are distinct from typical plasma membrane organic cation transporters. CONCLUSION: Our study indicates that p-TA elimination from the CSF is greater than that from the cerebral cortex. Moreover, it is suggested that cationic drug-sensitive transport systems in the BCSFB participate in this p-TA elimination from the CSF.