Validity and Reliability of a New Device to Measure Type of Actions in Indoor Sports.

The purpose of this study was to analyze the validity and the reliability of the intensity ranges, number of actions and changes of direction measured by a commercial inertial measurement unit. Eleven elite youth futsal players performed a circuit with different type of displacements as sprinting, running at low-medium intensity, standing up and changes of direction. Data recorded by the Overtraq system were compared with video-analyzer during the six trials of each player. Standard error mean, Intraclass Correlation Coeficient and Coefficient of variation, were calculated to analyze the reliability of the device, as well as the Root Mean Square Error and Confidence Interval with correlation of Pearson for its validity. The results reported good validity for three intensity ranges (R2>0.7) with high reliability (Intraclass Correlation Coeficient: 0.8-0.9), especially for high intensity actions (Intraclass Correlation Coeficient: 0.95, Coefficient of Variation: 3.06%). Furthermore, the validity for the number of different actions was almost perfect (96.3-100%), with only small differences regarding changes of activity (mean error: 2.0%). The Overtraq system can be considered as a valid and reliable technology for measuring and monitoring actions at different intensities and changes of direction in futsal, likewise common actions for other indoor sports.

The Relative Biological Effect of Spread-Out Bragg Peak Protons in Sensitive and Resistant Tumor Cells.

PURPOSE: Variations in the radiosensitivity of tumor cells within and between tumors impact tumor response to radiation, including the dose required to achieve permanent local tumor control. The increased expression of DNA-PKcs, a key component of a major DNA damage repair pathway in tumors treated by radiation, suggests that DNA-PKcs-dependent repair is likely a cause of tumor cell radioresistance. This study evaluates the relative biological effect of spread-out Bragg-peak protons in DNA-PKcs-deficient cells and the same cells transfected with a functional DNA-PKcs gene. MATERIALS AND METHODS: A cloned radiation-sensitive DNA-PKcs-deficient tumor line and its DNA-PKcs-transfected resistant counterpart were used in this study. The presence of functional DNA-PKcs was evaluated by DNA-PKcs autophosphorylation. Cells to be proton irradiated or x-irradiated were obtained from the same single cell suspension and dilution series to maximize precision. Cells were concurrently exposed to 6-MV x-rays or mid 137-MeV spread-out Bragg peak protons and cultured for colony formation. RESULTS: The surviving fraction data were well fit by the linear-quadratic model for each of 8 survival curves. The results suggest that the relative biological effectiveness of mid spread-out Bragg peak protons is approximately 6% higher in DNA-PKcs-mediated resistant tumor cells than in their DNA-PKcs-deficient and radiation-sensitive counterpart. CONCLUSION: DNA-PKcs-dependent repair of radiation damage is less capable of repairing mid spread-out Bragg peak proton lesions than photon-induced lesions, suggesting protons may be more efficient at sterilizing DNA-PKcs-expressing cells that are enriched in tumors treated by conventional fractionated dose x-irradiation.

Independent dose verification system with Monte Carlo simulations using TOPAS for passive scattering proton therapy at the National Cancer Center in Korea.

