Accelerator-based Boron Neutron Capture Therapy Research Articles

RTID-01. ACCELERATOR-BASED BORON NEUTRON CAPTURE THERAPY, RANDOMIZED CONTROLLED TRIAL FOR RECURRENT AND REFRACTORY HIGH-GRADE MENINGIOMAS

Abstract INTRODUCTION High-grade meningiomas (HGMs) recurred after X-ray treatment showed pessimistic prognosis. We started “A phase II investigator-lead RCT using accelerator-based BNCT system for refractory recurrent high-grade meningioma”. MATERIALS AND METHODS We prepared 2 study arms, BNCT test treatment arm (12 subjects) and control best supportive care arm (6 subjects) in randomized controlled trial (RCT) fashion. PFS judged by the third-party committee was primary endpoint and PFS judged by investigators themselves and OS of BNCT arm were secondary endpoints. Rescue BNCT was permitted for control group patients, if they showed progress disease (PD). RESULTS Three and two grade 3 subjects were included in BNCT and control arm, respectively. Others were grade 2 subjects. As of March 31, 2024, 10 out of 12 in BNCT arm and all 6 cases in control arm were judged as PD. mPFS judged by investigators showed 65 and 8 weeks for BNCT and control arm, respectively (P=0.0002, Wilcoxon). Six out of 12 in BNCT and 4 out of 6 cases in the control arm were dead. OS-2 year rates of BNCT and control arms are 91.7% and 33.3%, respectively (p=0.045, Wilcoxon). Five out of 6 cases in control arm received rescue BNCT after PD assessments. With regard to best response on MRI, PR, SD were 5 and 7 cases in treatment arms (ORR was 41.7%). CONCLUSION mPFS judged by third party committee is still being closed and unknown, so far. With regard to secondary endpoints, there are marked differences in both arms in mPFS judged by investigators. Recently, the results of RCT of “Trabectedine” organized by EORTC was reported. Unfortunately there was no effect of Trabectedine not only in PFS but in OS. In our current RCT results BNCT arm is extremely excellent in comparison with EORTC RCT of “Trabectedine” both in OS and PFS.

Development of an online neutron beam monitoring system for accelerator-based boron neutron capture therapy in a hospital.

Boron neutron capture therapy (BNCT) is a next-generation radiotherapy, utilizing both an external neutron beam and a -containing pharmaceutical. A compact accelerator for a high intensity neutron source was installed to conduct BNCT in a hospital. The dose administered to a patient was evaluated by measuring the proton beamcurrent. Neutron intensity should be monitored in real-time by measuring the neutrons emitted from the target during BNCT irradiation. This is crucial due to potential neutron target degradation. Online neutron beam monitoring systems are required for reliable measurements of the administered neutron dose. An online neutron beam monitoring system was developed to monitor neutron intensity irradiating on the patient at the National Cancer Center Hospital (NCCH). The neutron detector comprised a back-illuminated thin Si diode of 40- thickness and an ultrathin natural LiF neutron converter of 0.05- thickness. The neutron detector was installed on the neutron target unit, regardless of whether a patient was present, without any additional modifications to the setup. The response functions for high photon dose rates of upto 100 Gy/h were measured. The pulse heights were measured using the neutron beam monitor during BNCT neutron irradiation. Neutron temporal response measured using the online beam monitor was acquired and compared with the proton beam current and the measurements at a patient position. From this measurement at the patient position, the neutron fluence rate irradiating on a patient wasobtained. The neutron events were separated from the photon events. The neutron counting rates increased rapidly with the starting of proton beam irradiation and dropped to zero upon its termination. During intermittent drops and recoveries in the proton beam, the neutron beam monitor for counting rates responded quickly, synchronizing with the beam current. A scatter plot of the neutron counting rate and proton beam current indicated a good linear correlation. A direct relationship between the online neutron beam monitor's neutron counting rates and those of the patient neutron detector showed a good correlation coefficient of 0.84. A ratio of the both neutron counting rates showed a standard deviation of 6%. The correlation coefficient and standard deviation were improved to 0.94 and 1.5%, by re-binning the neutron temporal response with longer acquisition period than 1 s. Using the online neutron beam monitor, the neutron fluence rate was obtained from the direct relationship within 1.5%. Therefore, real-time monitoring of neutron intensity was achieved within the acceptable level as per the International Commission on Radiation Units and Measurementsreport. The online neutron beam monitoring system was developed to monitor the BNCT neutron beam intensity at NCCH. The temporal response of the neutron beam monitor was synchronized with the neutron counting rate at the patient position. Using the online neutron beam monitor, the neutron fluence rate irradiating on the patient can be monitored from the direct relationship. Fluctuation of the neutron beam intensity through BNCT irradiation and the degradation of the lithium target through the lifespan of the neutron target could be monitored using the neutron beammonitor.

