On dosimetric characteristics of detectors for relative dosimetry in small fields: a multicenter experimental study.

Objective. In this multicentric collaborative study, we aimed to verify whether the selected radiation detectors satisfy the requirements of TRS-483 Code of Practice for relative small field dosimetry in megavoltage photon beams used in radiotherapy, by investigating four dosimetric characteristics. Furthermore, we intended to analyze and complement the recommendations given in TRS-483.Approach. Short-term stability, dose linearity, dose-rate dependence, and leakage were determined for 17 models of detectors considered suitable for small field dosimetry. Altogether, 47 detectors were used in this study across ten institutions. Photon beams with 6 and 10 MV, with and without flattening filters, generated by Elekta Versa HDTMor Varian TrueBeamTMlinear accelerators, were used.Main results. The tolerance level of 0.1% for stability was fulfilled by 70% of the data points. For the determination of dose linearity, two methods were considered. Results from the use of a stricter method show that the guideline of 0.1% for dose linearity is not attainable for most of the detectors used in the study. Following the second approach (squared Pearson's correlation coefficientr2), it was found that 100% of the data fulfill the criteriar2> 0.999 (0.1% guideline for tolerance). Less than 50% of all data points satisfied the published tolerance of 0.1% for dose-rate dependence. Almost all data points (98.2%) satisfied the 0.1% criterion for leakage.Significance. For short-term stability (repeatability), it was found that the 0.1% guideline could not be met. Therefore, a less rigorous criterion of 0.25% is proposed. For dose linearity, our recommendation is to adopt a simple and clear methodology and to define an achievable tolerance based on the experimental data. For dose-rate dependence, a realistic criterion of 1% is proposed instead of the present 0.1%. Agreement was found with published guidelines for background signal (leakage).

Online Adaptive MRI-Guided Stereotactic Body Radiotherapy for Pancreatic and Other Intra-Abdominal Cancers.

A 1.5T MRI combined with a linear accelerator (Unity®, Elekta; Stockholm, Sweden) is a device that shows promise in MRI-guided stereotactic body radiation treatment (SBRT). Previous studies utilized the manufacturer's pre-set MRI sequences (i.e., T2 Weighted (T2W)), which limited the visualization of pancreatic and intra-abdominal tumors and organs at risk (OAR). Here, a T1 Weighted (T1W) sequence was utilized to improve the visualization of tumors and OAR for online adapted-to-position (ATP) and adapted-to-shape (ATS) during MRI-guided SBRT. Twenty-six patients, 19 with pancreatic and 7 with intra-abdominal cancers, underwent CT and MRI simulations for SBRT planning before being treated with multi-fractionated MRI-guided SBRT. The boundary of tumors and OAR was more clearly seen on T1W image sets, resulting in fast and accurate contouring during online ATP/ATS planning. Plan quality in 26 patients was dependent on OAR proximity to the target tumor and achieved 96 ± 5% and 92 ± 9% in gross tumor volume D90% and planning target volume D90%. We utilized T1W imaging (about 120 s) to shorten imaging time by 67% compared to T2W imaging (about 360 s) and improve tumor visualization, minimizing target/OAR delineation uncertainty and the treatment margin for sparing OAR. The average time-consumption of MRI-guided SBRT for the first 21 patients was 55 ± 15 min for ATP and 79 ± 20 min for ATS.

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine.

PURPOSE: Biology-guided radiotherapy (BgRT) is a new external beam radiation therapy modality combining PET-CT with a linear accelerator that has the potential to track and treat one or more tumors in real-time. The use of PET and radiopharmaceutical tracers introduces new processes that are different from the existing treatment processes. In this study, we have developed a process map for the clinical implementation of a prototype BgRT machine. METHODS: A team of 13 members from various radiation therapy disciplines at our institution participated in developing a prospective process map for a prototype BgRT machine. The methodology provided by the AAPM TG 100 report was followed. In particular, the steps unique to the BgRT workflow, using hypofractionated stereotactic body radiation therapy with fluorodeoxyglucose radiolabeled with fluorine-18 (FDG) to guide beam delivery, were analyzed. RESULTS: The multi-disciplinary team in the department of radiation oncology at our institution developed a prospective process map for the clinical BgRT workflow. By focusing on the appropriate level of detail, 15 major subprocesses, 133 steps, and 248 substeps were identified and the process map was agreed upon as being useful, implementable, and manageable. Seventy-four steps from nine subprocesses, 55.6% of the whole process, were analyzed to be the BgRT unique steps. They originate mainly from: (1) acquiring multiple PET images at the BgRT machine with separate patient visits, (2) creating a unique biological treatment volume for BgRT plan (PTVBgRT ), and (3) BgRT plan optimization and treatment delivery using PET images. CONCLUSION: Using BgRT to irradiate multiple metastases in the same session will impact clinical workflow, thus a graphical process map depicting the new clinical workflow with an appropriate level of detail is critical for efficient, safe, and high-quality care. The prospective process map will guide the successful setup and use of the new BgRT system.