For the independent validation of treatment plans, we developed a fully automated Monte Carlo (MC)-based patient dose calculation system with the tool for particle simulation (TOPAS) and proton therapy machine installed at the National Cancer Center in Korea to enable routine and automatic dose recalculation for each patient. The proton beam nozzle was modeled with TOPAS to simulate the therapeutic beam, and MC commissioning was performed by comparing percent depth dose with the measurement. The beam set-up based on the prescribed beam range and modulation width was automated by modifying the vendor-specific method. The CT phantom was modeled based on the DICOM CT files with TOPAS-built-in function, and an in-house-developed C++ code directly imports the CT files for positioning the CT phantom, RT-plan file for simulating the treatment plan, and RT-structure file for applying the Hounsfield unit (HU) assignment, respectively. The developed system was validated by comparing the dose distributions with those calculated by the treatment planning system (TPS) for a lung phantom and two patient cases of abdomen and internal mammary node. The results of the beam commissioning were in good agreement of up to 0.8 mm2 [Formula: see text] for B8 option in both of the beam range and the modulation width of the spread-out Bragg peaks. The beam set-up technique can predict the range and modulation width with an accuracy of 0.06% and 0.51%, respectively, with respect to the prescribed range and modulation in arbitrary points of B5 option (128.3, 132.0, and 141.2 mm2 [Formula: see text] of range). The dose distributions showed higher than 99% passing rate for the 3D gamma index (3 mm distance to agreement and 3% dose difference) between the MC simulations and the clinical TPS in the target volume. However, in the normal tissues, less favorable agreements were obtained for the radiation treatment planning with the lung phantom and internal mammary node cases. The discrepancies might come from the limitations of the clinical TPS, which is the inaccurate dose calculation algorithm for the scattering effect, in the range compensator and inhomogeneous material. Moreover, the steep slope of the compensator, conversion of the HU values to the human phantom, and the dose calculation algorithm for the HU assignment also could be reasons of the discrepancies. The current study could be used for the independent dose validation of treatment plans including high inhomogeneities, the steep compensator, and riskiness such as lung, head & neck cases. According to the treatment policy, the dose discrepancies predicted with MC could be used for the acceptance decision of the original treatment plan.

Consistency in quality correction factors for ionization chamber dosimetry in scanned proton beam therapy.

PURPOSE: The IAEA TRS-398 code of practice details the reference conditions for reference dosimetry of proton beams using ionization chambers and the required beam quality correction factors (kQ ). Pencil beam scanning (PBS) systems cannot approximate reference conditions using a single spot. However, dose distributions requested in TRS-398 can be reproduced with PBS using a combination of spots. This study aims to demonstrate, using Monte Carlo (MC) simulations, that kQ factors computed/measured for broad beams can be used with scanned beams for similar reference dose distributions with no additional significant uncertainty. METHODS: We consider the Alfonso formalism13 usually employed for nonstandard photon beams. To approach reference conditions similar as IAEA TRS-398 and the associated dose distributions, PBS must combine many pencil beams with range or energy modulation and shaping techniques that differ from those used in passive systems (broad beams). In order to evaluate the impact of these differences on kQ factors, ionization chamber responses are computed with MC (Geant4 9.6) in three different proton beams, with their corresponding quality factors (Q), producing a 10 × 10 cm2 field with a flat dose distribution for (a) a dedicated scanned pencil beam (Qpbs ), (b) a hypothetical proton source (Qhyp ), and (c) a double-scattering beam (Qds ). The tested ionization chamber cavities are a 2 × 2 × 0.2 mm³ air cavity, a Roos-type ionization chamber, and a Farmer-type ionization chamber. RESULTS AND DISCUSSION: Ranges of Qpbs , Qhyp , and Qds are consistent within 0.4 mm. Flatnesses of dose distributions are better than 0.5%. Calculated kQpbs,Qhypfpbs,fref is 0.999 ± 0.002 for the air cavity and the Farmer-type ionization chamber and 1.001 ± 0.002 for the Roos-type ionization chamber. The quality correction factors kQpbs,Qdsfpbs,fref is 0.999 ± 0.002 for the Farmer-type and Roos-type ionization chambers and 1.001 ± 0.001 for the Roos-type ionization chamber. CONCLUSION: The Alfonso formalism was applied to scanned proton beams. In our MC simulations, neither the difference in the beam profiles (scanned beam vs hypothetical beam) nor the different incident beam energies influenced significantly the beam correction factors. This suggests that ionization chamber quality correction factors in scanned or broad proton beams are indistinguishable within the calculation uncertainties provided dose distributions achieved by both modalities are similar and compliant with the TRS-398 reference conditions.

An effective dose assessment technique with NORM added consumer products using skin-point source on computational human phantom.