Medical staffs' required capability and workload for accelerator-based boron neutron capture therapy: correspondence.

Medical staffs' required capability and workload for accelerator-based boron neutron capture therapy: correspondence.

Long-term beam output stability of an accelerator-based boron neutron capture therapy system.

Accelerator-based boron neutron capture therapy (AB-BNCT) systems are becoming commercially available and are expected to be widely used in hospitals. To ensure the safety of BNCT, establishing a quality assurance (QA) program and properly managing the stability of the system are necessary. In particular, a high level of beam output stability is required to avoid accidents because beam output is a major factor in patient dose. However, no studies have analyzed the long-term beam output stability of AB-BNCT systems. This study aimed to retrospectively analyze the long-term stability of the beam output by statistical process control (SPC) based on the QA results over 3 years. The data analyzed are the results of daily QA (DQA) and weekly QA (WQA) in an AB-BNCT system and were taken between June 2020 and September 2023. The evaluation of the stability of the beam output was based on the reaction rate between gold and neutrons calculated using the activation foil method using a gold foil. In DQA, which can be performed in a short time, the gold foil was applied directly to the beam irradiation aperture in air. In WQA, measurements were performed at the phantom surface, 2-cm depth, and 6-cm depth using a dedicated water phantom. The acquired data were retrospectively analyzed by individuals and a moving range chart (I-MR chart), exponentially weighted moving average control chart (EWMA chart), and several process capability indexes (PCIs). Over 99% of the DQA I-MR chart results were within control limits, whereas the WQA I-MR chart results showed that 1.8%, 4.1%, and 2.0% of the measurements exceeded the control limits at the surface, 2-cm depth, and 6-cm depth, respectively. The variation in the reaction rate of the gold foil before and after the replacement of the target was<0.5%. The EWMA chart results revealed no significant beam output drift for either DQA or WQA. Most measured data were normal based on the results of the Anderson-Darling test and met the requirements for PCI evaluation; most PCI values were>1.0; however, the Cpmk of DQA and the 2- and 6-cm depth WQAs between August 2021 and November 2022 in treatment course 2 were 0.83, 0.77, and 0.87, respectively, which were<1.0. The long-term stability of beam output was confirmed using SPC in an AB-BNCT system. The results of the control chart revealed no significant variation or drift in the beam output, and the quantitative evaluation using PCI revealed high stability. A routine QA program will enable us to provide safe BNCT.

Design of a mixed material moderator in a beam-shaping assembly for proton accelerator-based boron neutron capture therapy

Boron Neutron Capture Therapy is being promoted with the development of accelerator neutron sources, and many new accelerator-based BNCT facilities are being built. In Particle Accelerator Facility project of Sun Yat-sen University, we plan to build a terminal for BNCT research based on an 8 MeV, CW 3 mA proton accelerator. In this paper, we present a beam-shaping assembly for this proton accelerator with such low 24 kW beam power, using composite moderator materials composed of five elements: Mg, Al, F, O, and Li. The calculation result of FLUKA with ENDF/B and JENDL libraries shows that the epithermal neutron beam flux is 1.57×109n/cm2/s with the CW 3 mA proton beam. The fast neutron component and the gamma ray component under free-air condition are 1.49×10−13Gy∙cm2 and 8.12×10−14Gy∙cm2 respectively, in line with IAEA-TECDOC-1223 design recommendations. The thermal analysis shows that the maximum temperature of beryllium target is 706.5 K, and the structure materials of BSA do not melt.