Application of TG-100 risk analysis methods to the acceptance testing and commissioning process of a Halcyon linear accelerator.

PURPOSE: A new type of linear accelerator (linac) was recently introduced into the market by a major manufacturer. Our institution is one of the early users of this preassembled and preconfigured dual-layer multileaf collimator (MLC), ring-gantry linac - Halcyon™ (1st version). We performed a set of full acceptance testing and commissioning (ATC) measurements for three Halcyon machines and compared the measured data with the standard beam model provided by the manufacturer. The ATC measurements were performed following the guidelines given in different AAPM protocols as well as guidelines provided by the manufacturer. The purpose of the present work was to perform a risk assessment of the ATC process for this new type of linac and investigate whether the results obtained from this analysis could potentially be used as a guideline for improving the design features of this type of linac. METHODS: AAPM's TG100 risk assessment methodology was applied to the ATC process. The acceptance testing process relied heavily on the use of a manufacturer-supplied phantom and the automated analysis of electronic portal imaging device (EPID) images. For the commissioning process, a conventional measurement setup and process (e.g., use of water tank for scanning) was largely used. ATC was performed using guidelines recommended in various AAPM protocols (e.g., TG-106, TG-51) as well as guidelines provided by the manufacturer. Six medical physicists were involved in this study. Process maps, process steps, and failure modes (FMs) were generated for the ATC procedures. Failure modes and effects analysis (FMEA) were performed following the guidelines given in AAPM TG-100 protocol. The top 5 and top 10 highest-ranked FMs were identified for the acceptance and commissioning procedures, respectively. Quality control measures were suggested to mitigate these FMs. RESULTS: A total of 38 steps and 88 FMs were identified for the entire ATC process. Fourteen steps and 34 FMs arose from acceptance testing. The top 5 FMs that were identified could potentially be mitigated by the manufacturer. For commissioning, a total of 24 steps and 54 potential FMs were identified. The use of separate measurement tools that are not machine-integrated has been identified as a cause for the higher number of steps and FMs generated from the conventional ATC approach. More than half of the quality control measures recommended for both acceptance and commissioning could potentially be incorporated by the manufacturer in the design of the Halcyon machine. CONCLUSION: This paper presents the results of FMEA and quality control measures to mitigate the FMs for the ATC process for Halcyon machine. Unique FMs that result from the differences in the ATC guidelines provided by the vendor and current conventional protocols, and the challenges of performing the ATC due to the new linac features and ring-gantry design were highlighted for the first time. The FMs identified in the present work along with the suggested quality control measures, could potentially be used to improve the design features of future ring-gantry type of linacs that are likely to be preassembled, preconfigured, and heavily reliant on automation and image guidance.

A dosimetric evaluation of the IAEA-AAPM TRS483 code of practice for dosimetry of small static fields used in conventional linac beams and comparison with IAEA TRS-398, AAPM TG51, and TG51 Addendum protocols.

PURPOSE: The International Atomic Energy Agency (IAEA) and the American Association of Physicists in Medicine (AAPM) have jointly published a new code of practice (CoP), TRS483, for the dosimetry of small static photon fields used in external beam radiotherapy. It gave recommendations on how to perform reference dosimetry in nonstandard machine-specific reference (msr) fields and measure field output factors in small fields. The purpose of this work was to perform a dosimetric evaluation of the recommendations given in this CoP. METHODS: All measurements were done in a Varian TrueBeam™ STx linear accelerator. Five ionization chambers were used for beam quality measurements, four Farmer type ionization chambers for performing reference dosimetry and two diodes for performing field output factor measurements. Field output factor measurements were done for fourteen field sizes (ranging from 0.5 cm × 0.5 cm to 10 cm × 10 cm). Beam energies used were: 6 MV WFF, 6 MV FFF, 10 MV WFF, and 10 MV FFF. Where appropriate, results from this study were compared with those obtained from the recommendations given in the IAEA TRS398 CoP, AAPM TG51 and TG51 Addendum protocols. RESULTS: Beam quality measurements show that for all beam energies and for equivalent square msr field sizes ranging from 4 cm × 4 cm to 10 cm × 10 cm, agreement between calculated and measured values of TPR20,10 (10) was within 0.6%. When %dd(10,10)X was used as beam quality specifier, the agreement was found to be within 0.8%. Absorbed dose to water per unit monitor unit at the depth of maximum dose zmax in a beam of quality Q, Dw,Qzmax/MU, was determined using both %dd(10,10)X and TPR20,10 (10) as beam quality specifiers. Measured ratios of Dw,Q (zmax )/MU, determined using the two approaches, ranged between 0.999 and 1.000 for all the beam energies investigated. Comparison with TRS398, TG51 and TG51 addendum protocols show that depending on beam energy, the mean values of the ratios TRS398/TRS483, TG51/TRS483, and TG51 Addendum/TRS483 of Dw,Q (zmax )/MU determined using both approaches show excellent agreement with TRS398 CoP (to within 0.05%); agreement with TG51 and TG51 addendum was to within 0.3% for all four beam energies investigated. Field output factors, determined using the two methods recommended in the TRS483 CoP, showed excellent agreement between the two methods. For the 1 cm collimator field size, the mean value of the field output factor obtained from an average of the two detectors investigated was found to be 2% lower than the mean value of the uncorrected ratio of readings. CONCLUSION: For beams with and without flattening filters, the values of Dw,Q (zmax )/MU obtained following the new CoP are found to be consistent with those obtained using TRS398, TG51 and TG51 addendum protocols to within 0.3%. Field output factors for small beams can be improved when the correction factors for different detectors included in TRS483 are appropriately incorporated into their dosimetry.