The aim of this study is to develop the assessment technique of the effective dose by calculating the organ equivalent dose with a Monte Carlo (MC) simulation and a computational human phantom for the naturally occurring radioactive material (NORM) added consumer products. In this study, we suggests the method determining the MC source term based on the skin-point source enabling the convenient and conservative modeling of the various type of the products. To validate the skin-point source method, the organ equivalent doses were compared with that by the product modeling source of the realistic shape for the pillow, waist supporter, sleeping mattress etc. Our results show that according to the source location, the organ equivalent doses were observed as the similar tendency for both source determining methods, however, it was observed that the annual effective dose with the skin-point source was conservative than that with the modeling source with the maximum 3.3 times higher dose. With the assumption of the gamma energy of 1MeV and product activity of 1Bqg-1, the annual effective doses of the pillow, waist supporter and sleeping mattress with skin-point source was 3.09E-16SvBq-1year-1, 1.45E-15SvBq-1year-1, and 2,82E-16SvBq-1year-1, respectively, while the product modeling source showed 9.22E-17SvBq-1year-1, 9.29E-16SvBq-1year-1, and 8.83E-17SvBq-1year-1, respectively. In conclusion, it was demonstrated in this study that the skin-point source method could be employed to efficiently evaluate the annual effective dose due to the usage of the NORM added consumer products.

Effective dose evaluation of NORM-added consumer products using Monte Carlo simulations and the ICRP computational human phantoms.

The aim of this study is to evaluate the potential hazard of naturally occurring radioactive material (NORM) added consumer products. Using the Monte Carlo method, the radioactive products were simulated with ICRP reference phantom and the organ doses were calculated with the usage scenario. Finally, the annual effective doses were evaluated as lower than the public dose limit of 1mSv y(-1) for 44 products. It was demonstrated that NORM-added consumer products could be quantitatively assessed for the safety regulation.

Lung cancer cell line screen links fanconi anemia/BRCA pathway defects to increased relative biological effectiveness of proton radiation.

PURPOSE: Growing knowledge of genomic heterogeneity in cancer, especially when it results in altered DNA damage responses, requires re-examination of the generic relative biological effectiveness (RBE) of 1.1 of protons. METHODS AND MATERIALS: For determination of cellular radiosensitivity, we irradiated 17 lung cancer cell lines at the mid-spread-out Bragg peak of a clinical proton beam (linear energy transfer, 2.5 keV/µm). For comparison, 250-kVp X rays and (137)Cs γ-rays were used. To estimate the RBE of protons relative to (60)Co (Co60eq), we assigned an RBE(Co60Eq) of 1.1 to X rays to correct the physical dose measured. Standard DNA repair foci assays were used to monitor damage responses. FANCD2 was depleted using RNA interference. RESULTS: Five lung cancer cell lines (29.4%) exhibited reduced clonogenic survival after proton irradiation compared with X-irradiation with the same physical doses. This was confirmed in a 3-dimensional sphere assay. Corresponding proton RBE(Co60Eq) estimates were statistically significantly different from 1.1 (P≤.05): 1.31 to 1.77 (for a survival fraction of 0.5). In 3 of these lines, increased RBE was correlated with alterations in the Fanconi anemia (FA)/BRCA pathway of DNA repair. In Calu-6 cells, the data pointed toward an FA pathway defect, leading to a previously unreported persistence of proton-induced RAD51 foci. The FA/BRCA-defective cells displayed a 25% increase in the size of subnuclear 53BP1 foci 18 hours after proton irradiation. CONCLUSIONS: Our cell line screen has revealed variations in proton RBE that are partly due to FA/BRCA pathway defects, suggesting that the use of a generic RBE for cancers should be revisited. We propose that functional biomarkers, such as size of residual 53BP1 foci, may be used to identify cancers with increased sensitivity to proton radiation.

Validation of an in-vivo proton beam range check method in an anthropomorphic pelvic phantom using dose measurements.