Properties analysis on interlayer within lithium target and its beam uniformity for accelerator-based Boron Neutron Capture Therapy

In order to enhance the performance and lifetime of the lithium target used in accelerator-based neutron sources for Boron Neutron Capture Therapy (BNCT) treatment, an exploration of target design was conducted based on the 2.8 MeV, 20 mA proton beam. A comparison between scanning magnets and octupole magnets was performed for beam uniform, with octupole magnets selected to effectively avoid localized high thermal densities over short durations. Exploration was conducted on the performance of tantalum and vanadium as interlayers within the lithium target, considering aspects such as cooling, hydrogen diffusion, and neutron performances. This study revealed that, as the majority of energy deposition occurs within the interlayer, the presence of an appropriately thick tantalum or vanadium interlayer has minimal impact on cooling effectiveness, ensuring temperatures remain below 144 °C. The addition of an interlayer effectively reduces the maximum hydrogen concentration in copper, thus preventing copper blistering. Within the investigated thickness range, the interlayer does not affect neutron spectrum in the forward direction of the target, mitigating concerns regarding its impact on beam shaping.

Implementation of optically simulated luminescent dosimeter for quality control of gamma ray dose of an accelerator-based neutron source.

Neutron beams utilized for performing BNCT are composed of a mixture of neutrons and gamma rays. Although much of the dose delivered to the cancer cells comes from the high LET particles produced by the boron neutron capture reaction, the dose delivered to the healthy tissues from unwanted gamma rays cannot be ignored. With the increase in the number of accelerators for BNCT, a detector system that is capable of measuring gamma ray dose in a mixed neutron/gamma irradiation field is crucial. Currently, BeO TLDs encased in quartz glass are used to measure gamma ray dose in a BNCT irradiation field. However, this type of TLD is no longer commercially available. A replacement dosimetry system is required to perform the recommended ongoing quality assurance of gamma ray measurement for a clinical BNCT system. The purpose of this study is to evaluate the characteristics of a BeO OSLD detector system under a mixed neutron and gamma ray irradiation field and to assess the suitability of the system for routine quality assurance measurements of an accelerator-based BNCT facility. The myOSLD system by RadPro International GmbH was evaluated using the accelerator-based neutron source designed for clinical BNCT (NeuCure BNCT system). The readout constancy, linearity, dose rate effect, and fading effect of the OSLD were evaluated. Free-in-air and water phantom measurements were performed and compared with the TLD results and Monte Carlo simulation results. The PHITS Monte Carlo code was used for this study. The readout constancy was found to be stable over a month-long period and similar to the TLD results. The OSLD readout signal was found to be linear, with a high coefficient of determination (R2≥0.999) up to a proton charge of 3.6C. There was no significant signal fading or dose rate dependency. The central axis depth dose and off-axis dose profile measurements agreed with both the TLD and Monte Carlo simulation results, within one standard deviation. The myOSLD system was characterized using an accelerator system designed for clinical BNCT. The experimental measurements confirmed the OSLD achieved similar, if not superior to, the currently utilized dosimetry system for routine QA of an accelerator-based BNCT system. The OSLD system would be a suitable replacement for the current TLD system for performing routine QA of gamma ray dose measurement in a BNCT irradiation field.

A national survey of medical staffs' required capability and workload for accelerator-based boron neutron capture therapy.

This study aimed to identify the required capabilities and workload of medical staff in accelerator-based boron neutron capture therapy (BNCT). From August to September 2022, a questionnaire related to the capabilities and workload in the accelerator-based BNCT was administered to 12 physicians, 7 medical physicists and 7 radiological technologists engaged in BNCT and 6 other medical physicists who were not engaged in BNCT to compare the results acquired by those engaged in BNCT. Only 6-21% of patients referred for BNCT received it. Furthermore, 30-75% of patients who received BNCT were treated at facilities located within their local district. The median required workload per treatment was 55h. Considering additional workloads for ineligible patients, the required workload reached ~1.2 times longer than those for only eligible patients' treatment. With respect to capabilities, discrepancies were observed in treatment planning, quality assurance and quality control, and commissioning between medical physicists and radiological technologists. Furthermore, the specialized skills required by medical physicists are impossible to acquire from the experience of conventional radiotherapies as physicians engaged in BNCT were specialized not only in radiation oncology, but also in other fields. This study indicated the required workload and staff capabilities for conducting accelerator-based BNCT considering actual clinical conditions. The workload required for BNCT depends on the occupation. It is necessary to establish an educational program and certification system for the skills required to safely and effectively provide BNCT to patients.