Comparison of the recommendations of the AAPM TG-51 and TG-51 addendum reference dosimetry protocols.

This work quantified differences between recommendations of the TG-51 and TG-51 addendum reference dosimetry protocols. Reference dosimetry was performed for flattened photon beams with nominal energies of 6, 10, 15, and 23 MV, as well as flattening-filter free (FFF) beam energies of 6 and 10 MV, following the recommendations of both the TG-51 and TG-51 addendum protocols using both a Farmer® ionization chamber and a scanning ionization chamber with calibration coefficients traceable to absorbed dose-to-water (Dw ) standards. Differences in Dw determined by the two protocols were 0.1%-0.3% for beam energies with a flattening filter, and up to 0.2% and 0.8% for FFF beams measured with the scanning and Farmer® ionization chambers, respectively, due to kQ determination, volume-averaging correction, and collimator jaw setting. Combined uncertainty was between 0.91% and 1.2% (k = 1), varying by protocol and detector.

Electromechanical and structural alterations in the aging rabbit heart and aorta.

Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5-9 mo) and old (3.5-6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 ± 0.36 vs. old, 4.35 ± 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 ± 0.5 vs. 4.95 ± 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 ± 4.2 vs. 33.14 ± 8.4 mmHg/ml, P < 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 ± 2.5 vs. 31.9 ± 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age-related changes that predispose the aging heart to arrhythmias and SCD.

ATLAS CONSTRUCTION FROM HIGH ANGULAR RESOLUTION DIFFUSION IMAGING DATA REPRESENTED BY GAUSSIAN MIXTURE FIELDS.

Groupwise image registration is an essential part of atlas construction which is a very import and challenging task in medical image analysis. In this paper, we present a novel atlas construction technique using a groupwise registration of high angular resolution diffusion (MR) imaging datasets each of which is represented by a Gaussian Mixture field. To solve the registration problem, an L(2) distance is used to measure the similarity between two Gaussian Mixtures, which leads to an energy function whose gradient can be computed in closed form. A projection method is developed to construct a "sharp" (not blurred) atlas from the result of this groupwise registration. Synthetic and real data experiments are presented to demonstrate the efficacy of the proposed method.

Regularized positive-definite fourth order tensor field estimation from DW-MRI.

In Diffusion Weighted Magnetic Resonance Image (DW-MRI) processing, a 2nd order tensor has been commonly used to approximate the diffusivity function at each lattice point of the DW-MRI data. From this tensor approximation, one can compute useful scalar quantities (e.g. anisotropy, mean diffusivity) which have been clinically used for monitoring encephalopathy, sclerosis, ischemia and other brain disorders. It is now well known that this 2nd-order tensor approximation fails to capture complex local tissue structures, e.g. crossing fibers, and as a result, the scalar quantities derived from these tensors are grossly inaccurate at such locations. In this paper we employ a 4th order symmetric positive-definite (SPD) tensor approximation to represent the diffusivity function and present a novel technique to estimate these tensors from the DW-MRI data guaranteeing the SPD property. Several articles have been reported in literature on higher order tensor approximations of the diffusivity function but none of them guarantee the positivity of the estimates, which is a fundamental constraint since negative values of the diffusivity are not meaningful. In this paper we represent the 4th-order tensors as ternary quartics and then apply Hilbert's theorem on ternary quartics along with the Iwasawa parametrization to guarantee an SPD 4th-order tensor approximation from the DW-MRI data. The performance of this model is depicted on synthetic data as well as real DW-MRIs from a set of excised control and injured rat spinal cords, showing accurate estimation of scalar quantities such as generalized anisotropy and trace as well as fiber orientations.