PURPOSE: In-vivo dosimetry and beam range verification in proton therapy could play significant role in proton treatment validation and improvements. In-vivo beam range verification, in particular, could enable new treatment techniques one of which could be the use of anterior fields for prostate treatment instead of opposed lateral fields as in current practice. This paper reports validation study of an in-vivo range verification method which can reduce the range uncertainty to submillimeter levels and potentially allow for in-vivo dosimetry. METHODS: An anthropomorphic pelvic phantom is used to validate the clinical potential of the time-resolved dose method for range verification in the case of prostrate treatment using range modulated anterior proton beams. The method uses a 3 × 4 matrix of 1 mm diodes mounted in water balloon which are read by an ADC system at 100 kHz. The method is first validated against beam range measurements by dose extinction measurements. The validation is first completed in water phantom and then in pelvic phantom for both open field and treatment field configurations. Later, the beam range results are compared with the water equivalent path length (WEPL) values computed from the treatment planning system XIO. RESULTS: Beam range measurements from both time-resolved dose method and the dose extinction method agree with submillimeter precision in water phantom. For the pelvic phantom, when discarding two of the diodes that show sign of significant range mixing, the two methods agree with ±1 mm. Only a dose of 7 mGy is sufficient to achieve this result. The comparison to the computed WEPL by the treatment planning system (XIO) shows that XIO underestimates the protons beam range. Quantifying the exact XIO range underestimation depends on the strategy used to evaluate the WEPL results. To our best evaluation, XIO underestimates the treatment beam range between a minimum of 1.7% and maximum of 4.1%. CONCLUSIONS: Time-resolved dose measurement method satisfies the two basic requirements, WEPL accuracy and minimum dose, necessary for clinical use, thus, its potential for in-vivo protons range verification. Further development is needed, namely, devising a workflow that takes into account the limits imposed by proton range mixing and the susceptibility of the comparison of measured and expected WEPLs to errors on the detector positions. The methods may also be used for in-vivo dosimetry and could benefit various proton therapy treatments.

Mapping (15)O production rate for proton therapy verification.

PURPOSE: This work was a proof-of-principle study for the evaluation of oxygen-15 ((15)O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. METHODS AND MATERIALS: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of (15)O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. RESULTS: PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of (15)O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using (15)O decay constant, whereas the live thigh activity decayed faster. Most importantly, the (15)O production rates agreed within 2% (P>.5) between conditions. CONCLUSIONS: We developed a new method for quantitative measurement of (15)O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of (15)O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, (15)O clearance rates may be useful in monitoring permeability changes due to therapy.

Range verification of passively scattered proton beams using prompt gamma-ray detection.

We performed an experimental study to verify the range of passively scattered proton beams by detecting prompt gamma-rays emitted from proton-nuclear interactions. A method is proposed using a single scintillation detector positioned near the distal end of the irradiated target. Lead shielding was used to attenuate gamma-rays emitted along most of the entrance path of the beam. By synchronizing the prompt gamma-ray detector to the rotation of the range modulation wheel, the relation between the gamma emission from the distal part of the target and the range of the incident proton beam was determined. In experiments with a water phantom and an anthropomorphic head phantom, this relation was found to be sensitive to range shifts that were introduced. The wide opening angle of the detector enabled a sufficient signal-to-background ratio to be achieved in the presence of neutron-induced background from the scattering and collimating devices. Uniform range shifts were detected with a standard deviation of 0.1 mm to 0.2 mm at a dose level of 30 cGy to 50 cGy (RBE). The detectable magnitude of a range shift limited to a part of the treatment field area was approximately proportional to the ratio between the field area and the area affected by the range shift. We conclude that it is feasible to detect changes in the range of passively scattered proton beams using a relatively simple prompt gamma-ray detection system. The method can be employed for in vivo verification of the consistency of the delivered range in fractionated treatments.

Range verification of passively scattered proton beams based on prompt gamma time patterns.

We propose a proton range verification technique for passive scattering proton therapy systems where spread out Bragg peak (SOBP) fields are produced with rotating range modulator wheels. The technique is based on the correlation of time patterns of the prompt gamma ray emission with the range of protons delivering the SOBP. The main feature of the technique is the ability to verify the proton range with a single point of measurement and a simple detector configuration. We performed four-dimensional (time-dependent) Monte Carlo simulations using TOPAS to show the validity and accuracy of the technique. First, we validated the hadronic models used in TOPAS by comparing simulations and prompt gamma spectrometry measurements published in the literature. Second, prompt gamma simulations for proton range verification were performed for the case of a water phantom and a prostate cancer patient. In the water phantom, the proton range was determined with 2 mm accuracy with a full ring detector configuration for a dose of ~2.5 cGy. For the prostate cancer patient, 4 mm accuracy on range determination was achieved for a dose of ~15 cGy. The results presented in this paper are encouraging in view of a potential clinical application of the technique.