Evaluation of calculation accuracy and computation time in a commercial treatment planning system for accelerator-based boron neutron capture therapy.

This study aims to evaluate the feasibility of using a commercially available boron neutron capture therapy (BNCT) dose calculation program (NeuCure® Dose Engine) in terms of calculation accuracy and computation time. Treatment planning was simulated under the following calculation parameters: 1.5-5.0mm grid sizes and 1-10% statistical uncertainties. The calculated monitor units (MUs) and computation times were evaluated. The MUs calculated on grid sizes larger than 2mm were overestimated by 2% compared with the result of 1.5mm grid. We established the two-step method for the routine administration of BNCT: multiple calculations involved in beam optimization should be done at a 5mm grid and a 10% statistical uncertainty (the shortest computation time: 10.3 ± 2.1min) in the first-step, and final dose calculations should be performed at a 2mm grid and a 10% statistical uncertainty (satisfied clinical accuracy: 6.9 ± 0.3h) in the second-step.

Computational design and evaluation of a quad-MOSFET device for quality control of therapeutic accelerator-based neutron beams

Accurate real-time monitoring of neutron beams and distinguishing between thermal, epithermal and fast neutron components in the presence of a photon background is crucial for the effectiveness of accelerator-based boron neutron capture therapy (AB-BNCT). In this work, we propose an innovative quadruple metal–oxide–semiconductor field-effect transistor (MOSFET) device for real-time, cost-effective beam quality control; one detector is kept uncovered while the other three are covered with either a B4C, cadmium and B4C or polyethylene converter.Individual MOSFET converter configurations were optimised via Monte Carlo simulations to maximise signal selectivity across neutron energy spectra. Results demonstrate the quad-MOSFET device’s efficacy in quantifying changes in neutron flux, underscoring its potential as a useful instrument in the AB-BNCT quality control process.

Evaluating optimal quality assurance and quality control conditions of activation measurements at the accelerator-based boron neutron capture therapy system employing a lithium target

Evaluating neutron output is important to ensure proper dose delivery for patients in boron neutron capture therapy (BNCT). It requires efficient quality assurance (QA) and quality control (QC) while maintaining measurement accuracy. This study investigated the optimal measurement conditions for QA/QC of activation measurements using a high-purity germanium (HP-Ge) detector in an accelerator-based boron neutron capture therapy (AB-BNCT) system employing a lithium target. The QA/QC uncertainty of the activation measurement was evaluated based on counts, reproducibility, and standard radiation source uncertainties. Measurements in a polymethyl methacrylate (PMMA) cylindrical phantom using aluminum-manganese (Al–Mn) foils and aluminum-gold (Al–Au) foils and measurements in a water phantom using gold wire with and without cadmium cover were performed to determine the optimal measurement conditions. The QA/QC uncertainties of the activation measurements were 4.5% for Au and 4.6% for Mn. The optimum irradiation proton charge and measurement time were determined to be 36 C and 900 s for measurements in a PMMA cylindrical phantom, 7.0 C and 900 s for gold wire measurements in a water phantom, and 54 C and 900 s at 0–2.2 cm depth and 3,600 s at deeper depths for gold wire measurements with cadmium cover. Our results serve as a reference for determining measurement conditions when performing QA/QC of activation measurements using HP-Ge detectors at an AB-BNCT employing a lithium target.

A method for delivering the required neutron fluence in an accelerator-based boron neutron capture therapy system employing a lithium target

Accelerator-based boron neutron capture therapy (BNCT) systems employing a solid-state lithium target indicated the reduction of neutron flux over the lifetime of a target, and its reduction could represent the neutron flux model. This study proposes a novel compensatory approach for delivering the required neutron fluence and validates its clinical applicability. The proposed approach relies on the neutron flux model and the cumulative sum of real-time measurements of proton charges. The accuracy of delivering the required neutron fluence for BNCT using the proposed approach was examined in five Li targets. With the proposed approach, the required neutron fluence could be delivered within 3.0%, and within 1.0% in most cases. However, those without using the proposed approach exceeded 3.0% in some cases. The proposed approach can consider the neutron flux reduction adequately and decrease the effect of uncertainty in neutron measurements. Therefore, the proposed approach can improve the accuracy of delivering the required fluence for BNCT even if a neutron flux reduction is expected during treatment and over the lifetime of the Li target. Additionally, by adequately revising the approach, it may apply to other type of BNCT systems employing a Li target, furthering research in this direction.

Effects of neutron sources and moderator materials on therapeutic dose delivery to deep-seated lesions in proton accelerator-based boron neutron capture therapy

This study aimed to identify the optimal conditions for delivering sufficient doses to deep-seated lesions within short irradiation times for two boron carriers of different T/N ratios. The therapeutic depth and irradiation time of a neutron beam for beam shaping assemblies (BSAs) with a Li or Be target and a MgF2 or CaF2 moderator were examined with the fast-neutron dose per epithermal neutron (FNR) as a parameter. When T/N = 3.61, the therapeutic depth was almost saturated at an FNR of about 10 × 10−13 Gy cm2; when the FNR value was about 10 × 10−13 Gy cm2, the therapeutic depth of the neutron beam for the BSA with a Be target and a MgF2 moderator was almost identical to that for the neutron beam for the BSA with a Be target and a CaF2 moderator, and slightly greater than those for the neutron beams for the BSAs with a Li target and a MgF2 or CaF2 moderator; moreover, the irradiation time of the neutron beam for the BSA with a Be target and a MgF2 moderator was shorter than that for the neutron beam for the BSA with a Be target and a CaF2 moderator. When T/N = 100, the therapeutic depths of the neutron beams for the BSAs varied greatly depending on the FNR, and were greater than the corresponding values for T/N = 3.61. We therefore concluded that the BSA with a Be target and a MgF2 moderator that produced a neutron beam with an FNR of about 10 × 10−13 Gy cm2 is optimal for delivering sufficient doses to deep-seated lesions in short irradiation times when T/N = 3.61, and stricter control over FNR is required when T/N = 100.

Field tuning study and RF electromagnetic design of a continuous-wave RFQ with ramped inter-vane voltage for AB-BNCT

A compact radio frequency quadrupole (RFQ) linac for accelerator-based boron neutron capture therapy is being developed at Xi'an Jiaotong University. By adopting a ramped inter-vane voltage in the beam dynamics design, the RFQ could accelerate a continuous wave proton beam to 2.6 MeV over a length of 4 m, effectively decreasing costs and saving space. To meet the beam-dynamics requirements, both the vane width and undercut were optimized during the electromagnetic design. In addition, π-mode stabilization loops were included to increase the mode separation, and fixed tuners with varying diameters were installed to obtain close frequency-tuning sensitivity. It was established that the field unflatness can be controlled within ±1.5% when all tuners remain at their nominal insertion depth. Optimized cooling-channel design was completed, and multi-physics analysis was conducted. The water tuning coefficients of the vane and wall channels were analyzed to establish the ability to fine tune the RFQ during operation.

Influence mechanism of lithium surface oxidation on neutron yield of lithium target for accelerator-based neutron source

Lithium is generally adopted as the target to generate epithermal neutrons based on 7Li(p,n)7Be nuclear reaction for the application of accelerator-based boron neutron capture therapy (AB-BNCT). The stability of neutron yields and neutron energy spectrum are key factors for the therapeutic effects of the AB-BNCT. Owing to the active chemical properties of lithium, the surface oxidation formation of lithium may influence the soundness of the target system and the stability of neutron yields. Experimental and simulation methods were performed for a better understanding of the passivation layer formation after air exposure and the influence of the passivation layer on the neutron yield and energy spectrum. On one hand, X-ray photoelectron spectroscopy was adopted to study the chemical states of lithium after air exposure. On the other hand, particle and heavy ion transport code system (PHITS) was used to evaluate the effect of surface chemical states variation on neutron yield and energy spectrum. The simulation results indicate that the formation of Li2O with a thickness of 2 μm could mainly influence the neutron yields at the neutron emission angle of 20–90° with a maximum reduction of ∼ 10.4%.