Proton radiography and proton computed tomography based on time-resolved dose measurements.

We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time­dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (~100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed pCT images of a cylindrical phantom containing inserts of different materials. As for all conventional pCT systems, the method illustrated in this work produces tomographic images that are potentially more accurate than x-ray CT in providing maps of proton relative stopping power (RSP) in the patient without the need for converting x-ray Hounsfield units to proton RSP. All phantom tests produced reasonable results, given the currently limited spatial and time resolution of the prototype detector. The dose required to produce one radiographic image, with the current settings, is ~0.7 cGy. Finally, we discuss a series of techniques to improve the resolution and accuracy of radiographic and tomographic images for the future development of a full-scale detector.

Clinical application of in-room positron emission tomography for in vivo treatment monitoring in proton radiation therapy.

PURPOSE: The purpose of this study is to evaluate the potential of using in-room positron emission tomography (PET) for treatment verification in proton therapy and for deriving suitable PET scan times. METHODS AND MATERIALS: Nine patients undergoing passive scattering proton therapy underwent scanning immediately after treatment with an in-room PET scanner. The scanner was positioned next to the treatment head after treatment. The Monte Carlo (MC) method was used to reproduce PET activities for each patient. To assess the proton beam range uncertainty, we designed a novel concept in which the measured PET activity surface distal to the target at the end of range was compared with MC predictions. The repositioning of patients for the PET scan took, on average, approximately 2 minutes. The PET images were reconstructed considering varying scan times to test the scan time dependency of the method. RESULTS: The measured PET images show overall good spatial correlations with MC predictions. Some discrepancies could be attributed to uncertainties in the local elemental composition and biological washout. For 8 patients treated with a single field, the average range differences between PET measurements and computed tomography (CT) image-based MC results were <5 mm (<3 mm for 6 of 8 patients) and root-mean-square deviations were 4 to 11 mm with PET-CT image co-registration errors of approximately 2 mm. Our results also show that a short-length PET scan of 5 minutes can yield results similar to those of a 20-minute PET scan. CONCLUSIONS: Our first clinical trials in 9 patients using an in-room PET system demonstrated its potential for in vivo treatment monitoring in proton therapy. For a quantitative range prediction with arbitrary shape of target volume, we suggest using the distal PET activity surface.

Immediate effects of plantar inputs on the upper half muscles and upright posture: a preliminary study.

This purpose of this study was to investigate the immediate effects of plantar inputs on both the upper half muscle activity (anterior temporal, masseter, digastric, sternocleidomastoid, upper and lower trapezius, cervical) and the body posture, by means of electromyography (EMG) and vertical force platform, respectively. Twenty four (24) healthy adults, between the ages of 24 and 31 years (25.3 +/- 1.9), with no history of craniomandibular disorder or systemic musculoskeletal dysfunction, were randomly divided into two groups: test group (fourteen subjects) and control group (ten subjects). A first recording session (TO) measured the baseline EMG and postural patterns of both groups. After this session, the test group wore test shoes with insoles that stimulated the plantar surfaces, while the control group wore placebo shoes. After one hour, a second set of measurements (T1) were performed. Significant differences between the groups at baseline were observed in the left anterior temporal, left cervical, and left upper trapezius, as well as at T1 in the left anterior temporal and right upper trapezius (p < 0.05). Within-test group analysis showed a significant increase of the right upper trapezius activity (p < 0.05), whereas no changes were found by within-control group analysis. Lower risk of asymmetric muscle patterns and postural blindness in the test group compared to the control group was observed. Further studies are warranted to investigate the short and long-term effects of this type of insole, in patients with both craniomandibular-cervical and lower extremity disorders.