A new proton injector based on PKU-type 2.45GHz PMECR ion source for BNCT facility

A first fully domestically Accelerator-based boron neutron capture therapy demonstration device(AB-BNCT) located in Yangtze River Delta region is being build recently. The project is held by “Xi’an Jiaotong University-Huzhou Neutron Science Laboratory” joint lab established by Xi’an Jiaotong University and Huzhou Industrial Group. The AB-BNCT facility requires a proton beam of 30 mA@40 keV at RFQ entrance, with its beam duty cycle between 0.5%-100%, and its normalized root mean square emittance less than 0.2 π.mm.mrad. Ion source group of Peking University (PKU) is in charge of the proton ion source and its low energy beam transportation section (LEBT). A PKU type compact permanent magnet 2.45 GHz ECR ion source (PKU-Type PMECR) and a two solenoid LEBT is under development for this purpose. So far, the PMECR ion source conditioning is complete and all parameters are better than required for this facility. The details will be presented in the present paper.

Neutron Activation Analysis Based on AB-BNCT Treatment Room.

Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10 B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 μSv h -1 after 13 min of shutdown meets the dose rate limit of 2.5 μSv h -1 , at which point it is safe for workers to enter the treatment room area.

Experimental designs for radiobiological characterization of an accelerator-based BNCT system in preclinical studies

Experimental designs for radiobiological characterization of an accelerator-based BNCT system in preclinical studies

The current status and future perspectives of clinical boron neutron capture therapy trials

PurposeSeveral hundreds of patients have been so far treated in clinical trials with boron neutron capture therapy (BNCT).MethodsThis is a non-systematic review of clinical trials with BNCT, with special emphasis on the more recent trials.ResultsThe conducted trials have been relatively small single-arm studies and included mostly the patients with head and neck carcinomas resistant to traditional treatment modalities and glioblastomas. In general, the efficacy results have been promising and BNCT has been relatively well tolerated, even in the patients who have already been treated with conventional radiotherapy or chemoradiation. The most frequent adverse events have been similar to those associated with the conventional radiotherapy. At present, there is no evidence how the efficacy of BNCT would compare to the standard treatment modalities in earlier treatment lines.ConclusionsMost of the existing studies have been performed with reactor-based facilities, but there is now a rapidly increasing number of linear accelerator-based BNCT sites, and the clinical research is apparently activating again. This, combined with the increased knowledge on cancer biology and novel types of oncological therapies, opens possibilities to study innovative boron carriers and to combine BNCT with modern oncological therapies in the future clinical trials. To conduct larger phase III trials, multicenter approaches are encouraged to be applied, keeping in mind the importance of joint instructions and quality control measurements.

Preparation and properties of chromium protective coatings on lithium targets for accelerator-based neutron sources

Chromium (Cr) with its high antioxidative properties acts as a protective layer for lithium targets in accelerator-based boron neutron capture therapy (AB-BNCT). Employing a controlled variable method, this study explores the impact of magnetron sputtering parameters (sputtering power, argon flow, and sputtering pressure) on the surface morphology and crystalline structure of Cr films. Under the optimal preparation parameters (300W, 20ssm, 0.5Pa), a dense and uniform film with a (110) phase was formed, and a compact Cr2O3 layer developed during air exposure. A 1 μm Cr coating provided effective protection for approximately 2 h, and increased thickness further improved the protection. Monte Carlo simulations revealed that a 1 μm Cr coating caused around 1.83% energy loss and 5.54% neutron yield reduction for 2.8 MeV protons, meeting AB-BNCT requirements with minimal impact on neutron angular distribution. This study demonstrates that by investigating the effects of magnetron sputtering preparation parameters on the surface morphology and crystalline structure of Cr coatings, optimal preparation parameters can be selected. The fabrication of a uniform and dense 1 μm Cr protective layer on a lithium target effectively prevents the degradation of the lithium target during short-term exposure to air, thereby enhancing its transportability and ease of handling.